Mariani C, Lorente DM, Frau J
… +3 more, Orti M, Ciarmatori S, Odetto D
Int J Gynecol Cancer
· 2026 Apr · PMID 42235255
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OBJECTIVE: Atypical endometrial hyperplasia and low-grade endometrial cancer are traditionally managed with hysterectomy. However, conservative treatment with a levonorgestrel-releasing intra-uterine system may be an alt...OBJECTIVE: Atypical endometrial hyperplasia and low-grade endometrial cancer are traditionally managed with hysterectomy. However, conservative treatment with a levonorgestrel-releasing intra-uterine system may be an alternative for selected patients. This study evaluated the efficacy of a levonorgestrel-releasing intra-uterine system in patients with atypical endometrial hyperplasia and low-grade endometrial cancer and identified factors associated with complete remission. METHODS: This retrospective cohort study included patients treated between January 2013 and June 2025 for atypical endometrial hyperplasia or International Federation of Gynecology and Obstetrics 2009 stage IA, grade 1 to 2 endometrioid endometrial cancer managed with a levonorgestrel-releasing intra-uterine system for fertility preservation, co-morbidities, or refusal of hysterectomy after comprehensive counseling regarding risks and oncologic outcomes. A minimum follow-up of 6 months was required. Treatment response was assessed using serial hysteroscopic biopsies. Multi-variable logistic regression analysis was used to identify predictors of complete remission. RESULTS: Forty-nine patients were included: 37 with atypical endometrial hyperplasia and 12 with endometrial cancer. Among the patients with cancer, 10 had grade 1 disease and 2 had grade 2 disease. Median follow-up was 2.6 years. The overall complete remission rate was 75.5% and was significantly higher in patients with atypical endometrial hyperplasia than in those with endometrial cancer (89.2% vs 33.3%). Focal lesions were associated with higher remission rates than diffuse endometrial involvement in univariate analysis (86.5% vs 42.0%, p <.01), but this association was not maintained in multi-variable analysis. A diagnosis of atypical endometrial hyperplasia independently predicted complete remission (adjusted odds ratio 17.4, 95% confidence interval 1.98 to 152, p =.009). No recurrences or severe adverse events were observed. CONCLUSIONS: A levonorgestrel-releasing intra-uterine system is highly effective for atypical endometrial hyperplasia, with high complete remission rates. In low-grade endometrial cancer, lower response rates were observed, and the results should be interpreted cautiously given the small sample size. These findings support the levonorgestrel-releasing intra-uterine system as a conservative option for selected patients and emphasize the need for careful selection and close surveillance.
Nolin A, Brown MD, Thomas SM
… +20 more, Strickland KC, Bean S, Neff JL, Pothuri B, Moore KN, Mullen M, Clark LH, Konecny G, Jackson AL, Ko EM, Whitaker R, Linhart S, March L, Hacker K, Washington C, Thaker P, Maxwell GL, Berchuck A, Secord AA, Previs RA
Int J Gynecol Cancer
· 2026 Apr · PMID 42235254
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OBJECTIVE: To determine the association between molecular classification and response in patients with endometrial intra-epithelial neoplasia or endometrial cancer treated with a levonorgestrel intra-uterine device. METH...OBJECTIVE: To determine the association between molecular classification and response in patients with endometrial intra-epithelial neoplasia or endometrial cancer treated with a levonorgestrel intra-uterine device. METHODS: Eligible patients were treated with a levonorgestrel intra-uterine device for endometrial intra-epithelial neoplasia or endometrial cancer for at least 6 months. Immunohistochemistry for MLH1, MSH2, MSH6, PMS2, and p53 was performed. Specimens were categorized using a modified Proactive Molecular Risk Classifier for Endometrial Cancer algorithm as deficient mismatch repair, p53 abnormal, or p53 wild-type. A subset underwent single-gene POLE sequencing. Best response was recorded as pathologic complete response, partial response, stable disease, or progressive disease. Kruskal-Wallis tests and Fisher exact tests were used for statistical analysis. RESULTS: There were 143 