OBJECTIVE:Sentinel lymph node (SLN) biopsy is an emerging technique in apparent early-stage ovarian cancer, with the potential to detect low-volume lymph node metastases. However, the prognostic value of low-volume metastases is still unknown. This study aimed to assess the incidence and the prognosis of low-volume metastases detected in patients with apparent early-stage ovarian cancer undergoing SLN biopsy as part of a clinical trial. METHODS:Retrospective, multi-center, international study. Inclusion criteria were apparent International Federation of Gynecology and Obstetrics 2014 stage I to II epithelial ovarian cancer, undergoing SLN biopsy with systematic bilateral pelvic and para-aortic lymphadenectomy, and complete peritoneal surgical staging, from October 2012 to December 2023. In the absence of lymph-node macro-metastasis, at least 4-level ultra-staging at the SLN was performed. Fertility-sparing surgery or no SLN detection were exclusion criteria. Low-volume metastases were defined as any tumor deposit ≤2 mm (isolated tumor cells as <0.2mm, micro-metastasis as 0.2-2 mm). Descriptive statistics and survival analyses, including multi-variable Cox regression, were performed. RESULTS:SLN mapping was attempted in 260 patients. At least 1 SLN was detected in 199 (76.5%) patients, and low-volume metastases were found in 14/199 (7.0%), including 7 (3.5%) isolated tumor cells and 7 (3.5%) micro-metastases. Macro-metastases were identified in 18/199 (9.0%) patients. Among patients with lymph node metastases, 29/32 (90.6%) received adjuvant chemotherapy, including 11/14 (78.6%) with low-volume metastases. Median follow-up was 37 months (95% confidence interval [CI] 34.5 to 39.5). Three-year disease-free survival was 89.9% in node-negative patients, 100.0% in patients with low-volume metastasis, and 64.2% in patients with macro-metastasis (p < .001). Three-year overall survival was 98.2%, 100.0%, and 87.8%, respectively (p < .001). Lymph node macro-metastasis was the only factor independently associated with worse disease-free survival (hazard ratio 1.532, 95% CI 1.111 to 2.112, p = .009) and overall survival (hazard ratio 1.894, 95% CI 1.091 to 3.286, p = .001). CONCLUSIONS:Lymph node low-volume metastases in apparent early-stage ovarian cancer were present in 7% of patients, and none of these patients experienced recurrence or death. Lymph node macro-metastasis independently impaired disease-free and overall survival.

Objectives To evaluate quality of life, patient-reported outcomes, and survivorship after different nodal staging strategies in endometrial cancer, with a focus on lower-extremity lymphedema after sentinel lymph node mapping versus lymphadenectomy. Methods A systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. MEDLINE (through PubMed), Embase, and Scopus were searched for studies published from 2010 to 2025. Eligible studies included women with endometrial cancer who underwent surgical nodal staging with sentinel lymph node mapping, lymphadenectomy, or combined approaches and reported validated quality-of-life or patient-reported outcomes. Results Nine comparative studies including 3298 patients treated between 2006 and 2023 were included. Sentinel lymph node mapping alone was performed in 1334 women, 1508 underwent lymphadenectomy with or without sentinel lymph node mapping, and 456 underwent hysterectomy alone. Patient-reported lower-extremity lymphedema was consistently less frequent after sentinel lymph node mapping than after lymphadenectomy. Reported lymphedema prevalence ranged from 2% to 36% after sentinel lymph node mapping versus 21% to 51% after lymphadenectomy. Studies using multi-variable analyses consistently identified more extensive nodal dissection as an independent predictor of increased lymphatic morbidity. Global quality-of-life scores showed no consistent differences between nodal staging strategies; however, symptom-specific and functional outcomes, particularly lower-extremity symptoms and physical functioning, more often favored sentinel lymph node mapping. Considerable heterogeneity was observed in surgical approach, outcome measures, and timing of assessment. Conclusion Although differences in global quality of life remain inconsistent, sentinel lymph node mapping appears to reduce patient-reported lymphatic morbidity compared with more extensive nodal dissection. These findings support the integration of patient-reported outcomes into nodal staging decision-making and reinforce the survivorship advantages of less extensive surgical staging strategies in endometrial cancer.

