Journal

International Journal of Clinical Oncology

Papers (136)

Postoperative lymphocyst formation after pelvic lymphadenectomy for gynecologic cancers: comparison between laparoscopy and laparotomy

The goal of this study was to evaluate, using definitive diagnostic criteria, the incidence of lymphocyst formation following pelvic lymphadenectomy for gynecological cancer, and to compare rates between the approaches of laparoscopy and laparotomy. We retrospectively reviewed the medical records of all patients who underwent pelvic lymphadenectomy for cervical or endometrial cancer between March of 2010 and March of 2016. We defined a lymphocyst as a circumscribed collection of fluid within the pelvic cavity, with a diameter of 2 cm or more, as diagnosed with ultrasound or computed tomography. During the six-year observational period, a pelvic lymphadenectomy was conducted in 196 women with clinical stage I uterine cancer; 90 cases underwent laparoscopy, 106 underwent laparotomy. The minimally invasive laparoscopic group had a lower estimated blood loss (p < 0.01), shorter hospital stay (p < 0.01). Lymphocysts were observed in 14.4% (13/90) of the laparoscopy cases, and in 15.1% (16/106) of the laparotomy cases which means no significant difference of lymphocyst (p = 1.00). The median size of symptomatic lymphocyst was significantly larger in laparotomy group than in laparoscopy group (4.8 cm v.s. 2.8 cm, median) (p = 0.04). Symptomatic lymphocysts were more common in laparotomy [7/90 (7.8%) vs 14/106 (13.2%) (p = 0.253)]. In a retrospective analysis with a strict diagnostic criteria, we could find no statistical difference in lymphocyst occurrence between laparoscopy and laparotomy. The median size of the lymphocyst was bigger and lymphocyst was likely to be symptomatic in the laparotomy group.

Human epidermal growth factor receptor 3 expression in patients with epithelial ovarian cancer: a potential target for ovarian mucinous and clear cell carcinoma

Human epidermal growth factor receptor 3 (HER3), a tyrosine kinase belonging to the HER family, is a known target for cancer therapy; recently, an anti-HER3 antibody-drug conjugate (ADC) is developing. To understand HER3 expression in epithelial ovarian cancer (EOC), this study was conducted. We investigated the expression of HER3 in 202 patients with EOC using immunohistochemistry (IHC), and the association between HER3 expression, clinicopathological features, prognosis, and treatment timing. Of all the cases, 55.4% had a HER3 IHC score ≥ 1 + . In particular, 78.0% of the patients with clear cell carcinoma (CCC) and 87.9% of the patients with mucinous carcinoma (MC) had a HER3 IHC score ≥ 1 + . Regarding clinicopathological features, early disease stage, feasibility of primary debulking surgery, no residual tumor, and low CA125 levels were more frequently observed in patients with a HER3 IHC score ≥ 1 + . Furthermore, a HER3 no-expression showed a significant association with a relatively short progression-free survival (PFS). And, for patients with mucinous carcinoma, those with a HER3 IHC score ≥ 1 + had poorer PFS and overall survival than those with a HER3 no-expression (no statistically significant difference). In addition, we analyzed HER3 expression at primary tumor and recurrence tumor in same patients. Thus, we observed the HER3 IHC score tended to change from 0 to ≥ 1 + in recurrence cases compared with primary cases. These observations suggested that patients with MC, CCC and recurrence of all histological type may potentially benefit from future clinical trials of HER3-directed therapies.

Real-life observational study on niraparib in older patients with primary tubo-ovarian cancer: a focus on safety and efficacy

Abstract Background Niraparib is approved for maintenance treatment of tubo-ovarian cancer patients, but data on older patients are limited. This retrospective study evaluated its safety and efficacy in primary advanced tubo-ovarian cancer, focusing on patients ≥ 75 years. Methods Women aged ≥ 50 years diagnosed with primary high-grade serous tubo-ovarian cancer, treated with niraparib between 2019–2023, were enrolled. Patients were stratified into three groups: A (50–64 years), B (65–74 years), and C (≥ 75 years). The primary outcome was progression-free survival. The secondary outcomes were toxicity and dose reduction. Results 127 patients were identified: 62 (48.8%) group A, 26 (20.5%) group B, and 39 (30.7%) group C. Baseline characteristics were comparable across groups, excluding a higher proportion of interval cytoreductive surgeries ( p  = 0.001), residual tumor ( p  = 0.01) and Eastern Cooperative Oncology Group (ECOG) &gt; 1 ( p  = 0.01) in group C. Most patients started niraparib at 200 mg/day with dose reductions primarily occurred within fourth cycle. Dose reductions were observed in 77.4%, 69.2% and 56.4% of patients in groups A, B, and C, respectively ( p  = 0.08). In patients ≥ 75 years, 26 (66.7%) discontinued treatment due to disease progression (48.7%) or toxicity (17.9%). There were no significant differences in common or grade ≥ 3 adverse events between groups. Progression-free survival was 12 months (95%CI: 2.0–25.0) for group A, 29 months (95%CI: 11.0–52.0) for group B, and 16 months (95%CI: 1.0–31.0) for group C ( p  = 0.78). Conclusions Our findings suggest that niraparib is safe and well-tolerated in aged ≥ 75 years. Concerns about toxicity should not preclude the enrollment of elderly patients in treatment regiments.

Trends in fertility preservation treatments in Japan until 2023: analysis of the Japan Oncofertility Registry

Abstract Background Fertility preservation for patients with cancer or other diseases who receive gonadotoxic treatment has gained importance as cancer survival rates increase. In Japan, a database for registering all fertility preservation patients, named the Japan Oncofertility Registry (JOFR), was established in 2018. This study aimed to analyze recent trends in fertility preservation in Japan utilizing data from the JOFR. Methods Data was extracted from the JOFR for patients who consulted fertility preservation teams until May 2024. A descriptive analysis was conducted to examine trends in patient demographics, cancer types, fertility preservation treatments, complications, and outcomes. The data covered the period from diagnosis to fertility preservation and subsequent usage or disposal of frozen specimens. Results A total of 11,510 patients were recorded, with 9491 undergoing fertility preservation treatments. The number of patients increased steadily after 2006. After 2021, the number of female patients was much higher than the number of male patients. The most common primary diseases were breast cancer among women and testicular tumors and leukemia among men. There were some complications including ovarian hyperstimulation syndrome (5.0%), bleeding (0.12%), and infections (0.05%) for women. Seven hundred and sixty clinical pregnancies were recorded, with 440 using preserved specimens. The discard rate was 16.3% for men and 3.7% for women. Conclusion The study highlights recent trends in the growing number of cases undergoing fertility preservation in Japan. It also identifies several issues to be solved in fertility preservation in Japan, regarding its efficacy and safety, as well as the medical provision system.

Cytokine dynamics and quality of life: unraveling the impact of cell-free and concentrated ascites reinfusion therapy in ovarian cancer patients

Abstract Background The quality of life (QOL) of ovarian cancer patients is often impaired by refractory ascites. Cell-free and concentrated ascites reinfusion therapy (CART) is a palliative treatment for refractory ascites, but adverse events, such as fever, are problematic. Several cytokines have been suggested to be responsible for the adverse events, but they have not been investigated in detail. Thus, we comprehensively analyzed cytokines in ascites fluid (AF) and serum before and after CART to determine the influence of cytokines on the safety and efficacy of CART. Methods Thirteen ovarian cancer patients with refractory malignant ascites who underwent CART were enrolled. We comprehensively analyzed 27 cytokines in AF and serum before and after CART. Simultaneously, vital measurements, blood tests, adverse event recordings, and QOL assessments were performed to examine the relationships between the cytokines in AF and serum. Results Interleukin (IL)-5, IL-6, IL-10, and monocyte chemoattractant protein-1 levels were increased in the concentrated AF and in the serum immediately after reinfusion, but they decreased after 24 h. Body temperature also increased immediately after reinfusion, and decreased after 24 h. The CRP level at 24 h after reinfusion was increased, and was positively correlated with the IL-6 level. A QOL assessment using the Cancer Fatigue Scale revealed significantly lower scores after CART. Conclusions The results indicate that the cytokine-induced fever and increased inflammatory response after CART were temporary, and that CART is safe. Additionally, QOL improved after CART. Thus, CART appears safe and effective for treating patients with refractory cancerous ascites.

Incidence and molecular characteristics of deficient mismatch repair conditions across nine different tumors and identification of germline variants involved in Lynch-like syndrome

Abstract Background Based on molecular characteristics, deficient DNA mismatch repair (dMMR) solid tumors are largely divided into three categories: somatically MLH1-hypermethylated tumors, Lynch syndrome (LS)-associated tumors, and Lynch-like syndrome (LLS)-associated tumors. The incidence of each of these conditions and the corresponding pathogenic genes related to LLS remain elusive. Methods We identified dMMR tumors in 3609 tumors from 9 different solid organs, including colorectal cancer, gastric cancer, small-bowel cancer, endometrial cancer, ovarian cancer, upper urinary tract cancer, urinary bladder cancer, prostate cancer, and sebaceous tumor, and comprehensively summarized the characterization of dMMR tumors. Characterization of dMMR tumors were performed as loss of at least one of MMR proteins (MLH1, MSH2, MSH6, and PMS2), by immunohistochemistry, followed by MLH1 promotor methylation analysis and genetic testing for MMR genes where appropriate. Somatic variant analysis of MMR genes and whole exome sequencing (WES) were performed in patients with LLS. Results In total, the incidence of dMMR tumors was 5.9% (24/3609). The incidence of dMMR tumors and the proportion of the three categorized dMMR tumors varied considerably with different tumor types. One to three likely pathogenic/pathogenic somatic MMR gene variants were detected in 15 out of the 16 available LLS tumors. One patient each from 12 patients who gave consent to WES demonstrated non-MMR germline variants affect function (POLQ or BRCA1). Conclusions Our data regarding the LS to LLS ratio would be useful for genetic counseling in patients who are suspected to have LS, though the genetic backgrounds for the pathogenesis of LLS need further investigation.

Trends in the management and prognosis of mucinous borderline ovarian tumors: analysis of 12,766 cases from the JSOG Gynecologic Tumor Registry (2004–2018)

Abstract Background Mucinous borderline ovarian tumors (MBOTs) are rare neoplasms with excellent prognosis, yet the optimal surgical extent remains controversial. No large-scale study in Japan has evaluated treatment trends and prognostic factors for MBOTs. This study aimed to clarify their clinicopathological features, management patterns, and survival outcomes using a nationwide registry. Methods Data were obtained from the Japan Society of Obstetrics and Gynecology Gynecologic Tumor Registry, including 96,476 ovarian tumors treated between 2004 and 2018. Among them, 12,766 MBOT cases were identified. Surgical procedures—hysterectomy, omentectomy, lymphadenectomy, and adjuvant chemotherapy—were analyzed. Survival analyses of 8564 cases with complete prognostic data were performed using Kaplan–Meier and Cox proportional hazards models. Results Over 90% of MBOTs were stage I, and the median age was 52 years. Hysterectomy was performed in 50.8%, omentectomy in 57.9% (2015–2018 subset), and lymphadenectomy in 7.6%. Only 2.6% received adjuvant chemotherapy. The 5-year overall survival exceeded 95%. Multivariate analysis identified age ≥ 50 years (HR 2.5, 95% CI 1.8–3.6) and stage IC (HR 2.7, 95% CI 1.9–3.6) as independent adverse factors. Omentectomy showed a marginal survival benefit (HR 0.6, p  = 0.05), whereas hysterectomy, lymphadenectomy, and chemotherapy conferred no advantage. Chemotherapy correlated with poorer outcomes, likely due to confounding by indication. Conclusions This nationwide cohort—the largest MBOT series reported to date—demonstrates conservative management with excellent prognosis in Japan. Radical surgery and chemotherapy provide no survival benefit, whereas fertility-sparing surgery appears appropriate for younger patients.

Prognostic factors of lenvatinib plus pembrolizumab therapy for advanced or recurrent endometrial cancer: analysis of a multicenter cohort study in Japan

Abstract Background Lenvatinib plus pembrolizumab (LP) therapy has emerged as an effective treatment for patients with advanced or recurrent endometrial cancer. However, limited data are available regarding its outcomes in real-world settings. This study aimed to identify prognostic factors associated with the efficacy of LP therapy. Methods This multicenter observational study was conducted across 15 institutions in Japan and examined patients with endometrial cancer, including uterine carcinosarcoma, who experienced disease progression after receiving at least one platinum-based chemotherapy, including adjuvant treatment, and subsequently received LP therapy. The prognostic factors for progression-free survival were assessed using a multivariate Cox proportional hazards model. Results A total of 105 patients met the inclusion criteria. Improved progression-free survival was independently associated with performance status of 0 (adjusted hazard ratio [aHR] 0.42, 95% confidence interval [CI] 0.23–0.75), platinum-free interval (PFI) of ≥ 6 months (aHR 0.46, 95% CI 0.28–0.78), histology of grade 1–2 endometrioid carcinoma (aHR 0.52, 95% CI 0.30–0.91), and relative dose intensity during the initial 8 weeks (8w-RDI) of lenvatinib of ≥ 50% (aHR 0.53, 95% CI 0.31–0.91). Patients with PFI of ≥ 6 months also demonstrated improved overall survival (HR 0.44, 95% CI 0.25–0.76) and objective response rate (44.0% versus 20.0%, P  = 0.011) compared with those with PFI of &lt; 6 months. Additionally, 8w-RDI of lenvatinib ≥ 50% was associated with improved overall survival (HR 0.53, 95% CI 0.30–0.92) compared to those with &lt; 50%. Conclusions This study identified several novel prognostic factors for LP therapy. Among them, PFI may inform treatment selection for recurrent endometrial cancer following chemotherapy. Clinical trial registration University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) 000049997.

Impact of obesity on the outcomes and cost of robotic surgery for Stage IA endometrial cancer: a regional perspective from Japan

Abstract Background The incidence of endometrial cancer in Japan has more than doubled over the past 2 decades because of increasing obesity rates and the unique physiological traits of Asian populations. The aim of this retrospective study was to examine the impact of obesity on surgical outcomes, prognosis, and costs. Methods A total of 197 patients with stage IA endometrial cancer who underwent robot-assisted hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy/biopsy from 2018 onward were included. Patients were divided into the BMI &lt; 30 kg/m 2 group (n = 117) and the BMI ≥ 30 kg/m 2 group (n = 80). The clinical and pathological factors, surgical outcomes, perioperative complications, and treatment costs were compared. The median follow-up period was 34.9 months (range: 6.1–84.2). Results In the BMI ≥ 30 kg/m 2 group, significant differences in comorbidities, including diabetes mellitus (19.7% vs. 51.3%), hypertension (43.6% vs. 58.8%), and hyperlipidemia (29.9% vs. 50%), were detected. However, no significant differences were found in operative time, blood loss volume, perioperative complication rates, or 5-year cancer-specific survival rates (97.6% vs. 100%). Surgical and hospitalization costs were higher in the BMI ≥ 30 kg/m 2 group, indicating a financial burden for both patients and healthcare facilities. Additionally, a higher prevalence of newly developed lifestyle-related diseases, such as cardiovascular diseases and diabetes, was observed during the follow-up (2.5% vs. 10%). Conclusions While obesity (BMI ≥ 30) did not significantly impact surgical outcomes or cancer prognoses, it did increase treatment costs and the risk of lifestyle-related diseases. Thus, preventive strategies, including lifestyle counseling, are needed to reduce obesity-related health burdens.

Clinical outcomes of sentinel node navigation surgery in patients with preoperatively estimated stage IA endometrial cancer and evaluation of validity for continuing sentinel node navigation surgery based on dispersion of recurrence probability

Abstract Background To evaluate the feasibility of the use and continuation of sentinel lymph node navigation surgery (SNNS) as an alternative to pelvic lymph node dissection (PLND) for patients with preoperatively estimated stage IA endometrial cancer. Methods This retrospective study selected the electronic medical records of all patients who had received CT scans and MRI imaging before surgery from April 1, 2009 to March 31, 2021. Sentinel lymph nodes (SLNs) were detected by administrating 99m Tc-phytate and/or indocyanine green into the cervix, and the clinical outcomes of the patients who underwent SNNS or PLND were evaluated. Furthermore, in case of nodal recurrence, a new procedure to determine whether the facility should continue with SNNS or not was developed that compares the maximum likelihood hypothesis and an alternative one based on recurrence rates. Results Among 137 patients, SLN biopsies with ultrastaging were performed on 91 patients. The SLN detection rate was 95.6%. Over a 59-month median observation period, no statistically significant differences were shown in overall survival, disease-specific survival and disease-free survival between the SNNS and PLND groups when introducing the propensity score method (p-values: 0.06, 0.153, and 0.625, respectively). Our procedure demonstrated that, in our department without recurrence up to the 65th attempt, it was possible to continue SNNS if a recurrence occurs at the 66th attempt. Conclusion This study suggests the validity of SNNS as an alternative to PLND. Even in the absence of evidence from randomized controlled trials, we can confirm the validity of continuing SNNS using our procedure.

Lymphadenectomy and chemotherapy are effective treatments for patients with 2023 international federation of gynecology and obstetrics stage IIC-high risk endometrial cancer in Japan

Abstract Background In early-stage endometrial cancer (EC), the treatment of aggressive histological subtypes (endometrioid carcinoma grade 3, serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed carcinoma, and carcinosarcoma) is controversial. We aimed to investigate the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage IIC EC according to the 2023 classification. Methods We retrospectively identified patients with FIGO 2023 stage IC, IIC-intermediate risk (IIC-I), and IIC-high risk (IIC-H) EC who underwent adjuvant therapy or observation after surgery at eight medical institutions from 2004 to 2023. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier estimates and univariate and multivariate analyses. Results The PFS and OS were significantly worse in patients with FIGO 2023 stage IIC-H EC than in those with FIGO 2023 stage IIC-I EC (PFS: p = 0.008 and OS: p = 0.006). According to the FIGO 2023 stage IIC-H classification, lymphadenectomy and chemotherapy resulted in better prognoses regarding both PFS and OS (p &lt; 0.001 for both) than other treatments. Our findings suggest that lymphadenectomy and chemotherapy effectively reduced vaginal stump and lymph node metastases in FIGO 2023 stage IIC-H EC (p &lt; 0.001 and p = 0.008, respectively). Furthermore, in the multivariate analysis, not undergoing lymphadenectomy or chemotherapy were independent predictors of recurrence and poor prognoses in patients with FIGO 2023 stage IIC-H EC (p &lt; 0.001 and p = 0.031, respectively). Conclusion Lymphadenectomy and chemotherapy resulted in better prognoses regarding both recurrence and survival in patients with FIGO 2023 stage IIC high-risk EC.

Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer

Japan's health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology. We analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne Out of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with other). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results. Through multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients' prognosis and performance status should be considered before performing the test.

Evaluation of neoadjuvant chemotherapy followed by radical hysterectomy in cervical cancer: a single-center study

Abstract Background The efficacy of neoadjuvant chemotherapy (NACT) before radical hysterectomy (RH) in cervical cancer remains unclear. We evaluated stage-specific outcomes of NACT-RH at a high-volume center. Methods This retrospective cohort study included patients with non-metastatic cT1b1–2b cervical cancer who underwent RH between 2013 and 2022. For cT1b cases, prognostic outcomes were compared between patients with cT1b3 (any N) who underwent NACT-RH (High-risk, NACT(+)) and those with cT1b1–1b2 N0 who underwent primary RH (Low-risk, NACT(−)), using propensity score matching. For cT2 cases, NACT-RH versus primary RH was compared using inverse probability weighting to adjust for baseline differences. Results Among 191 patients who underwent RH (cT1: n  = 99; cT2: n  = 92), the matched cT1 cohort comprised 15 High-risk, NACT(+) and 30 Low-risk, NACT(−) patients. Five-year progression-free survival (PFS) was 75.0% (95% confidence interval [CI], 53.4–100.0%) versus 89.9% (95% CI, 79.6–100.0%) ( p  = 0.427). Overall survival (OS) was 100% in both groups with a median follow-up of &gt; 70 months. In cT2, NACT-RH ( n  = 73) versus primary RH ( n  = 19) showed hazard ratios of 2.88 for PFS (95% CI, 0.69–11.97) and 5.64 for OS (95% CI, 0.70–45.35) after baseline adjustment. Among cT2 patients who underwent NACT-RH, PFS and OS were worse in those without an objective response to NACT ( n  = 18, all cT2b) than in responders. Conclusion NACT-RH was associated with encouraging long-term outcomes in cT1b3, whereas outcomes in cT2 cases remain uncertain, supporting careful selection and response-adapted strategies.