patients, including 83 with endometrial intra-epithelial neoplasia and 60 with endometrial cancer. Fertility preservation was desired in 35.7%, 53.8% had significant medical co-morbidities precluding hysterectomy, and 10.5% had levonorgestrel intra-uterine device placement for other indications, including patient preference, placement during the coronavirus disease 2019 pandemic, and logistical considerations for other cancer diagnoses. Molecular characterization showed 90.9% p53 wild-type, 7.0% deficient mismatch repair, and 2.1% p53 abnormal. Only 4.4% of specimens with sequencing had a POLE mutation (2 of 45). The overall response rate was 86.7% (endometrial cancer: complete response 38.3%, partial response 36.7%; endometrial intra-epithelial neoplasia: complete response 67.5%, partial response 27.7%). In patients with endometrial cancer, the response rate was 75% (45 of 60), varying by molecular sub-group: 50% in the p53 abnormal group (1 of 2) and 50% in the deficient mismatch repair group (5 of 10). Only 1 patient with endometrial intra-epithelial neoplasia had p53 abnormal expression; the remaining patients had intact MMR expression and p53 wild-type. CONCLUSIONS: The complete response to levonorgestrel intra-uterine device therapy was lower than expected for endometrial intra-epithelial neoplasia. Response rates varied by molecular classification, with worse outcomes observed in deficient mismatch repair and p53 abnormal sub-types. Although limited by sample size, these findings suggest that levonorgestrel intra-uterine device therapy may not be sufficient for all molecular sub-groups.
Frenel JS, Heudel PE, Guinaudeau E
… +8 more, Bossard C, Lindahl G, Rynkiewicz J, Salhi S, Salhi Y, Chetritt J, Pujade-Lauraine E, Ray-Coquard I
Int J Gynecol Cancer
· 2026 Apr · PMID 42235122
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OBJECTIVE: Homologous recombination deficiency is a critical biomarker for guiding first-line treatment with poly(adenosine diphosphate-ribose) polymerase inhibitors in ovarian cancer. While genomic assays are the curren...OBJECTIVE: Homologous recombination deficiency is a critical biomarker for guiding first-line treatment with poly(adenosine diphosphate-ribose) polymerase inhibitors in ovarian cancer. While genomic assays are the current standard, they remain costly, time-consuming, and often inaccessible worldwide. With the widespread adoption of whole-slide imaging in pathology, artificial intelligence offers a promising alternative for identifying homologous recombination deficiency directly from routine hematoxylin and eosin-stained slides. METHODS: We developed a fully automated deep-learning pipeline using attention-based multiple-instance learning and pre-trained vision transformers to predict homologous recombination deficiency status from whole-slide images. The model was trained on 257 patients with available homologous recombination deficiency status and validated externally on 468 patients from the PAOLA-1/ENGOT-ov25 phase III trial cohort and 89 patients from The Cancer Genome Atlas database. RESULTS: The model achieved an area under the curve of 0.73 on the internal test sets, 0.69 on The Cancer Genome Atlas cohort, and 0.70 on the PAOLA-1/ENGOT-ov25 phase III trial cohort (0.72 in BRCA wild-type patients), demonstrating strong transferability and generalization. High negative predictive values (up to 0.98) were observed, indicating strong performance in ruling out homologous recombination-proficient cases. Kaplan-Meier survival analyses in the PAOLA-1/ENGOT-ov25 phase III trial cohort demonstrated that artificial intelligence-predicted negative groups showed progression-free survival curves nearly identical to Myriad-defined negative groups, especially among BRCA wild-type patients. CONCLUSIONS: Our results demonstrate that deep learning applied to whole-slide images can predict homologous recombination deficiency status with clinically meaningful accuracy and strong generalization across datasets. The model is particularly effective at identifying homologous recombination-proficient patients and may serve as a valuable tool to support or triage molecular testing. Integrating this artificial intelligence tool into routine pathology workflows could improve diagnostic efficiency, reduce costs, and accelerate access to targeted therapies in ovarian cancer.