Hereditary tubo-ovarian cancer risk assessment has evolved from a BRCA1/2-centered consultation to an integrated prevention pathway that begins at diagnosis and extends to unaffected relatives. Germline testing is now justified for patients with epithelial tubo-ovarian cancer because actionable pathogenic variants are common enough that family-history-only referral misses many carriers. The central clinical challenge is no longer whether testing matters, but whether testing is interpreted and implemented in a way that prevents cancer. BRCA1 and BRCA2 remain the highest-impact tubo-ovarian cancer predisposition genes, but Lynch syndrome genes, BRIP1, RAD51C, RAD51D, PALB2, and selected rare histology-directed syndromes require distinct counseling. Gene-specific penetrance, age-specific risk, family history, comorbidities, reproductive plans, and menopause consequences should shape the timing of risk-reducing surgery. Tumor testing improves therapeutic selection and can identify possible hereditary variants, but tumor-only testing does not replace germline testing when hereditary evaluation is indicated. Cascade testing should be measured and resourced as part of tubo-ovarian cancer care rather than treated as a passive family responsibility. Mainstream testing, traceback programs, and navigation-supported cascade testing offer pragmatic implementation models, but access gaps remain. For gynecologic oncology clinicians, modern hereditary risk assessment should be understood as a multi-disciplinary prevention intervention: testing is the entry point, not the endpoint. This narrative review synthesizes gene-specific counseling, tumor-germline interpretation, and implementation strategies into a clinically oriented pathway from diagnosis to prevention for patients and relatives.

Objective The updated European Society of Gynaecological Oncology guidelines recommend routine molecular classification to refine risk assessment and guide adjuvant treatment. However, the prognostic impact of sentinel lymph node involvement and molecular classification in apparent early-stage endometrial cancer remains incompletely defined. Methods PROMISE-EC is a multi-center retrospective study including patients with apparently uterine-confined endometrial cancer who underwent surgical staging with sentinel lymph node biopsy at 16 European institutions (January 2014-February 2024). Clinicopathologic characteristics, sentinel lymph node status, and Cancer Genome Atlas-based molecular classification were collected and analyzed. The primary endpoint was progression-free survival. Results Among 2732 records, 2003 patients met inclusion criteria. International Federation of Gynecology and Obstetrics 2009 stage I was observed in 1585 patients (79.4%). Sentinel lymph node involvement was present in 282 patients (14.1%). p53-abnormal tumors were associated with poorer progression-free survival (p <.0001), whereas patients with POLE-mutated tumors showed excellent outcomes, with no significant difference compared with non-specific molecular profile (p =.103). Patients with deficient mismatch repair tumors showed intermediate outcomes (p =.484). In unadjusted Kaplan-Meier analysis, progression-free survival worsened with increasing sentinel lymph node tumor burden (p =.047). In multi-variable analysis, high-grade disease (p =.003) and p53 abnormal status (p <.001) remained independent predictors of recurrence. The association between sentinel lymph node tumor burden and recurrence was attenuated, with only macrometastatic involvement retaining independent prognostic significance. In multi-variable logistic regression, lymphovascular space invasion was the strongest predictor of sentinel lymph node metastases (p <.00001), while patients with POLE-mutated tumors were less likely to harbor clinically relevant nodal involvement (p =.032). Conclusions Our study supports the prognostic relevance of both sentinel lymph node assessment and molecular classification in early-stage endometrial cancer, with potential implications for post-operative risk stratification and management.

BackgroundSentinel lymph node (SLN) mapping has increasingly replaced systematic lymphadenectomy in apparent uterine-confined endometrial cancer (EC). However, concerns persist regarding the risk of recurrence following nodal surgical de-escalation, particularly in patients with aggressive histologic subtypes. We aimed to evaluate the oncologic safety of SLN-based nodal de-escalation by analyzing recurrence patterns and recurrence-free survival in patients with apparent early-stage EC.MethodsWe conducted a retrospective multi-institutional study including women with apparent uterine-confined EC who underwent primary surgery including SLN mapping, with or without pelvic and/or para-aortic lymphadenectomy. Patients were grouped according to nodal staging strategy: SLN-only, SLN plus pelvic lymphadenectomy (PLND), and SLN plus PLND plus para-aortic lymphadenectomy (PALND). The primary endpoints were progression-free survival (PFS) and patterns of recurrence.ResultsWe included 2123 patients from 15 centers in six countries. SLN-only staging was performed in 1,341 patients (63.2%), SLN+PLND in 483 (22.8%), and SLN+PLND+PALND in 299 (14.1%). With a median follow-up of 44.9 months (IQR 19.1–73.4), 121 recurrences were observed (5.6%). No statistically significant differences in PFS were observed among nodal staging groups. On multivariable Cox analysis, SLN-only staging was not associated with inferior PFS compared with SLN+PLND (HR 1.12, p=0.61), and the addition of PALND did not confer a significant benefit. Endometrioid high-grade histology, non-endometrioid high-risk histotypes, deep myometrial invasion, and lymphovascular space invasion were independently associated with recurrence. Isolated nodal relapse was uncommon (14.9%) and similarly distributed across groups. Exploratory molecular analysis did not show statistically significant differences in PFS across molecular subgroups, although expected survival trends were observed.ConclusionsIn apparent uterine-confined EC, no significant differences in recurrence or nodal relapse were observed across nodal staging strategies. These findings support the use of SLN mapping as an adequate staging approach within a biology-driven framework, although they should be interpreted in light of the retrospective design.

