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Background: Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear., Methods: In this prospective, randomized, noninferiority trial, we investigated the omission of axillary surgery as compared with sentinel-lymph-node biopsy in patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size, ≤5 cm) who were scheduled to undergo breast-conserving surgery. We report here the per-protocol analysis of invasive disease-free survival (the primary efficacy outcome). To show the noninferiority of the omission of axillary surgery, the 5-year invasive disease-free survival rate had to be at least 85%, and the upper limit of the confidence interval for the hazard ratio for invasive disease or death had to be below 1.271., Results: A total of 5502 eligible patients (90% with clinical T1 cancer and 79% with pathological T1 cancer) underwent randomization in a 1:4 ratio. The per-protocol population included 4858 patients; 962 were assigned to undergo treatment without axillary surgery (the surgery-omission group), and 3896 to undergo sentinel-lymph-node biopsy (the surgery group). The median follow-up was 73.6 months. The estimated 5-year invasive disease-free survival rate was 91.9% (95% confidence interval [CI], 89.9 to 93.5) among patients in the surgery-omission group and 91.7% (95% CI, 90.8 to 92.6) among patients in the surgery group, with a hazard ratio of 0.91 (95% CI, 0.73 to 1.14), which was below the prespecified noninferiority margin. The analysis of the first primary-outcome events (occurrence or recurrence of invasive disease or death from any cause), which occurred in a total of 525 patients (10.8%), showed apparent differences between the surgery-omission group and the surgery group in the incidence of axillary recurrence (1.0% vs. 0.3%) and death (1.4% vs. 2.4%). The safety analysis indicates that patients in the surgery-omission group had a lower incidence of lymphedema, greater arm mobility, and less pain with movement of the arm or shoulder than patients who underwent sentinel-lymph-node biopsy., Conclusions: In this trial involving patients with clinically node-negative, T1 or T2 invasive breast cancer (90% with clinical T1 cancer and 79% with pathological T1 cancer), omission of surgical axillary staging was noninferior to sentinel-lymph-node biopsy after a median follow-up of 6 years. (Funded by the German Cancer Aid; INSEMA ClinicalTrials.gov number, NCT02466737.)., (Copyright © 2024 Massachusetts Medical Society.)

Purpose: The CDK4/6 inhibitor palbociclib inhibits cyclin A, which is overexpressed in endometrial cancer. Combining palbociclib with endocrine therapy improves efficacy in hormone receptor-positive breast cancer. We investigated palbociclib combined with endocrine therapy for estrogen receptor-positive advanced/recurrent endometrial cancer., Patients and Methods: This placebo-controlled double-blind, randomized phase II screening trial (NCT02730429) enrolled women with measurable/evaluable estrogen receptor-positive endometrioid endometrial cancer that was primary metastatic or had relapsed after ≥1 prior systemic therapy. Patients were randomized in a 1:1 ratio, stratified by number of prior chemotherapy lines, measurable versus evaluable non-measurable disease, and prior medroxyprogesterone/megestrol acetate treatment, to receive oral letrozole 2.5 mg on days 1-28 plus either oral palbociclib 125 mg or placebo on days 1-21, repeated every 28 days until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS)., Results: Among 77 patients randomized between February 16, 2017, and December 21, 2018, 73 were treated (36 with palbociclib-letrozole, 37 with placebo-letrozole). Median follow-up was 21.9 (95 % CI, 16.7 to 22.3) months. Median PFS was 8.3 (95 % CI, 4.6 to 11.2) versus 3.1 (95 % CI, 2.7 to 6.8) months, respectively. In a landmark analysis at 12 months the PFS hazard ratio was 0.57 (95 % CI, 0.32 to 0.99; P = .044). Grade ≥ 3 adverse events were more common with palbociclib-letrozole (67 %) than placebo-letrozole (30 %), most commonly neutropenia (44 % v 0 %, respectively)., Conclusion: These results support a potential role of the palbociclib-letrozole combination as treatment for hormone receptor-positive advanced/recurrent