Low-grade serous ovarian carcinoma (LGSOC) is a rare epithelial malignancy characterized by frequent mitogen-activated protein kinase (MAPK) pathway alterations, hormone receptor expression, relative resistance to cytotoxic chemotherapy, and a prolonged, relapsing clinical course. Since publication of the 2023 international expert consensus, significant advances have reshaped the management of both newly diagnosed and recurrent disease. The 2026 LGSOC Consensus Conference convened an international multidisciplinary panel of experts in the field to review emerging evidence and update recommendations across pathology, molecular testing, translational biology, frontline and recurrent treatment, imaging, treatment-associated toxicity, regulatory strategy, patient advocacy, and future research priorities. Recommendations were informed by contemporary clinical evidence, multidisciplinary discussion, and patient perspectives. The updated consensus incorporates practice-changing data from NRG-GY019 supporting chemotherapy-containing postoperative therapy as the current reference approach for stage II–IV disease while recognizing selected circumstances in which endocrine monotherapy may represent individualized de-escalation. It also integrates recent advances in recurrent disease, including the US Food and Drug Administration's accelerated approval of avutometinib in combination with defactinib for KRAS-mutated LGSOC, emerging evidence supporting endocrine therapy combined with CDK4/6 inhibition, and refined guidance for biomarker-directed treatment selection, imaging assessment, toxicity management, and patient-centered survivorship. The panel emphasizes treatment-specific biomarker interpretation, multidisciplinary care, central pathology review for clinical trials, and the continued need for prospective studies addressing treatment sequencing, predictive biomarkers, and quality-of-life outcomes. This updated international consensus provides an evidence-based framework for the diagnosis and management of LGSOC while identifying priorities for future clinical research and drug development.
Objectives To describe the current landscape of hormone replacement therapy (HRT) to treat surgical menopause following bilateral salpingo-oophorectomy (BSO) in individuals with hereditary ovarian cancer risk in British Columbia, Canada. We aimed to describe current use of HRT, identify factors associated with HRT use and identify potential barriers for uptake and access. Methods Individuals with germline pathogenic/likely pathogenic variants in an ovarian cancer susceptibility gene were identified through the BC Cancer Hereditary Cancer Program (HCP) Progeny database. A cross-sectional survey was administered to collect participant demographics, personal and family cancer history, and participant experiences with HRT. Descriptive statistics were used to characterize the sample and logistic regression used to explore associations between sociodemographic variables and reported HRT use. Open text fields were analyzed using inductive quantitative content analysis. Results In total, 374 responses were received from 1284 potential participants (29.1% response rate). Of participants who have had a BSO, 41% (101/245) report HRT use. In open-text responses, 22% of participants reported lack of support by healthcare professionals and 26% described gaps in counselling about HRT and surgical menopause. In the regression analysis, HRT use was less likely in individuals who: were of increasing age, reported a history of any cancer type and who reported receiving no counselling about HRT (all p < 0.0011 after Bonferroni correction). Conclusion Barriers to HRT access and uptake exist for individuals at increased risk of ovarian cancer. Together this data indicates that patients require additional support in this area particularly as it relates to education and resources.
Objectives The survival outcomes of advanced or recurrent endometrial cancer (EC) have not improved markedly despite the expanding therapeutic options. We performed molecular characterization of EC to identify therapeutic targets and prognostic biomarkers. Methods Whole-exome sequencing (WES)-based somatic mutation profiling was performed in tumor samples obtained from 67 EC patients (41 early-stage and 26 advanced/recurrent cases). The frequencies of somatic mutations were compared between early and advanced/recurrent EC. Copy number variation analysis was also performed. Survival outcomes and recurrences according to mutational status were analyzed. Results TP53 and KRAS mutations tended to be more frequent in advanced/recurrent disease than early-stage EC. Deletions were also more common in advanced EC (42.3% vs. 17.1%). Among the advanced EC patients (n=26), 16 patients recurred. Recurrent cases had significantly higher TP53 mutation rates (56.3% versus 10%) and lower PTEN mutation rates (25% versus 80%) than non-recurrent cases. KRAS and CTNNB1 mutations also tended to be enriched. Although KRAS mutation alone only showed a trend of shorter OS (p=0.179) in advanced EC, KRAS-TP53 co-mutation exhibited the worst survival outcomes (p=0.011). KRAS-TP53 co-mutation was associated with chemoresistance: all the co-mutated cases were chemoresistant, whereas patients without either mutation were chemosensitive. Among copy-number low (CNL) and microsatellite instability-high (MSI-H) tumors (n=46), KRAS-TP53 co-mutation was strongly associated with adverse survival outcomes (p=0.003). Conclusions KRAS-TP53 co-mutation represents a potential molecular biomarker of poor prognosis and chemoresistance in advanced EC. It may enable refinement of TCGA classification, especially for CNL and MSI-H subgroups, and support investigation of KRAS-targeted therapeutic strategies.
Objective This study examined both National Comprehensive Cancer Network (NCCN) guideline concordance and steroid taper duration with clinical outcomes in patients with gynecologic malignancies experiencing immune-related AEs. Methods This single-institution retrospective cohort included patients with gynecologic malignancies treated with immune checkpoint inhibitor (ICI) from August 2016 to September 2025 who developed grade 3 or 4 immune-related AEs requiring systemic steroids. Clinical and steroid treatment data were abstracted. NCCN guideline concordance and outcomes were assessed. Results 63 patients contributing 73 steroid tapers were included. Most patients had endometrial (41.3%), cervical (27.0%), or ovarian cancer (23.8%), and pembrolizumab was the most used ICI (74.6%). 46 tapers (63.0%) were NCCN guideline concordant and 27 (37.0%) were NCCN guideline discordant, with discordance most often driven by taper length and premature initiation. 14 (19.2%) were < 28 days, and 59 (80.8%) were ≥ 28 days. NCCN discordant tapers were more likely to require additional supportive medications for irAE management (e.g. secondary steroids) than concordant tapers (81.5% vs 56.2%, p = 0.0300). NCCN concordance was associated with longer time to ICI restart (56 vs 21 days, p = 0.0241). Tapers <28 days were more likely to require additional supportive medications (100% vs 57.6%, p = 0.0027) and steroids (35.7% vs 8.4%, p = 0.0253) than tapers ≥28 days. Tapers ≥28 days were associated with higher rates of ICI discontinuation due to toxicity (59.3% vs 28.6%, p = 0.0381). Rates of hospitalization, ICU admission, and AE resolution did not differ by NCCN concordance or taper duration. Conclusions Corticosteroid taper practices varied substantially in patients with gynecologic malignancies experiencing severe irAEs; shorter and guideline-discordant tapers were associated with greater treatment escalation and steroid reinitiation.