Comparison of nedaplatin and cisplatin in concurrent chemoradiotherapy for cervical cancer: a systematic review and meta-analysis

Abstract Background Cisplatin-based concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer; however, its nephrotoxicity and gastrointestinal toxicity often limit treatment eligibility and completion. Nedaplatin, a cisplatin analogue with reduced renal and gastrointestinal toxicity, has been increasingly used in East Asia, but its comparative efficacy and safety in cervical cancer have not been comprehensively evaluated. Methods We systematically searched MEDLINE, Embase, CENTRAL, CNKI, Ichushi Web, ICTRP, and ClinicalTrials.gov for randomized controlled trials comparing nedaplatin versus cisplatin-based CCRT. The primary efficacy outcome was all-cause mortality at 3 years, and the primary safety outcome was renal toxicity. Secondary outcomes included mortality at 1 and 5 years, progression or mortality, hematologic and gastrointestinal toxicities, liver dysfunction, and quality of life. Random-effects meta-analyses were performed using risk ratios. Results Seventeen trials met the eligibility criteria. All-cause mortality at 3 years did not differ significantly between the groups (RR 0.88; 95% CI 0.51–1.51; I 2  = 0%). Nedaplatin significantly reduced renal toxicity (RR 0.25; 95% CI 0.20–0.31; I 2  = 0%). Short-term outcomes favored nedaplatin, including lower 1 year mortality (RR 0.61; 95% CI 0.40–0.93) and fewer 1 year progression or mortality events (RR 0.63; 95% CI 0.44–0.91). The incidences of anemia and severe nausea/vomiting were also lower with nedaplatin. No eligible study assessed quality of life. Conclusion Nedaplatin showed fewer adverse effects and comparable or improved short-term outcomes compared with cisplatin. These findings support nedaplatin as a potential alternative for patients who are cisplatin-intolerant or frail. Confirmation in large, high-quality trials with long-term follow-up and patient-reported outcomes is warranted.

Safety and oncologic outcomes of total laparoscopic versus abdominal hysterectomy following diagnostic conization for adenocarcinoma in situ and stage IA1 cervical cancer: a multicenter retrospective study

Abstract Background While simple hysterectomy is the standard treatment for adenocarcinoma in situ (AIS) and stage IA1 cervical cancer, minimally invasive surgery has been increasingly adopted. However, evidence on the safety and efficacy of total laparoscopic hysterectomy (TLH) for these conditions remains limited. We compared the safety and efficacy of TLH and total abdominal hysterectomy (TAH) in patients undergoing simple hysterectomy following diagnostic conization. Methods We conducted a multicenter retrospective study of 196 patients with cervical intraepithelial neoplasia grade 3 (CIN3), AIS, or stage IA1 cervical cancer who underwent simple hysterectomy following diagnostic conization. Patients were divided into TLH and TAH groups, and intraoperative and postoperative complications and oncologic outcomes were compared. Results Operative time was significantly longer in the TLH group, whereas intraoperative blood loss was lower and postoperative hospital stay shorter. No significant difference was noted in severe complication rates, although their patterns varied between groups. Recurrence occurred in one patient (0.5%), a case of CIN3 at the vaginal cuff in the stage IA1 TAH group. No recurrences were observed in patients with AIS or stage IA1 disease in the TLH group. Conclusions TLH following diagnostic conization for AIS or stage IA1 cervical cancer demonstrated oncologic efficacy comparable to TAH, with a favorable safety profile. TLH may be a reasonable treatment option for carefully selected patients.

Lack of molecular mimicry between HPV vaccine L1 antigen and human proteins by a computational analysis

Abstract Background Although human papillomavirus (HPV) vaccines effectively prevent cervical cancer, the HPV vaccination rates in Japan remain low because of concerns about alleged neurological adverse events. Darja Kanduc proposed a flawed hypothesis that molecular mimicry between HPV and human proteins could induce cross-reactive antibodies, causing autoimmune organ damage, even when only the portions of amino acid (AA)-sequences of the epitopes were identical between HPV and human proteins. Methods In this study, we conducted the same computational data analysis as Kanduc, using 22 linear epitopes (9–23 AA-length) of the HPV type 16 L1 protein (HPV16L1) registered in the database. Results We found that no human epitopes had identical AA-sequences to any HPV16L1 epitopes, demonstrating that HPV16L1 had no molecular mimicry with linear epitopes that have the potential to induce cross-reactive autoantibodies. On the other hand, we identified various numbers of human protein epitopes whose AA-sequences were partially identical with epitopes of HPV16L1, hepatitis B virus (HBV), and respiratory syncytial virus (RSV). We found that HPV16L1 had a smaller number of such proteins having “partial molecular mimicry” than HBV and RSV. Conclusions Our current in silico analysis provided no evidence that HPV vaccinations could induce cross-reactive autoantibodies. The flawed molecular mimicry data should not be used as a scientific basis for alleged HPV vaccine-induced adverse events.

Robotic dual-docking surgery for para-aortic lymphadenectomy in endometrial cancer: a prospective feasibility study

Abstract Background The standard for robotic para-aortic lymphadenectomy has not been fully established. Para-aortic lymphadenectomy performed by sharing the same ports with pelvic procedures, a procedure known as dual-docking surgery, can be performed using the latest robotic system. We prospectively examined the ability of standardized dual-docking robotic surgery in endometrial cancer patients. Methods This study prospectively verified the feasibility and safety of dual-docking robotic surgeries performed between March 2017 and December 2021. The laterally placed ports were aligned with the umbilicus. Primary outcome was the surgical completion rate; secondary outcomes were blood loss, operative time, unexpected port placement, conversion, complications, length of hospital stay, and survival. Results Most patients (14/15, 93%) underwent surgery using our methods without additional port placements, and one patient was converted to laparotomy. Median blood loss was 162 mL (range: 20–685 mL). Median operative time was 183 and 206 min in the upper and lower abdomen. Median number of resected para-aortic lymph nodes was 19 (range: 6–29), and pelvic lymph nodes was 28 (range: 15–42). Although there was no difficulty in moving the forceps intraoperatively, major complications including vessel injury, and pelvic abscesses were observed. The lateral ports could be placed 6–10 cm apart in patients with any range of body type. Conclusion Dual-docking surgery for endometrial cancer has the potential to be a standard procedure for robotic endometrial cancer surgery, although a greater number of cases are needed to acquire proficiency.

The ‘best friend effect’: a promising tool to encourage HPV vaccination in Japan

In Japan, HPV vaccination rates has dramaticaly declined since 2013. Since mothers are the ones making the decision to vaccinate their daughters against HPV, we probed the mothers' intention to receive vaccinations for themselves and to vaccinate their daughters against HPV, and their reasoning. An internet survey was conducted in March of 2021. Through the screening, 1576 participants were extracted from a survey panel and divided into 3 groups based on their daughter's birth fiscal year (Group 1: 1994 to 1999, Group 2: 2000 to 2003, Group3: 2004 to 2008). The chi-square test and residual analysis were used for the statistical analysis of comparison among the groups. Logistic regression analysis was used to identify independent variables with mothers intention to get their daughters vaccinated under specific situations. The percentage of respondents without anxiety regarding their daughter's general vaccination was significantly higher in Group 1 (p < 0.05). In the mothers of daughters born in or after 2000 when vaccination rates declined (Groups 2 and 3), a situation in which 'The daughter's best friends were vaccinated before her' made the mothers think positively about HPV vaccination, and to the same degree as a situation in which 'You received a notice from your local government recommending vaccination' (Group 2: 41.6% (214/514) and 40.5% (208/514), Group 3: 48.5% (257/530) and 47.0% (249/530)). If mothers who have had their daughters vaccinated were to recommend HPV vaccination to their close friends, 'the best friend effect' should promote others to be vaccinated.

Outcomes of cases with complete hydatidiform mole coexisting with a fetus: a single-center study

Abstract Background Complete hydatidiform moles coexisting with a fetus (CHMCF) are uncommon. Although CHMCF is associated with perinatal complications and post-molar gestational trophoblastic neoplasia (GTN), necessitating post-delivery chemotherapy, live birth remains feasible. This report presents 14 cases of CHMCF in Japan. Methods  We reviewed medical records of patients with CHMCF treated at our hospital from 2000 to 2020 and summarized clinical data, including maternal age, pregnancy details, delivery outcomes, fertility treatments, serum human chorionic gonadotropin (hCG) levels, and ultrasonography findings. Results Fourteen cases of CHMCF were diagnosed. The average age of the mothers was 30.6 years, with the majority conceiving following fertility treatment. The mean gestational age at diagnosis was 12 weeks. Six patients maintained their pregnancies, leading to two live births through emergency cesarean section. Eight patients exhibited spontaneous regression following treatment and pregnancy interruption, achieving negative serum hCG levels within 17.4 weeks. Six patients experienced post-molar GTN, including the two who had live births. One patient presented with FIGO stage I disease, while five patients had stage III lung metastases. All patients received chemotherapy, averaging nine courses, achieving remission within 13.7 weeks. Conclusion  The occurrence of GTN was higher after CHMCF than after typical complete hydatidiform moles. Despite the heightened risk of premature birth, some patients with CHMCF who maintain their pregnancies can successfully deliver live babies. Informed consent is essential for patients with CHMCF when considering pregnancy continuation. A team approach involving gynecological oncologists, obstetricians, and neonatologists is essential for effective diagnosis and treatment.

Effects of steroid use for stenosis prevention after endoscopic submucosal dissection for cervical esophageal cancer

Esophageal stenosis is a serious complication after endoscopic submucosal dissection (ESD) for thoracic esophageal cancer (TEC), and steroid has been applied for stenosis prevention. However, the rate of stenosis and effect of steroid for ESD of cervical esophageal cancer (CEC) remain unknown. The aim was to clarify the rate and managements of post-ESD stenosis for CEC. A total of 325 lesions with 272 patients who underwent ESD for esophageal cancers were enrolled and were divided to the CEC group (43 lesions) or the TEC group (282 lesions). Patient characteristics, clinicopathological features, procedure-related outcomes of esophageal ESD, stenosis rate and clinical outcome of steroid use cases were evaluated. More patients in the CEC group received preventive steroid treatment compared to the TEC group (37.2% vs 14.5%, P = 0.001). The rate of post-ESD stenosis tended to be higher in the CEC group (11.6%) than in the TEC group (6.7%). For cases of 3/4 ≤ of circumference, local injection with oral steroid had lower stenosis rate than local injection only in both groups (CEC 40% vs 100%, TEC 30.7% vs 56.3%). More sessions and longer duration of dilation were needed to release the stenosis in the CEC group (20 times vs. 5 times, P = 0.015; 196 days vs. 55 days, P = 0.043). The post-ESD stenosis rate of CEC tended to be higher than that of TEC. More intensive preventive measures for post-ESD stenosis may be needed for CEC than TEC.

Robotic trachelectomy with sentinel lymph node biopsy for cervical cancer: a prospective study investigating minimally invasive radicality

Abstract Objective The importance of minimally invasive fertility-sparing surgery for cervical cancer is gaining increasing interest, both to achieve a cure and for future fertility. Procedures for robotic radical trachelectomy involving uterine reconstruction are not fully established. Methods This study prospectively verified the feasibility and safety of robotic radical trachelectomy between February 2018 and May 2022. The criteria were almost identical to those for our standard abdominal radical trachelectomy. Larger tumors (&gt; 2 cm in diameter) were acceptable for surgery, provided a secure ≥ 1 cm cancer-free space was identified between the tumor and internal os. Results Eight patients (median age, 32 y) were registered; the median body mass index was 21.8, and the median tumor size was 11.5 mm (range 0–30 mm). Robotic radical trachelectomy could be achieved in all patients with hybrid sentinel lymph node navigation surgery, confirming the precise cervical amputation line with a newer small knob ultrasonography probe, adequate cervical cerclage with non-absorbable monofilament stitches, and avoiding looseness between vaginal–uterine anastomosis with uninterrupted barbed U-shaped sutures. None of the cases were converted to laparotomy or radical hysterectomy, and there were no major complications. The median follow-up period was 49.5 mo (range 21–58 mo) and no patient had disease recurrence. Conclusion Robotic radical trachelectomy is safe and feasible using newer technologies without reducing radicality; it is also less invasive. Procedures are consistently reproducible and have the potential to be generalized to minimally invasive approaches.

Long-term outcomes of sentinel lymph node navigation surgery for early-stage cervical cancer

Abstract Background Sentinel lymph node navigation surgery, which identifies the sentinel lymph node in early cervical cancers and omits systemic pelvic lymphadenectomy in cases where no lymph node metastasis is present, has recently gained attention. However, there are few reports on lymph node recurrence and the long-term outcomes of cervical cancer surgery performed using sentinel lymph node navigation surgery. In this study, we aimed to evaluate the long-term outcomes of sentinel node navigation surgery for early-stage cervical cancer. Methods One hundred thirty-eight patients with cervical cancer were enrolled. Sentinel lymph nodes were identified by injecting 99 m Technetium-labeled phytate and indocyanine green into the uterine cervix. Surgery and survival outcomes were also analyzed. Results The median age and body mass index of the patients were 40 years (20–78) and 21.7 kg/m2 (16.5–50.4), respectively. Open surgery, laparoscopic surgery, and robotic surgery were performed in 77 (56%), 53 (38%), and 8 (6%) patients, respectively. The overall and bilateral detection rates of the sentinel lymph node were 100% and 94%, respectively. Only one case (0.7%) exhibited lower extremity lymphedema, and pelvic lymphocele was observed in three cases (2.2%). Four cases (3%) experienced recurrence over a median follow-up of 57.5 months (range, 2–115 months), with five-year recurrence-free and overall survival rates of 97% and 97.3%, respectively. Conclusions Our results demonstrate that sentinel node navigation surgery may be safe and effective for early-stage cervical cancer.

Comorbid thrombosis as an adverse prognostic factor in patients with ovarian clear cell carcinoma regardless of staging

Patients with ovarian clear cell carcinoma (OCCC) often present with thrombosis. While cancer patients with concomitant thrombosis were generally reported to have worse prognoses than those without, the association between thrombosis and prognosis has not been elucidated in OCCC. This study aimed to determine how the co-occurrence of thrombosis affects OCCC prognoses. We retrospectively examined 115 patients with OCCC who were diagnosed and treated at the University of Tokyo Hospital between 2009 and 2019. Of 115 patients with OCCC, thrombosis was present in 12.5% of 80 patients and in 42.8% of 35 patients who had OCCC stage I/II and stage III/IV, respectively. In stage I/II, the 5-year progression-free survival was 20.6% and 91.8% among patients with thrombosis and among those without, respectively, while the corresponding 5-year overall survival rates were 50.0% and 94.1%. Therefore, the outcomes were significantly poorer among patients with thrombosis (p < 0.0001 and p < 0.0001, respectively). In stage III/IV, the 5-year progression-free survival was 26.7% and 52.8% among patients with thrombosis and among those without, respectively, while the corresponding 5-year overall survival rates were 32.0% and 62.2%. Similarly, the outcomes were significantly poorer among patients with thrombosis (p = 0.0139 and p = 0.369, respectively). We determined that thrombosis is more likely to develop in advanced OCCC stages than in early stages, and its co-occurrence is associated with a poor prognosis, regardless of disease stage.

Impact of age on clinicopathological features and survival of epithelial ovarian neoplasms in reproductive age

Little is known about the effect of age on the prognosis of epithelial ovarian neoplasms. In the reproductive age, fertility-sparing surgery had been widely implemented. This study aimed to elucidate impact of age on the clinicopathologic characteristics and survival of epithelial ovarian neoplasms in the reproductive age. The clinical records of patients diagnosed as epithelial ovarian cancer or epithelial borderline ovarian tumor at the age of 40 years or younger at multiple institutions in the Tokai Ovarian Tumor Study Group were reviewed retrospectively. All patients were stratified into two age groups: group A (≤ 30 years) and group B (31-40 years). Univariate and multivariate analyses were performed to evaluate overall survival and disease-free survival. A total of 583 patients (325 patients: cancer, 258 patients: borderline) were included. The median follow-up time was 62.0 months (range 1-270 months). Compared with group B, group A had a significantly higher rate of borderline tumor (66.7% vs. 32.7%, p < 0.001); stage I disease (85.9% vs. 70.4%, p < 0.001); mucinous type (69.2% vs. 35.6%, p < 0.001); conservative surgery (83.8% vs. 41.6%, p < 0.001); no adjuvant chemotherapy (67.2% vs. 44.7%, p < 0.001); and CA125 ≤ 35 U/mL (39.4% vs. 28.8%, p < 0.05). There was a significant difference in the overall survival (p = 0.0051) and the disease-free survival (p = 0.0039) between the two groups. Multivariate analysis revealed that the independent prognostic factors for the overall survival were age, stage, histology, and ascitic fluid cytology. In epithelial ovarian neoplasms, younger patients had a survival advantage over older patients.

Current state of fertility preservation for adolescent and young adult patients with gynecological cancer

Although the incidence of the various gynecological cancers has been increasing in recent years, long-term survival is now possible for many patients thanks to advances in multimodality treatment. When treating gynecological cancer in adolescent and young adult (AYA) patients who desire future pregnancy, it is necessary to preserve the reproductive organs and their function to prevent loss of fertility. However, because treatment targets these organs, in the large majority of cases, patients must have these organs removed. In the subfield of oncofertility, treatment of the underlying disease takes priority, and the main principle is preventing delay in treatment. Close cooperation between obstetricians and gynecologists involved in reproductive medicine and oncologists involved in cancer treatment is necessary. In addition, it is important that clinicians work closely not only with other specialists but also with such medical professionals as nurses and counselors so that cancer patients of the AYA generation can be provided the support they need to fight their cancer with hope. Herein, we describe the current status of fertility-sparing therapy for AYA patients with gynecological cancer (cervical cancer, endometrial cancer, or ovarian cancer). In addition, we explain points to keep in mind during a patient's pregnancy after fertility preservation, the latest findings on assisted reproductive technology, and the challenges and prospects of fertility preservation therapy for patients with gynecologic cancer.

Adjuvant taxane plus platinum chemotherapy for stage I ovarian clear cell carcinoma with complete surgical staging: are more than three cycles necessary?

Previous studies on adjuvant chemotherapy for patients with ovarian clear cell carcinoma (OCCC) have included a limited number of Asian patients with surgical stage I OCCC, despite differences in OCCC survival by race and stage. The aim of this study was to estimate the survival effect of the number of cycles of adjuvant taxane plus carboplatin chemotherapy in Asian patients with surgical stage I OCCC. We retrospectively identified 227 patients with surgical stage I OCCC at 14 institutions from 1995 to 2017. Kaplan-Meier analysis and Cox proportional hazard regression with inverse probability of treatment weighting (IPTW) adjustment were performed to evaluate overall survival (OS) and recurrence-free survival (RFS) in patients receiving ≤ 3 and 4-6 cycles of taxane plus platinum adjuvant chemotherapy. Eighty-nine and 138 patients received ≤ 3 and 4-6 cycles of adjuvant chemotherapy, respectively. There was no between-group difference in OS or RFS with or without IPTW adjustment. In Cox proportional hazards analysis, 4-6 cycles of adjuvant chemotherapy were not associated with improved OS (HR 1.090; 95% CI 0.518-2.291; p = 0.821) or RFS (HR 1.144; 95% CI 0.619-2.114; p = 0.669) compared to ≤ 3 cycles, even with IPTW adjustment. Subgroup analysis in different substages of stage I OCCC showed that the number of cycles of adjuvant chemotherapy had no impact on OS or RFS. Three or fewer cycles of taxane plus carboplatin chemotherapy may be a reasonable treatment regime for patients with surgical staging I OCCC.

Who are the long-term survivors of recurrent ovarian carcinoma?: a retrospective analysis of a multicenter study

The aim of the present study was to investigate the incidence and hallmarks of long-term survivors of recurrent ovarian carcinoma (LTSROC) in a large-scale retrospective cohort of patients from a multicenter study group. We performed a regional multicenter retrospective study between January 1986 and September 2021 using clinical data collected under the central pathological review system. Patients who underwent surgery for primary OC at diagnosis and developed recurrent tumors after the initial treatment were included. We defined LTSROC as patients who survived for 5 years or longer after initial tumor recurrence and examined factors affecting the long-term survival of ROC and outcomes of LTSROC. We collected information on patients with malignant ovarian tumors and finally 657 of them that developed ROC were included in the study population. Sixty-eight (10.4%) patients were LTSROC while 399 (60.7%) were short-term survivors of recurrent ovarian carcinoma. In a multivariate logistic regression analysis, negative ascites cytology [odds ratio (OR) 1.865; 95% CI 1.026-3.393; p = 0.041] and a recurrence-free interval (RFI) of 1 year or longer (OR 2.896; 95% CI 1.546-5.425; p < 0.001) were identified as independent factors associated with LTSROC. Approximately 80% of LTSROC presented with solitary recurrent tumors. Furthermore, more than 50% of LTSROC underwent tumor debulking surgery for the first recurrent tumor with or without chemotherapy. RFI of 1 year or longer and negative ascites cytology in the initial surgery were identified as independent predictive factors for LTSROC.