endometrial cancer. Based on these encouraging results, phase III evaluation of letrozole combined with a CDK4/6 inhibitor is planned., Clinical Trial Information: NCT02730429., Competing Interests: Declaration of competing interest MRM reports leadership roles and stock for Karyopharm Therapeutics and Sera Prognostics; honoraria from Roche, AstraZeneca, Genmab/Seattle Genetics, GSK, Merck, Mersana, Takeda, Zai Lab, Geneos, and Allarity Therapeutics; consulting/advisory roles for AstraZeneca, Genmab, Karopharm Therapeutics, Pfizer, and GSK; research funding (to institution) from AstraZeneca, Boehringer Ingelheim, Pfizer, Tesaro, Clovis Oncology, Ultimovacs, Apexigen, and GSK; grants and personal fees from Tesaro, AstraZeneca, Pfizer, and Clovis Oncology; travel/accommodation/expenses from AstraZeneca, Karyopharm Therapeutics, Pfizer, Roche, Tesaro, and SeraCare; and other relationships with ENGOT, GCIG, and ESGO. LB reports speaker's bureau participation for GSK and MSD and research funding from AstraZeneca. FM reports honoraria from Roche/Genentech, Novartis, Pfizer, AstraZeneca, Clovis Oncology, Eisai, Genomic Health, PharmaMar, Amgen, MSD Oncology, Seagen, Myriad Genetics, Pierre Fabre, GSK, Agendia, Lilly, Gilead, Daiichi Sankyo, and Immunomedics; consulting/advisory roles for Pfizer, Genomic Health, CureVac, Amgen, Eisai, GSK, Gilead, Seagen, Clovis Oncology, AstraZeneca, Roche, Vaccibody, and Immunomedics; research funding from Roche/Genentech, Novartis, AstraZeneca, Tesaro, Clovis Oncology, MSD Oncology, Vaccibody, Gilead, and GSK; and travel/accommodation/expenses from Roche, Pfizer, AstraZeneca, and Gilead Sciences. RdPC reports employment and stock ownership from Y-mAbs Therapeutics and consulting/advisory role for Karyopharm. MGM reports consulting/advisory roles for AstraZeneca; speakers' bureau for GSK and MSD Oncology; and travel/accommodation/expenses from AstraZeneca, GSK, and MSD Oncology. AA reports consulting/advisory roles and travel/accommodation/expenses from GSK and MSD. BA reports honoraria from Roche, AstraZeneca, MSD, GSK, Eisai Europe, Novartis, Lilly, and Pfizer; consulting/advisory roles for Roche, MSD, Sanofi Aventis GmbH, GSK, and Eisai Europe; and travel/accommodation/expenses from Roche, AstraZeneca, GSK, Lilly, and Daiichi Sankyo/AstraZeneca. VS reports honoraria from AstraZeneca, MSD Oncology, GSK, PharmaMar, and Novocure; consulting/advisory roles for AstraZeneca and Novocure; and travel/accommodation/expenses from GSK and PharmaMar. AR reports consulting/advisory roles for AstraZeneca, GSK, Boehringer Ingelheim, MSD, and Pharma&; speakers' bureau for AstraZeneca, GSK, MSD, and Pharma&; and travel/accommodation/expenses from AstraZeneca. KL reports honoraria from AstraZeneca; consulting/advisory roles for Eisai, MSD, GSK, and Nycode; research funding (inst) from GSK; and is Deputy Medical Director of NSGO-CTU. FT reports research funding and personal fees from AstraZeneca, Clovis, Eisai, ImmunoGen, MSD, SAGA diagnostics, and Tesaro/GSK. MPBG reports consulting/advisory roles for AstraZeneca, GSK, MSD Oncology, Eisai Europe, Clovis Oncology, PharmaMar, and Pharma&; speakers' bureau for AstraZeneca Spain, GSK, Eisai Europe, and MSD Oncology; and travel/accommodation/expenses from AstraZeneca, GSK, and MSD Oncology. JEK reports employment (immediate family member) with MSD; consulting/advisory roles for AstraZeneca, MSD, and GSK; and travel/accommodation from AstraZeneca, Eisai, PharmaMar, and GSK. JS reports honoraria from AstraZeneca, Eisai, Clovis Oncology, Olympus Medical Systems, Johnson & Johnson, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GSK, and Bayer; consulting/advisory roles for AstraZeneca, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, Johnson & Johnson, Roche Diagnostics, NGRESS-Health, Riemser, Sobi, GSK, Novartis, and Alkermes; research funding (inst) from AstraZeneca, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, and Roche; travel/accommodation/expenses from AstraZeneca, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, and Olympus. No other potential conflicts of interest were reported., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC)., Methods: We conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000-12/31/2015 