Ignacio Zapardiel

Effect of tumor burden and radical surgery on survival difference between upfront, early interval or delayed cytoreductive surgery in ovarian cancer

We sought to evaluate the impact on survival of tumor burden and surgical complexity in relation to the number of cycles of neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer (OC) with minimal (CC-1) or no residual disease (CC-0). This retrospective study included patients with International Federation of Gynaecology and Obstetrics IIIC-IV stage OC who underwent debulking surgery at 4 high-volume institutions between January 2008 and December 2015. We assessed the overall survival (OS) of primary debulking surgery (PDS group), early interval debulking surgery after 3-4 cycles of NACT (early IDS group) and delayed debulking surgery after 6 cycles (DDS group) with CC-0 or CC-1 according to peritoneal cancer index (PCI) and Aletti score. Five hundred forty-nine women were included: 175 (31.9%) had PDS, 224 (40.8%) early IDS and 150 (27.3%) DDS. Regardless of Aletti score, median OS after PDS was significantly higher than after early IDS or DDS, but the survival difference was higher in women with an Aletti score 10, there were no differences between PDS and early IDS, but DDS was associated with decreased OS. The benefit of complete PDS compared with NACT was maximal in patients with a low complexity score. In patients with low tumor burden, there was a survival benefit of PDS over early IDS or DDS. In women with high tumor load, DDS impaired the oncological outcome.

Adapting Radicality in Early Cervical Cancer When Quality of Life Becomes a Prominent Issue

European Society of Gynaecological Oncology Guidelines for the Management of Patients with Vulvar Cancer - Update 2023

As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer

To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

ESGO/ESTRO quality indicators for radiation therapy of cervical cancer

The European Society of Gynaecological Oncology (ESGO) has previously defined and established a list of quality indicators for the surgical treatment of cervical cancer. As a continuation of this effort to improve overall quality of care for cervical cancer patients across all aspects, ESGO and the European SocieTy for Radiotherapy and Oncology (ESTRO) initiated the development of quality indicators for radiation therapy of cervical cancer. To develop a list of quality indicators for radiation therapy of cervical cancer that can be used to audit and improve clinical practice by giving to practitioners and administrators a quantitative basis to improve care and organizational processes, notably for recognition of the increased complexity of modern external radiotherapy and brachytherapy techniques. Quality indicators were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for identification of potential quality indicators and documentation of scientific evidence, consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians (n=99). Using a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are detailed to define how the quality indicators will be measured in practice. Targets were also defined for specifying the level which each unit or center should be aiming to achieve. Nineteen structural, process, and outcome indicators were defined. Quality indicators 1-6 are general requirements related to pretreatment workup, time to treatment, upfront radiation therapy, and overall management, including active participation in clinical research and the decision making process within a structured multidisciplinary team. Quality indicators 7-17 are related to treatment indicators. Quality indicators 18 and 19 are related to patient outcomes. This set of quality indicators is a major instrument to standardize the quality of radiation therapy in cervical cancer. A scoring system combining surgical and radiotherapeutic quality indicators will be developed within an envisaged future ESGO accreditation process for the overall management of cervical cancer, in an effort to support institutional and governmental quality assurance programs.

Sentinel lymph node biopsy without systematic pelvic lymphadenectomy in females with early-stage cervical cancer: final outcome of the SENTIX prospective, single-arm, noninferiority, international trial

Sentinel lymph node (SLN) biopsy with ultrastaging is standard in endometrial and vulvar cancers, whereas systematic pelvic lymphadenectomy (PLND) remains recommended in cervical cancer. The SENTIX trial prospectively evaluated the safety of SLN biopsy without PLND in early-stage cervical cancer. Female patients, International Federation of Gynaecology and Obstetrics 2018 stage IA1/LVSI+ to IB2 disease, were enrolled between 2016 and 2020 across 47 sites in 18 countries. All underwent SLN biopsy followed by hysterectomy/trachelectomy. Patients with undetected, unilateral or intraoperatively metastatic SLNs were excluded from the intention-to-treat cohort. SLNs were assessed by pathological ultrastaging. Of 731 patients enrolled, 594 formed the intention-to-treat cohort. SLN metastases were identified in 82 patients (12%), 56.1% intraoperatively and 43.9% by ultrastaging. At 2 years, the recurrence rate was 6.1% (one-sided 95% CI 7.9%), confirming noninferiority to the 7% reference rate. Two-year disease-free and overall survival rates were 93.3% (95% CI 94.9-91.6) and 97.9% (95% CI 98.9-97.0), respectively. Here we show that SLN biopsy without systematic PLND did not increase the risk of recurrence in patients with early-stage cervical cancer. Pathological ultrastaging of SLNs detected about 44% of N1 cases, which would be missed by a standard lymph node assessment. Trial registration: ClinicalTrials.gov ( NCT02494063 ).

