The role of systematic pelvic and para-aortic lymphadenectomy in presumed early-stage ovarian cancer remains controversial due to the lack of high-quality prospective evidence. No therapeutic benefit has been confirmed for systematic lymphadenectomy during surgical staging for apparent early-stage ovarian cancer. Lymphadenectomy may improve progression-free survival but has demonstrated no impact on overall survival, except for clear cell ovarian cancer, where a potential survival benefit has been suggested in retrospective studies. Systematic lymphadenectomy retains a diagnostic role in identifying occult nodal metastases (9% to 30% across series) undetected on pre-operative imaging or intra-operative assessment. The decision to perform lymphadenectomy should be individualized based on several factors, including histological sub-type, tumor grade, stage, and biomarker profile. Key considerations include the anticipated risk of lymph node metastasis, the opportunity to tailor adjuvant treatment by either omitting chemotherapy or offering maintenance targeted therapy, peri-operative morbidity, long-term sequelae impacting quality of life (eg, lower limb lymphedema), and cost-effectiveness. Systematic lymphadenectomy is guideline-recommended for high-grade tumors, including high-grade serous, high-grade endometrioid, and clear cell histologies, whereas it can be omitted in low-grade endometrioid and expansile mucinous sub-types. Its significance in low-grade serous and infiltrative mucinous ovarian cancers remains unclear, although guidelines frequently advocate for lymphadenectomy in these cases. To optimize patient selection, large-scale prospective studies with proper stratification by histotype and molecular profile are required. Emerging approaches to lymph node assessment, such as sentinel lymph node biopsy, artificial intelligence-assisted pre-operative imaging, and liquid biopsy, hold promise for improving staging accuracy.

Objective: Single-port robotic surgery is an emerging technology in Europe, offering potential advantages for minimally invasive gynecologic procedures. However, its application in gynecologic oncology remains limited, and evidence regarding its feasibility, safety, and technical challenges is scarce. This study aimed to prospectively evaluate the feasibility and safety of single-port robotic surgery in gynecologic oncology within a high-volume referral center. Methods: We conducted a prospective cohort study of all consecutive patients who underwent a single-port robotic approach for suspected or confirmed gynecologic cancer at the European Institute of Oncology, Milan, between July 2024 and June 2025. Surgical procedures were performed by a dedicated gynecologic oncology team following international guidelines. Patient demographics, intra-operative characteristics, and postoperative outcomes were prospectively collected. Results: A total of 63 patients were included, with a median age of 57 years (inter-quartile range, [IQR]; 46-65) and a median body mass index of 24.4 kg/m2 (IQR; 22.0-27.3). Endometrial cancer was the most common indication (47.6%). All procedures were completed without conversion to multi-port or open surgery. Median operative time was 131 minutes (IQR; 105-155), and median estimated blood loss was 50 mL (IQR; 30-100). No intra-operative complications occurred. Post-operative pain was minimal, with median Numerical Rating Scale scores of 1 at all assessed time points. The median hospital stay was 2 days (IQR; 2-2). Three major post-operative complications occurred within 30 days (4.8%), all managed surgically: 2 pelvic hematomas and 1 pelvic abscess. Conclusions: Single-port robotic surgery appears feasible and safe for selected patients with gynecologic malignancies, with no conversions and no intra-operative complications. However, larger, multi-institutional studies with longer follow-up are needed to confirm oncologic safety and define its role in practice.

Purpose. High-grade serous ovarian carcinoma (HGSOC) is characterized by pronounced biological and spatial heterogeneity and is frequently diagnosed at an advanced stage. Neoadjuvant chemotherapy (NACT) followed by delayed primary surgery is commonly employed in patients unsuitable for primary cytoreduction. The Chemotherapy Response Score (CRS) is a validated histopathological biomarker of response to NACT, but it is only available postoperatively. In this study, we investigate whether pre-treatment computed tomography (CT) imaging and clinical data can be used to predict CRS as an investigational decision-support adjunct to inform multidisciplinary team (MDT) discussions regarding expected treatment response. Methods. We proposed a 2.5D multimodal deep learning framework that processes lesion-dense omental slices using a pre-trained Vision Transformer encoder and integrates the resulting visual representations with clinical variables through an intermediate fusion module to predict CRS. Results. Our multimodal model, integrating imaging and clinical data, achieved a ROC-AUC of 0.95 alongside 95