were included. Oncologic outcomes were assessed for patients based on adjuvant treatment received, including chemotherapy, radiation, or chemotherapy with radiation., Results: Of 125 patients identified and analyzed, 77 (61.6%) had clear cell histology and 118 (94.4%) had stage I disease. Median age at diagnosis was 65 years (range, 33-91). All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Twenty-five patients (20.0%) underwent surgical management alone and 100 (80.0%) received adjuvant therapy: 20 (16.0%) received postoperative chemotherapy, 47 (37.6%) received postoperative radiation, and 33 (26.4%) received postoperative chemotherapy with radiation. Median follow-up was 88.4 months (range, <1-234). Progression-free survival (PFS) or overall survival (OS) did not significantly differ between surgery alone and type of adjuvant therapy (P = 0.18 and P = 0.56, respectively). Patients with mixed ECCC did not have a survival advantage over those with pure ECCC (5-year PFS rate, 85.0% vs 82.7%, P = 0.77; 5-year OS rate, 88.3% vs 91.2%, P = 0.94)., Conclusions: Receipt of adjuvant therapy in surgically staged I/II ECCC did not appear to offer a survival advantage over observation alone. Adjuvant therapy in early-stage ECCC with consideration of molecular classification should be evaluated., Competing Interests: Declaration of competing interest Dr. Leitao reports personal fees from Medtronic, Intuitive Surgical, J&J/Ethicon, and Immunogen. Dr. Abu-Rustum reports research funding paid to the institution from GRAIL. Dr. Eriksson reports speaker fees from Intuitive Surgical and AstraZeneca. Dr. Makker reports unpaid consulting/advisory roles with the following: Duality, Novartis, Morphosys, AstraZeneca, Eisai, Clovis Oncology, Karyopharm Therapeutics, GlaxoSmithKline, Merck, ArQule, Cullinan, Faeth Therapeutics, Jazz, Immunocore, Iteos Therapeutics, Ideaya, Kartos Therapeutics, Lilly, Moreo, Prelude, Takeda, and Zymeworks; research funding from the following: Merck (Inst), Eisai (Inst), AstraZeneca (Inst), Clovis Oncology (Inst), Bayer (Inst), Takeda (Inst), Duality (Inst), Zymeworks (Inst), Karyopharm Therapeutics (Inst), Faeth Therapeutics (Inst), Bristol-Myers Squibb (Inst), Lilly (Inst), and Cullinan (Inst); travel, accommodations, and expenses from the following: Eisai, Merck, AstraZeneca; and a relationship with IBM. Dr. du Bois reports honoraria/expenses from Amgen, AstraZeneca, BIOCAD, Clovis, GSK/Tesaro, Roche, and Zodiac; and consulting/advisory board role for Amgen, AstraZeneca, BIOCAD, Clovis, Genmab/Seattle Genetics, GSK/Tesaro, MSD, Roche, Pfizer. The other authors do not have potential conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess clinicopathologic features and survival outcomes of patients with endometrial carcinoma involving adnexal, full-thickness serosal, or combined involvement., Methods: This international, multi-institutional, retrospective study examined patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IIIA endometrial cancer and tumors involving the uterine serosa and/or adnexa, who were surgically staged between 2000 and 2019. Patients with sarcoma histology, concurrent endometrial/ovarian malignancy, neoadjuvant treatment, positive lymph nodes, or peritoneal disease were excluded., Results: Of 185 patients identified, 139 had tumors with adnexal-only, 40 with serosal-only, and six with combined adnexal/serosal involvement. Median age at diagnosis was 60 years (range 23-89). Among tumors of endometrioid histology, 12 (48%) with serosal-only and 17 (19%) with adnexal-only involvement were FIGO grade 3 (p=0.007). Twenty-three tumors with serosal-only (64%) and 50 with adnexal-only (37%) involvement had lymphovascular invasion (p=0.004). Non-endometrioid histology was present in five tumors (83%) with combined adnexal/serosal, 15 (38%) with serosal-only, and 50 (36%) with adnexal-only involvement.Median follow-up was 77 months (range 0.6-254). Five-year progression-free survival and overall survival rates for all patients with stage IIIA disease were 73.8% (SE 3.5%) and 81.0% (SE 3.1%), respectively. For patients with adnexal-only, serosal-only, and combined adnexal/serosal involvement, 5-year progression-free survival rates were 80% (SE 3.8%), 