SLYMEC II study: Overall survival analysis of the impact of LVSI in apparent early stage endometrioid endometrial cancer

In our initial report of the SLYMEC study we published the results evaluated the prognostic impact of substantial lymphovascular space invasion (LVSI) on the sentinel lymph node status and the impact of the different types of LVSI on 3-year disease-free survival. The aim of the SLYMEC II study was to assess the impact of focal and substantial lymphovascular space invasion on 5-years overall survival in the subgroup of patients with endometrioid endometrial cancer. A total of 2030 patients were included in the analysis from the original data set. Focal LVSI were identified in 131 patients (6.4 %), whereas 319 patients (15.7 %) showed substantial LVSI at final pathology. Among 1876 patients who underwent minimally invasive surgery (92.6 %), 442 patents (21.8 %) underwent robotic assisted surgery, whereas and 150 patients (7.6 %) patients underwent open surgery. Rate of overall survival at 5 years was 83.6 % versus 100 % for substantial and focal LVSI groups, respectively (HR for death = 2.1 [95 % CI, 1.4 to 3.2]; P < 0.0001). Patients with endometrioid endometrial cancer having substantial LVSI after surgery showed an increased risk of death in the after 5-years overall survival when compared to patients with negative, or focal LVSI. The presence of positive LVSI in patients with positive sentinel nodes showed a trend toward reduced 5-year overall survival compared to SLN-negative patients, although it did not reach statistical significance.

Growing teratoma syndrome: diagnostic challenges and outcomes

The aim of this case report is to emphasize the significance of the growing teratoma syndrome. Growing teratoma syndrome is frequently misdiagnosed due to its low prevalence, with an estimated incidence of 19% among all immature ovarian teratomas and a lack of experience among healthcare professionals. It is characterized by the growth of benign tumoral tissue during or after chemotherapy for malignant germ cell tumors. Our case is about a 46-year-old patient diagnosed with an immature teratoma who was treated unsuccessfully with surgery and chemotherapy. The patient was then referred to our hospital for a second opinion, where this unknown entity was diagnosed and underwent complete surgical debulking, including abdominal wall resection and subsequent repair. Physicians need to be aware of rapidly growing masses during or after chemotherapy because early recognition of this syndrome is essential for the adequate treatment of our patients.

Pelvic exenteration for vulvar cancer: contemporary outcomes from a multinational cohort study

Women with vulvar cancer are considerably older than those with other gynaecological malignancies, raising concerns about the tolerability of radical surgery. Yet, for locally advanced or recurrent disease, pelvic exenteration may be the only curative option. Robust evidence to guide decision-making in this population is lacking. This multicentre observational cohort study used data from the COREPEX registry including women who underwent anterior or total pelvic exenteration between 2005 and 2023 across 20 European tertiary referral centres. The primary outcome was overall survival (OS); secondary outcomes were progression-free survival (PFS) and major postoperative complications. Associations were assessed using multivariable Cox and binomial regression models adjusted for relevant covariates. Among 861 women, 79 (9.2%) had vulvar cancer. Median follow-up was 49 months for OS and 40 months for PFS. Women with vulvar cancer were older and more often overweight. Five-year OS was 32% (95% CI, 19-46) in vulvar cancer versus 29% (95% CI, 25-34) in other cancers, adjusted HR 1.05 (95% CI, 0.75-1.46). Five-year PFS was 34% versus 29%, adjusted HR 0.96 (95% CI, 0.69-1.34). Major complications occurred in 33% vs 29%, adjusted RR 1.12 (95% CI, 0.77-1.58). Lymph node metastases, positive margins, and recurrent or persistent disease independently predicted poorer survival. Despite their older age, women with vulvar cancer had survival and morbidity comparable to those with other gynaecological malignancies. These findings support pelvic exenteration as a curative option for selected women with vulvar cancer when complete resection is feasible.

European Society of Gynaecological Oncology resource-stratified guidelines for the management of patients with cervical cancer.