BACKGROUND:Complete gross resection (CGR) a key determinant of survival in advanced ovarian cancer (AOC). Preoperative imaging is used to predict residual disease (RD) and surgical complexity in the primary setting, but its performance after neoadjuvant chemotherapy (NACT) remains unclear. We evaluated the ability of computed tomography (CT)-based models in predicting RD and surgical complexity at interval debulking surgery (IDS). METHODS:This multicentre retrospective cohort study included 246 patients with FIGO stage IIIC-IV AOC undergoing NACT-IDS between 2016 and 2021. The Memorial Sloan Kettering (MSK) CT-based predictive model for RD was applied and recalibrated. Pre- and post-NACT CT scans were independently reviewed by six radiologists for 18 predefined disease sites. Logistic regression identified radiologic and clinical predictors of RD and advanced surgical procedures. RESULTS:CGR was achieved in 61% of patients; 35% had ≤1 cm RD, and 4% had >1 cm. The MSK model demonstrated limited discrimination for RD in the IDS setting (c-statistic 0.670). A revised model incorporating optimized age, CA-125 thresholds together with selected radiologic features improved discrimination (c-statistic 0.711). A model predicting the need for advanced surgical procedures achieved moderate performance (c-statistic 0.736). Subcapsular and perihepatic lesions were associated with diaphragm procedures; however absence on CT imaging did not preclude diaphragmatic stripping. CONCLUSIONS:MSK algorithm demonstrated limited discrimination in predicting CGR during IDS. A revised model incorporating optimized age and CA-125 thresholds improved performance. While specific CT findings may help anticipate the need for targeted surgical techniques and multidisciplinary involvement, their absence does not preclude the need for such procedures.

Objective To develop a three-dimensional deep learning model using preoperative computed tomography (CT) images to predict optimal cytoreduction in patients with advanced-stage epithelial ovarian cancer. Methods This retrospective study included patients with advanced epithelial ovarian cancer who underwent an upfront cytoreductive attempt at the European Institute of Oncology (2015-2023). Patients were classified according to their cytoreduction outcome: an optimal cytoreduction cohort including patients with residual tumor ≤10 mm, and a suboptimal cytoreduction cohort including patients with residual tumor >10 mm, using random selection to achieve 1:1 enrollment. OvSeg, an AI-based algorithm for automatic tumor segmentation, was used to obtain lesion contours on preoperative abdomen-pelvis CT scans. Data augmentation, consisting of minor image transformation (rotations, zooming, translations), was applied to enrich data variability and model generalizability. A three-dimensional ResNet-10 deep learning model was trained and tested on pre-processed and segmented images; performance was evaluated using a 5-fold cross-validation approach. Results A total of 218 patients were included, 109 in each cohort. The classification model yielded a median accuracy of 77% [55-86], sensitivity of 73% [73-73], specificity of 73% [45-82], an F1 score of 76% [62-84], positive predicted value of 79% [54-80], and negative predicted value of 75% [57-79], and ROC-AUC of 77% [58-86] in the 5-fold cross-validation test set. Conclusions This preliminary study supports the feasibility of using preoperative CT scans and automated tumor segmentation within a three-dimensional deep learning framework to estimate the likelihood of optimal cytoreduction in patients with advanced ovarian cancer. Further model development and external validation are required before clinical implementation.

OBJECTIVE:Patients with advanced ovarian cancer receiving neoadjuvant chemotherapy are at increased risk of venous thromboembolism, although the reported incidence, risk factors, and its impact on the timing of interval debulking surgery remain heterogeneous. This study evaluates the rate and predictors of venous thromboembolism during neoadjuvant chemotherapy, its effect on surgical timing, and contextualizes the findings through a targeted narrative review of the literature. METHODS:We conducted a retrospective cohort study of patients with International Federation of Gynecology and Obstetrics stage III-IV epithelial ovarian cancer treated with neoadjuvant chemotherapy followed by interval debulking surgery at the European Institute of Oncology between January 2014 and December 2023. Routine thromboprophylaxis was not administered. Clinicopathologic data were collected, and logistic regression analyses were performed to identify predictors of venous thromboembolism and delayed surgery, defined as receiving ≥5 cycles of neoadjuvant chemotherapy prior to surgery. A targeted narrative review of PubMed (2012-2025) summarized venous thromboembolism rates and associated risk factors. RESULTS:Among 694 patients, 32 (4.6%) developed venous thromboembolism during neoadjuvant chemotherapy, including 23 deep vein thromboses (71.9%) and 9 pulmonary embolisms (28.1%). No baseline clinical or pathological factors predicted thromboembolism. However, it was independently associated with surgical delay; affected patients were more than twice as likely to undergo surgery after ≥5 cycles of chemotherapy (adjusted odds ratio 2.15, 95% confidence interval 1.04 to 4.43, p =.04). CONCLUSIONS:Venous thromboembolism during neoadjuvant chemotherapy is relatively uncommon but clinically relevant, as it delays surgery. Early detection and preventive strategies may mitigate its impact in this high-risk population.