61% (SE 8.3%), and 33% (SE 19.2%), respectively (p<0.01); 5-year overall survival rates were 85% (SE 3.3%), 70% (SE 7.8%), and 60% (SE 21.9%), respectively (p=0.09). On univariate analysis, tumors having serosal involvement with/without adnexal involvement, non-endometrioid histology, and lymphovascular invasion were significantly associated with progression. On multivariate analysis, tumors having serosal involvement with/without adnexal involvement remained significantly associated with recurrence (adjusted HR=2.2, 95% CI 1.2 to 4.3; p=0.01)., Conclusions: Patients with 2009 FIGO stage IIIA endometrial cancer have distinct survival outcomes depending upon adnexal and/or serosal involvement. Progression-free survival was worse for patients with serosal involvement after adjusting for histology, adjuvant treatment, and lymphovascular space invasion., Competing Interests: Competing interests: ML reports personal fees from Medtronic, Intuitive Surgical, J&J/Ethicon, and Immunogen. NRA-R reports research funding paid to the institution from GRAIL. AGE reports speaker fees from Intuitive Surgical and AstraZeneca. DZ reports institutional research support from AstraZeneca, Merck, Plexxikon, Synthekine, and Genentech; consulting fees from AstraZeneca, Synthekine, Astellas, Tessa Therapeutics, Memgen, Celldex, Crown Biosciences, Hookipa Biotech, Kalivir, Xencor, and GSK; royalties from Merck; and stock options from Accurius Therapeutics, ImmunOS Therapeutics, and Calidi Biotherapeutics, all outside the submitted work. The other authors do not have potential conflicts of interest to declare., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The Craniofacial Condition Quality of Life Scale (CFC-QoL) was used to evaluate the relationship between surgical burden and quality of life (QoL)., Design: Patient-parent dyads completed the CFC-QoL which queries the following QoL domains: Bullying, Peer Problems, Psychological Impact, Family Support, Appearance Satisfaction, and Desire for Appearance Change. Stepwise multivariate linear regressions were performed for each QoL domain., Setting: Urban tertiary care center., Patients, Participants: Pediatric patients with facial differences, and their parents., Intervention: Survey study., Main Outcome Measure(s): Demographic, diagnostic, and surgical characteristics were collected. Surgical burden was calculated as the standard deviation from the mean number of surgeries per diagnostic cohort., Result: Patients ( N   =  168) were majority female (57.1%) and Hispanic (64.3%). Diagnoses were cleft lip and/or palate (CLP, n   =  99) or other craniofacial conditions (CFC, n   =  69). Average patient age was 2.3  ±  5.6 years at first reconstructive surgery and 12.3  ±  3.4 years at study enrollment. Patients received an average of 4.3  ±  4.1 reconstructive surgeries.Worse Bullying was associated with higher surgical burden. Worse Peer Problems was associated with higher surgical burden, but only for children with non-CLP CFCs. Worse Family Support was associated with CFC diagnosis, female sex, and higher surgical burden. Worse Psychological Impact was associated with higher surgical burden. Worse Appearance Satisfaction was associated with younger age and with lower surgical burden. Greater Desire for Appearance Change was associated with older age, higher surgical burden, CLP diagnosis, female sex, and non-Hispanic ethnicity. Socioeconomic status did not predict QoL per patient self- or parent-proxy report., Conclusions: Higher surgical burden was associated with worse QoL outcomes in multiple domains., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: In the ENGOT-EN6-NSGO/GOG3031/RUBY trial, dostarlimab+carboplatin-paclitaxel demonstrated significant improvement in progression free survival and a positive trend in overall survival compared with placebo+carboplatin-paclitaxel, with manageable toxicity, in patients with primary advanced or recurrent endometrial cancer. Here we report on patient-reported outcomes in the mismatch repair-deficient/microsatellite instability-high population, a secondary endpoint in the trial., Methods: Patients were randomized 1:1 to dostarlimab+carboplatin-paclitaxel or placebo+carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo monotherapy every 6 weeks for ≤3 years or until disease progression. Patient-reported outcomes, assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Endometrial Cancer Module, were prespecified secondary endpoints. A mixed model for repeated measures analysis, a prespecified exploratory analysis, was conducted to generate least-squares means to compare between-treatment differences while adjusting for correlations across multiple time points within a patient and controlling for the baseline value. Results are provided with 2-sided, nominal p values., Results: Of 494 patients enrolled, 118 were mismatch repair-deficient/microsatellite instability-high. In this population, mean change from baseline to end of treatment showed visual improvements in global quality of life (QoL), emotional and social function, pain, and back/pelvis pain for dostarlimab+carboplatin-paclitaxel. Meaningful differences (least-squares mean [standard error]) favoring the dostarlimab arm were reported for change from baseline to end of treatment for QoL (14.7 [5.45]; p=0.01), role function (12.7 [5.92]); p=0.03), emotional function (14.3 [4.92]; p<0.01), social function (13.5 [5.43]; p=0.01), and fatigue (-13.3 [5.84]; p=0.03)., Conclusions: Patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer receiving dostarlimab+carboplatin-paclitaxel demonstrated improvements in several QoL domains over patients receiving placebo+carboplatin-paclitaxel. The observed improvements in progression free survival and overall survival while improving or maintaining QoL further supports dostarlimab+carboplatin-paclitaxel as a standard of care in this setting., Trial Registration: ClinicalTrials.gov NCT03981796., Competing Interests: Competing interests: GV reports consulting fees from GSK; honoraria from AstraZeneca, GSK, and MSD; travel support from AstraZeneca and PharmaMar; participation in advisory boards for AstraZeneca, Eisai, GSK, and MSD. MAP reports consulting fees from GSK, Tesaro, Merck, Eisai, SeaGen, Clovis Oncology, and AstraZeneca. SH reports consulting fees from AstraZeneca, Eisai, GSK, and MSD and honoraria from AstraZeneca and GSK. EMM reports advisory board meeting fees from AstraZeneca, GSK, and Tempus; honoraria from OncLive and Opinions in Gyn Malignancies; and support for attending meetings from Opinions in Gyn Malignancies and OncLive. ZN reports honoraria from Sofmedica, AstraZeneca, and MSD; support for attending meetings from Sofmedica and Preglem; participation on a data safety monitoring board or advisory board for AstraZeneca and Richter Gedeon; stock options from Richter Gedeon; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from AstraZeneca. RH reports honoraria from GSK, AstraZeneca, Clovis Oncology, Eisai, and Merck. DD reports receiving consulting fees from AstraZeneca, GSK/Tesaro, Roche, Eisai Germany, and MSD Oncology; honoraria for advisory roles from Roche, AstraZeneca, GSK/Tesaro, Intuitive Surgical, KLS Martin, MSD, PharmaMar, and Seagen; and travel support from AstraZeneca. TM reports honoraria from Immunogen. LG reports institutional grants from Alkermes, AstraZeneca, Clovis Oncology, Esperas, IMV, ImmunoGen, Karyopharm, MSD, Mersana, Novocure, OncoQuest Pharmaceuticals, Pfizer, Roche, and Tesaro; consulting fees from Merck; honoraria from Alkermes, AstraZeneca, Eisai, Eisai-Merck, and GSK. BA reports honoraria from AstraZeneca, Eisai, GSK, MSD, Norartis, and Roche; support for attending meetings from AstraZeneca, GSK, and Roche; participation on a data safety monitoring board or advisory board for Eisai, GSK, MSD, Roche, and Sanofi Aventis. RG reports participation on a data safety monitoring board or advisory board for Pionyr Pharmaceuticals and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Bausch+Lomb. NC reports advisory board fees for Aadii, GSK, Kartos, Novita Pharmaceuticals, Tarveda Therapeutics, Toray, Umoja, and Zentalis. BJM reports consulting fees from Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Macrogenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL and speakers’ bureau honoraria from AstraZeneca, Clovis Oncology, Eisai, Merck, Roche/Genentech, and Tesaro/GSK. TJH reports personal consulting fees from Aadi, AstraZeneca, Caris, Clovis