Sentinel lymph node (SLN) mapping is being explored as a less invasive alternative to systematic lymphadenectomy in early-stage epithelial ovarian cancer. Existing evidence, mainly from feasibility and diagnostic accuracy studies, shows that SLN detection by mapping is achievable, but results remain inconsistent due to heterogeneity in methodology. Detection rates of SLN vary widely across studies, influenced by tracer type, injection technique, timing, and the extent of pathological assessment. Dual-tracer protocols combining radiotracers and indocyanine green generally yield higher detection rates than single tracers do, while injection into both infundibulopelvic and utero-ovarian ligaments yields adequate coverage of para-aortic and pelvic regions. However, detection of pelvic SLNs remains limited. In this context, cervical injection has been proposed as an alternative, with preliminary data showing enhanced pelvic lymph node detection. As for injection timing, pre-adnexectomy injection preserves native lymphatics but is technically demanding; post-adnexectomy injection is technically easier and more widely used. While ultra-staging enhances diagnostic sensitivity, its clinical implications for detecting micro-metastases and isolated tumor cells in epithelial ovarian cancer are still undefined and require further investigation. To support safe and standardized research-based implementation, we propose a unified framework that integrates levels of evidence with grades of recommendation across each procedural domain. This structured approach provides a foundation for protocol development, prospective data collection, and future clinical trials, aiming to bridge the gap between experimental mapping and potential clinical integration in early-stage epithelial ovarian cancer.

OBJECTIVE:Silva pattern is associated with higher risk of lymph node metastasis in cervical adenocarcinoma. However, no study specifically assessed the correlation between Silva pattern and sentinel lymph node (SLN) metastasis after ultrastaging. The primary aim of this study was to assess the incidence of low volume metastases in SLN of patients undergoing primary surgery with SLN biopsy for cervical adenocarcinoma, according to Silva pattern. Secondary aims were to assess risk factors for lymph node metastasis and prognosis. METHODS:Retrospective, multi-center study. Patients with cervical adenocarcinoma clinical FIGO stage IA1 to IIA2, treated with primary surgery between 04/2015 and 12/2023 and undergoing SLN mapping attempt, were included. Low volume metastases were defined as any tumor deposit ≤2 mm (ITC as <0.2 mm, micro-metastasis as 0.2-2 mm). Appropriate statistical analysis was performed to assess study endpoints. RESULTS:153 patients were included. Bilateral SLN mapping was achieved in 133 (86.9%) women. Silva pattern A was present in 47 (30.7%), B in 51 (33.3%) and C in 55 (35.9%) patients. 14 (9.1%) patients had metastatic SLN and 2 (1.4%) had metastatic non-SLN. The incidence of low-volume metastasis was 10/133 (7.5%) in patients with bilateral SLN mapping: 7 (5.3%) in Silva C, 1 (0.7%) in Silva B, and 2 (1.5%) in Silva A, while macro-metastases occurred in 4/133 (3.0%): 3 (2.2%), 0 and 1 (0.7%) cases, respectively (p = 0.027). Silva pattern C was the only factor independently associated to lymph node metastasis at multivariable analysis (OR: 9.724; 95%CI: 1.468-64.402; p = 0.018). No difference in disease-free survival and overall survival was evident when comparing Silva patterns (p = 0.210 versus p = 0.305, respectively). CONCLUSION:Low-volume metastases are more frequent than macro-metastases in patients with cervical adenocarcinoma undergoing SLN biopsy. Silva pattern C was associated with higher incidence of low volume lymph node metastasis, and it was the only factor independently associated with lymph node metastasis. Lymph node macro- and low-volume metastases were found also in Silva pattern A and B, highlighting the potential need for nodal assessment by SLN biopsy also in these sub-groups of patients.

