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Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10-8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

Background: Endometriosis is known to be a common chronic disease that often affects the quality of life of patients. Especially for deep endometriosis (DE), the most challenging form of the disease, surgery remains an important component of treatment. However, long-term outcomes after surgery are poorly studied. Therefore, we aimed to evaluate the postoperative clinical course of women with DE who underwent surgery, particularly with regard to pain relief, fertility, and re-operations. Methods: Thus, women who underwent surgical treatment for DE between 2005 and 2015 were included in this retrospective questionnaire-based analysis. Results: A total of 87.0% of the patients who underwent surgery for pain reported a postoperative relief of their complaints. Moreover, 44.6% even stated that they were free of pain at the time of the questionnaire. Patients who underwent surgery for infertility and tried to become pregnant postoperatively gave birth to a child in 45.9% of cases. Approximately one-third of the patients had to undergo another surgery because of endometriosis-related symptoms. The main reasons for re-operation were pain and infertility. The median time to re-operation was 2.1 years. Conclusions: In this extraordinarily long follow-up with a remarkable response rate, we show that surgical treatment of DE leads to pain relief and improved fertility in most cases. However, the risk of recurrence and the need for re-operation remains remarkable. [ABSTRACT FROM AUTHOR]

Background: Until now, limited clinical significance had been reported for disseminated tumor cells (DTCs) in gynecologic malignancies. DTCs were previously reported not to be associated with established risk factors, L1CAM immunoreactivity, and outcome in endometrial carcinoma (EC). This study's primary objective was to investigate potential correlations of DTCs in the bone marrow (BM) of EC patients with disease-related survival, and a secondary objective was to evaluate associations between molecular classification of EC and DTCs. Methods: Patients treated for primary EC at Tuebingen University women's hospital between 2003 and 2016 were identified. A total of 402 patients with a complete set of BM cytology, molecular, and clinical data were evaluable. Results: DTC occurrence was distributed equally among all four molecular groups (p = 0.651). DTC positivity was associated with a less favorable disease-free survival (HR: 1.86, 95% CI: 1.03–3.36, p = 0.036) and progression-free survival (HR: 1.86, 95% CI: 1.01–3.44, p = 0.045). Presence of DTCs was associated with a higher frequency of distant disease recurrence (p = 0.017). Conclusions: In line with our previous findings, tumor cell dissemination is not associated with molecular features in our large cohort of primary EC patients. Since DTCs seem to be associated with survival and location of disease recurrence, further studies are needed to decisively define their role in EC survival. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) has four molecular subtypes with strong prognostic value and therapeutic implications. The most common subtype (NSMP; No Specific Molecular Profile) is assigned after exclusion of the defining features of the other three molecular subtypes and includes patients with heterogeneous clinical outcomes. In this study, we employ artificial intelligence (AI)-powered histopathology image analysis to differentiate between p53abn and NSMP EC subtypes and consequently identify a sub-group of NSMP EC patients that has markedly inferior progression-free and disease-specific survival (termed 'p53abn-like NSMP'), in a discovery cohort of 368 patients and two independent validation cohorts of 290 and 614 from other centers. Shallow whole genome sequencing reveals a higher burden of copy number abnormalities in the 'p53abn-like NSMP' group compared to NSMP, suggesting that this group is biologically distinct compared to other NSMP ECs. Our work demonstrates the power of AI to detect prognostically different and otherwise unrecognizable subsets of EC where conventional and standard molecular or pathologic criteria fall short, refining image-based tumor classification. This study's findings are applicable exclusively to females. Endometrial cancer (EC) has four molecular subtypes; of these, the No Specific Molecular Profile (NSMP) subtype encompasses patients with heterogeneous outcomes. Here, the authors use artificial intelligence and histopathology images to differentiate p53abn and NSMP subtypes in EC, and identify one distinct subgroup within NSMP with unfavourable outcome. [ABSTRACT FROM AUTHOR]