Oncology, Eisai, Epsilogen, Genentech, GSK, Immunogen, J&J, Merck, Mersana, and Seagen; participation on a data safety monitoring board or advisory board for Corcept; and leadership role on the GOG Foundation Board and President of GOG Partners. AS reports royalties as an UptoDate reviewer. BP reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, SeaGen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, and VBL Therapeutics; consulting fees from AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, I-Mab Biopharma, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, and Toray; support for attending meetings from GOG Foundation; advisory board fees from Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Eisai, Elevar Therapeutics, GOG Foundation, I-Mab Biopharma, Lilly, Merck, Mersana, Seagen, Sutro Biopharma, Tesaro/GSK, Toray, and VBL Therapeutics; and noncompensated leadership fees from NYOB Society Secretary, SGO Clinical Practice Committee Chair, and SGO COVID-19 Taskforce Co-Chair. AAS reports support paid to her institution from GSK for the present IGCS abstract; institutional grant support from AbbVie, Aravive, AstraZeneca, Clovis Oncology, Eisai, Ellipses, I-Mab Biopharma, Immunogen, Merck, Oncoquest/Canaria Bio, Roche/Genentech, Seagen, TapImmune, Tesaro/GSK, and VBL Therapeutics; honoraria from @Point of Care Clinical Care Options Curio Science, Peerview, Bio ASCEND, RTP, GOG Foundation (Highlight reel), and GOG Foundation Symposium; patent issued for 'blood based biomarkers in ovarian cancer'; noncompensated participation on a data safety monitoring board/advisory board from AstraZeneca, Clovis Oncology, Gilead, Immunogen, Imvax, Merck, Mersana, Natera, Onconova, and OncoQuest; uncompensated leadership roles with SGO, AAOGF, and NRG and compensated role from GOG; receipt of medical writing support from AstraZeneca; and uncompensated Clinical Trial Steering Committees for the AXLerate trial (Aravive), AtTEnd trial (Hoffman-LaRoche), Oval Trial (VBL Therapeutics), FLORA-5 trial (CanariaBio), and QPT-ORE-004 (CanariaBio). DC reports consultant fees from AstraZeneca and GSK and honoraria from AstraZeneca, GSK, Seagen/Genmab, and Immunogen. MRM reports consulting fees from AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, and Zai Lab; speakers’ bureau fees from AstraZeneca and GSK; research funding (to institution) from Apexigen, AstraZeneca, Deciphera (trial chair), GSK, and Ultimovacs; and personal financial interest in Karyopharm (stocks/shares, member of board of directors). DB reports institutional grant fees from GSK; fees for being a member of GOG Partners Investigational Council; and medical director/owner of Trials365. AMT, KPP, EF, OZ, LML, IP, and SS have nothing to disclose. OM, VV, and JG are employees of GSK., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: To investigate the role of BRCA1/2 mutations in early ovarian cancer (eOC) (International Federation of Gynecology and Obstetrics FIGO 2014 stage I-II), and its impact on prognosis after relapse., Methods: In this multicenter retrospective study, clinical and survival data from high-grade serous (HGS)-eOC patients at presentation and recurrence were compared according to BRCA status: BRCA-mutated (BRCAmut) vs. BRCA wild-type (BRCAwt)., Results: Among 191 HGS-eOC patients, 89 were BRCAmut and 102 BRCAwt. There was no significant difference according to the BRCA status in terms of Progression-Free Survival (PFS). A longer Overall Survival (OS) was found in BRCAmut patients. Stage I patients had significantly improved PFS vs stage II, regardless of BRCA status. At multivariate analysis, stage at diagnosis was the only variable with a significant effect on PFS. No factors were significantly relevant on OS, albeit younger age and BRCA mutation showed a slight impact. Post-Recurrence Survival (PRS) in the BRCAmut population was significantly improved compared with BRCAwt. At multivariate analysis, Secondary Cytoreductive Surgery was the strongest predictor for longer PRS, followed by PARPi maintenance at recurrence., Conclusions: BRCA-status is not a prognostic factor in early ovarian cancer regarding PFS. However, our data suggest a better prognosis after relapse in BRCAm population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)