In 2023, the European Society of Gynaecological Oncology (ESGO), jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP), published evidence-based guidelines for the management of patients with cervical cancer. Acknowledging that limitations exist even in high-income countries, some of these established standards of care are not applicable in clinical practice in some areas of the world. Following a global ESGO survey involving 256 clinicians from 57 countries, which pointed out potential limitations, barriers, and missing guidelines, ESGO decided to develop alternative management strategies for situations when optimal resources are unavailable or limited. A multi-disciplinary international development group consisting of 22 experts, utilizing feedback from the survey conducted mostly in low- and middle-income regions, identified potential limitations to the standards of care as defined in the updated ESGO-ESTRO-ESP guidelines published in 2023 and suggested alternative approaches. New resource-stratified guidelines on the management of women living with the human immunodeficiency virus have been newly proposed. To ensure a global perspective, the guidelines were reviewed by 188 independent international practitioners from Asia, Africa, Europe, and South, Central, and North America. These resource-stratified guidelines focus on achieving the best patient outcomes, with alternative management strategies based on expert opinions in areas with limited evidence. They should be used as a guide for the next best alternatives in multi-disciplinary care settings such as diagnostics, pathology, surgery, radiotherapy, systemic therapy, palliative care, and follow-up management. Efforts should always focus on providing optimal available care. In the absence of key resources, the primary effort should be directed toward consulting and referring patients to other facilities that provide better conditions.

Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of ESS, UTROSCT, and UUS with Prognostic Insights.

Low-grade endometrial stromal sarcomas (LG-ESS), high-grade ESS (HG-ESS), undifferentiated uterine sarcomas (UUS), and uterine tumors resembling ovarian sex cord tumors are distinct non-smooth muscle cell neoplasms with varying clinical outcomes, often exhibiting overlapping characteristics. Diagnosis can be supported by identifying characteristic recurrent translocations, which may be absent in some cases, complicating the distinction of equivocal cases. Additionally, cases with overlapping features of low-grade and high-grade characteristics are recognized. To address these challenges, we analyzed RNA-seq profiles of 262 cases. Our results revealed that LG-ESS, with and without recurrent fusions, clustered into 2 partially overlapping expression profiles associated with distinct overall and relapse-free survival outcomes, with the cluster containing a majority of fusion-negative tumors demonstrating better prognoses. uterine tumors resembling ovarian sex cord tumors expression profiles closely resembled those of both LG-ESS subgroups, with NCOA3 fusion-positive cases clustering in groups with better survival outcomes. Furthermore, a distinct cluster for HG-ESS with BCOR and YWHAE fusions was identified, differentiating these tumors from HG-ESS without fusions. ONECUT3 emerged as a potential specific marker for this HG-ESS-fusion entity. A significant expression overlap was observed between monomorphic HG-ESS without fusions and pleomorphic UUS. These samples separated further into 2 mixed clusters distinguished by differences in immune activity, which significantly influenced overall survival and relapse-free survival outcomes. Unsupervised clustering of UUS revealed subgroups resembling either HG-ESS or muscle-cell-differentiated tumors, suggesting that UUS may include poorly differentiated distinct entities, such as leiomyosarcoma, and that the distinction from HG-ESS may, in some cases, be arbitrary. Our transcriptome analysis highlights several entities with distinct survival characteristics, providing a foundation for further characterization of these rare, often difficult-to-classify, tumors.

Prognostic value of isolated tumor cells in sentinel lymph nodes in intermediate-risk endometrial cancer: results from an international, multi-institutional study

This study assessed oncologic outcomes of patients with intermediate-risk endometrioid endometrial cancer and isolated tumor cells (ITC) (≤0.2 mm or ≤200 cells) in sentinel lymph nodes (SLNs). Patients with SLN-ITC diagnosed between 2012 and 2019 were identified from 19 centers worldwide, while SLN-negative patients were identified at Mayo Clinic, Rochester between 2014 and 2018. Only patients with endometrioid endometrial cancer and intermediate-risk factors (low-grade endometrioid histology and myometrial invasion ≥50%; high-grade endometrioid histology and myometrial invasion <50%) were included. Oncologic outcomes were evaluated by grouping patients according to prognostic factors: SLN-ITC and lymphovascular space invasion (LVSI). SLN-ITC patients with post-operative observation or vaginal brachytherapy (VB) alone were compared with similar node-negative patients. Of the 166 patients included, those with simultaneous presence of SLN-ITC and LVSI were at higher risk of non-vaginal recurrence (HR 3.73 [95% CI 1.17 to 11.84], p = .01) compared with patients who were node-negative with no LVSI. Among the 122 patients (28 SLN-ITC, 94 node-negative) who underwent post-operative observation or VB alone, 1 isolated vaginal recurrence was documented in a node-negative patient, while non-vaginal recurrence occurred in 3 of 28 (10.7%) SLN-ITC and 7 of 94 (7.4%) node-negative patients. The median follow-up was 2.4 years (interquartile range; 1.8-3.0) among the remaining 25 ITC patients and 2.8 years (interquartile range; 0.8-4.2) among the remaining 87 node-negative patients. There was no difference in non-vaginal recurrence-free survival (SLN-ITC: 87.3% [95% CI 74.7% to 100.0%] vs node-negative: 82.2% [95% CI 69.1% to 97.9%], p = .46) or overall survival (SLN-ITC: 76.4% [95% CI 54.3 to 100.0] vs node-negative: 84.5% [95% CI 75.0 to 95.2], p = .28) between the 2 cohorts. In patients with endometrioid endometrial cancer and intermediate-risk factors (including patients who received chemotherapy/external beam radiotherapy), the combination of SLN-ITC and LVSI was associated with worse prognosis compared with patients with no risk factors or only 1 risk factor. In the sub-group of patients who received post-operative observation or VB alone, SLN-ITC did not worsen prognosis relative to node-negative patients.