Purpose: Simple hysterectomy and pelvic node assessment (SHAPE) is a phase III randomized trial (ClinicalTrials.gov identifier: NCT01658930) reporting noninferiority of simple compared with radical hysterectomy for oncologic outcomes in low-risk cervical cancer. This study presents secondary outcomes of sexual health and quality of life (QOL) of the SHAPE trial., Methods: Participants were randomly assigned to receive either radical or simple hysterectomy. Sexual health was assessed up to 36 months postoperatively using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised and QOL using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Cervical Cancer-Specific Module (QLQ-CX24) questionnaires., Results: Among participants with at least one QOL measure, clinical and pathologic characteristics were balanced and with no differences in preoperative baseline scores for sexual health or QOL between groups. FSFI total score met the cutoff for dysfunction up to 6 months ( P = .02) in the radical hysterectomy group. Group differences favored simple hysterectomy for FSFI subscales: desire and arousal at 3 months ( P ≤ .001) and pain and lubrication up to 12 months ( P ≤ .018). Both groups met the cutoff for sexual distress but was higher in radical hysterectomy at 3 months ( P = .018). For QLQ-CX24, symptom experience was significantly better up to 24 months ( P = .031) and body image better at 3, 24, and 36 months ( P ≤ .01) for simple hysterectomy. Sexual-vaginal functioning was significantly better up to 24 months ( P ≤ .022) and more sexual activity up to 36 months ( P = .024) in the simple hysterectomy arm. Global health status was significantly higher at 36 months for simple hysterectomy ( P = .025)., Conclusion: Simple hysterectomy was associated with lower rates of sexual dysfunction than radical hysterectomy, with a lower proportion of women having sustained sexual-vaginal dysfunction. These results further support the benefit of surgical de-escalation for low-risk cervical cancer.

Purpose: To evaluate atezolizumab combined with platinum-based chemotherapy (CT) followed by maintenance niraparib for late-relapsing recurrent ovarian cancer., Methods: The multicenter placebo-controlled double-blind randomized phase III ENGOT-OV41/GEICO 69-O/ANITA trial (ClinicalTrials.gov identifier: NCT03598270) enrolled patients with measurable high-grade serous, endometrioid, or undifferentiated recurrent ovarian cancer who had received one or two previous CT lines (most recent including platinum) and had a treatment-free interval since last platinum (TFIp) of >6 months. Patients were stratified by investigator-selected carboplatin doublet, TFIp, BRCA status, and PD-L1 status in de novo biopsy and randomly assigned 1:1 to receive either atezolizumab or placebo throughout standard therapy comprising six cycles of a carboplatin doublet followed (in patients with response/stable disease) by maintenance niraparib until progression. The primary end point was investigator-assessed progression-free survival (PFS) per RECIST v1.1., Results: Between November 2018 and January 2022, 417 patients were randomly assigned (15% BRCA- mutated, 36% PD-L1-positive, 66% TFIp >12 months, 11% previous poly [ADP-ribose] polymerase inhibitor after frontline CT, and 53% previous bevacizumab). Median follow-up was 28.6 months (95% CI, 26.6 to 30.5 months). Atezolizumab did not significantly improve PFS (hazard ratio, 0.89 [95% CI, 0.71 to 1.10]; P = .28). Median PFS was 11.2 months (95% CI, 10.1 to 12.1 months) with atezolizumab versus 10.1 months (95% CI, 9.2 to 11.2 months) with standard therapy. Subgroup analyses generally showed consistent results, including analyses by PD-L1 status. The objective response rate (ORR) was 45% (95% CI, 39 to 52) with atezolizumab and 43% (95% CI, 36 to 49) with standard therapy. The safety profile was as expected from previous experience of these drugs., Conclusion: Combining atezolizumab with CT and maintenance niraparib for late-relapsing recurrent ovarian cancer did not significantly improve PFS or the ORR.

Introduction: Fertility-sparing treatment (FST) for patients with cervical cancer intends to achieve oncologic outcomes comparable to those after radical treatment while maximizing reproductive outcomes, including the ability to conceive and minimizing the risk of prematurity., Methodology: International multicentre retrospective FERTISS study focused on patients treated with FST analysed timing of FST relative to pregnancy, conception attempts and methods, abortion rates, prophylactic procedures reducing the risk of severe prematurity, pregnancy duration, and delivery mode., Results: Of the 733 patients treated at 44 centres in 13 countries, 49.7% attempted to conceive during median follow-up of 72 months and 22.6% (166/733) patients achieved a successful pregnancy. Success rate was significantly higher after non-radical surgery (63.2%; 122/193) compared to radical trachelectomy (25.7%; 44/171, p < 0.001). Available perinatological data shows that 89.5% (111/124) of the patients became pregnant naturally. There was no significant difference in the abortion rate in the first pregnancy nor delivery success rates between non-radical and radical procedures patients. Preterm delivery (<38 weeks gestation) occurred more frequently after radical than non-radical procedures (76.5% vs. 57.7%, p = 0.15). Almost all patients (97.3%; 73/75) who underwent regular ultrasound cervicometry in pregnancy with subsequent prophylactic procedures delivered a live fetus, compared to 30.6% (15/49) women without such management, p < 0.001., Conclusion: Patients who underwent non-radical surgery had significantly higher pregnancy rates. Most pregnancies resulted in a viable fetus, but radical trachelectomy led to a higher rate of preterm births in the severe prematurity range. Half of the patients did not attempt pregnancy after FST., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)