Efficacy and safety of olaparib maintenance monotherapy for Japanese patients with platinum-sensitive relapsed ovarian, fallopian tube, and primary peritoneal cancer

Olaparib maintenance therapy for platinum-sensitive relapsed ovarian cancer has been approved in Japan since April 2018. Here, we report the experience administering this therapy in our hospital, with the aim of evaluating efficacy and safety in the Japanese population. The study included 52 patients with platinum-sensitive relapsed ovarian, fallopian tube, and primary peritoneal cancer. All patients started olaparib at a dose of 300 mg twice daily. Information about treatment efficacy and adverse effects was collected retrospectively from medical records. Median age was 58 years old (range: 33-80), and 82.7% of the patients were diagnosed with high-grade serous carcinoma. Sixteen patients (30.8%) possessed the BRCA1/2 pathogenic variant (15 germline and 1 tissue), 3 (5.8%) possessed variants of unknown significance (2 germline and 1 tissue), 16 (30.8%) possessed wild type, and 17 (32.7%) were not analyzed. Median progression-free survival was 15.3 months (95% CI 9.0-21.6). Patients with BRCA1/2 pathogenic variants showed significantly longer PFS than patients with wild-type BRCA1/2 (p = 0.007). Disease progression caused 34 cases to discontinue olaparib. Eighteen (34.6%) individuals exhibited ≥ grade 3 anemia, although they recovered in response to appropriate management. One patient discontinued olaparib because of prolonged renal dysfunction. Another patient presented with grade 3 fatigue, but recovered after 2 weeks of interruption and continued olaparib treatment. Olaparib maintenance therapy for platinum-sensitive recurrent ovarian cancer in the Japanese population is sufficiently safe and no less effective than reports from previous studies.

Surgical outcomes of early-stage primary vaginal nonsquamous cell carcinoma

Definitive radiation therapy (RT), using external beam RT and/or brachytherapy, is a standard treatment option for primary vaginal carcinoma. However, this treatment has poor prognosis when applied to vaginal nonsquamous cell carcinoma (non-SCC). We aimed to clarify treatment outcome and surgical safety in early-stage primary vaginal non-SCC. After receiving approval from the institutional review board, we retrospectively reviewed the clinical records and pathological samples of patients treated at our hospital between 1991 and 2018. Among 49 patients with primary vaginal carcinoma, 12 with histologically confirmed early-stage primary vaginal non-SCC were included in this study. In total, 40% of patients with primary vaginal carcinoma treated at our hospital had primary vaginal non-SCC. The average observation time was 34 months (median 53.3 months). Three patients had local recurrence: 2 in pelvic lymph nodes and 1 in the vagina. Furthermore, 2 patients died of their disease. Five-year local control rate of stage I and stage II non-SCC was 75% and 100%, respectively. Disease-specific survival rate of stage I and stage II non-SCC was 81.8% and 100%, respectively. No major morbidity was observed. Three patients required allogeneic blood transfusion, whereas 1 underwent autotransfusion. None of the 12 patients were discharged with self-catheterization. Five-year local control and disease-specific survival rates of patients surgically treated for vaginal non-SCC were favorable. Therefore, surgery could be a safe and reasonable option for early-stage primary vaginal non-SCC.

Platinum rechallenge treatment using gemcitabine plus carboplatin with or without bevacizumab for platinum-resistant ovarian cancer

Platinum-resistant ovarian cancer (PROC) is usually treated with single-agent chemotherapy. A synergistic effect of gemcitabine and platinum has been reported in PROC. We evaluated the efficacy and safety of gemcitabine and carboplatin with or without bevacizumab (GC ± B) in patients with PROC. From April 2014 to April 2018, patients with PROC received gemcitabine on days 1 and 8, and carboplatin on day 1, with or without bevacizumab (Bev) on day 1 every 3 weeks. The primary endpoint was objective response rate (ORR). The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and rate of adverse events. In total, 215 cycles were administered to 31 patients, of whom 21 received Bev and the median number of cycle for each patient was 6 (range, 2-19). The median platinum-free interval (PFI) was 4 months. The ORR and DCR were 51.9% and 92.6%, respectively. Median PFS and OS were 7.9 months and 16.1 months, respectively. PFS and OS of patients with 3-6 months PFI were significantly longer than those with PFI < 3 months (median PFS, 9.7 vs. 5.8 months; p < 0.01; median OS, 20.0 vs. 12.1 months; p = 0.03). Grade 3 or 4 hematological toxicities observed included neutropenia (71.0%), leukopenia (54.8%), anemia (51.6%), and thrombocytopenia (25.8%). No other grade 2-4 nonhematological toxicity was observed except for hypertension in one and CBDCA hypersensitivity reaction in two. GC ± B may be effective and safe treatment alternative for PROC, especially with PFI of 3-6 months, despite hematological toxicity.

Evaluation of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer: a single-institution experience

To avoid the loss of fertility, chemotherapy should be chosen as an adjuvant treatment after trachelectomy. Our study evaluated the effectiveness and safety of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer. Our institutional review board approved this clinical study, and informed consent was obtained from each patient. We began performing abdominal trachelectomy at our institution in 2005. Deep stromal invasion (more than two-thirds) with lymphovascular space invasion, diffuse cervical invasion, skip lesions in the vagina, and lymphovascular space invasion in the cardinal ligament and vagina were defined as intermediate-risk factors, and parametrial invasion and pelvic lymph node metastasis were defined as high-risk factors. Patients who had intermediate- or high-risk factors received post-trachelectomy adjuvant treatment. The medical records and information of the patients were reviewed retrospectively. Through January 2020, we performed 212 trachelectomies. Among the included patients, 16 and 7 patients with intermediate- and high-risk cancer, respectively, received adjuvant chemotherapy after trachelectomy (2 and 21 patients underwent abdominal modified radical trachelectomy and radical trachelectomy, respectively). Among these patients, only one (4.3%) experienced relapse and subsequent death of the disease after a median postoperative follow-up of 80 months (range 12-146 months). The 5-year survival rate was 95.5%. Chemotherapy-related life-threatening acute adverse events were not observed. Persistent ovarian dysfunction and late adverse events did not occur. One woman achieved three pregnancies, and two infants were delivered. Adjuvant chemotherapy after abdominal trachelectomy could be an alternative treatment option from the aspects of effectiveness, safety, and fertility preservation.

Phase II study of a new multidisciplinary therapy using once every 3 week carboplatin plus dose-dense weekly paclitaxel before and after radical hysterectomy for locally advanced cervical cancer

We proposed a novel treatment strategy, consisting of triweekly cisplatin plus dose-dense weekly paclitaxel before and after radical hysterectomy without adjuvant radiation therapy to treat locally advanced cervical cancer. However, cisplatin-related severe non-hematologic toxicities were frequent during this strategy. This study aimed to assess the applicability of replacing cisplatin with carboplatin in our proposed strategy. Women with International Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB2, IIA2, or IIB cervical cancer received three cycles of carboplatin (based on an area under the curve of six), each 21 days apart, starting on day 1, and 80 mg/m Between September 2014 and July 2016, 50 women (13 women with FIGO stage IB2, 5 with stage IIA2, and 32 with stage IIB) were enrolled in this study. The overall response rate to chemotherapy was 92%, including 22% with pathological complete response. Forty-nine women (98%) completed the planned radical hysterectomy, and 11 (22%) women with one or more high-risk factors received three additional cycles of chemotherapy. Only four women (8%) received concurrent chemoradiation therapy after surgery. The 2- and 3-year progression-free survival rates were 88.0% and 83.8%, respectively, and the 2- and 3-year overall survival rates were 98.0% and 95.4%, respectively. Only two patients reported grade 3 or higher non-hematologic toxicities including grade 3 nausea in one patient and grade 3 liver dysfunction in one patient. Replacement the platinum agent resulted in equivalent efficacy, with reduced toxicity, in women with locally advanced cervical cancer. This strategy could considerably diminish the application of radiation therapy without reduced survival. A study to identify those patients who will benefit from this new multidisciplinary strategy is warranted.

Laparoscopic versus abdominal radical hysterectomy for stage IB1 cervical cancer patients with tumor size ≤ 2 cm: a case-matched control study

To investigate the survival outcomes of stage IB1 cervical cancer patients with tumor size ≤ 2 cm who underwent laparoscopic or abdominal radical hysterectomy. We retrospectively analyzed stage IB1 cervical cancer patients with a tumor size ≤ 2 cm who underwent laparoscopic or abdominal radical hysterectomy in China between 2004 and 2016. A real-world study (RWS) and 1:1 matching was used in the study. After 1:1 matching, laparoscopic (n = 926) and abdominal radical hysterectomy (n = 926) had similar 5-year overall survival and disease-free survival rates in stage IB1 cervical cancer with a tumor size ≤ 2 cm. Subsequently, in cervical squamous carcinoma with tumor size ≤ 2 cm, the laparoscopic and abdominal groups (724 cases, respectively) showed comparable 5-year overall survival and disease-free survival rates. Finally, in cervical adenocarcinoma or adenosquamous carcinoma with tumor size ≤ 2 cm, the laparoscopic group (n = 174) had a similar 5-year overall survival rate but a lower disease-free survival rate compared to those of the abdominal group (disease-free survival: 89.9% vs. 98.0%, respectively, P = 0.006; hazard ratio (HR), 5.094; 95% confidence interval (CI), 1.400-18.535; P = 0.013; n = 174). The RWS results were similar to the 1:1 matching results. Patients with squamous cell carcinoma in stage IB1 cervical cancer with tumor size ≤ 2 cm might be suitable for laparoscopic surgery, while patients with adenocarcinoma or adenosquamous carcinoma with tumor size ≤ 2 cm are not candidates for laparoscopic surgery.

HPV vaccination in Japan: can educational intervention promote a father’s intention to encourage his daughter’s vaccination?

HPV vaccines are well known to prevent several devastating HPV-associated cancers-when administered before sexual activity begins. We have previously found that mothers in Japan play an important role in a young girl's vaccination decision-making, and that educational intervention with the mothers positively changed their attitude towards the HPV vaccine. The role of fathers is still unclear. We report here similar effects can be achieved by an educational intervention with the fathers. We conducted an online survey of 1648 Japanese fathers as having 13-18 year-old daughters. In this group, 1450 fathers had HPV-unvaccinated daughters. Roughly half, 721, were supplied an educational sheet concerning cervical cancer, which included information regarding the safety and efficacy of the HPV vaccine, the other 729 did not receive the sheet. Afterwards, a self-administered questionnaire obtained information from both groups of fathers. We evaluated their attitudes and intentions to inoculate their daughters and willingness to be associated with the vaccination decision-making process. Paternal education with an information sheet was associated with an increased odds ratio for changing the father's attitude in a positive direction, but it was not associated with improving the father's intention to their have their daughters inoculated, nor the father's willingness to be associated with the decision-making process. While educational intervention can promote a father's positive attitude towards HPV vaccination, it is ineffective at promoting a positive intention to follow through to inoculate their daughters or improving their willingness to assist in the decision-making process.

The role of additional hysterectomy after concurrent chemoradiation for patients with locally advanced cervical cancer

The standard treatment for cervical cancer is chemoradiation although some patients showed treatment resistance. The purpose of this study was to investigate the clinical efficacy of surgery after chemoradiation for cervical cancer. Patients with FIGO stage IB2 to IIB cervical cancer were included in the study between 2005 and 2015. A total of 50 patients who underwent surgery after neoadjuvant chemoradiation and 76 patients who received only chemoradiation were compared. Baseline differences between the two groups were adjusted with inverse probability of treatment weighting method using propensity scores composed of the following independent variables: age, stage, tumor size, lymph node metastasis, and histological subtypes. Median follow-up was 64.8 (range 4.8-143.9) months. After adjustment with inverse probability of treatment weighting, Kaplan-Meier curves showing adjusted progression-free survival and overall survival were significantly longer in the neoadjuvant chemoradiation compared with the chemoradiation-only group (p = 0.027 and p = 0.017, respectively). Moreover, in patients with squamous cell carcinoma, recurrence in previously irradiated field and recurrence both in and out of previously irradiated field were significantly decreased in the neoadjuvant chemoradiation compared with the chemoradiation-only group (3.1% and 18.4%, respectively; OR 0.142, p = 0.001]. Adverse events of surgery after chemoradiation were acceptable, although temporary hydronephrosis was frequently observed (23.1%). Surgery after chemoradiation reduced pelvic recurrence, and as a result, patients who underwent neoadjuvant chemoradiation showed more favorable survival outcomes compared with those who only underwent chemoradiation.

Comparison of survival outcomes of abdominal radical hysterectomy and radiochemotherapy IIA2 (FIGO2018) cervical cancer: a retrospective study from a large database of 63,926 cases of cervical cancer in China

This study aimed to compare the 5-year overall survival (OS) and 5-year DFS disease-free survival (DFS) of abdominal radical hysterectomy (ARH) and radiochemotherapy (R-CT) for stage IIA2 (FIGO 2018) cervical cancer patients. Based on this multicenter, retrospective cohort study based on data from the clinical diagnosis and treatment of cervical cancer in China (Four C) database, 609 cases with 2018 FIGO stage IIA2 cervical cancer from 2004 to 2018 were reviewed. The 5-year OS and 5-year DFS of patients with either of the two treatment methods were compared by means of a multivariate Cox regression model and the log-rank method in the total study population and after propensity score matching (PSM). We selected 609 of 63,926 patients and found that R-CT was associated with a significantly worse 5-year OS (71.8% vs. 95.3%, P < 0.001; hazard ratio (HR) = 6.596, 95% CI 3.524-12.346) and 5-year DFS (69.4% vs. 91.4%, P < 0.001; HR = 4.132, 95% CI 2.570-6.642, P < 0.001) than ARH in the total study population. After matching (n = 230/230), among FIGO 2018 IIA2 patients, the 5-year OS and DFS were lower in the R-CT group than in the ARH group (OS: 73.9% vs. 94.7%, P < 0.001; HR = 5.633, 95% CI 2.826-11.231, P < 0.001; DFS: 69.2% vs. 91.1%, P < 0.001; HR = 3.978, 95% CI 2.336-6.773, P < 0.001, respectively). In patients with stage FIGO 2018 IIA2 cervical cancer, ARH offers better 5-year OS and DFS outcomes than R-CT; however, due to the inherent biases of retrospective studies, this needs to be confirmed by randomized trials.

Survival impact of adjuvant concurrent chemoradiotherapy after radical hysterectomy in FIGO stage IIIC1 cervical adenocarcinoma

We evaluated the survival effect of adjuvant concurrent chemoradiotherapy after radical hysterectomy in patients with clinical pelvic node-positive cervical adenocarcinoma. Patients with pelvic node-positive cervical adenocarcinoma diagnosed between 2000 and 2016 at our institution were identified. Survival was compared between patients who underwent radical hysterectomy alone and those who received concurrent chemoradiotherapy as an adjuvant treatment. Survival analysis using log-rank test and Cox proportional hazards model was performed. We identified 80 patients who underwent radical hysterectomy for clinical pelvic node-positive cervical adenocarcinoma; of these, four with pathological pelvic node-negative adenocarcinoma were excluded. Of the 76 patients, 27 underwent radical hysterectomy alone and 49 received radical hysterectomy followed by concurrent chemoradiotherapy. With a median follow-up of 53 months, the 5-year overall survival rate was 51.0% in patients who underwent radical hysterectomy alone versus 53.0% in patients who received additional concurrent chemoradiotherapy (log-rank p = 0.455). The addition of concurrent chemoradiotherapy after radical hysterectomy did not significantly improve survival among patients with pelvic node-positive cervical adenocarcinoma. More appropriate treatment strategies are needed to improve the survival outcomes of these patients.

Long-term outcomes of individualized management after sentinel lymph-node biopsy for vulvar cancer

The management for patients with vulvar cancer after sentinel lymph-node biopsy (SLNB) remains controversial. The aim of this study was to investigate the long-term outcomes of individualized management after SLNB for early stage vulvar cancer. The medical records of patients with vulvar cancer treated by surgery involving SLNB between 2004 and 2019 were retrospectively reviewed. During this period, the inguinofemoral lymphadenectomy (IL) were performed with individualized strategy, while the postoperative intensity-modulated radiotherapy was planned with a consistent policy. We identified 138 patients with at least one sentinel node detected, of whom 64 underwent further IL while 74 had SLNB only. Nodal metastases (pN+) were confirmed in 22 patients with IL and 16 without. Radiotherapy was scheduled with the dose of 60-70 Gy for all pN+ patients and finally completed in 15 with IL and 15 without. The median follow-up time was 56 months (6-156 months). Recurrence was observed in 24 patients, of whom 10 were pN- at primary treatment. The 3-year overall survival (OS) was 97.2, 95.2, 68.3, and 71.8%; 3-year disease-free survival (DFS) was 94.5, 91.4, 60.2, and 59.2%, respectively, for patients with pN- and IL, pN- and SLNB, pN+ and IL, and pN+ and SLNB. Neither OS nor DFS showed significant difference between SLNB and IL in pN- (P = 0.564 for OS, P = 0.423 for DFS), or pN + patients (P = 0.920 for OS, P = 0.862 for DFS). With appropriate adjuvant radiotherapy, SLNB alone provided similar long-term survival compared with IL for both patients with and without sentinel node metastasis.

Clinicopathologic and survival analysis of patients with adenoid cystic carcinoma of vulva: single-institution experience

The purpose of this study was to elucidate our experience in the diagnosis and treatment of adenoid cystic carcinoma of the vulva (ACC-vulva) and to assess the clinicopathological characteristics and prognosis among ACC-vulva patients. A retrospective study of seventeen patients was performed to illustrate the demographic information, clinical performance, pathological characteristics, treatment modality, and development of local recurrence or distant metastasis, as well as the survival outcome. The median age at diagnosis was 56 years (range, 26-71 years). Radical local excision was performed on fifteen patients, and two patient received radical hemi-vulvectomy. Six patients received ipsilateral inguinal lymphadenectomy. Involvement of the resection margin was observed in six patients. The postoperative pathologic diagnosis showed no proof of inguinal lymph node metastasis in all the six patients receiving lymphadenectomy. However, the perineural invasion was observed in all patients. Postoperative adjuvant radiotherapy was applied to five patients who had positive resection margin. The mean survival time except for that in four patients (recent case) was 47.8 months (range, 23-78 months). Radical resection towards negative margins seems to be acceptable as initial treatment. Adjuvant radiotherapy is a preferable treatment modality for patients with high-risk factors pathologically or patients with local recurrence.

Comparison of treatment outcomes of pelvis external radiotherapy with and without vaginal brachytherapy for cervical cancer patients with positive or close vaginal resected margins

We evaluated whether there is a difference in the local recurrence and survival after pelvic external radiotherapy (ERT) with and without boost vaginal brachytherapy (VB) in cervical cancer patients with positive or close vaginal resected margins (RM). We retrospectively reviewed FIGO stage IA-IIB cervical cancer patients treated with postoperative ERT between 1997 and 2018. The sixty patients showing close (safety margin < 5 mm) or positive vaginal RM were included. ERT was delivered with median 50.4 Gy in 28 fractions to the pelvis and VB with median 30 Gy in 6 fractions. The median follow-up duration was 46 months. Five out of 30 patients treated with ERT alone experienced vaginal recurrence within 2 years after surgery. The 5-year local control (LC) was 100% in patients receiving ERT + VB compared with 81.3% in patients receiving ERT alone (log rank p = 0.022). The 5-year pelvic control (PC) was 95.8% for patients receiving ERT + VB and 76.8% for ERT alone (p = 0.041). The 5-year overall survival and recurrence-free survival (RFS) were not significantly different between treatment groups. In multivariate analysis, perineural invasion was a significant risk factor for PC (p = 0.024). Parametrial involvement (p = 0.044) and vascular invasion (p = 0.032) were unfavorable prognostic factors for RFS. Late toxicity occurrences were not significant in both groups. VB after ERT improved LC and PC in cervical cancer patients with close or positive RM after hysterectomy. The toxicities were not increased after VB was added to ERT.

Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan

The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

Efficacy of local salvage therapy for recurrent uterine cervical cancer after definitive radiotherapy

The prognosis of patients with recurrence of uterine cervical cancer after definitive radiotherapy and the efficacy of local salvage therapy for recurrence were evaluated. We retrospectively reviewed 110 patients who were treated with definitive radiotherapy/chemoradiotherapy for uterine cervical cancer between 2008 and 2017 at our institution. Local salvage therapy was defined as any surgery or radiotherapy described in the medical record as intended for local control or cure. We identified 25 patients who developed recurrence after definitive radiotherapy/chemoradiotherapy. The median follow-up time post-recurrence was 18.9 months. Thirteen patients (52%) reported recurrence in the isolated extra-pelvic lymph node (EPLN). The 2-year overall survival after first recurrence (OSr) for patients with isolated EPLN recurrence was 83.1%, compared to that of 31.2% for patients with other patterns of recurrence (p < 0.001). The 2-year OSr for patients who underwent local salvage therapy was 75.2%, whereas that for patients who did not undergo therapy was 41.6% (p = 0.04). Among patients who had recurrence in the isolated EPLN and received local salvage therapy, 20% of the patients reported recurrence in visceral and/or bone metastases after local salvage therapy, and 50% of the patients experienced another EPLN recurrence, which was salvaged with repeating local therapy. Patients with uterine cervical cancer with isolated EPLN recurrence had favorable prognoses. The indications of local salvage therapy should be considered, especially for patients with isolated EPLN recurrence.