Teodorico E, Moro F, Criscione M
… +8 more, Culcasi C, Bizzarri N, Anchora LP, Pasciuto T, Giannarelli D, Fanfani F, Fagotti A, Testa AC
Int J Gynecol Cancer
· 2026 May · PMID 42235121
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OBJECTIVE: To assess the accuracy of ultrasound in identifying residual cervical tumors following conization, using histology as the gold standard. METHODS: This retrospective, single-center study included patients with...OBJECTIVE: To assess the accuracy of ultrasound in identifying residual cervical tumors following conization, using histology as the gold standard. METHODS: This retrospective, single-center study included patients with early-stage cervical cancer (International Federation of Gynecology and Obstetrics IA1-IB1 and early IB2) who underwent conization followed by secondary surgical treatment (re-conization, hysterectomy, or trachelectomy). Patients with locally advanced disease were excluded. All patients underwent trans-vaginal or trans-rectal ultrasound after conization and before definitive surgery between January 2015 and May 2025. Ultrasound findings were classified as follows: a) absence of residual tumor, b) presence of residual tumor, or c) uncertain (suggestive of either residual disease or post-conization artifacts). For statistical analysis, uncertain cases were conservatively considered positive for residual disease. Additionally, a secondary analysis was performed in which "uncertain" cases were classified as negative. Ultrasound results were compared with final histopathology, and diagnostic performance metrics with 95% confidence intervals were calculated. RESULTS: A total of 166 patients were included (mean age, 44.4 ± 9.2 years). Residual tumor was found at final histology in 75 patients (45.2%), while 91 (54.8%) had no residual disease. The median tumor diameter at conization was 9.8 ± 6.2 mm, and the mean interval between conization and ultrasound was 61.2 ± 45.5 days. Ultrasound correctly identified residual tumor in 40/75 cases (53.3%), while false-positive findings occurred in 16/91 patients (17.6%). Uncertain ultrasound findings were reported in 43 cases (25.9%), of which 16 (37.2%) had residual disease at histology. Residual tumors were predominantly hypoechoic and showed moderate (45.0%) or rich (35.0%) vascularization on color Doppler imaging. Ultrasound demonstrated a sensitivity of 74.7% (95% confidence interval 64.8 to 84.5), specificity of 52.7% (95% confidence interval 42.5 to 63.0), and overall accuracy of 62.7% (95% confidence interval 53.1 to 72.2). CONCLUSIONS: This study shows that ultrasound has sub-optimal performance in detecting residual tumor after conization for cervical cancer, indicating that optimal timing and accurate assessment of residual disease remain clinically relevant challenges.
Zhai Z, Wang Y, Zhu A
… +3 more, Wu Y, Wang J, Li X
Int J Gynecol Cancer
· 2026 Apr · PMID 42229119
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OBJECTIVE: This study aimed to establish a predictive model for evaluating the efficacy of fertility-sparing treatment in patients with atypical endometrial hyperplasia or endometrial carcinoma using pre-treatment baseli...OBJECTIVE: This study aimed to establish a predictive model for evaluating the efficacy of fertility-sparing treatment in patients with atypical endometrial hyperplasia or endometrial carcinoma using pre-treatment baseline clinical and pathological indicators. METHODS: A total of 334 patients with atypical endometrial hyperplasia or endometrial carcinoma who received fertility-sparing treatment at Peking University People's Hospital were enrolled and randomly divided into a training cohort (n = 223) and a validation group (n = 111) in a 2:1 ratio. We integrated 10 machine learning algorithms and explored 101 algorithm combinations through leave-one-out cross-validation to develop an immunohistochemistry score model based on estrogen receptor, progesterone receptor, Ki67, and P53. Univariate and multi-variate Cox proportional hazards regression analyses were performed to identify independent risk factors affecting time to complete remission. RESULTS: Elevated fasting insulin (hazard ratio 0.96, 95% confidence interval 0.93 to 0.98, p =.006), elevated total cholesterol (hazard ratio 0.36, 95% confidence interval 0.2 to 0.62, p =.002), higher pathological grade (grade 1 endometrioid carcinoma: hazard ratio 0.34, 95% confidence interval 0.15 to 0.77, p =.009; grade 2 endometrioid carcinoma: hazard ratio 0.29, 95% confidence interval 0.09 to 0.94, p =.038), and high-risk immunohistochemistry score (hazard ratio 0.20, 95% confidence interval 0.09 to 0.46, p =.001) were identified as independent risk factors for delayed complete remission. Incorporation of the immunohistochemistry score significantly enhanced predictive performance (area under the curve 0.782 for model 1, area under the curve 0.840 for model 2, p =.032). CONCLUSIONS: This study concludes that an immunohistochemistry score model, together with identified independent risk factors, including elevated fasting insulin, elevated cholesterol, higher pathological grade, and a high-risk immunohistochemistry score, significantly improves the predictive accuracy of efficacy of fertility-sparing treatment in patients with atypical endometrial hyperplasia or endometrial carcinoma.
