Maximilian Klar

Stage IC grade 1 endometrioid adenocarcinoma of the ovary: assessment of post-operative chemotherapy de-escalation

Given limited real-world practice data evaluating the National Comprehensive Cancer Network clinical practice guidelines for possible post-operative chemotherapy omission as a treatment option for patients with stage IC grade 1 endometrioid ovarian carcinoma, this population-based study examined the association between post-operative chemotherapy and overall survival in this tumor group. The National Cancer Institute's Surveillance, Epidemiology, and End Results program was retrospectively queried. The study population was 1207 patients with stage IC grade 1-3 endometrioid ovarian carcinoma who received primary cancer-directed surgery from 2007 to 2020. Overall survival was assessed with multivariable Cox proportional hazard regression model. The median age was 52, 54, and 55 years for grade 1, 2, and 3 groups, respectively (p=0.02). Grade 1 and 2 tumors were more common than grade 3 tumors (n=508 (42.1%), n=493 (40.8%), and n=206 (17.1%), respectively). Chemotherapy use rate for grade 1 tumors was lower compared with grade 2-3 tumors (67.9%, 76.5%, and 78.6%, respectively, p<0.001). When nodal evaluation was performed for grade 1 tumors, among patients who did not receive post-operative chemotherapy and among those who did, 5-year overall survival rate exceeded 90% (93.3% and 96.0%, respectively), with statistically non-significant hazard estimates (adjusted hazard ratio (aHR) 1.54, 95% CI 0.63 to 3.73). In contrast, post-operative chemotherapy omission for patients who did not undergo nodal evaluation was associated with decreased overall survival (5-year rates 82.3% vs 96.0%, aHR 5.41, 95% CI 1.95 to 15.06). Results were similar for node-evaluated grade 2 tumors (5-year overall survival rates, 94.6% and 94.4% for node-evaluated post-operative chemotherapy omission and administration, respectively), but not in grade 3 tumors. The results of this population-based study may partially support the current clinical practice guidelines for post-operative chemotherapy omission as a possible option for patients with stage IC grade 1 endometrioid adenocarcinoma of the ovary for those who had lymph node evaluation. Observed data were also supportive for node-evaluated grade 2 tumors, warranting further evaluation.

Malignant peritoneal cytology in endometrial cancer: Areas of unmet need for evidence

Treatment and survival of patients with malignant ovarian sex cord‐stromal cell tumours: An analysis of the Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) study group CORSETT database

AbstractBackgroundMalignant sex cord‐stromal cell tumours (SCST) account for only 7% of ovarian malignancies. The Arbeitsgemeinschaft fuer Gynaekologische Onkologie (AGO) study group has established a clinicopathological database to provide an overview of the current treatment strategies and survival of SCST patients and to identify research needs.MethodsTwenty centres provided mixed retro‐ and prospective data of patients with tumour specimens and second‐opinion pathology review treated between 2000 and 2014. Descriptive analyses of treatment strategies, Kaplan–Meier curves and cox regression analyses were conducted.ResultsTwo hundred and sixty‐two SCST patients were included. One hundred and ninety‐one Granulosa‐cell tumour (GCT) and 17 Sertoli‐Leydig cell tumour (SLCT) patients were stage I disease (&gt;80%). Forty four GCT (18.7%) and two (8.3%) SLCT patients received adjuvant systemic treatment. After a median observation time of 78.2 months, 46% of all SCST patients experienced disease recurrence, treated predominantly with secondary debulking surgery (&gt; 90%). Advanced FIGO stage, lymph node involvement and intra‐operative capsule rupture were associated with disease recurrence on univariate analysis (all p &lt; 0.05). Median OS time was not reached.DiscussionIn this analysis of SCST patients, adjuvant chemotherapy was unable to prevent disease recurrence. Despite high recurrence rates, overall survival rates were excellent.

Diagnosis-shift between low-grade serous ovarian cancer and serous borderline ovarian tumor: A population-based study