A retrospective assessment of the safety and efficacy of laparoscopic radical hysterectomy in Japan during the early years following its introduction: a Japanese Gynecologic Oncology Group study (JGOG1081S)

To evaluate the safety and efficacy of laparoscopic radical hysterectomy (LRH) for cervical cancer, in terms of morbidity and short-term oncologic outcome following LRH's introduction into Japan. We conducted a retrospective analysis of patients with early-stage cervical cancer (FIGO staging IA2, IB1, and IIA1) who underwent LRH from Dec 2014 to Dec 2016. We assessed the morbidity, overall survival (OS) and recurrence-free survival (RFS), and prognostic factors for RFS. A total of 251 patients were included from 22 facilities across Japan. There were 8 cases of stage IA2 cervical cancer, 226 of IB1, and 17 of IIA1. The median operating time was 343 min and the median blood loss was 190 ml. Two patients (0.8%) had a postoperative complication with a Clavien-Dindo classification of grade 3 or higher. After a median follow-up time of 15.6 months, the 2-year RFS was 87.4%, and the 2-year OS was 97.8%. When the 2-year RFS rate was compared with whether the patient pathologically had tumors of less than 2 cm, versus 2 cm or more, the RFS was 95.8% and 80.4%, respectively. Multivariate analysis found that tumor size and the route of lymph node removal were independent prognostic factors for recurrence. When LRH was first introduced into Japan, we found that the route of lymph node removal was an independent prognostic factor for recurrence in addition to large tumors (≥ 2 cm). Our results suggest that prognosis may be secured by paying attention to the lymph node removal route.

Prognostic outcomes and risk factors for recurrence after laser vaporization for cervical intraepithelial neoplasia: a single-center retrospective study

Cervical intraepithelial neoplasia (CIN) is a precancerous lesion that may progress to invasive cervical cancer without intervention. We aim to examine the prognostic outcomes and risk factors for recurrence after laser vaporization for CIN 3, CIN 2 with high-risk human papillomavirus (HPV) infection, and CIN 1 persisting for more than 2 years. Between 2008 and 2016, a total of 1070 patients underwent cervical laser vaporization using a carbon dioxide laser. We performed a retrospective review of their medical records to assess their clinical characteristics, pathologic factors, and prognostic outcomes. The mean patient age was 34 years (range 18-64 years). The preoperative diagnosis was CIN 1 in 27 patients, CIN 2 in 485 patients, and CIN 3 in 558 patients. Over a median follow-up period of 15 months, the 2-year recurrence rate was 18.9%, and the 5-year recurrence rate was 46.5%. The 2-year retreatment rate was 12.6%, and the 5-year retreatment rate was 30.5%. We diagnosed 9 patients with invasive cancer after treatment; all patients underwent combined multidisciplinary treatment, and there were no deaths during follow-up. The recurrence-free interval was correlated with patient age (hazard ratio [HR], 1.028; 95% CI 1.005-1.051; P = 0.0167), body mass index (HR, 1.052; 95% CI 1.008-1.098; P = 0.0191), and glandular involvement (HR, 1.962; 95% CI 1.353-2.846; P = 0.0004). Cervical laser vaporization is effective and useful for patients with CIN who wish to preserve fertility. However, patients with glandular involvement, older age, and higher body weight require close follow-up for recurrence.

Performance of the Matsumiya scoring system in cervical cancer patients with bone metastasis: an external validation study

Accurate prognostic prediction of survival in cervical cancer patients with bone metastasis is important for treatment planning. We aimed to externally validate the Matsumiya scoring system using external patient data. We collected a retrospective cohort of patients with cervical cancer diagnosed with bone metastasis at Chiang Mai University Hospital from 1st January 2007 to 31st December 2016. The Matsumiya score was composed of 5 predictors, including the presence of extraskeletal metastasis, ECOG performance status, history of previous chemo- or radiotherapy, the presence of multiple bone metastasis, and bone metastasis-free interval < 12 months. Harrell's C-statistics and score calibration plots were used to evaluate the score performance. We also reconstructed the development study to estimate apparent performance values for comparison during external validation. A total of 124 cervical cancer patients with bone metastasis were included in this study. The 13-, 26-, and 52-week survival probabilities in the validation study were 70.1%, 50.5%, and 25.7%, respectively. Several differences were identified between development and validation studies regarding clinical characteristics, case-mix, and predictor-outcome associations. Harrell's C-statistics in the development and validation study were 0.714 and 0.567. The score showed poor agreement between the observed and the predicted survival probabilities in the validation study. Score reweighting and refitting showed only modest improvement in performance. A prognostic scoring system by Matsumiya et al. performed poorly in our cohort of Thai cervical cancer patients with bone metastasis. We suggested that the score should be sufficiently updated before being used.

Human papillomavirus testing and cytology using physician-collected uterine cervical samples vs. self-collected vaginal samples and urine samples

Human papillomavirus (HPV) testing using self-collected vaginal samples and urine samples is convenient and effective for improving the screening rate. But, to serve as an alternative cervical cancer screening technique, such tests must offer sensitivity equivalent to the HPV testing of physician-collected cervical samples. To examine the effectiveness of HPV testing using self-collected samples and urine samples, we compared the results of HPV testing using these samples with those of HPV testing using physician-collected samples and cytological examinations. The study population included 300 women (age: 20-50 years) with abnormal cervical cytology. The results of HPV testing using self-collected samples and urine samples and physician-collected samples and cervical cytology were compared. For all HPV types, the κ-value was 0.773 for physician- and self-collected samples and 0.575 for physician-collected and urine samples. The κ-value for HPV type 16-positive samples was 0.988 for physician- and self-collected samples and 0.896 for physician-collected and urine samples. The κ-value for HPV type 18-positive samples was 0.856 for physician- and self-collected samples and 0.831 for physician-collected and urine samples. For other HPV types, the value was 0.809 for physician- and self-collected samples and 0.617 for physician-collected and urine samples. The obtained results were consistent between physician- and self-collected samples as well as between physician-collected and urine samples. Considering that the agreement rate was particularly high for the high-risk HPV types 16 and 18, HPV testing using physician-collected samples, self-collected samples, and urine samples was equally effective for the types with high carcinogenicity.

Risk assessment in the patients with uterine cervical cancer harboring intermediate risk factors after radical hysterectomy: a multicenter, retrospective analysis by the Japanese Gynecologic Oncology Group

Adjuvant therapy is usually considered for surgically treated patients with uterine cervical cancer harboring intermediate risk (IR) factors such as large tumor diameter, stromal invasion to the outer half, and lymphovascular space invasion (LVSI). However, the indications and types of adjuvant therapy for the IR group remain controversial. This study aimed to analyze the differences in patient outcomes in the IR group to provide novel insights for tailoring adjuvant therapy. Data from 6192 patients with cervical cancer who underwent radical hysterectomy at 116 institutions belonging to the Japanese Gynecologic Oncology Group were reviewed. In total, 1688 patients were classified into the IR group, of whom 37.3% did not receive adjuvant therapy. Conversely, approximately equal proportions of the remaining patients received adjuvant radiotherapy, concurrent chemoradiotherapy, and chemotherapy. Patients with all three risk factors showed worse overall survival than those with one or two risk factors. In addition to LVSI, non-squamous cell carcinoma histology, and vaginal invasion were identified as independent risk factors for both recurrence and mortality in multivariate analyses. Tumor diameter greater than 40 mm and surgical center volume were identified as independent risk factors for recurrence. Stromal invasion to the outer half and ovarian metastasis were identified as independent risk factors for mortality. This study revealed the significant differences in prognosis in the IR group. The indications for adjuvant therapy should be further studied, focusing on conventional risk factors and other pathological findings.

Sentinel node navigation surgery in cervical cancer: a systematic review and metaanalysis

Sentinel node navigation surgery (SNNS) is used in clinical practice for the treatment of cervical cancer. This study aimed to elucidate the appropriate sentinel lymph node (SLN) mapping method and assess the safety and benefits of SNNS. We searched the PubMed, Ichushi, and Cochrane Library databases for randomized controlled trials (RCT) and studies on SLN in cervical cancer from January 2012 to December 2020. Two authors independently assessed study quality and extracted data. We quantitatively analyzed the detection rate, sensitivity/specificity, and complications and reviewed information, including the survival data of SLN biopsy (SLNB) without pelvic lymphadenectomy (PLND). The detection rate of SLN mapping in the unilateral pelvis was median 95.7% and 100% and in the bilateral pelvis was median 80.4% and 90% for technetium-99 m (Tc) with/without blue dye (Tc w/wo BD) and indocyanine green (ICG) alone, respectively. The sensitivity and specificity of each tracer were high; the area under the curve of each tracer was 0.988 (Tc w/wo BD), 0.931 (BD w/wo Tc), 0.966 (ICG), and 0.977 (carbon nanoparticle). Morbidities including lymphedema, neurological symptoms and blood loss were associated with PLND. One RCT and five studies all showed SNNS without systematic PLND does not impair recurrence or survival in early-stage cervical cancer with a tumor size ≤ 2-4 cm. Both Tc w/wo BD and ICG are appropriate SLN tracers. SNNS can reduce the morbidities associated with PLND without affecting disease progression in early-stage cervical cancer.

Attitudes and behaviors of obstetricians and gynecologists toward HPV vaccination: a 7-year follow-up survey in Japan

In Japan, the government suspended HPV vaccine recommendation in 2013, resulting in dropping vaccination uptake to almost zero. We conducted four serial surveys on our colleague' attitude to HPV vaccination between 2014 and 2021. Here, we evaluate the result of the survey in 2021 and compare it to previous surveys. The subjects were 567 obstetricians and gynecologists who had been trained in our university hospital or our affiliated hospitals. We used a questionnaire similar in format to those used in 2014, 2017, and 2019. A total of 340 doctors (60.0%) completed the survey. Among them, 93.2% (317/340) of respondents thought that the government should restart HPV vaccination recommendation, and that 63.2% (215/340) think male teenagers should also vaccinate against HPV. The percentage of teenaged daughters inoculated with HPV vaccination after Japanese government had suspended its recommendation was 43.5% (20/46), an increasing trend from the previous surveys. 39 out of the 46 daughters (84.8%) would be expected to receive full HPV vaccination after they take junior high school entrance examination or after 9-valent HPV vaccination is designated as a national routine-immunization. This study revealed increasing number of our colleagues think HPV vaccination is necessary for prevention of cervical cancer. The Japanese government's decision to resume its recommendation of the HPV vaccine in November 2021 will lead to a change in the public's thinking and behavior toward the HPV vaccine.

Survival after minimally invasive vs. open radical nephrectomy for stage I and II renal cell carcinoma

A recently reported phase III randomized trial comparing open and minimally invasive hysterectomy showed significantly higher rates of local recurrence after minimally invasive surgery (MIS) for cervical cancer. This raised concerns regarding patterns of recurrences and survival after MIS in general. This study aims to determine the effect of MIS on all-cause mortality among patients undergoing radical nephrectomy for Stage I and II renal cell carcinoma (RCC). We utilized the National Cancer Database to identify patients diagnosed with clinical stage I-II RCCs between 2010 and 2013. Patients for whom a laparoscopic or robotic radical nephrectomy was attempted were compared to patients who underwent open radical nephrectomy (ORN). Adjusted regression models with inverse probability propensity score weighting (IPW) were utilized to identify independent predictors of receiving MIS. All-cause mortality rates were compared using IPW survival functions and log-rank tests. Adjusted Cox proportional hazard models were fitted to determine independent predictors of OS. 27,642 patients were identified; 11,524 (41.7%) had MIS, while 16,118 (58.3%) had ORN. Kaplan-Meier survival curves in the IPW cohort showed significant OS advantage for patients who underwent MIS (p < 0.001). Furthermore, length of hospital stays (3 vs. 4 days), 30 day readmission rates (2.4 vs. 2.87%), 30 day (0.53 vs. 0.96%) and 90 day mortality rates (1.04 vs. 1.77%) were significantly higher in the ORN group (p < 0.001). MIS was associated with better OS outcomes compared to ORN for stage I and II RCC. In addition, MIS had lower post-operative readmission, 30- and 90 day mortality rates.

Extreme leanness, lower skeletal muscle quality, and loss of muscle mass during treatment are predictors of poor prognosis in cervical cancer treated with concurrent chemoradiation therapy

Human papillomavirus vaccination is not widespread in Japan, and the low screening rates result in many cases of locally advanced cervical cancer. We investigated the prognostic significance of sarcopenia in patients with cervical cancer to guide healthcare policies to improve treatment outcomes. This retrospective study included 83 patients with cervical cancer without distant metastasis who underwent primary concurrent chemoradiotherapy between 2013 and 2018. We analyzed the indicators of physical condition and muscle quantity using the SYNAPSE VINCENT software. Muscle mass and the relationship between treatment toxicity and prognosis were evaluated. The patients' median age was 60 (range 33‒80) years. Cancer stage distribution was as follows: cT2b or higher, 84.3%; N1, 65.1%; and MA, 27.7%. The overall sarcopenia (skeletal muscle index [SMI] < 38.5) rate was 30.1%, and the rate was 33.9 and 22.2% in patients aged < 64 and ≥ 65 years, respectively. No correlation was observed between clinical stage and musculoskeletal indices. Treatment resulted in decreased body weight and SMI; after treatment, the sarcopenia rate increased to 37.3%. A higher intramuscular adipose tissue content (IMAC) reduced the number of chemotherapy cycles needed. Treatment-associated SMI decreases of ≥ 7% indicated poor prognosis, with significant differences in progression-free survival and overall survival (p = 0.013 and p = 0.012, respectively). Patients who were very lean (body mass index < 18.5 kg/m Our findings emphasize the importance of assessing original nutritional status and maintaining muscle mass and quality during the treatment of patients with cervical cancer.

Status of cervical cancer screening among adolescents and young adults (AYA) in Japan

Cervical cancer ranks high among the cancers that affect people in their 20s and 30s. Cervical cancer is characterized by the presence of precancerous lesions, which can be detected by cancer screenings; some precancerous lesions are amenable to treatment, which can halt the progression to invasive cancer. As a result, cervical cancer screening has been shown to reduce the incidence of invasive cancer and its mortality. On the other hand, many precancerous lesions do not progress to invasive cancer, but stagnate or disappear spontaneously. In Japan, there is a nationwide cytological screening program for residents, and the screening is performed every two years after the age of 20. There are also screening programs provided by the workplaces in Japan. According to the National Health Survey 2019, the checkup rates of any type of cervical cancer screenings are low: 15.1% for those aged 20-24, 36.6% for those aged 25-29, and 49.4% for those aged 30-34. Statistics are reported every year for the nationwide screening, and according to them, the positive screening rate is 2.1% for all ages, but 4.5% and 3.2% for those in their 20s and 30s, respectively. On the other hand, the percentage of people with positive test results who undergo follow-up examinations or confirmatory tests should be at least 90%, but it is 72.1% for all ages, 72.0% for those in their 30s, and even lower for those in their 20s, at 67.1%. Improving the rate of people getting screenings and subsequent examinations is a challenge even among the young.

Long-term progression-free survivors (“super responders”) to olaparib maintenance in recurrent ovarian cancer: a multicenter real-world study (KCOG-G2101s)

PARP inhibitors have been shown to improve progression-free survival in patients with recurrent ovarian cancer. However, their potential for long-term response and cure remains unclear in real-world practice. We conducted a multicenter, retrospective study of patients with recurrent ovarian, fallopian tube, or peritoneal cancer who were treated with olaparib maintenance therapy in the Kansai Clinical Oncology Group. We analyzed clinical outcomes according to histological tissue type, platinum sensitivity, BRCA mutation status, and SLFN11 expression. Epithelial ovarian cancers were classified into type I (low-grade serous carcinoma, clear cell carcinoma, low-grade endometrioid carcinoma) and type II (high-grade serous carcinoma, high-grade endometrioid carcinoma and undifferentiated carcinoma). A total of 72 patients were registered. The median progression-free survival and overall survival were 12.0 and 42.0 months, respectively. Type II tumors exhibited significantly longer progression-free survival than type I tumors (p = 0.027). Among type II tumors, those with platinum-sensitive recurrence and a response to chemotherapy (PSR-R, n = 51) had significantly better progression-free survival than non PSR-R (p < 0.0001). Notably, eight PSR-R patients (15.7%) achieved greater than five years of progression-free survival ("super responders"), and all had no evidence of disease at the last follow-up. BRCA mutations and SLFN11 expression were not associated with progression-free survival or super responders. In this real-world cohort, a subset of patients with recurrent ovarian cancer achieved durable, potentially curative responses with olaparib maintenance, regardless of their BRCA mutation status. When evaluating PARP inhibitor therapy, long-term progression-free survival should be considered a key endpoint.

Platinum-rechallenge in epithelial ovarian cancer relapsing within 6 months after first-line treatment: a propensity score matching analysis

Prognosis for patients with early platinum-resistant Epithelial Ovarian Cancer (EOC) relapse after first-line chemotherapy remains poor. This study explores whether platinum rechallenge may be an option in this setting. In this retrospective, single-institute, observational study, we enrolled BRCA1/2 wild-type (BRCAwt) patients who underwent surgery (January 2017-July 2021) and relapsed within 6 months after first-line platinum-based chemotherapy. Platinum (P) rechallenge was compared with pegylated liposomal doxorubicin (PLD) or non-platinum/non-PLD therapy (weekly paclitaxel/gemcitabine/topotecan, PGT). To minimize selection bias, propensity score matching (PSM) analysis was performed. Overall, 87 patients were identified: 18 (20.7%, P cohort), 50 (57.5%, PLD cohort) and 19 (21.8%, PGT cohort); after PSM, 54/87 patients were identified with similar characteristics, 18 for each group. Grade 3/4 toxicity events were more frequent in P group patients (13/18, 72.2%), compared to PDL (5/18, 27.8%) and PGT (7/18, 38.9%)(PvsPDL: p = 0.008; PvsPGT: p = 0.044; PDLvsPGT: p = 0.479; PvsPDLvsPGT: p = 0.021). Median progression-free survival (mPFS) was 9 months (P cohort) (CI 95%; 4.842-13.158), achieving a 4-month and 3-month increase compared to PLD (mPFS 5 months, p < 0.002) and PGT group (mPFS 6 months, p < 0.05), respectively. Median overall survival (mOS) benefit was preserved: 32 months (P cohort) compared to PLD (13 months, p = 0.001) and PGT (18 months, p = 0.01) groups. On multivariate analysis, platinum rechallenge was an independent prognostic factor for PFS (HR: 0.416; 95% CI: 0.215-0.807; p = 0.009) and OS (HR: 0.175; 95% CI: 0.061-0.503; p = 0.001). Results were consistent with the whole population. Platinum rechallenge showed promising survival outcomes for BRCAwt patients recurring within 6 months after first-line platinum-based chemotherapy.

Therapeutic effect of dose-dense paclitaxel plus carboplatin with or without bevacizumab for Japanese patients with epithelial ovarian cancer

Evidence regarding chemosensitivity to different therapeutic regimens in epithelial ovarian cancer (EOC) remains limited. This study aimed to investigate EOC implementation in daily clinical practice and reveal favorable regimens for EOC among Japanese patients. We retrospectively collected clinical data of patients newly diagnosed with EOC from 2012 to 2021 at our affiliated institutions. We evaluated overall survival (OS) and progression-free survival (PFS) of conventional paclitaxel plus carboplatin (TC) vs. dose-dense TC (ddTC) according to the eligibility of GOG262 and JGOG3016 and those with bevacizumab (BEV) vs. without BEV based on GOG218. Further, we evaluated OS and PFS of ddTC and ddTC + BEV to TC + BEV among patients with stage III/IV. The ddTC group (n = 402) demonstrated longer PFS and OS than the TC group (n = 165) (adjusted hazard ratios [aHRs] [95% confidential intervals (CIs)]: 0.69 [0.55-0.88] and 0.67 [0.50-0.90], respectively). The group with BEV (n = 158) demonstrated a longer PFS than those without BEV (n = 296) (0.74 [0.57-0.95]), but not for OS (0.84 [0.60-1.17]). The ddTC and ddTC + BEV groups (n = 259 and 117) demonstrated no statistically significant differences in PFS and OS than the TC + BEV group (n = 75) (1.09 [0.79-1.50] and 0.74 [0.52-1.08] for PFS and 0.89 [0.59-1.34] and 0.73 [0.50-1.05] for OS, respectively). Our study may indicate ddTC, BEV, and their combination regimen as the promising first-line chemotherapy option among Japanese patients with advanced EOC.