Int J Gynecol Cancer
· 2026 May · PMID 42229118
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Achieving the World Health Organization's cervical cancer elimination targets requires high screening coverage and timely follow-up of abnormal results. These functions depend on robust cervical screening registries capa...Achieving the World Health Organization's cervical cancer elimination targets requires high screening coverage and timely follow-up of abnormal results. These functions depend on robust cervical screening registries capable of tracking the full continuum from invitation to testing, triage, management, and outcomes. However, most countries lack such systems; existing registries typically capture cancer incidence rather than screening pathways. The transition to human papillomavirus primary testing, the rapid expansion of self-sampling, and the need to monitor every step of the elimination cascade make modern screening registries essential. However, no global guidance exists on how to design or implement them. This narrative review proposes a comprehensive framework for cervical screening registries suited to contemporary screening strategies. The framework outlines 6 core functions that will further enable evaluation of the screening program, including defining the eligible population; monitoring or issuing invitations and reminders; screening history including human papillomavirus and triage testing; tracking follow-up and management; linking to pathology and cancer registries; and supporting routine quality assurance. A minimal data set is described, covering population records, eligibility, invitations, sample characteristics (including self-sampling), human papillomavirus results, triage investigations, follow-up procedures, and outcomes including cervical intra-epithelial neoplasia grade 2 or worse and interval cancers. The framework also details key implementation principles, including inter-operability across health information systems, digital architecture options, data quality assurance, governance and privacy considerations, and equity-focused strategies for underserved or displaced populations. The framework is adaptable across diverse health-system contexts. Establishing or strengthening cervical screening registries will be essential to support modern human papillomavirus-based screening and accelerate progress toward cervical cancer elimination.
Prost P, Angeles MA, Segier B
… +9 more, Gauroy E, Ricotta G, Del M, Ferron G, Bataillon G, Gladieff L, Cabarrou B, Betrian S, Martinez A
Int J Gynecol Cancer
· 2026 Mar · PMID 42225543
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OBJECTIVE: This study aimed to assess the prognostic impact of celiac lymph node involvement in patients with advanced high-grade serous ovarian cancer. METHODS: We conducted a retrospective, single-center study includin...OBJECTIVE: This study aimed to assess the prognostic impact of celiac lymph node involvement in patients with advanced high-grade serous ovarian cancer. METHODS: We conducted a retrospective, single-center study including patients who underwent celiac lymph node resection during either upfront or interval complete cytoreductive surgery as frontline treatment for advanced high-grade serous ovarian cancer between January 2002 and December 2022. Patients were categorized into 2 groups based on celiac lymph node status. Univariable and multi-variable analyses were performed, and survival rates were estimated using the Kaplan-Meier method. RESULTS: Among 820 patients who underwent cytoreductive surgery for ovarian cancer during the study period, 65 (7.9%) had celiac lymph node resection and were included. Celiac lymph node metastases were identified in 42 (64.6%) cases. Celiac lymph node-positive patients had a higher tumor burden (p =.001), more frequent bowel involvement (p =.026), and higher rates of left hemicolectomy (17.1% vs 0.0%) and inguinal lymphadenectomy (16.7% vs 0.0%). Median overall survival was 30.9 months in the celiac lymph node-positive group and 50.6 months in the celiac lymph node-negative group (p =.270); median disease-free survival was 10.8 and 14.6 months (p =.082), respectively. In multi-variable analysis, celiac lymph node involvement was significantly associated with decreased disease-free survival (hazard ratio 2.87 [1.38 to 5.93], p =.005). CONCLUSIONS: Celiac lymph node involvement is associated with a higher tumor burden and significantly associated with a decrease in disease-free survival in cases of advanced high-grade serous ovarian cancer. These results highlight the need to identify celiac lymph node involvement for better risk stratification.