To determine changes in the characteristics of low-grade serous ovarian cancer (LGSOC) and serous borderline ovarian tumor (serous-BOT) in a time-specific manner. We conducted a population-based retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Trends, demographics, and outcomes of 775 women with well-differentiated serous ovarian cancer, used as a surrogate for LGSOC, were compared to 3937 women with serous-BOT. In the multivariable analysis, women with LGSOC were more likely to be older, have stage II-IV disease, and have undergone hysterectomy at surgery, but less likely to be a Western U.S. resident compared to those with serous-BOT (all, adjusted-P < 0.05). During the study period, the number of LGSOCs decreased by 25.9%, particularly stage I disease (37.6% relative decrease) compared to stage II-IV disease (21.1% relative decrease) (all, P < 0.05). With a median follow-up of 16.9 years, there was a decreasing trend in the 15-year overall survival rates among LGSOC (28.7% relative decrease, P = 0.056) but not in serous-BOT (2.5% relative increase, P = 0.416) as a whole cohort. The magnitude of hazard risk from all-cause death for women with LGSOC compared to those with serous-BOT increased by 68.9% from 1988 to 2000 (P < 0.001). LGSOC remained an independent prognostic factor for decreased overall survival compared to serous-BOT (adjusted-P < 0.05). Our study suggests that the decreasing number and survival of LGSOC over time may be due to a diagnosis-shift from LGSOC to serous-BOT. Given the distinct characteristics and outcomes of LGSOC compared to serous-BOT, our study endorses the importance of making the correct diagnosis upfront. Whether this diagnostic-shift supports a hypothesis that serous-BOT is a precursor lesion of LGSOC merits further investigation.

Evolving population-based statistics for rare epithelial ovarian cancers

To describe how population-based statistics for rare epithelial ovarian cancers are evolving. This is a retrospective observational study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2016. Overall survival (OS) of clear cell (OCCC), mucinous (MOC), and low-grade serous (LGSOC) ovarian cancers were compared to high-grade serous ovarian cancer (HGSOC) by fitting a propensity score matching. Among 113,365 ovarian malignancies, 5780 OCCCs (5.1%), 7561 MOCs (6.7%), and 2021 LGSOCs (1.8%) were compared to 38,199 HGSOCs. OCCCs and MOCs were more likely to be diagnosed with stage I disease compared to HGSOC (57.0-59.5% versus 8.6%, P<0.001). For early-stage disease, OCCC (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.82-1.01) and MOC (HR 0.94, 95%CI 0.85-1.04) had similar OS to HGSOC whereas LGSOC had superior OS (HR 0.93, 95%CI 0.89-0.97) versus HGSOC. Conversely, for advanced-stage disease, OCCC (HR 1.42, 95%CI 1.32-1.53) and MOC (HR 1.11, 95%CI 1.09-1.13) had poorer OS whereas LGSOC (HR 0.86, 95%CI 0.84-0.89) had superior OS compared to HGSOC. OCCC (HR range, 1.92-2.45) and MOC (HR range, 1.73-2.22) had particularly poorer OS in the first three years following diagnosis compared to HGSOC. Population-level statistics for advanced-stage disease showed that 5-year OS rates have increased in HGSOC (16.9% to 36.8%, P<0.001) and LGSOC (50.8% to 66.4%, P=0.010); but remain unchanged for OCCC (21.0% to 28.2%, P=0.174) and MOC (21.4% to 16.5%, P=0.102). OCCC, MOC, and LGSOC comprise 2-7% of ovarian malignancies, have distinct characteristics and survival compared to HGSOC. While these rare tumors have a favorable to comparable prognosis in early-stage disease, disproportionally poor survival in advanced-stage OCCC and MOC highlights the need for further research into novel treatment strategies.

Secondary haematologic malignancies in women with ovarian cancer receiving poly-ADP ribose polymerase inhibitor therapy

Effect of delay in surgical therapy for early-stage cervical cancer: An implication in the coronavirus pandemic

Association between hospital surgical volume and perioperative outcomes of fertility-sparing trachelectomy for cervical cancer: A national study in the United States

To examine the association between hospital surgical volume and perioperative outcomes for fertility-sparing trachelectomy performed for cervical cancer. This is a population-based retrospective observational study utilizing the Nationwide Inpatient Sample from 2001 to 2011. Women aged ≤45 years with cervical cancer who underwent trachelectomy were included. Annualized hospital surgical volume was defined as the average number of trachelectomies a hospital performed per year in which at least one case was performed. Perioperative outcomes were assessed based on hospital surgical volume in a weighted model, specifically comparing the top-decile centers to the lower volume centers. There were a total of 815 trachelectomies performed at 89 centers, and 76.4% of the trachelectomy-performing centers had a minimum surgical volume of one trachelectomy per year. The top-decile group had a higher rate of lymphadenectomy performance compared to the lower volume group (96.4% versus 82.4%, odds ratio [OR] 5.65, 95% confidence interval [CI] 2.81-11.4, P < 0.001). There was a significant inverse linear association between annualized surgical volume and the number of perioperative complications (P = 0.020). The top-decile group also had a lower rate of perioperative complications (9.7% versus 21.0%, P < 0.001) and prolonged hospital stay ≥7 days (2.0% versus 6.5%, P = 0.006) compared to the lower volume group. In a multivariable analysis, the top-decile group had a 65% relative decrease in perioperative complication risk compared to the lower volume group (adjusted-OR 0.35, 95%CI 0.20-0.59, P < 0.001). Fertility-sparing trachelectomy for young women with cervical cancer is a rare surgical procedure; <90 centers performed this procedure from 2001 to 2011 and most hospitals perform a small number of cases annually. Higher hospital surgical volume for trachelectomy may be associated with reduced perioperative morbidity.