Questionnaire-based survey on the extent of lymph node dissection during interval debulking surgery after neoadjuvant chemotherapy for patients with advanced ovarian cancer in the Gynecologic Cancer Study Group of JCOG

The significance of lymph node dissection (LND) in primary debulking surgery (PDS) for advanced ovarian cancer was demonstrated in the LION trial. However, the role and the current practices of LND during interval debulking surgery (IDS) remains unclear. We aimed to conduct a survey of the current LND practices. A questionnaire-based survey regarding the criteria and extent of LND for advanced ovarian cancer was conducted by the Gynecologic Cancer Study Group of the Japan Clinical Oncology Group (JCOG). We defined enlarged lymph nodes as 10 mm or more in the short axis on imaging. This study included data from 51 institutions. Factors contributing to the decision regarding the extent of LND included performance status, completeness of cytoreductive surgery excluding the lymph nodes, and age. Regarding PDS cases with enlarged lymph nodes, 90% of all institutions opted for systematic LND (SyLND) or removal of only the enlarged lymph nodes (SeLND). In IDS cases with enlarged lymph nodes after neoadjuvant chemotherapy (NACT), 15 (29%) and 35 (69%) institutions opted for SyLND and SeLND, respectively. In contrast, in IDS cases in which enlarged lymph nodes were reduced after NACT, approximately half the institutions opted for no LND. This study found no established standard treatment for LND during IDS in patients with enlarged lymph nodes among the JCOG institutions. Thus, further prospective studies comparing the prognostic outcomes with or without LND are warranted.

AMIGO2 is involved in the spread of peritoneal metastasis in serous ovarian cancer via promoting adhesion to the peritoneal mesothelial cells

Amphoterin-induced gene and open reading frame 2 (AMIGO2) have been reported to be related to the prognosis of colorectal, gastric, and cervical cancer. However, their association with ovarian cancer remains unclear. This study aimed to elucidate the role of AMIGO2 in ovarian cancer. AMIGO2 expression was evaluated using immunohistochemistry in patients with ovarian serous carcinoma. We validated in vitro studies using four serous ovarian cancer cell lines and in vivo studies using a murine model. The AMIGO2-high group had significantly shorter progression-free survival (PFS) than the AMIGO2-low group. The predictive index of the AMIGO2-high group was considerably higher than that of the AMIGO2-low group. The rate of complete cytoreductive surgery was lower in the AMIGO2-high group than in the AMIGO2-low group. Moreover, in vitro studies revealed that four serous ovarian cancer cell lines exhibited AMIGO2 expression and adhesion to mesothelial cells. Adhesion to mesothelial cells was attenuated by AMIGO2 knockdown in SKOV3 and SHIN3 cells. Furthermore, AMIGO2 downregulation in SKOV3 cells significantly suppressed peritoneal dissemination in the murine model. These results suggest that high AMIGO2 expression in serous ovarian carcinoma cells contributes to a poor prognosis by promoting peritoneal metastasis through enhanced cell adhesion to mesothelial cells.

Trends in incidence and hormonal management of endometrial cancer during potentially reproductive age in Japan: a population-based study

We aimed to investigate the trends in the incidence and treatment of endometrial cancer (EC) during potentially reproductive age in Japan, with a special focus on the relative oncologic safety of hormonal therapy (HT) over surgery. This population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry from 2004 to 2018. Women with EC were first identified and then distributions of age, stage, histology, and initial treatment were examined. Then, the relative oncologic safety of HT over surgery in patients under the age of 50 years was evaluated. Among the 9417 patients with EC, 1937 were diagnosed during their potentially reproductive age (< 50 years). The incidence of EC during potentially reproductive age has increased from 18.5% in 2004-2011 to 21.9% in 2012-2018. ECs during potentially reproductive age more frequently displayed favorable characteristics, such as endometrioid histology, and lower histological grade than those in non-potentially reproductive age. Among the 1223 patients diagnosed with localized endometrioid EC, 74 cases (6.0%) received HT as an initial treatment, while 1100 cases (90.0%) underwent surgery as their initial treatment. When the two treatment groups were compared, there was no significant difference in overall survival (p = 0.3713). The estimated 5-year survival rates were 100 and 98.8% in the HT and surgery groups, respectively. EC is increasingly diagnosed during potentially reproductive age in Japan. The use of HT as an initial treatment is increasing, and achieved comparable survival outcomes to urgery against localized endometrioid EC during the potentially reproductive age.

Prediction of response to promising first-line chemotherapy in ovarian cancer patients with residual peritoneal tumors: practical biomarkers and robust multiplex models

Platinum/taxane (TC) chemotherapy with debulking surgery stays the mainstay of the treatment in ovarian cancer patients with peritoneal metastasis, and recently its novel modality, intraperitoneal carboplatin with dose-dense paclitaxel (ddTCip), was shown to have greater therapeutic impact. Nevertheless, the response varies among patients and consequent recurrence, or relapse often occurs. Discovery of therapeutic response predictor to ddTCip and/or TC therapy is eagerly awaited to improve the treatment outcome. Using datasets in 76 participants in our ddTCip study and published databases on patients received TC therapy, we first validated a total of 75 previously suggested markers, sought out more active biomarkers through the association analyses of genome-wide transcriptome and genotyping data with progression-free survival (PFS) and adverse events, and then developed multiplex statistical prediction models for PFS and toxicity by mainly using multiple regression analysis and the classification and regression tree (CART) algorithm. The association analyses revealed that SPINK1 could be a possible biomarker of ddTCip efficacy, while ABCB1 rs1045642 and ERCC1 rs11615 would be a predictor of hematologic toxicity and peripheral neuropathy, respectively. Multiple regression analyses and CART algorithm finally provided a potent efficacy prediction model using 5 gene expression data and robust multiplex toxicity prediction models-CART models using a total of 4 genotype combinations and multiple regression models using 15 polymorphisms on 12 genes. Biomarkers and multiplex models composed here could work well in the response prediction of ddTCip and/or TC therapy, which might contribute to realize optimal selection of the key therapy.

Impact of COVID-19 on gynecological cancer incidence: a large cohort study in Japan

The influence of the coronavirus disease 2019 (COVID-19) pandemic on the number of newly diagnosed gynecological cancers has not been extensively investigated in Japan. This study determined the impact of COVID-19 on the incidence of gynecological cancer. Using the Japanese Society of Obstetricians and Gynecologic Oncology registry database, the distribution of the number of patients based on clinical staging or tumor-node-metastasis classifications before and during the COVID-19 pandemic was analyzed to compare the trends. The clinical staging classification of cervical cancer in Japan was based on the International Federation of Gynecology and Obstetrics (FIGO) 2008 from 2018 to 2020 and on the FIGO 2018 from 2021. Since FIGO-2018 classified N1 cases as stage IIIC, we focused on T classification without referencing the clinical staging (FIGO staging) of patients with cervical cancer in 2021. The number of patients with endometrial cancer and malignant ovarian tumors of all clinical stages increased uniformly yearly, while that of those with stage III cervical cancer rapidly increased in 2021 owing to the adoption of the revised classification. On comparing cases of cervical cancer in 2020 and 2021, we found that T1 cases decreased and T2 and T3 cases increased in 2021 compared to those in 2020 (p = 0.006). Cervical intraepithelial neoplasia/adenocarcinoma in situ incidence decreased in 2020 compared to that in 2019 but increased again in 2021. The number of patients with cervical cancer decreased in most prefectures in 2020. The incidence of locally advanced cervical cancer increased during the COVID-19 pandemic.

Obstetric outcomes after medroxyprogesterone acetate treatment for early stage endometrial cancer or atypical endometrial hyperplasia: a single hospital-based study

To investigate perinatal outcomes in pregnancy after high-dose medroxyprogesterone acetate (MPA) therapy for early stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) and to determine whether pregnancy after MPA therapy is at a higher risk of placenta accreta. Data of 51 pregnancies in 46 women who received MPA therapy for EC or AEH and delivered after 22 weeks of gestation at Keio University Hospital were reviewed. A retrospective matched case-control study was performed to determine the risk of placenta accreta in pregnancy after MPA therapy compared with singleton pregnancies without any history of maternal malignancy treatments. The incidence of placenta accreta was higher in the MPA group than in the control group (15.7 vs. 0%, p = 0.0058). However, no differences in other perinatal outcomes were observed between groups. While gestational weeks at delivery in the MPA group were later than those in the control group (p = 0.0058), no difference in the incidence of preterm delivery was recorded between groups. In the MPA therapy group, the number of patients who underwent ≥ 6 dilation and curettage (D&C) was higher in the placenta accreta group than in the non-placenta accreta group (50.0 vs. 14.0%, p = 0.018). Patients with ≥ 6 D&Cs demonstrated a 6.0-fold increased risk of placenta accreta (p = 0.043, 95% CI 1.05-34.1) than those receiving ≤ 3 D&Cs. Pregnancy after MPA therapy is associated with a high risk of placenta accreta. In cases in which the frequency of D&C is high, placenta accreta should be considered.

Prognostic significance of adjuvant chemotherapy in stage I–II endometrial carcinoma patients who underwent lymphadenectomy

Endometrial carcinoma, the most common gynecologic carcinoma, has an excellent prognosis post-surgery when diagnosed early. The role of postoperative adjuvant chemotherapy in stages I-II endometrial carcinoma remains controversial. This study assesses the efficacy of adjuvant chemotherapy in improving prognosis for these patients. A retrospective analysis was conducted on 1223 stage I-II endometrial carcinoma patients who underwent surgical treatment including total hysterectomy, bilateral salpingo-oophorectomy, and lymph-node biopsy or dissection across four Jikei University School of Medicine-affiliated facilities between 2001 and 2018. Patients were divided into low intermediate risk (LIR) and high intermediate risk (HIR) groups based on recurrence risk. Propensity score matching adjusted for various covariates was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received adjuvant chemotherapy and those who did not. The study included 443 eligible patients, with 288 in the LIR group and 155 in the HIR group. Post propensity score matching, no significant difference in PFS or OS was observed between the observation and adjuvant chemotherapy groups within both risk categories. Notably, the 5-year OS for LIR was 97.6% in the observation group and 96.7% in the chemotherapy group; for HIR, the 5-year OS was similarly high with no significant difference. The findings suggest that postoperative adjuvant chemotherapy does not significantly contribute to the improvement of recurrence or prognosis in patients with stage I-II endometrial carcinoma who are categorized outside the low-risk group and have no lymph-node metastasis.

Real-world practice of estrogen therapy after surgery for endometrial cancer: a descriptive study using a Japanese claims database

Estrogen therapy (ET) plays a key role in maintaining the post-surgical quality of life of patients with endometrial cancer. This study investigated the reality of the use of ET after endometrial cancer surgery in Japan. Using a healthcare database in Japan, patients who underwent surgery for endometrial cancer between the ages of 40 and 59 years from January 2006 to March 2021 were included. The cumulative prescriptions of ET after endometrial cancer surgeries in patients who had received chemotherapy or radiation therapy (adj-group) and those who did not (non-adj-group) was estimated using the Kaplan-Meier method. Of the 1475 patients, 115 received ET, among whom transdermal estradiol was initiated in 100 (87.0%) individuals. The cumulative proportions of ET prescription 24 months after surgery [95% confidence intervals (CIs)] were 0.088 [0.072, 0.11] in the non-adj-group and 0.058 [0.040, 0.084] in the adj-group. The cumulative proportion [95% CI] of women who received ET at 24 months after surgeries decreased with increasing age, ranging from 0.29 [0.21, 0.38] in the 40‒44 years old to 0.009 [0.002, 0.034] in the 55‒59 years old women in the non-adj-group and from 0.17 [0.094, 0.31] in the 40‒44 years old to 0 in the 55‒59 years old women in the adj-group. The present study shows that ET after endometrial cancer surgery may be underused, even in women who underwent surgery between 40 and 44 years of age and without adjuvant therapy.

Prognostic and clinicopathological implications of mismatch-repair deficiency and MLH1 promoter methylation status in endometrial carcinoma

The prevalence of MSI-H and MLH1 promoter hypermethylation (MLH1-PHM) as well as Lynch syndrome in Japanese patients with endometrial cancer (EC) has not been fully revealed. There is also a recent report that the prognosis of MLH1-PHM is worse than MLH1 non-PHM in EC; however, no large-scale studies have been conducted in Japan. We investigated the prevalence of MSI-H, MLH1-PHM and Lynch syndrome in EC cases and characteristic and prognosis of them. The 677 patients who were pathologically diagnosed with EC at the Saitama Cancer Center Hospital between 2013 and 2023 were investigated in this study. The MSI and abnormal DNA methylation of the MLH1 promoter were tested in all cases. Patients with MSI-H EC or a family history provided informed consent and examined germline testing for Lynch syndrome. Among the 677 ECs, 170 (25.1%) were MSI-high (MSI-H), and 105 were involved MLH1 hypermethylation. Two of 13 Lynch syndrome cases had MLH1-PHM in ECs. The MSI-H group had more G3 histology, but had a favorable prognosis with 5-year PFS and OS compared with the MSS group. The group with MLH1-PHM have more patients with G1/2 histology and more advanced disease. There was no difference in prognosis between MLH1-PHM and non-PHM groups. This study provides information on the prevalence of MSI-H and MLH1-PHM in EC in Japan. Besides, the prognostic of the MSI-H group is better than that of the MSS group, but no differences were found between the MLH1-PHM and MLH1 non-PHM groups.

Advances in endometrial cancer screening: a comprehensive review of current methods and emerging technologies

Endometrial cancer represents a major global health concern, with rising incidence particularly in developed countries despite declining mortality rates. This comprehensive review examines the evolution of endometrial cancer screening techniques, encompassing traditional methods, emerging technologies, and integrated approaches. Traditional screening methods including transvaginal ultrasound and hysteroscopy demonstrate varying diagnostic capabilities. Hysteroscopy combined with endometrial biopsy exhibits superior diagnostic accuracy with sensitivity ranging from 62.5 to 100% and specificity from 67.8 to 98.9%. Recent advances in molecular diagnostics show promising potential for non-invasive screening, with DNA methylation analysis achieving sensitivity of 91.8% and specificity of 95.5% when utilizing specific gene panels. Cell-based screening methods including liquid-based cytology and immunocytochemistry provide additional diagnostic pathways, demonstrating sensitivity of 84% and specificity of 98%. Digital image analysis integrated with deep learning technologies enables molecular subtype prediction from histopathological images without requiring expensive sequencing. Combination screening approaches, particularly integrating molecular diagnostics with traditional imaging, demonstrate enhanced diagnostic performance while potentially reducing costs through decreased unnecessary procedures. Molecular testing carries broader implications beyond individual patients, as detection of germline mutations such as Lynch syndrome enables cascade genetic screening benefiting family members through early detection and surveillance programs. While universal screening remains cost-prohibitive for asymptomatic populations, evidence strongly supports personalized screening strategies based on individual risk factors including obesity, diabetes, and hereditary cancer syndromes. Future developments will likely emphasize integrated approaches combining molecular diagnostics with traditional methods to optimize diagnostic accuracy, accessibility, and cost-effectiveness.

Efficacy and safety of bevacizumab-combined single-agent chemotherapy for platinum-resistant ovarian cancer that recurred during PARP inhibitor treatment

Currently, there are no reports on the subsequent treatment of patients with ovarian cancer who exhibited platinum-resistant recurrence during treatment with poly (ADP-ribose) polymerase (PARP) inhibitors. This retrospective study was aimed at evaluating the efficacy and safety of single-agent chemotherapy combined with bevacizumab (BEV) in such patients. The efficacy and safety of the treatment were evaluated in 16 patients with ovarian cancer, fallopian tube cancer, or primary peritoneal cancer diagnosed with platinum-resistant recurrence during PARP inhibitor treatment between April 2019 and June 2025. Chemotherapy was administered with paclitaxel alone or nogitecan alone in combination with BEV and generally continued until the disease progressed. The median number of single-agent chemotherapy cycles with BEV was 6 (range: 1-20). The objective response and disease control rates were 31.3% and 75.0%, respectively. The median progression-free survival 2 and post-progression survival were 5.5 months [95% confidence interval (CI) = 4.0-6.0] and 17 months (95%CI = 10.0-29.0), respectively. Grade 3 or higher hematological toxicities were observed, including leukopenia, neutropenia, anemia, and thrombocytopenia in 7, 9, 1, and 3 patients, respectively. Non-hematological toxicities included hypertension in three patients and nausea, vomiting, fatigue, proteinuria, thrombosis, ileus, and heart failure in one patient each. None of the patients discontinued chemotherapy because of adverse events or treatment-related deaths. BEV-combined single-agent chemotherapy has potential efficacy even in the challenging setting of platinum-resistant recurrence during PARP inhibitor treatment of ovarian cancer.

Impact of immunohistochemistry-based molecular classification with conventional risk stratification on recurrence and survival outcomes in endometrial cancer

The conventional histomorphology-based risk classification for endometrial cancer (EC) does not consider the molecular heterogeneity that influences prognosis and treatment response. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) system uses next-generation sequencing to assess DNA polymerase epsilon (POLE) mutations, but its high cost limits its accessibility. This study evaluated the prognostic value of a novel algorithm that combined immunohistochemistry (IHC) testing with conventional risk factors. This retrospective study included 237 patients with stage I-III EC who underwent surgery. Low-risk patients were classified without IHC, while intermediate- and high-risk patients were categorized as MMR-deficient (MMRd), p53-abnormal (p53abn), or nonspecific molecular profile (NSMP) groups based on IHC. Additionally, L1CAM expression was also evaluated. Survival outcomes were analyzed using Kaplan-Meier curves and Cox regression models. Data from 233 cases were analyzed; the median follow-up duration was 63 months. Among 87 low-risk patients, only 1 experienced recurrence. The intermediate- and high-risk groups were subdivided into 42 MMRd, 16 p53abn, and 88 NSMP patients. The 5-year disease-free survival (DFS) rates were 98.8% (low-risk), 94.7% (NSMP), 80.6% (MMRd), and 59.8% (p53abn), highlighting the poorer prognosis of p53abn. p53abn independently predicted recurrence (hazard ratio [HR], 10.1) and mortality (HR, 25.6). L1CAM positivity correlated with worse DFS but was not an independent prognostic factor. Conventional risk classification combined with IHC classification using p53 and MMR is a cost-effective prognostic tool that enables risk stratification and personalized treatment decisions, even when genetic testing is unavailable.

The value of vaginal cytology for postoperative surveillance of endometrial cancer

The value of conducting vaginal cytology surveillance after endometrial cancer (EC) surgery has not been fully established, yet in Japan it is still performed routinely in many institutions. We have retrospectively examined its diagnostic and prognostic values. We studied 759 EC cases that underwent hysterectomy at our hospital in Osaka, Japan from January 2010 to December 2019. Information on the clinicopathological factors at the time of initial and postoperative treatments, and the sites and diagnostic timing of recurrences were extracted from medical records and analyzed. Recurrences from primary EC were observed in 11.2% of the patients (85/759). In 23.5% of the cases (20/85), the recurrence included a vaginal component. The two most common single-sites of recurrence were vagina (14.1%, 12/85) and lung (12.9%, 11/85). The diagnosis of vaginal recurrence was made from symptoms and gynecological examination in 14 of the 20 cases. Only one was diagnosed solely by vaginal cytology; in that case, macroscopic lesions appeared two months after obtaining the abnormal cytology. We found that, in postoperative follow-up surveillance for EC, most cases of vaginal recurrence were first diagnosed by a careful pelvic examination. For current routine postoperative practice, monitoring critical symptoms and conducting careful gynecological examinations has been shown to be more important than cytological examinations.

Immunotherapy for endometrial cancer

Advanced recurrent endometrial cancer (EC) has a poor prognosis and new treatment options are needed. In 2013, EC was classified by genomic analysis into four groups: the POLE ultra-mutated group, the MSI-high hypermutated group (MSI-H), the copy number low group, and the copy number high group. The prognosis differs based on the classification, which should enable the individualization of treatment. The MSI-H and POLE types can induce PD-L1 expression in cancer cells. Among the gynecological cancers, EC exhibits the highest levels of PD-1 and PD-L1 expression and has the highest proportion of MSI-H. Thus, an immune checkpoint inhibitor (ICI) is expected to be effective. The first ICI to show efficacy in recurrent EC was the anti-PD1 antibody pembrolizumab, which exhibited efficacy in MSI-H EC. The combination of pembrolizumab and the multi-kinase inhibitor lenvatinib significantly prolongs OS/PFS compared with single-agent chemotherapy in previously treated recurrent EC, regardless of MSI status. ICIs are now moving from second-line and beyond to first-line treatment regimens. The efficacy of paclitaxel plus carboplatin (TC) and ICI combinations compared with TC have been demonstrated, including an ongoing Phase III trial comparing chemotherapy with the combination of pembrolizumab and lenvatinib. Although ICIs are becoming the mainstay of EC, they cause systemic inflammatory side effects known as irAEs. The incidence of irAEs is higher for combination therapy with CT or lenvatinib compared with ICI therapy alone. Even though they are rarely fatal, irAEs should be addressed promptly.