Int J Gynecol Cancer
· 2026 Apr · PMID 42214817
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The Society of Gynecologic Oncology Annual Meeting on Women's Cancer 2026 represents the leading global scientific forum dedicated to gynecologic malignancies, bringing together multi-disciplinary experts to present cutt...The Society of Gynecologic Oncology Annual Meeting on Women's Cancer 2026 represents the leading global scientific forum dedicated to gynecologic malignancies, bringing together multi-disciplinary experts to present cutting-edge research, clinical trials, and evolving standards of care. The 2026 meeting, centered on the theme "Advancing Science. Empowering Teams. Embracing Change," provided a comprehensive overview of the current landscape and future directions in gynecologic oncology. This narrative review synthesizes the most impactful data presented at Society of Gynecologic Oncology 2026, prioritizing practice-changing phase III trials, biomarker-driven strategies, and emerging therapeutic approaches across ovarian, endometrial, and cervical cancers.
Int J Gynecol Cancer
· 2026 Apr · PMID 42202504
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OBJECTIVE: The reliability of phase II results informing phase III outcomes has been inconsistent across multiple tumor treatment settings. We aim to quantify the magnitude of treatment effect attenuation between phase I...OBJECTIVE: The reliability of phase II results informing phase III outcomes has been inconsistent across multiple tumor treatment settings. We aim to quantify the magnitude of treatment effect attenuation between phase II and III gynecologic oncology trials. METHODS: We systematically identified phase III gynecologic cancer trials published between 2010 and 2025 through ClinicalTrials.gov. Each phase III study was paired with its preceding phase II trial evaluating the same intervention. Study demographics, design, and efficacy outcomes were extracted. Correlations between phase II and phase III progression-free survival and overall survival were assessed using Spearman's rank coefficients, and directional differences were compared with paired and non-parametric tests. RESULTS: Of 221 screened phase III trials, 25 matched phase II-phase III pairs were included. The median progression-free survival data were 11.3 months (inter-quartile range; 6.1-16.8) in phase III versus 7.2 months (inter-quartile range; 4.1-13.2) in phase II (p =.11). Progression-free survival data values were correlated (ρ = 0.59, p =.005). Phase III superior pairs (n = 13) had a median gain of 4.6 months (inter-quartile range; 2.2-9.4) versus 2.3 months (inter-quartile range; 0.5-9.8) for phase II superior pairs. The median overall survival was 20.4 months (inter-quartile range; 13.2-38.2) versus 14.9 months (inter-quartile range; 10.8-21.3) (p =.06); overall survival values were correlated (ρ = 0.57, p =.002). The median overall survival gain was 5.9 months (inter-quartile range; 2.7-17.0) for phase III superior versus 3.2 months (inter-quartile range; 2.8-3.5) for phase II superior pairs (p =.022). The hazard ratios for progression-free survival and overall survival did not differ significantly between phases and were not correlated. CONCLUSIONS: Phase II and phase III gynecologic oncology trials demonstrate moderate concordance of progression-free and overall survival, without systematic inflation of early-phase effect estimates. Greater use of randomized phase II designs and improved demographic reporting may enhance translational validity.