OBJECTIVE:The primary aim of this study was to assess the factors associated with bilateral mapping failure in patients with apparent early-stage cervical cancer undergoing sentinel lymph node (SLN) biopsy using indocyanine green (ICG). Secondary aims were sensitivity, negative predictive value and lymph node recurrence. METHODS:Retrospective multi-center study. Patients with cervical cancer apparent FIGO stage IA1 to IIA2, treated with primary surgery between 04/2015 and 12/2023 and undergoing SLN mapping attempt with ICG injection, were included. Appropriate statistical analysis was performed to assess study endpoints. Timeframe was divided in first period 04/2015-12/2019 and second period 01/2020-12/2023. RESULTS:618 patients were included. Bilateral SLN mapping was achieved in 531 (85.9 %) women (36 of them, 5.8 %, underwent cervical re-injection of ICG). SLN unilateral mapping and mapping failure was observed in 71 (11.5 %) and 16 (2.6 %), respectively. The sensitivity, negative predictive value and accuracy were 85.9 %, 98.1 % and 98.3 %, respectively. False negative rate was 4/68 (5.9 %) in patients with unilateral mapping versus 6/316 (1.9 %) in those with bilateral mapping (p = 0.061). BMI>30 (p = 0.001) and pathologic tumor diameter >20 mm (p = 0.023) were the only factors independently associated with bilateral SLN mapping failure. ICG re-injection increased the rate of bilateral SLN detection from 81.3 % to 85.9 %. The rate of bilateral detection was 82.8 % versus 88.3 % in the first versus second study period, respectively (p = 0.061). 3-year DFS and OS in all patients were 89.7 % and 98.2 %, respectively. Seven patients (1.2 %) had lymph node recurrence in the group of any SLN mapping versus 1 (6.3 %) in no mapping group (p = 0.190). CONCLUSION:High BMI and larger tumors were associated with bilateral SLN mapping failure using ICG. The ICG cervical re-injection increased the rate of bilateral mapping. No lymph node recurrence difference was found in patients undergoing SLN mapping versus patients with mapping failure.

OBJECTIVE:The one-step nucleic acid amplification (OSNA) method has emerged as a potential alternative to ultrastaging for diagnosing lymph node metastasis. This study aims to assess the cost-effectiveness of the OSNA technique compared to ultrastaging for detecting SLN metastasis in patients with early-stage endometrial cancer (EC). METHODS:This retrospective, observational, single-center study included 30 patients with EC who underwent surgical treatment. SLN mapping was performed using an intracervical injection of indocyanine green. SLNs were analyzed and classified as negative, as having isolated tumor cells, micrometastases, or macrometastases. The study evaluated and quantified the costs of the OSNA and ultrastaging procedures in euros. RESULTS:A total of 54 lymph nodes were analyzed using both the OSNA and ultrastaging methods. Concordant negativity was identified in 48 cases (89 %), while micrometastases were detected concordantly in 1 case (1.8 %). The cost for a single ultrastaging lymph node analysis, including immunohistochemistry, is approximately € 250, with a total processing time of 2 days. The cost for a single OSNA analysis is approximately € 236, boasting a significantly shorter processing time of 30-40 min. While materials and staff costs are comparable between both techniques, considering time-related expenses, the OSNA method proves to be more cost-effective than ultrastaging (p < 0.001). CONCLUSIONS:The OSNA method demonstrates diagnostic accuracy comparable to histopathological examination in detecting lymph node metastases, reinforcing its reliability for lymph node assessment in patients with EC. Our cost analysis reveals that the OSNA method is more cost-effective than ultrastaging when time-related expenses are considered.

BACKGROUND: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. PRIMARY OBJECTIVE: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. STUDY HYPOTHESIS:We hypothesize that patients with low-risk endometrial cancer and ITCs will have a worse recurrence-free survival than patients who are node-negative. TRIAL DESIGN: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. MAJOR INCLUSION/EXCLUSION CRITERIA: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. PRIMARY END POINT:The primary end point is recurrence-free survival, measured from the date of surgery to the date of recurrence, death, or last disease evaluation. SAMPLE SIZE: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. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS:The study duration will be 60 months: 24 for enrollment and 36 for follow-up. The results are expected in 2029. TRIAL REGISTRATION:ClinicalTrials.gov: NCT06689956.

OBJECTIVE: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.