Sentinel lymph node biopsy for vulvar melanoma: trends in tumor stage-specific utilization

Clinical and pathological characteristics and outcomes of small cell neuroendocrine carcinoma of the uterine cervix

To describe the clinical and pathological characteristics and outcomes of small cell neuroendocrine carcinoma of the uterine cervix at the population level in the United States. The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was retrospectively queried. The study population included 54,987 patients with cervical cancer from 2004 to 2021. Descriptive analysis was performed based on histology. Histology types included squamous cell carcinoma (n = 38,145, 69.4%), adenocarcinoma (n = 14,333, 26.1%), adenosquamous carcinoma (n = 1,970, 3.6%), and small cell neuroendocrine carcinoma (n = 539, 1.0%). Over the 18-year study period, the incidence rate of small cell neuroendocrine carcinoma increased by 3.2% per year (95% CI 1.2 to 5.7, p = .003). Based on this trajectory, the incidence of small cell neuroendocrine carcinoma is estimated to reach 2.0% by 2035. Small cell neuroendocrine carcinoma was associated with larger cervical tumors (60 mm versus 27-40 mm), a higher lymph node metastasis ratio (25.0% versus 14.3%-15.4%), higher distant metastasis rate even in small tumor (10 mm, 10.3% versus 0.5-2.6%; and 20 mm, 14.8% versus 3.9-5.3%), and stage IV disease (40.1% versus 11.9%-15.2%) than other histologies (p < .001). Among distant metastasis cases, small cell neuroendocrine carcinoma was more likely to spread to the liver (36.1% versus 14.3%-15.4%) or bone (28.8% versus 17.3%-19.1%) and to involve multiple distant organ metastases (≥2 organs: 37.3% vs 27.8%-30.2%; and ≥3 organs: 18.1% vs 9.2%-10.1%) compared with other histologies (p < .001). Across stages I to IV, small cell neuroendocrine carcinoma had lower 5-year overall survival rates than other histologies: stage I, 58.0% versus 82.5% to 91.3%; stage II, 38.4% versus 60.7% to 64.6%; stage III, 31.3% versus 49.5% to 51.4%; and stage IV, 8.1% versus 18.2% (p < .05). Early-death rates within two months from diagnosis of small cell neuroendocrine carcinoma were substantially higher than other histologies (9.0% vs 2.2%, p < .001). This population-based assessment suggests that, although rare, the incidence of small cell neuroendocrine carcinoma of the uterine cervix is gradually increasing in the United States. Multiple distant organ metastases, especially to the liver and bone, and poor survival outcomes characterize small cell neuroendocrine carcinoma of the uterine cervix.

International Federation of Gynecology and Obstetrics 2023 stage IIIB2 endometrial cancer with pelvic peritoneal metastasis: assessment of adjuvant therapy effect on survival

The 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging schema classifies pelvic peritoneum only metastasis as stage IIIB2 disease. In this retrospective cohort study of 193 patients with FIGO 2023 stage IIIB2 endometrial cancer who underwent primary hysterectomy from 2006 to 2015 identified in the Commission-on-Cancer's National Cancer Database, systemic chemotherapy without external beam radiotherapy was the most frequent adjuvant therapy type (48.7%), followed by combination systemic chemotherapy and external beam radiotherapy (42.0%) and external beam radiotherapy without systemic chemotherapy (9.3%). After controlling for patient age, race and ethnicity, co-morbidity, and histology, combination systemic chemotherapy and external beam radiotherapy was associated with 40% reduction of all-cause mortality compared with systemic chemotherapy without external beam radiotherapy (5-year rates: 63.1% vs 45.7%, adjusted-hazard ratio 0.60, 95% confidence interval 0.40-0.92). This reduction of all-cause mortality for combination systemic chemotherapy and external beam radiotherapy compared with systemic chemotherapy without external beam radiotherapy increased to 55% among non-endometrioid histology (5-year overall survival rates: 52.0% vs 33.4%, adjusted-hazard ratio 0.45, 95% confidence interval 0.23-0.88). In conclusion, the results of this investigation suggest that, despite peritoneal disease spread, multi-modal treatment with combination systemic and local therapies may improve survival in FIGO 2023 stage IIIB2 endometrial cancer, especially in non-endometrioid histology.