JGOG2046: a feasibility study of neoadjuvant chemotherapy followed by debulking surgery for clinically diagnosed FIGO stage IVb endometrial cancer

We evaluated the feasibility of neoadjuvant chemotherapy, followed by debulking surgery, for clinically diagnosed FIGO stage IVb endometrial cancer (protocol number: JGOG2046). The experimental treatment consisted of 3 cycles of paclitaxel (180 mg/m2) plus carboplatin (AUC5) followed by debulking surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and 3 cycles of adjuvant chemotherapy. Patients were considered as eligible if they were pathologically diagnosed as primary endometrial cancer, and had both endometrial tumor and distant metastasis confirmed by imaging examinations. The primary endpoint was the incidence of patients who completed debulking surgery after the neoadjuvant chemotherapy. While 51 patients were enrolled from 23 hospitals, the final study cohort consisted of 49 patients with a mean age of 59.0 years. Although the response ratio of the neoadjuvant chemotherapy was 65.3% (95% CI 50.4-78.3%), 67.3% (95% confidence interval (CI) 52.5-80.1%) underwent debulking surgery after the neoadjuvant chemotherapy and 59.2% (95% CI 45.2-71.8%) completed the protocol treatment including 3 courses of adjuvant chemotherapy. The median disease-free survival time was 9.1 months (95% CI 6.5-11.9), while the median overall survival time was 23.2 months (95% CI 11.9-27.8). A patient with sigmoid colon cancer and another with cervical cancer were included in this study. Neoadjuvant chemotherapy followed by debulking surgery was a feasible and acceptable treatment for metastatic endometrial cancer. (225 words).

Indocyanine green-guided sentinel lymph node mapping during laparoscopic surgery with vaginal cuff closure but no uterine manipulator for cervical cancer

Lymph node metastasis is a critical prognostic factor in cervical cancer. Considering the potential complications of lymphadenectomy and desirability of avoiding systemic lymphadenectomy, accurate intraoperative prediction of the existence of lymph node metastasis is important in patients undergoing surgery for cervical cancer. We evaluated the feasibility and value of indocyanine green (ICG) use for sentinel lymph node (SLN) mapping during laparoscopic surgery performed for cervical cancer. This single-center cohort study included 77 patients undergoing a new laparoscopic radical surgery method with pelvic lymphadenectomy for early-stage cervical cancer. The surgery, performed without using a uterine manipulator, included creation of a vaginal cuff. Bilateral ICG-guided SLN mapping and rapid histopathological examination were performed, and results were analyzed in relation to final histopathologic diagnoses. The SLN pelvic side-specific detection rate was 93.5%, sensitivity (SLN-positive cases/SLN-detected pelvic lymph node-positive cases) was 100%, intraoperative negative predictive value (NPV) was 97.8%, and final pathological NPV was 100%. The detection rate was significantly lower for tumors ≥ 2 cm in diameter than for tumors < 2 cm in diameter. Micrometastases were missed by intraoperative examination in 3 cases. The high NPV suggests the feasibility and usefulness of ICG-based SLN mapping plus rapid intraoperative examination for identification of metastatic SLNs. Use of ICG-based mapping for intraoperative identification of SLNs in patients undergoing this new laparoscopic surgery method for early-stage cervical cancer was particularly effective for tumors < 2 cm in diameter. However, incorporating a search for micrometastases into rapid intraoperative histopathologic examination may be necessary.

Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan

The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

Oncologic outcomes for patients with endometrial cancer who received minimally invasive surgery: a retrospective observational study

Laparoscopic hysterectomy has been performed for patients with endometrial cancer as minimally invasive surgery; however, the long-term outcomes of high-risk disease compared to open surgery remain unclear. Eight hundred and eighty-three patients with endometrial cancer who underwent laparoscopic or abdominal hysterectomy were categorized into three groups. Low-risk disease was defined as stage IA disease with endometrioid carcinoma of grade 1 or 2. Uterine-confined disease was defined as stage IA disease with high-grade tumors or stage IB and II disease. Advanced disease was defined as stage III or IV disease. The progression-free survival (PFS) and overall survival (OS) rates were compared between laparoscopic and laparotomic hysterectomy. Among 478 patients with low-risk disease, including 226 with laparoscopy and 252 with laparotomy, the prognosis was not significantly different between the groups (3-year PFS rate, 97.4% vs. 97.1%, p = 0.8; 3-year OS rate, 98.6% vs. 98.3%, p = 0.9). Among the 229 patients with uterine-confined disease, including 51 with laparoscopy and 178 with laparotomy, the prognosis was not significantly different between the groups (3-year PFS rate, 90.5% vs. 85.5%, p = 0.7; 3-year OS rate, 91.3% vs. 92.5%, p = 0.8). Among the 176 patients with advanced disease, including 24 with laparoscopy and 152 with laparotomy, laparoscopic hysterectomy had a higher PFS rate and OS rate than laparotomic hysterectomy (3-year PFS rate, 74.5% vs. 51.5%, p = 0.01; 3-year OS rate, 92.3% vs. 75.1%, p = 0.03). Laparoscopic procedures are not associated with a poorer outcome than laparotomy in patients with advanced endometrial cancer or uterine-confined endometrial cancer.

Novel classification of ovarian metastases originating from colorectal cancer by radiological imaging and macroscopic appearance

Diagnosis of secondary ovarian tumors originating from colorectal cancer has previously been based upon history of malignancy and radiological findings of bilateral masses with a "stained glass appearance." The purpose of this study was to perform a detailed investigation of the radiological and macroscopic features of ovarian metastases originating from colorectal cancer, which remain to be fully characterized. Study participants were 48 consecutive patients with ovarian metastases from colorectal cancer who underwent resection of ovarian tumors at the National Cancer Center Hospital between August 1998 and January 2019. Ovarian tumors were classified into subgroups using computed tomography (CT), magnetic resonance imaging (MRI), and macroscopic appearance. CT/MRI findings and macroscopic appearance were classified into the following four types: type 1 (oval, homogeneous-solid) (n = 5); type 2 (heterogeneous-solid, small in size with multinodular surface) (n = 3); type 3 (solid-cystic, predominantly solid) (n = 18); and type 4 (cystic-solid, multilocular with solid components) (n = 22). Type 1 mimics Krukenberg tumors, type 2 mimics ovarian metastases from breast cancer, type 3 mimics primary ovarian endometrioid cancer, and type 4 mimics primary ovarian mucinous cancer, with a "stained glass appearance". Twenty-eight (58%) patients had bilateral metastases. Eleven patients (23%) underwent hysterectomy and/or pelvic lymph node dissection in addition to ovarian resection. We introduced a novel classification system for ovarian metastases originating from colorectal cancer, which may be beneficial for assessing ovarian metastases from colorectal cancer and avoiding unnecessary surgery due to misdiagnosis of primary ovarian tumors.

Prognostic significance of solid growth in endometrioid endometrial adenocarcinoma

Endometrioid endometrial cancer is the most common histological subtype of endometrial adenocarcinoma. In the FIGO grading scheme, both architectural and nuclear grade are taken into consideration. However, the specific impact of solid growth alone on endometrioid endometrial adenocarcinoma outcome is not well documented. We sought to assess the degree of impact of solid growth on lymphovascular space invasion (LVSI), myometrial invasion, tumor size, FIGO stage, lymph node metastasis (LNM), relapse-free survival (RFS) and disease-specific survival (DSS). Paraffin blocks of 269 patients treated for endometrioid endometrial cancer were retrospectively analyzed with morphometry for solid growth percentages. A statistically significant cut-off value of 1% solid growth was found for predicting LNM and advanced stage (III or IV), myometrial invasion and LVSI (p  75% solid growth (p  75% (p > 0.05). Although > 75% solid growth was most significantly associated with many of the adverse prognostic factors, this subset did not provide prognostic superiority in predicting adverse survival when compared to subsets within 6-75% solid growth. In conclusion, although no statistically significant difference in survival was found among subdivisions of architectural grades 2 and 3, solid growth, especially ≥ 8%, appeared to be an independent prognostic factor for survival in patients with early-stage endometrioid endometrial cancer.

Comparison of treatment outcomes between first-line chemotherapy with or without bevacizumab for advanced ovarian, fallopian tube, and primary peritoneal cancer (Tohoku gynecologic cancer unit: TGCU-RS001 study)

Outcomes with and without bevacizumab as first-line chemotherapy in Japanese-only ovarian cancer patients have not been reported. In this study, we report a retrospective study conducted at the Tohoku Gynecologic Cancer Unit. The study included 453 patients with stage III/IV ovarian, fallopian tube, and primary peritoneal cancer who received first-line platinum-based chemotherapy. The patients were divided into two groups: bevacizumab (168 patients) and without bevacizumab (285 patients). The primary endpoint was the rate of platinum-resistant recurrence and the secondary endpoints were the antitumor response, progression-free survival, overall survival, and adverse events. The objective response rates for patients with measurable diseases treated with and without bevacizumab were 84.5% and 73.0%, respectively (P = 0.0066). Platinum-resistant recurrence in the groups treated with and without bevacizumab was noted in 31 (18.4%) and 111 (38.6%) patients, respectively (P < 0.0001). The median progression-free survival for the bevacizumab and without bevacizumab groups was 23 and 15 months, respectively (P = 0.0002), and the median overall survival was not reached and 49 months, respectively (P = 0.0005). Hypertension of grade 3 or higher was observed in 21 patients (12.5%) in the bevacizumab group (P < 0.001), and proteinuria was observed in 18 patients (10.7%) and 1 patient (0.3%) in the bevacizumab and without bevacizumab groups, respectively (P < 0.001). Intestinal perforation was observed in only one patient (0.6%) in the bevacizumab group. Combination and maintenance with bevacizumab in primary chemotherapy for advanced ovarian, fallopian tube, and primary peritoneal cancer was effective in reducing platinum-resistant recurrence rates and prolonging progression-free and overall survival.

Clinical and pathological outcomes of risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer

To clarify the clinical as well as pathological outcomes in Japanese women with germline pathogenic BRCA1/2 variants who underwent risk-reducing salpingo-oophorectomy (RRSO). This prospective study examined the rate of occult cancer and primary peritoneal cancer after RRSO at our institution in the period from 2011 to 2020. Clinical records of genetically confirmed patients with germline pathogenic BRCA1/2 variants who desired to undergo RRSO were reviewed. Specimens obtained during RRSO were pathologically diagnosed as per SEE-FIM protocol. All the participants underwent magnetic resonance imaging (MRI) about 1 month preoperatively. One hundred and seventeen women underwent RRSO during this period. Of these, the numbers of women with germline pathogenic BRCA1 and BRCA2 variants were 72 and 45, respectively. The mean observational time after RRSO was 35.8 months. Despite negative preoperative screening results, three (2.6%) serous tubal intraepithelial carcinoma and three (2.6%) invasive carcinomas were identified. Of the three invasive carcinomas cases, two were International Federation of Gynecology and Obstetrics (FIGO) stage I primary fallopian tube cancer, and the third case was double cancer (ovarian cancer and fallopian tube cancer) with FIGO stage IC3. The rate of occult neoplasms was similar to those reported by studies performed in other countries. Although women with occult cancer were diagnosed with FIGO stage I, the MRI performed 1 month preoperatively did not show any such malignant findings. Thus, RRSO is the only promising method that can improve the prognosis in women with germline pathogenic BRCA1/2 variants.

Peripheral blood lymphocyte and eosinophil dynamics with chemotherapy and pembrolizumab in cervical cancer

Cervical cancer poses a significant global health burden, particularly in its metastatic and recurrent forms, for which treatment options are limited. Although immune checkpoint inhibitors (ICIs) such as pembrolizumab have improved outcomes, predictive markers for efficacy are still undefined. This retrospective study investigated changes in peripheral blood eosinophil and lymphocyte counts as potential prognostic indicators in patients with metastatic or recurrent cervical cancer undergoing pembrolizumab-based therapy. Forty-one patients treated with pembrolizumab plus taxane-platinum chemotherapy (± bevacizumab) were analyzed. Peripheral blood eosinophil and lymphocyte counts were measured before and 3 weeks after treatment initiation. Statistical analyses included Kaplan-Meier curves, Cox regression, and log-rank tests. Immune-related adverse events ≥ grade 2 emerged as a significant independent factor associated with prolonged progression-free survival (PFS) in this cohort (p = 0.014). Patients with decreased eosinophil count ratios post-treatment demonstrated longer PFS, particularly among those with recurrence and those who had received prior radiotherapy (p = 0.0001). Conversely, increased lymphocyte count ratios correlated with improved PFS in patients undergoing primary treatment (p = 0.018). Changes in peripheral eosinophil and lymphocyte counts following pembrolizumab initiation may serve as predictive indicators of treatment efficacy in specific cervical cancer subgroups. Incorporating these hematologic parameters could help optimize patient selection and therapeutic strategies. Further research is needed to clarify their role as predictive markers of pembrolizumab efficacy in cervical cancer.

Real-world safety and efficacy of immune checkpoint inhibitors in Japanese patients with persistent, recurrent, or metastatic cervical cancer: a multicenter prospective and retrospective study

To evaluate the real-world safety and efficacy of immune checkpoint inhibitors (ICIs) in Japanese patients with persistent, recurrent, or metastatic cervical cancer. In this multicenter observational study at four Japanese institutions, 100 patients with recurrent, persistent, or advanced cervical cancer received pembrolizumab or cemiplimab. Primary endpoints were objective response rate (ORR) and the incidence of immune-mediated adverse events (imAEs) and grade 3-5 AEs. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Logistic and Cox regression were used to explore prognostic factors. Eighteen patients (18%) achieved complete response and 44 (44%) partial response, yielding an ORR of 62.0% and a disease control rate of 77.0%. Median PFS and OS were 10.4 and 22.0 months, respectively. ORR was 74.0% in the first-line setting and 29.6% in the second-line setting. Among patients who met KEYNOTE-826 eligibility criteria, ORR was 82.9% and median PFS 16.1 months. Cemiplimab, which was mainly used as off-label retreatment in frail or previously ICI-exposed patients, showed limited activity (ORR 5.6%). ImAEs occurred in 45.0% of patients, with grade 3-5 events in 19.0% and six treatment-related deaths. Poor performance status and recurrent disease were associated with lower response and shorter PFS, whereas PD-L1 tumor proportion score ≥ 50% and grade 3-5 imAEs were associated with longer PFS. In this real-world cohort, ICIs, particularly pembrolizumab, demonstrated substantial antitumor activity with acceptable toxicity in Japanese patients with advanced cervical cancer, especially when used as first-line therapy and in patients fulfilling KEYNOTE-826 eligibility criteria.

Real-world multicenter study of immune checkpoint inhibitors in advanced cervical cancer across HPV-associated and HPV-independent subtypes

Cervical cancer remains a major health problem, and HPV-independent subtypes such as gastric-type adenocarcinoma carry dismal outcomes. Although immune checkpoint inhibitors (ICIs) have improved survival in large trials, their real-world effectiveness including HPV-independent tumors is not well established. We conducted a retrospective multicenter study of two surrogate cohorts representing refractory cervical cancer: patients treated with bevacizumab (Bev-cohort, n = 65) and those undergoing comprehensive genomic profiling (CGP-cohort, n = 42). Early ICI administration was evaluated using landmark analysis (Bev: 180 days; CGP: 6 months), with differences in restricted mean survival time (ΔRMST) as the primary endpoint. Multivariable Cox models adjusting for stage, histology, and treatment interval were performed as secondary analyses. Exploratory analyses assessed HPV and molecular status for associations with ICI response. In the Bev-cohort, 14 ICI-treated patients achieved significantly longer survival than 48 non-ICI patients (ΔRMST + 19.4 days at 180 days; + 56.2 days at 360 days). Multivariable Cox confirmed ICI as an independent predictor of survival (HR 0.15, 95%CI 0.01-0.69). In the CGP-cohort, 11 ICI-treated patients also experienced superior survival compared with 20 non-ICI patients (ΔRMST + 1.05 months at 6 months; + 2.33 months at 12 months). Among 36 ICI-treated cases overall, efficacy was not clearly associated with PD-L1 or tumor mutation burden status. Importantly, HPV-independent tumors, including gastric-type adenocarcinoma, demonstrated progression-free survival comparable to HPV-associated tumors. ICIs improved survival in advanced refractory cervical cancer across two real-world cohorts. HPVI may respond favorably, but further studies are needed.

Prognostic significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in uterine carcinosarcoma

Uterine carcinosarcoma (UCS) and uterine sarcomas (US) are rare but aggressive cancer with poor prognoses. The prognostic value of systemic inflammatory response (SIR) indicators, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), in predicting outcomes of UCS and US remains unclear. This study investigated the prognostic significance of SIR indicators for UCS and US. Clinicopathological data from 237 patients diagnosed with UCS or US across 14 hospitals from January 2008 to December 2017 were retrospectively analyzed. NLR, PLR, and MLR values were calculated from preoperative blood counts. Prognostic impact was evaluated using Kaplan-Meier survival analysis, Cox regression models, and receiver operating characteristic (ROC) curve analysis. Elevated NLR, PLR, and MLR were associated with poorer progression-free survival (PFS) in UCS. Additionally, a high NLR also indicated worse overall survival (OS) in UCS. In patients with US, only PLR was significantly associated with poorer PFS. Combining SIR indicators provided a stronger prognostic prediction for UCS compared to individual indicators. Multivariate analysis revealed that high levels of SIR indicators were an independent poor prognostic factor for both PFS and OS in UCS. SIR indicators, particularly when combined, are valuable prognostic markers in UCS, reflecting the inflammatory status and aiding in stratifying patients for tailored therapeutic strategies. These findings support the incorporation of SIR indicators into clinical practice for better management of patients with UCS.

Utility of circulating human papillomavirus DNA as a biomarker for detection and prognosis of cervical cancer in Japanese patients

Cervical cancer (CC), the fourth most common cancer in women, is caused predominantly by human papillomavirus (HPV). Although measuring serum squamous cell carcinoma antigen (SCC Ag) can be useful for detecting recurrence of SCC, a major type of CC, its prognostic value remains unclear. This study focuses on the utility of circulating cell-free HPV (ccfHPV) DNA in plasma as a biomarker, with particular emphasis on its relevance to high-risk HPV subtypes prevalent in Japan. A prospective study of 26 CC patients and 23 females diagnosed with pre-cancerous lesions was conducted. Patients were selected carefully to include only those with single high-risk HPV subtypes (i.e., HPV16, 18, 52, or 58), reflecting regional HPV epidemiology. ccfHPV DNA was isolated from plasma and analyzed by droplet digital PCR targeting the HPV E7 genes. The detection rate of ccfHPV DNA in CC patients before clinical treatment was 57.7%. The detection rate correlated significantly with tumor size (r = 0.624, P < 0.01) and clinical stage (r = 0.844, P < 0.01). No ccfHPV DNA was detected in the females with pre-cancerous lesions. By contrast, of the 13 concurrent chemoradiotherapy cases, two relapsed within 6 months post-treatment. In those cases, ccfHPV DNA levels rose earlier than SCC Ag levels. The 11 CC cases in which no ccfHPV DNA was detected within 1 month post-treatment did not relapse. ccfHPV DNA is a useful biomarker for advanced-stage CC and for predicting prognosis, particularly in the Japanese clinical setting.

Re-evaluating prognostic factors for cervical cancer with lymph node metastasis: a Japanese multicenter cohort study based on FIGO 2018

In 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its cervical cancer staging system to enhance clinical relevance, notably by categorizing lymph node metastases (LNM) as an independent stage IIIC. This multicenter study evaluates the prognostic implications of the FIGO 2018 classification within a Japanese cohort. This study included 1468 patients with cervical cancer. Initial FIGO 2009 stages were restaged under FIGO 2018. Stage IIIC was further compared based on the location of LNM (pelvic or para-aortic, i.e., IIIC1 and IIIC2, respectively), local tumor stage, and histology. A total of 345 cases (27.4%) were upstaged to stage IIIC, which exhibited a poorer prognosis compared to stage II (HR, 2.12; 95% CI 1.29 - 3.48; p = 0.004) and better than stage IIIAB (HR, 0.46; 95% CI 0.27 - 0.78; p = 0.004). Notably, stage IIIC2 showed a significantly worse prognosis than IIIC1 (HR, 2.32; 95% CI 1.37 - 3.93; p = 0.003). Subdivisions of stage IIIC1 (T1, T2, and T3AB) displayed significantly varied prognoses, with the prognosis for IIIC1-T3AB similar to that of stage IIIAB. In contrast, all subdivisions of IIIC2 showed uniformly poor outcomes. Multivariate analysis of stage IIIC patients revealed that para-aortic LNM, adenocarcinoma and adenosquamous carcinoma histology, and local T3AB tumor remained significant. The classification of para-aortic LNM as stage IIIC2 has proven to be of critical relevance in the Japanese cohort. However, the prognostic impact of stage IIIC1 remains influenced by local tumor factors and histological subtypes.

Ovarian serous borderline tumors with recurrent or extraovarian lesions: a Japanese, retrospective, multi-institutional, population-based study

Ovarian serous borderline tumors (SBT) are typically unilateral and are primarily treated using hysterectomy and bilateral salpingooophorectomy (SO). However, most young patients prefer fertility-sparing surgeries (FSS) with tumorectomy or unilateral SO. Micropapillary morphology and invasive implants have been designated as histopathological risk indicators for recurrence or metastasis, but their clinical impact remains controversial because of limitations like diagnostic inconsistency and incomplete surgical staging. A nationwide multi-institutional population-based retrospective surveillance was conducted with a thorough central pathology review to reveal the clinical features of SBT. Of 313 SBT patients enrolled in the Japanese Society of Clinical Oncology's Surveillance of Gynecologic Rare Tumors, 289 patient records were reviewed for clinical outcomes. The glass slides of patients at stage II-IV or with recurrence or death were re-evaluated by three gynecological pathologists. The 10-year overall and progression-free survival (PFS) rates were 98.6% and 92.3%. The median recurrence period was 40 months and 77.0% was observed in the contralateral ovary within 60 months. Patients aged ≤ 35 years underwent FSS more frequently and relapsed more (p < .001). A clinic-pathological analysis revealed diagnosis during pregnancy, FSS, and treatment at non-university institutes as well as advanced stage and large diameter were independent risk factors of recurrence. Among patients having pathologically confirmed SBTs, PFS was not influenced by the presence of micropapillary pattern or invasive implants. The recurrence rate was lower in this cohort than previous reports, but the clinical impacts of incomplete resection and misclassification of the tumor were still significant on the treatment of SBT.