Current Limitations of Sentinel Node Biopsy in Vulvar Cancer

Background: Vulvar cancer is a rare gynecologic malignancy with increasing incidence. Lymph node status is the most critical prognostic factor, traditionally assessed through inguinofemoral lymphadenectomy, a procedure associated with significant morbidity. Sentinel lymph node biopsy (SLNB), in selected cases, has emerged as a less invasive alternative with favorable oncologic outcomes. Objective: This review summarizes current evidence on the indications, technique, safety, and oncologic outcomes of SLNB in vulvar cancer, with a focus on controversial scenarios such as recurrent and larger tumors. Methods: A narrative review of PubMed-indexed studies published in English over the last 35 years was conducted. Eligible studies included original research, systematic reviews, meta-analyses, randomized controlled trials, and case-control studies. Results: SLNB is recommended for unifocal vulvar tumors &lt; 4 cm with stromal invasion &gt; 1 mm and clinically negative nodes. Landmark trials, including GROINSS-V-I and GOG-173, confirmed its accuracy and lower morbidity compared to lymphadenectomy. SLNB utilization has increased since its inclusion in guidelines, with a concurrent decline in lymphadenectomy rates. Combined detection techniques are mandatory, while indocyanine green (ICG) is an emerging option. Future studies should focus on refining patient selection criteria, improving detection techniques, and clarifying the implications of low-volume nodal disease to further optimize outcomes for patients with vulvar cancer. Conclusion: SLNB is a validated, minimally invasive staging approach in early-stage vulvar cancer. Further research is needed to refine its role in high-risk cases and optimize detection methods.

Outcomes of low-risk endometrial cancer with isolated tumor cells in the sentinel lymph nodes: a prospective, multi-center, single-arm, observational study (ENDO-ITC study)

It is unclear whether isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) adversely affect prognosis, especially in low-risk endometrial cancer. In a retrospective study, we showed a worse recurrence-free survival for low-risk endometrial cancer with ITCs than the node-negative group. Our aim is to evaluate whether the likelihood of disease recurrence differs between a prospective cohort of patients with low-risk endometrial cancer with ITCs and an historical cohort with negative SLNs. We hypothesize that patients with low-risk endometrial cancer and ITCs will have a worse recurrence-free survival than patients who are node-negative. This is a prospective, multi-center, single-arm observational study. Consecutive patients with low-risk endometrial cancer with ITCs in the SLNs will be accrued. Observation only will be suggested after surgery. We will include patients with endometrial cancer undergoing pelvic SLN biopsy and ultra-staging with the following characteristics: endometrioid histology, grades 1 to 2, <50% myometrial invasion, without substantial/extensive lympho-vascular space invasion. ITCs in SLNs are defined as tumor cell aggregates ≤0.2 mm or <200 cells. The primary end point is recurrence-free survival, measured from the date of surgery to the date of recurrence, death, or last disease evaluation. With a sample size of 132 women with low-risk endometrial cancer and ITCs, a 1-sided log-rank test achieves 85% power at a 0.05 significance level to detect an HR of 2.1. The expected number of events during the study is 17.3. The study duration will be 60 months: 24 for enrollment and 36 for follow-up. The results are expected in 2029. ClinicalTrials.gov: NCT06689956.