MRI-based volumetric tumor parameters before and during chemoradiation predict tumor recurrence and patient survival in locally advanced cervical cancer: a subgroup analysis of a phase II prospective trial

This subgroup analysis of a prospective phase II trial aimed to identify valuable and accessible prognostic factors for overall survival (OS) and progression-free survival (PFS) of patients with locally advanced cervical cancer (LACC). Patients with FIGO II to IVA cervical cancer were assessed in this study. All patients underwent concurrent chemoradiotherapy (CCRT) followed by brachytherapy. Tumor parameters based on MRI scans before and during CCRT were evaluated for Overall survival (OS) and Progression-free survival (PFS). A total of 86 patients were included in this analysis with a median follow-up period of 31.7 months. Three-year OS and PFS rates for all patients were 87.1% and 76.5%, respectively. Univariate Cox regression analysis showed that restaging tumor size (rTS) over 2.55 cm (p  2.55 cm showed statistically significant with OS (HR: 5.47, 95% CI 1.80-9.58, p = 0.035) and PFS (HR: 3.83, 95% CI 1.50-11.45; p = 0.025). Initial tumor size and restaging tumor volume that are easily accessible during radiotherapy provide valuable prognostic information for cervical cancer. MRI-based measurable volumetric scoring system can be readily applied in real-world practice of cervical cancer. This study is a subgroup analysis of prospective trial registered at ClinicalTrials.gov Identifier: NCT02993653.

Neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian cancer: GOTIC-019 study

Abstract Introduction Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice. Patients and methods We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy. Results Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93). Conclusions NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.

A single institution’s experience with minimally invasive surgery for ovarian cancer, and a systematic meta-analysis of the literature

Abstract Background This study assesses the feasibility of minimally invasive surgery (MIS) for well-selected epithelial ovarian cancer (EOC) patients. Methods We performed a review of data prospectively collected from a single center from 2017 to 2022. Only patients with histologically confirmed EOC, with a tumor diameter of less than 10 cm, were eligible. We also performed a meta-analysis of similar studies comparing the outcomes of laparoscopy and laparotomy. We used MINORS (Methodological Index for Non-Randomized Studies) to assess the risk of bias and calculated the odds ratio or mean difference. Results Eighteen patients were included; 13 in re-staging group, four in PDS group, and one in IDS group. All achieved complete cytoreduction. One case was converted to laparotomy. The median number of removed pelvic lymph nodes was 25 (range 16–34), and 32 (range 19–44) for para-aortic nodes. There were two (15.4%) intraoperative urinary tract injuries. The median follow-up was 35 months (range 1–53). Recurrence was observed in one case (7.7%). Thirteen articles for early-stage ovarian cancer were included in our meta-analysis. Analysis of the pooled results found that MIS had a higher frequency of spillage (OR, 2.15; 95% CI 1.27–3.64). No differences were observed in recurrence, complications, or up-staging. Conclusions Our experience supports the possibility of conducting MIS for EOC in well-selected patients. Except for spillage, our meta-analysis findings are consistent with previous reports, the majority of which were also retrospective. Ultimately, randomized clinical trials will be needed to authenticate the safety.

Intentions for catch-up HPV vaccination in Japan: an internet survey

Abstract Purpose In Japan, Japan’s Ministry of Health, Labor, and Welfare decided to suspend govermental recommendation for HPV vaccination in FY 2013. The HPV vaccination rate for those born in FY 2000 or thereafter declined dramatically. In 2021, the “suspension of recommendation” ended. The catch-up vaccinations for the unvaccinated have been offered nationwide from FY 2022 to FY 2024. We aimed to quantify the vaccination intentions and characteristics of those young women now eligible for catch-up vaccination.  Methods In February of 2022, we conducted an internet survey targeted women who were born in 1997–2004 but who had not yet been HPV vaccinated. Results We received 1,648 valid responses. 41.6% of the respondents wanted to uptake the catch-up HPV vaccination, 29.7% were undecided, and 28.7% did not want to be vaccinated. The intention to uptake catch-up HPV vaccination was associated with a good history of gynecological visits, intention to receive cervical cancer screening, sexual activity, degree of anxiety about cervical cancer, familiarity with problems associated with cervical cancer, experience with vaccination recommendations, and knowledge about cervical cancer (p &lt; 0.05, respectively). In the vaccinated generation, the proportion of the group that did not want to be vaccinated was significantly higher (p &lt; 0.05). In the vaccine-suspended generation, the proportion of the group that wanted to be vaccinated was significantly higher (p &lt; 0.05). Conclusion Our survey revealed that catch-up vaccination intentions differed depending on the vaccination environment. It is necessary for all organizations involved with HPV vaccination, such as government, medical institutions, and educational institutions, to make recommendations based on an understanding of the characteristics of the “vaccinated generation” and the “vaccine-suspended generation”.

Re-administration of platinum-based chemotherapy for recurrent endometrial cancer: an ancillary analysis of the SGSG-012/GOTIC-004/Intergroup study

AbstractBackgroundWe previously demonstrated the applicability of the concept of “platinum sensitivity” in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study.MethodsAmong the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data.ResultsIn 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: &lt; 12 months, 14/48 (29%); 12–23 months, 18/43 (42%); 24–35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: &lt; 12 months, 3/48 (6%); 12–23 months, 0/19 (0%); 24–35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)].ConclusionsRe-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering.

Prognostic significance of peritoneal cytology in low-risk endometrial cancer: comparison of laparoscopic surgery and laparotomy

Abstract Background There is uncertainty surrounding the prognostic value of peritoneal cytology in low-risk endometrial cancer, especially in laparoscopic surgery. The objective of this retrospective study is to determine the prognostic significance of positive peritoneal cytology among patients with low-risk endometrial cancer and to compare it between laparoscopic surgery and conventional laparotomy. Methods From August 2008 to December 2019, all cases of pathologically confirmed stage IA grade 1 or 2 endometrial cancer were reviewed at Osaka Medical College. Statistical analyses used the Chi-square test and the Kaplan–Meier log rank. Results A total of 478 patients were identified: 438 with negative peritoneal cytology (232 who underwent laparotomy and 206 who undertook laparoscopic surgery) and 40 with positive peritoneal cytology (20 who underwent laparotomy and 20 who received laparoscopic surgery). Survival was significantly worse among patients with positive peritoneal cytology compared to patients with negative peritoneal cytology. However, there was no significant difference among patients with negative or positive peritoneal cytology between laparoscopic surgery and laparotomy. Conclusion This retrospective study suggests that, while peritoneal cytology is an independent risk factor in patients with low-risk endometrial cancer, laparoscopic surgery does not influence the survival outcome when compared to laparotomy.

FOXM1 transcriptional regulation of RacGAP1 activates the PI3K/AKT signaling pathway to promote the proliferation, migration, and invasion of cervical cancer cells

Cervical cancer (CC) is the most common gynecological tumor disease in women, which occurs at the junction of cervical squamous columnar epithelium. We investigated the effect and mechanism of transcription factor FOXM1 synergizing RacGAP1 in the proliferation, migration, and invasion of CC cells. Here, we analyzed the correlation between FOXM1 and RacGAP1 and the clinicopathological features of 68 CC patients. RT-qPCR was used to assess FOXM1 and RacGAP1 mRNA expression in CC tissues and cells. Cell proliferation was assessed by CCK-8 and EDU assays. Transwell assay was applied to test migration and invasion. Cell apoptosis was evaluated utilizing flow cytometry. ChIP and dual-luciferase reporter assays confirmed the interaction of FOXM1 and RacGAP1. Protein levels of FOXM1 and RacGAP1, as well as PI3K/AKT, were analyzed by Western blot. FOXM1 expression was correlated with FIGO stage and histological grade, and RacGAP1 expression was correlated with histological grade. FOXM1 and RacGAP1 levels were increased in CC tissues, and higher expressed in human CC cell lines than that in an immortalized HPV-negative skin keratinocyte line (HaCaT). Depleted RacGAP1 suppressed CC cell proliferation, migration and invasion, and promoted apoptosis. RacGAP1 was a target gene of FOXM1, and FOXM1 positively regulated RacGAP1 expression. FOXM1 had a synergistic effect with RacGAP1 to exert oncogenic function in CC by activating the PI3K/AKT signaling. FOXM1 cooperates with RacGAP1 to induce CC cell proliferation, migration and invasion, inhibit apoptosis, and regulate PI3K/AKT signaling to promote CC progression.

Stage IA and IC adult granulosa cell tumors: Clinical features, long-term outcomes and prognostic factors in a 333-patient cohort over three decades

Abstract Background Adult granulosa cell tumors (AGCTs) are rare low-grade malignant ovarian tumors, with 80–90% diagnosed at FIGO stage I. This study aimed to identify prognostic factors and refine management for stage I AGCT. Methods In this 30-year retrospective cohort study, patients with stage I AGCT between January 1988 and January 2024 were selected and reviewed in total cohort and subgroups according to tumor stage. Results This retrospective study analyzed 333 eligible AGCT cases, including 196 patients (58.9%) with FIGO stage IA and 137 (41.1%) with stage IC. After a median follow-up of 138.5 ± 108.0 months, recurrence occurred in 55 patients (40.1%) in the IC group, significantly higher than that in the IA group (38 patients, 19.4%; P  &lt; 0.001, FDR = 0.005). Approximately half of recurrences in both groups were intra-abdominal, with comparable median recurrence intervals. Multivariate logistic regression identified stage IC ( P  = 0.001), incomplete staging surgery ( P  = 0.015) and adjuvant chemotherapy ( P  = 0.002) independent predictors of increased recurrence. In the propensity-matched cohort ( n  = 188), adjuvant chemotherapy showed no significant association with recurrence ( P  = 0.067). Cox multivariate analysis revealed stage IC and incomplete staging surgery as independent prognostic factors for worse DFS in early-stage disease ( P  = 0.001 and 0.012, respectively). Notably, complete staging surgery was associated with improved DFS specifically in stage IC patients ( P  = 0.016). Conclusions Unilateral salpingo-oophorectomy instead of simple cystectomy demonstrated a favorable safety profile in reproductive patients with stage I AGCT. Comprehensive surgical staging without lymphadenectomy should be considered as a viable treatment strategy, especially in the stage IC disease, manifesting a significantly higher recurrence rate and shorter DFS compared to stage IA counterparts.

Visceral-to-subcutaneous fat ratio is a possible prognostic factor for type 1 endometrial cancer

Abstract Background Associations have been observed between obesity defined by the body mass index (BMI) and the incidence of endometrial cancer. However, the impact of obesity on the prognosis of endometrial cancer is not yet clear. Recently, visceral fat has been considered to have a greater impact on malignant disease in obese patients than subcutaneous fat. In this study, we investigated the association between prognostic factors of type 1 and type 2 endometrial cancer and obesity parameters. Methods The impacts of clinical factors on the progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively in 145 primary endometrial cancer patients. The factors included age, BMI, pathological findings, Federation of Gynecology and Obstetrics (FIGO) stage, status of lymph node metastasis, and the amounts of visceral and subcutaneous fat obtained from computed tomography (CT) data. Results Only the visceral-to-subcutaneous fat ratio (V/S ratio) (cutoff value 0.5) corresponded to a significant difference in OS and PFS in type 1 endometrial cancer (p = 0.0080, p = 0.0053) according to the results of log-rank tests of Kaplan–Meier curves. The COX regression univariate analysis revealed that only the V/S ratio was a significant prognostic factor for PFS, but not OS (p = 0.033 and p = 0.270, respectively). Conclusion A V/S ratio &gt; 0.5 is a possible factor for poor prognosis in type 1 endometrial cancer. Further research is needed to investigate the preventive and therapeutic effects of reducing visceral fat on the prognosis of this type of cancer.

Heterogeneous effects of cytotoxic chemotherapies for platinum-resistant ovarian cancer

Abstract Background Single-agent chemotherapy with or without bevacizumab (Bev) is a standard therapy for platinum-resistant ovarian cancer (PR-OC). However, there is a lack of literature on chemotherapy agent selection in heterogenous PR-OC. Therefore, we aimed to clarify the heterogeneous treatment effects of each chemotherapy agent. Methods Patients who underwent single-drug chemotherapy agents or Bev combination therapy for PR-OC between January 2009 and June 2022 were included in this study. We assessed the impact of each chemotherapy agent on the time to treatment failure (TTF) according to histological type, platinum-free interval (PFI), and Bev usage. Results A total of 158 patients received 343 different chemotherapy regimens. In patients with clear cell carcinoma/mucinous carcinoma (CC/MC), gemcitabine (GEM) had the strongest effect with a median TTF of 5.3 months, whilst nedaplatin (NDP) had the lowest effect with a median TTF of 1.4 months. In contrast, in the non-CC/MC group, irinotecan (CPT-11) and NDP had a better TTF than GEM and pegylated liposomal doxorubicin (PLD). There were notable differences in the treatment efficacy of NDP according to PFI. Specifically, NDP prolonged the TTF in patients with a PFI ≥ 3 months. Compared with GEM alone, GEM + Bev tended to prolong the TTF more effectively; however, an additive effect was not observed with PLD + Bev. Conclusions This study demonstrated that the effect of chemotherapy agents differed according to the tumor and background characteristics of the patient. Our findings will improve selection of effective therapies for patients with PR-OC by considering their background characteristics.

The efficacy and safety profile of 2-weekly dosing of bevacizumab-containing chemotherapy for platinum-resistant recurrent ovarian cancer

Abstract Background Despite being widely used, to date (June 2021), the regimen of bevacizumab 10 mg/kg every 2 weeks (Q2W) combined with chemotherapy is not approved in Japan for patients with platinum-resistant recurrent ovarian cancer. In this retrospective analysis, we evaluated the usage patterns of bevacizumab administered for platinum-resistant recurrent ovarian cancer. Methods We obtained clinical data from 155 Japanese medical facilities between November 2013 and December 2018 via a survey. Items included the number of cases of platinum-resistant recurrent ovarian cancer treated with bevacizumab according to dosage. For regimens including bevacizumab 10 mg/kg Q2W, additional information was requested relating to concomitantly administered agents, and the efficacy and safety of the regimen. Results Of 1739 bevacizumab-containing regimens reported in 1633 patients with recurrent ovarian cancer, 264 used 10 mg/kg Q2W. The overall response rate (ORR) with this regimen was 26.1%. Response rates varied according to regimen and were particularly favorable when bevacizumab 10 mg/kg Q2W was administered with paclitaxel (ORR, 53.0%) versus liposomal doxorubicin (15.0%; P  &lt; 0.0001) and irinotecan (7.7%; P  &lt; 0.028). The most frequent Grade ≥ 3 adverse events associated with bevacizumab 10 mg/kg Q2W were neutropenia (11.7%) and hypertension (11.7%). The most frequent bevacizumab-associated Grade ≥ 3 adverse events with bevacizumab plus paclitaxel versus bevacizumab plus liposomal doxorubicin were hypertension (9.0% versus 13.9%) and proteinuria (3.0% versus 8.4%). Conclusions Bevacizumab 10 mg/kg Q2W appears efficacious for patients with recurrent ovarian cancer, with a manageable toxicity profile. Approval of this regimen is clinically desirable for Japanese patients with ovarian cancer.

A phase I study of combined trabectedin and pegylated liposomal doxorubicin therapy for advanced relapsed ovarian cancer

Abstract Background Advanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited. Methods This phase I trial investigated the dosage, safety, pharmacokinetics and efficacy of trabectedin plus pegylated liposomal doxorubicin (PLD) in Japanese patients with advanced relapsed ovarian, fallopian tube, or primary peritoneal cancer. Patients received trabectedin 0.9 or 1.1 mg/m2 immediately after PLD 30 mg/m2; both drugs were given by intravenous infusion. Treatment was repeated every 21 days until disease progression or unacceptable toxicity. The maximum tolerated dose (MTD) was determined in an initial dose escalation phase, and this was used in a subsequent safety assessment phase. Safety and tumor response were monitored throughout the trial, and drug concentrations for pharmacokinetic analysis were measured during cycle 1. Results Eighteen patients were included. The MTD of trabectedin was determined as 1.1 mg/m2. Gastrointestinal adverse events were experienced by all patients, but were mostly grade 1 or 2 in intensity. Most patients had grade ≥ 3 elevations in transaminase levels or grade ≥ 3 reductions in neutrophil count, but these events were generally manageable through dose reduction and/or supportive therapies, as appropriate. There were no deaths during the trial. Trabectedin exposure increased in a dose-dependent manner. The overall response rate was 27.8%. Conclusions Trabectedin, in combination with PLD, may have clinical benefits in Japanese patients with relapsed advanced ovarian cancer. The recommended dosage of trabectedin for further study in this population is 1.1 mg/m2 once every 21 days. Clinical trial registration number: JapicCTI-163164

Validation of tissue factor pathway inhibitor 2 as a specific biomarker for preoperative prediction of clear cell carcinoma of the ovary

Abstract Background Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinoma (CCC) from borderline ovarian tumors (BOTs) and non-clear cell epithelial ovarian cancers (EOCs). Here, we examined the performance of TFPI2 for preoperative diagnosis of CCC. Methods Serum samples were obtained preoperatively from patients with ovarian masses, who needed surgical treatment at five hospitals in Japan. The diagnostic powers of TFPI2 and cancer antigen 125 (CA125) serum levels to discriminate CCC from BOTs, other EOCs, and benign lesions were compared. Results A total of 351 patients including 69 CCCs were analyzed. Serum TFPI2 levels were significantly higher in CCC patients (mean ± SD, 508.2 ± 812.0 pg/mL) than in patients with benign lesions (154.7 ± 46.5), BOTs (181 ± 95.5) and other EOCs (265.4 ± 289.1). TFPI2 had a high diagnostic specificity for CCC (79.5%). In patients with benign ovarian endometriosis, no patient was positive for TFPI2, but 71.4% (15/21) were CA125 positive. TFPI2 showed good performance in discriminating stage II–IV CCC from BOTs and other EOCs (AUC 0.815 for TFPI2 versus 0.505 for CA125) or endometriosis (AUC 0.957 for TFPI2 versus 0.748 for CA125). The diagnostic sensitivity of TFPI2 to discriminate CCC from BOTs and other EOCs was improved from 43.5 to 71.0% when combined with CA125. Conclusions High specificity of TFPI2 for preoperative detection of CCC was verified with the defined cutoff level of TFPI2 in clinical practice. TFPI2 and CA125 may contribute substantially to precise prediction of intractable CCC.

Suppressive effect upon carboplatin hypersensitivity reaction via pegylated liposomal doxorubicin combination therapy

Occurrence of hypersensitivity reaction (HSR) in patients having received multiple doses of carboplatin has been reported. Several studies demonstrated reduction of carboplatin-associated HSR with in combination with pegylated liposomal doxorubicin (PLD). The objective of this study was to determine the suppressive effect on carboplatin-induced HSR via combined treatment with PLD within clinical practice. We reviewed the medical records of women with primary or recurrent ovarian, fallopian tube, or peritoneal cancer treated with carboplatin containing regimen at our hospital between January 2009 and March 2019. We compared the incidence of carboplatin-induced HSR among patients who received more than one cycle of PLD plus carboplatin (PLD-C) therapy (i.e., PLD-C group) versus patients who never received PLD-C therapy (non-PLD-C group). A total of 414 women were included in this study (48: PLD-C group, 366: non-PLD-C group). Carboplatin-induced HSR occurred in 34 total patients (8.2%) [1/48 (2.1%) in the PLD-C group and 33/366 (9.0%) in the non-PLD-C group], with a median cycle number of carboplatin administration at onset of HSR being 9. Incidences of carboplatin-induced HSR within the PLD-C versus non-PLD-C group at the 8th, 12th, and 16th cycles of carboplatin administration were 2.2% vs 11.2%, 2.2% vs 28.6%, and 2.2% vs 39.1%, respectively [hazard ratio: 19.2 (95% confidence interval: 9.82-39.4), p < 0.0001]. Based on the data analyzed here, a suppressive effect on carboplatin-induced HSR via combination therapy with PLD was confirmed within clinical practice.

Veliparib with frontline chemotherapy and as maintenance in Japanese women with ovarian cancer: a subanalysis of efficacy, safety, and antiemetic use in the phase 3 VELIA trial

Abstract Background The phase 3 VELIA trial evaluated veliparib with carboplatin/paclitaxel and as maintenance in patients with high-grade serous ovarian carcinoma. Methods Patients with previously untreated stage III–IV high-grade serous ovarian carcinoma were randomized 1:1:1 to control (placebo with carboplatin/paclitaxel and placebo maintenance), veliparib-combination-only (veliparib with carboplatin/paclitaxel and placebo maintenance), or veliparib-throughout (veliparib with carboplatin/paclitaxel and veliparib maintenance). Randomization stratification factors included geographic region (Japan versus North America or rest of the world). Primary end point was investigator-assessed median progression-free survival. Efficacy, safety, and pharmacokinetics were evaluated in a subgroup of Japanese patients. Results Seventy-eight Japanese patients were randomized to control (n = 23), veliparib-combination-only (n = 30), and veliparib-throughout (n = 25) arms. In the Japanese subgroup, median progression-free survival for veliparib-throughout versus control was 27.4 and 19.1 months (hazard ratio, 0.46; 95% confidence interval, 0.18–1.16; p = 0.1 [not significant]). In the veliparib-throughout arm, grade 3/4 leukopenia, neutropenia, and thrombocytopenia rates were higher for Japanese (32%/88%/32%) versus non-Japanese (17%/56%/28%) patients. Grade 3/4 anemia rates were higher in non-Japanese (65%) versus Japanese (48%) patients. Early introduction of olanzapine during veliparib monotherapy maintenance phase may help prevent premature discontinuation of veliparib, via its potent antiemetic efficacy. Conclusions Median progression-free survival was numerically longer in Japanese patients in the veliparib-throughout versus control arm, consistent with results in the overall study population. Pharmacokinetics were comparable between Japanese and non-Japanese patients. Data for the subgroup of Japanese patients were not powered to show statistical significance but to guide further investigation.

The prognostic role of systemic inflammatory markers in apparent early-stage ovarian cancer

Abstract Background Few studies analyzed the prognostic role of systemic inflammatory markers in early-stage ovarian cancer. The primary endpoint of the present study was to assess the prognostic impact of baseline inflammatory markers in early-stage ovarian cancer. The secondary endpoints were to compare the disease-free survival (DFS) of inflammatory markers with standard risk factors and to correlate these with BRCA mutational status. Methods Retrospective, single-center, observational study. Patients with FIGO-stage I–II and IIIA1 epithelial ovarian cancer undergoing primary surgery between 10/2012 and 12/2019 were included. Inflammatory markers were evaluated on the results of the complete blood count and coagulation tests, performed before ovarian cancer surgery. The Receiver Operating Characteristic curve was used to determine the optimal cut-off value of different baseline inflammatory biomarkers for the DFS analysis. Results Three hundred fifty-nine patients were included in the study period. Baseline neutrophil–lymphocyte ratio (NLR) ≥ 3 and systemic immune inflammation index (SII, defined as platelet x neutrophil–lymphocyte ratio) ≥ 1000 were associated with worse 3 year DFS and baseline SII ≥ 1000 was associated with worse 3 year OS. BRCA-mutated patients with SII ≥ 1000 and with NLR ≥ 3 had significantly worse DFS compared to SII &lt; 1000 and with NLR &lt; 3. FIGO stage &gt; I was the only independent risk factor for higher risk of recurrence. Conclusion SII ≥ 1000 and NLR ≥ 3 were associated with worse 3 year DFS and SII ≥ 1000 was associated with worse 3 year OS. The subgroups of BRCA-mutated patients with higher inflammation markers (SII ≥ 1000 and NLR ≥ 3) were associated with worse DFS. These findings might be helpful to design personalized treatment and more intensive surveillance.

Clinicopathological characteristics and prognosis analysis of ovarian metastases in colorectal cancer: a single-center experience

This study aimed to improve the management of ovarian metastases (OM) in colorectal cancer (CRC) by evaluating the clinicopathological characteristics, therapeutic strategies, and prognostic factors associated with OM originating from CRC. Medical records of patients who were histopathologically diagnosed with OM of CRC origin were reviewed from January 2011 to December 2018 in our medical center. Data related to clinicopathological characteristics, therapeutic strategies, and survival time were recorded and analyzed. Survival and prognosis analyses were carried out to identify variables significantly associated with the outcomes. Forty-six patients were included in the study with a median follow-up of 14 months. Premenopausal (< 50 years) and colon cancer patients were more likely to develop OM. Synchronous OM was found in 34 patients and elevated carbohydrate antigen 125 value could be seen in 67.4% of patients. Bilateral ovarian involvement (27/46, 58.8%) and combined extra-ovarian metastases (32/46, 69.6%) were common in included patients. Complete cytoreduction surgery (R0 resection) was finally achieved in 19 of included patients and 41 patients received postoperative chemotherapy. However, the overall prognosis remains poor, with a median survival time of only 12 months. In univariate analysis, histological types (P = 0.002), peritoneal metastasis (P < 0.0001), the extent of metastatic lesions (P = 0.0001), and completeness of cytoreduction surgery (P < 0.0001) were found to be closely related to prognosis. Finally, completeness of cytoreduction surgery was considered to be the independent determinant of patients' outcome (HR 0.186, 95% CI 0.047-0.727, P = 0.016) by multivariate analysis. In multitudinous factors, complete cytoreduction surgery (R0 resection) may provide survival benefits in patients with OM of CRC origin. Thus, it is reasonable to recommend aggressive surgery with curative intent even if extra-ovarian metastases are present. Furthermore, postoperative chemotherapy may exert a positive effect on the treatment, but needs to be confirmed by large-scale trials with more participants in the future.

Phase II clinical trial of gemcitabine plus oxaliplatin in patients with metastatic pancreatic adenocarcinoma with a family history of pancreatic/breast/ovarian/prostate cancer or personal history of breast/ovarian/prostate cancer (FABRIC study)

A family/personal history of breast, ovarian, or pancreatic cancer is a useful predictive marker for response to platinum-based chemotherapy in treating patients with pancreatic cancer. These cancers, and prostate cancer, are known as BRCA-related malignancies. We evaluated the efficacy of gemcitabine plus oxaliplatin (GEMOX) in patients with metastatic pancreatic cancer with a family/personal history of these cancers. Chemotherapy-naïve patients with metastatic pancreatic cancer with a family history of pancreatic/breast/ovarian/prostate cancer or a personal history of breast/ovarian/prostate cancer were included. Patients received fixed dose-rate gemcitabine (1000 mg/m Among the first 43 enrolled patients, the 1-year survival rate was 27.9% [90% confidence interval (CI) 17.0-41.3], which did not meet the primary endpoint. Median overall survival, progression-free survival, and response rates were 7.6 months (95% CI 6.0-10.7), 4.0 months (95% CI 2.0-4.6), and 26.7% (95% CI 14.6-41.9), respectively, in all registered patients. The GEMOX regimen was generally tolerated; the most common grade three or higher adverse events were hematological toxicities. GEMOX did not show the expected efficacy in patients with metastatic pancreatic cancer with a family or personal history of pancreatic/breast/ovarian/prostate cancer. Selection of GEMOX based on family/personal history is not recommended. UMIN000017894.

Aggressive surgery for advanced ovarian cancer decreases the risk of intraperitoneal recurrence

This study investigated the pattern of first recurrence of advanced ovarian cancer before and after the introduction of aggressive surgery. We investigated 291 patients with stage III/IV epithelial ovarian, fallopian tube, and peritoneal cancer. Aggressive surgery including gastrointestinal and upper abdominal surgeries was introduced for advanced ovarian cancer in 2008. The site and time until first recurrence were compared between 70 patients treated without aggressive surgery (2000-2007) and 221 patients who underwent aggressive surgery (2008-2016). The intraperitoneal recurrence rate was significantly lower in patients treated during 2008-2016 than in patients treated during 2000-2007 (55% [82/149] vs. 81% [46/57], p < 0.001). The median time to intraperitoneal recurrence was significantly longer during 2008-2016 than during 2000-2007 (36.2 months, 95% confidence interval [CI] 31.7-60.0 vs. 14.6 months, 95% CI 11.3-20.1, log-rank test: p < 0.001). However, extraperitoneal recurrence rate was significantly higher during 2008-2016 than during 2000-2007 (27% [40/149] vs. 2% [1/57], p < 0.001). Extraperitoneal recurrence occurred during 2008-2016 in the pleura/lungs and the para-aortic lymph nodes above the renal vessels. Cox proportional hazards regression analysis revealed that treatment period (HR 0.49, 95% CI 0.34-0.71, p < 0.001) and bevacizumab use (HR 0.58, 95% CI 0.39-0.87, p = 0.009) were independently associated with intraperitoneal recurrence; stage IV disease (HR 1.87, 95% CI 1.14-3.06, p = 0.034) was independently associated with extraperitoneal recurrence. Aggressive surgery reduced intraperitoneal recurrence and prolonged time to recurrence, contributing to better patient survival.

Dose-dense paclitaxel and carboplatin vs. conventional paclitaxel and carboplatin as neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: a retrospective study

The purpose of this study was to determine the optimal regimen of neoadjuvant chemotherapy (NAC) for advanced epithelial ovarian, fallopian tube, and peritoneal cancers. A clinical information survey involving 171 patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer was conducted. These patients underwent NAC followed by interval debulking surgery at the Hyogo Cancer Center (Hyogo, Japan) between January 2006 and December 2015. The median observation period was 41 (range 4-138) months. Dose-dense paclitaxel and carboplatin (TC) was administered in 101 patients (59%); tri-weekly TC was administered 70 patients (41%). Median progression-free survival was 21 [95% confidence interval (CI) 18-23] months and 15 (95% CI 13-17) months in the dose-dense TC and conventional-TC group [hazard ratio (HR) = 0.69, 95% CI 0.46-0.96; p = 0.02], respectively. The median overall survival was 59 (95% CI 46-72) and 40 (95% CI 32-57) months in the dose-dense TC group and conventional-TC group (HR = 0.72, 95% CI 0.48-1.06; p = 0.09). Multivariate analysis for progression-free survival demonstrated that dose-dense TC represented an independent prognostic factor (HR = 0.70, 95% CI 0.50-0.99; p = 0.04). Dose-dense TC is a promising regimen of NAC for advanced epithelial ovarian cancer.

Bevacizumab-associated events in Japanese women with cervical cancer: a multi-institutional survey of Obstetrical Gynecological Society of Kinki district, Japan

The development of perforations or fistulas in the Gastrointestinal (GI) tract or genitourinary (GU) system is a serious adverse effect of bevacizumab. The aim of this study was to investigate the incidences of these GI/GU events as well as their association with previous radiotherapy (RT) in Japanese women with cervical cancer. We conducted a written questionnaire survey among 14 gynecological institutions belonging to the Oncology Research Committee of the Obstetrical and Gynecological Society of Kinki District, Japan. The severity of GI/GU events was classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0. All data were extracted from survey responses and maintained in an Excel spreadsheet and summarized using descriptive statistics. The information of 224 Japanese women with cervical cancer (152 recurrent and 72 advanced) who were treated with bevacizumab-containing chemotherapy was collected from 14 institutions. Of these, 65% had been previously treated with RT. GI/GU events of any grade developed in 25 (11.2%) patients, leading directly to death in 3 (1.3%) patients. When compared, the incidence of GI/GU events was higher in recurrent disease patients than in advanced disease patients (13.8% vs 5.6%, p = 0.0728). When examined according to the history of RT, the incidence of GI/GU events was greater in patients with a history of RT than in those without (14.5% vs 5.1%, p = 0.044). More than 10% of patients experience GI/GU events during or after receiving bevacizumab-containing chemotherapies. Prior RT is a risk factor for bevacizumab-associated GI/GU events.

Definitive radiotherapy consisting of whole pelvic radiotherapy with no central shielding and CT-based intracavitary brachytherapy for cervical cancer: feasibility, toxicity, and oncologic outcomes in Japanese patients

Abstract Background This prospective study investigated the feasibility, toxicity, and oncologic outcomes of definitive radiotherapy (RT) consisting of whole pelvic radiotherapy with no central shielding (noCS-WPRT) and CT-based intracavitary brachytherapy (ICBT) in Japanese patients with cervical cancer. Methods Patients with cervical cancer of FIGO stages IB1–IVA were eligible. The treatment protocol consisted of noCS-WPRT of 45 Gy in 25 fractions and CT-based high dose-rate ICBT of 15 or 20 Gy in 3 or 4 fractions prescribed at point A. The prescribed ICBT dose was decreased if the manual dwell time/position optimization failed to meet organs-at-risk constraints. Graphical optimization and additional interstitial needles were not applied. Results We enrolled 40 patients. FIGO stages were IB1: 11, IB2: 13, IIA2: 1, IIB: 11, IIIB: 3, and IVA: 1. Median (range) pretreatment tumor diameter was 47 (14–81) mm. Point A doses were decreased in 19 of 153 ICBT sessions (12%). The median follow-up duration was 33 months. The 2-year rates of pelvic control, local control (LC), and progression-free survival were 83%, 85%, and 75%, respectively. Pre-ICBT tumor diameter, high-risk clinical target volume (HR-CTV), total HR-CTV D90, and overall treatment time (OTT) significantly affected LC. Late adverse events (grade ≥ 3) were observed in 3 patients (2 in the bladder, 1 in the rectum). Conclusions Definitive RT consisting of noCS-WPRT and CT-based ICBT was feasible for Japanese patients with cervical cancer. To further improve LC, additional interstitial needles for patients with a large HR-CTV and shorter OTT should be considered.

Operation for locally advanced cervical cancer after concurrent chemoradiotherapy

This paper aimed to discuss the scope of operation and clinical effects for locally advanced cervical cancer (LACC) after concurrent chemoradiotherapy (CCRT). We retrospectively reviewed the records of 444 patients with stages IB2-IIB cervical cancer who were divided into two groups whether or not they received CCRT before radical operation in our institute from January 2013 to December 2016. Patients' characteristics, treatments, and outcomes were analyzed. The total efficiency (CR + PR) of the CCRT + operation group was 96.2%. Specifically, the CR rate was 9.1%, and the PR rate was 87.1%. The positive rates of cervical deep interstitial infiltration, lymphatic metastasis, and lymphangial infiltration of the operation group were significantly higher than those of the CCRT + operation group (P < 0.05). A total of 24 and 162 patients in the CCRT + operation group and the operation group, respectively, received adjuvant therapy (P < 0.05). The incidence rate of edema of the lower extremity, radiation enteritis, and radiocystitis after postoperative adjuvant radiotherapy in the operation group was significantly higher than that of the CCRT + operation group (P < 0.05). The 5-year survival rates and 5-year progression-free survival (PFS) rates of the CCRT + operation and operation groups were 79.3% versus 64.0% and 68.9% versus 45.2%, respectively (P < 0.05). Comprehensive treatment that combines CCRT and radical operation to LACC achieves satisfying clinical effects without increasing the occurrence rate of intraoperative and postoperative complications. Moreover, such treatment can improve the 5-year PFS rate and OS rate.

Can serial evaluation of serum SCC-Ag-level predict tumor recurrence and patient survival in squamous-cell carcinoma of uterine cervix treated with definitive chemoradiotherapy? A multi-institutional analysis

Tumor marker screening may be useful to evaluate tumor response and detect tumor recurrence. However, usefulness and cut-off value of squamous-cell carcinoma antigen (SCC-Ag) for recurrence and survival has not yet established in cervical cancer. From January 2010 to October 2016, 304 patients with cervical squamous-cell carcinomas with FIGO stage IB-IVA who underwent curative chemoradiotherapy followed by brachytherapy at four institutions were included in this study. Serum SCC-Ag level was measured before treatment, re-measured after completion of treatment, and again at the time of relapse during follow-up. SCC-Ag levels at each measurement point were analyzed using receiver operating characteristic (ROC) curve. Their associations with recurrence-free survival (RFS) and overall survival (OS) were analyzed. During a median follow-up time of 36.5 months, there were 66 (21.7%) recurrences and 76 (25.0%) deaths. The ROC curve showed optimal Youden indices were 4, 1.5, and 4 ng/mL at pretreatment, treatment, and recurrence, respectively. In patients with SCC-Ag ≥ 4 ng/mL, not SCC-Ag < 4 ng/mL before treatment, post-treatment SCC-Ag level (≥ 1.5 ng/mL vs. < 1.5 ng/mL) showed significant differences in 3-year RFS (65.5% vs. 45.0%, p < 0.001) and OS (78.5% vs. 55.4%, p < 0.001). In 66 recurrent patients, patients with SCC-Ag ≥ 4 ng/mL at recurrence showed a significantly lower OS rate than others (59.5% vs. 33.0%, p = 0.041). SCC-Ag level after treatment and at recurrence was useful for predicting recurrence and survival only when its pretreatment value was high (≥ 4 ng/mL).

Impact of a reduction in follow-up frequency on life expectancy in uterine cervical cancer patients

The appropriate interval of post-treatment follow-up appointments for uterine cervical cancer is unclear. The aim of this study was to investigate the impact of reducing the frequency of post-treatment follow-up examinations on life expectancy and medical expenses in cervical cancer patients. Cervical cancer patients who were treated with radiotherapy between 2008 and 2017, underwent a less frequent follow-up program, and subsequently developed recurrent disease were included in consecutive group (CG). Non-randomized groups of cervical cancer patients who underwent a frequent follow-up program after radiotherapy between 1997 and 2007, and subsequently developed recurrent disease were also identified through a chart review and served as a comparison group (primary group [PG]). Clinical data regarding the primary disease, follow-up, recurrence, and survival were collected. Univariate and multivariate analyses of predictors of survival were performed. A total of 263 recurrent cervical cancer patients (PG: 154, CG: 109) were included in the current study. A reduction in follow-up frequency of up to 40% did not increase the frequency of symptomatic recurrence (PG: vs. CG: 31.2% vs. 35.8%, p = 0.43) or reduce the median overall survival periods of recurrent cervical cancer patients (PG vs. CG: 32 months vs. 36 months, p = 0.15). However, the reduction in the follow-up frequency significantly reduced follow-up costs. Reducing the frequency of follow-up by up to 40% did not result in shorter overall survival compared with a conventional follow-up program. The results of this study provide a rationale for future studies investigating the optimal follow-up schedule for patients with cervical cancer.

Lower accuracy of cytological screening for high-grade squamous intraepithelial neoplasia in women over 50 years of age in Japan

Abstract Background As the population ages in developed countries, the number of Pap smears for cervical cancer screening of older women is increasing. There is concern that cervical atrophy may cause misinterpretation of results for this segment of the population. The present study evaluated the accuracy of screening for high-grade intraepithelial lesions (HSILs) in women younger or older than 50 years, to determine whether aging affects cytological interpretation. Methods Patients with HSIL cytology (N = 1565) were dichotomized into those aged 20–49 years or aged ≥ 50 years. Association between histology results and age was examined. Pearson’s chi-squared test and Cochran-Armitage trend test were used for statistical analysis. Results The positive predictive value (PPV) for cervical intraepithelial neoplasia (CIN)2 and worse was 65.2% (62/95) in older women but 87.3% (482/552) in younger women (p &lt; 0.001). Older patients had a significantly lower PPV (p = 1.69 × 10–8). Separately analyzing chronic cervicitis, CIN1 and overt cancer grouped together, compared with another group composed of CIN2 and CIN3, we found that the PPV for CIN2 and CIN3 was lower in older than in younger women [44.2% (42/95)-vs-82.4% (455/552), p &lt; 0.001], respectively. Conclusions HSILs are associated with a wide range of disease categories as age increases, and the accuracy of HSIL interpretation is lower in older women.

Incidence of fistula occurrence in patients with cervical cancer treated with bevacizumab: data from real-world clinical practice

Abstract Background This study aimed to determine the incidence of pelvic fistulas in cervical cancer patients treated with bevacizumab in Japanese clinical practice. Methods A post-marketing surveillance (PMS) study was conducted between June 2016 and February 2018 to survey physicians who treated advanced or recurrent cervical cancer patients with bevacizumab (according to the product label). The clinical/treatment status of patients with pelvic fistulas was assessed in an additional retrospective case series study. Results 142 patients were included in the PMS study (median age 51 years; 66.9% squamous cell carcinoma; 66.2% recurrent cervical cancer; 64.1% previous radiotherapy). Patients received a median of seven bevacizumab doses. Six patients, all of whom had a history of pelvic irradiation, developed seven fistulas (4.2%; 95% confidence interval, 1.56–8.96), and five patients had also undergone pelvic surgery. The case series study of the patients who developed fistulas indicated that three patients had high cumulative bladder and rectal doses of radiation, and two of them had undergone salvage re-irradiation for pelvic recurrence. The other three patients underwent both radical hysterectomy and adjuvant radiotherapy, but did not receive an excessive radiation dose to the bladder or rectum. Conclusions This study found that the upper limit of the 95% confidence interval for pelvic fistula incidence did not exceed the incidence reported in the GOG 240 study. To ensure an adequate benefit-risk assessment of bevacizumab in cervical cancer patients, a comprehensive evaluation of prior treatment is essential and the possibility of unexpected fistulas, even after careful evaluation, should be considered.

Publisher

Springer Science and Business Media LLC

ISSN

1341-9625