The impact of Substantial LYMphovascular space invasion on sentinel lymph nodes status and recurrence in Endometrial Cancer patients: SLYM-EC a multicenter retrospective study

To evaluate the prognostic impact of substantial lymph vascular space invasion (LVSI) on the sentinel lymph node involvement and recurrence rate of patients with apparent uterine-confined endometrial cancer. We enrolled consecutive patients with apparent confined endometrial cancer who underwent surgical staging with sentinel node mapping from 14 European reference centers. LVSI was analyzed semi-quantitatively, according to a 3-tiered scoring system classified as absent, focal, and substantial. Among 2352 eligible patients, 1980 were included in the analysis. Upon final pathology 226 patients (11.4 %) had SLNs involvement. LVSI was diagnosed focal in 152 patients (7.7 %), whereas 357 patients (18.0 %) showed substantial LVSI. Focal or substantial LVSI rate were significantly higher in patients with positive SLNs when compared to patients without SLNs involvement (p < 0.0001). On overall patient-based analysis, the sensitivity, specificity, positive predictive value, and negative predictive value of LVSI for sentinel lymph node metastases were 73 %, 80 %, 32 %, and 96 %, respectively. The 3-year multivariate analysis of recurrence-free survival showed that only the presence of substantial LVSI, and grade 3 disease were associated with relapse. Neither positive sentinel lymph node, deep myometrial infiltration, nor age at surgery were statistically significant. In patients having undergone sentinel node biopsy, positive LVSI demonstrated moderate sensitivity and reasonable specificity in detecting SLN involvement. LVSI positivity does not correlate with nodal involvement. The presence of substantial LVSI remains a strong independent risk factor for recurrence, indicating a role for potential hematogenous dissemination in patients with early-stage disease.

ESGO/EURACAN/GCIG guidelines for the management of patients with uterine sarcomas

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer

The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

Prognostic factors in young women with epithelial ovarian cancer: the Young Ovarian Cancer-Care (YOC-Care) study

To determine oncological outcomes and to identify prognostic factors in women aged <45 years with epithelial ovarian cancer. A multicenter retrospective study was performed of patients treated for epithelial ovarian cancer aged <45 years between January 2010 and December 2019. A total of 998 patients with epithelial ovarian cancer from 55 different institutions in Spain were collected. The median age of the study population was 40.8 years (range 35.6-43.4). The grouped International Federation of Gynecology and Obstetrics (FIGO) stage distribution was 508 (50.9%) patients in initial stages (I and II) and 490 (49.1%) with advanced stages (III and IV). Three hundred and twenty-five (32.6%) patients presented with recurrent disease after a median follow-up of 33.1 months (range 16.1-66.4). The type of staging surgery (incomplete vs complete), type of initial treatment modality (primary cytoreduction vs interval surgery), and amount of residual disease were all significantly associated with overall survival. Tumor rupture was noted in 288 (27.9%) cases, but it was not associated with oncologic outcomes (p=0.11 for overall survival). In the multivariate analysis, the response based on radiological findings (HR 3.24, 95% CI 2.14 to 4.91 for partial response; HR 6.93, 95% CI 4.79 to 10.04 for progression), neoadjuvant chemotherapy (HR 1.42, 95% CI 1.04 to 1.94), and FIGO stage (HR 1.68, 95% CI 1.40 to 2.02) were identified as independent prognostic factors associated with worse oncologic outcomes (p<0.001). The partial and progression radiology-based response after chemotherapy, neoadjuvant chemotherapy, and advanced FIGO stage are independent prognostic factors associated with worse oncological outcomes in women aged <45 years with epithelial ovarian cancer.

Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study

The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.

In Vitro Study of [18F]F-FAPI-74 Feasibility in Vulvar Cancer

This study aims to investigate the expression of FAP by phosphor imaging in invasive vulvar squamous cell carcinoma specimens. This in vitro study will include all consecutive tumour specimens stored both in optimal cutting temperature (OCT) compound and formalin-fixed paraffin-embedded (FFPE) from patients with a first diagnosis of vulvar squamous cell carcinoma who underwent surgery at Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Sentinel Lymph Node Biopsy in Patients With Early Stages Cervical Cancer

To evaluate whether a less radical surgical approach with sentinel lymph node biopsy is non-inferior to treatment with systematic pelvic lymphadenectomy. The null hypothesis is that the recurrence rate after SLN biopsy is non-inferior to the reference recurrence rate of 7 % (at the 24th month of follow-up) in patients after systematic pelvic lymphadenectomy, but that the less radical surgery is associated with significantly lower postoperative morbidity.