In advanced ovarian cancer, complete cytoreductive surgery is a cornerstone of treatment, yet defining which patients are "fit for surgery" remains challenging. Although guidelines emphasize comprehensive pre-operative evaluation, standardized assessment tools are lacking, and clinical practices vary widely across institutions. This narrative review synthesizes current evidence on individual patient-related factors that influence surgical fitness, reviews risk-assessment algorithms designed to guide patient selection, and examines the emerging role of pre-habilitation in optimizing perioperative outcomes. A structured literature search of MEDLINE, Embase, and Cochrane databases (January 2004-September 2024), supplemented by targeted PubMed searches (January 2005-April 2025), identified studies evaluating aging, comorbidity, frailty, nutrition, sarcopenia, and pre-habilitation in relation to surgical outcomes. Eligible studies included systematic reviews, randomized controlled trials, and prospective or retrospective cohorts of patients undergoing primary or interval cytoreduction. After application of the inclusion criteria, 33 studies encompassing 41,580 patients were included. The evidence consistently demonstrates that older age (particularly ≥80 years), frailty, comorbidity burden, and malnutrition are associated with increased post-operative complications and mortality following cytoreductive surgery. Several predictive models and nomograms integrating these factors have been developed to estimate perioperative risk, though most lack multi-center external validation. Implementation of an evidence-based triage algorithm that incorporates key patient characteristics and anticipated surgical complexity has been associated with meaningful reductions in post-operative mortality in institutional practice. Emerging data on multi-modal pre-habilitation suggest feasibility and potential benefits, including lower complication rates, shorter hospital stays, and earlier initiation of chemotherapy, though evidence remains preliminary. Current evidence on surgical fitness in ovarian cancer is limited by heterogeneous definitions, retrospective study designs, lack of prospective validation, and inconsistent reliance on clinical judgment alone. Standardized, externally validated tools, consensus-based thresholds for surgical candidacy, and results from ongoing randomized pre-habilitation trials are needed to guide clinical decision-making and improve patient outcomes.

Ovarian cancer is the most lethal gynecologic malignancy: around 60

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.

Ovarian cancer is frequently diagnosed at an advanced stage, making preoperative contrast-enhanced computed tomography (CT) central to staging and surgical planning; yet the scarcity of annotated imaging data, compounded by privacy regulations, limits the development of generalizable computational models in this domain. Text-conditioned 3D CT synthesis has shown promise, but existing pipelines depend on paired radiology reports and have been evaluated only on chest CT. We propose OvESyn (Ovarian Evidence-based Synthesis), a framework that constructs standardized Findings and Impression sections directly from CT-derived imaging descriptors and routine clinical metadata, without any original radiology report, and uses them to condition a latent diffusion model adapted to 493 high-grade serous ovarian carcinoma patients. This is the first text-conditioned 3D CT synthesis framework adapted to an abdomino-pelvic oncologic setting. A systematic ablation over two adaptation axes, vision-language encoder alignment and generator fine-tuning, identifies generator domain adaptation as the operative mechanism for crossing the domain gap and establishing the target anatomy: without it, synthesis remains anchored to the thoracic pretraining domain, with Precision and Recall collapsing to zero and FID2.5D exceeding 140, regardless of encoder alignment. Encoder alignment instead refines intensity and fine detail. The full OvESyn attains the best distributional and intensity fidelity (FID2.5D 29.35, Precision 0.671, Wasserstein-1 0.044), while the generator-only variant maximizes coverage (Recall 0.645), reflecting a fidelity/coverage trade-off governed by encoder adaptation. Requiring only automatic segmentations and routine preoperative metadata, OvESyn supports transferability to report-scarce settings and provides a foundation for synthetic cohort generation in abdomino-pelvic oncologic imaging.

OBJECTIVE:To evaluate the effect of secondary cytoreductive surgery on survival outcomes in patients with ovarian cancer recurring more than 6 months after first-line therapy, treated at specialized high-volume centers. METHODS:Exploratory data analysis of prospective registries from 5 cancer centers in Europe and the USA (2004-2022). Patients with a first recurrence of any epithelial ovarian cancer >6 months following first-line chemotherapy were eligible. To minimize selection bias, all eligible patients who received any anti-cancer treatment were evaluated. Overall and progression-free survival were calculated from the date of recurrence. All statistical tests were 2-sided. RESULTS:Of 3109 included patients, 38.7% underwent secondary cytoreduction; 83.6% achieved complete clearance. Mean and median platinum-free intervals were 33 and 23 months, respectively (range; 6-300). All 3 scores (Arbeitsgemeinschaft Gynäkologische Onkologie, iMODEL, and Memorial Sloan Kettering criteria) had similar predictive values for complete clearance. Median overall survival was 81 months (95% confidence interval 73 to 88) after complete clearance versus 39 months (95% confidence interval 33 to 44) with residual disease (p <.001). Median overall survival with chemotherapy alone was 34 months (95% confidence interval 33 to 36). BRCA1/2 mutations were associated with significantly improved progression-free survival after secondary cytoreduction (27.4 vs. 21.3 months, p <.0021) but not overall survival and did not retain their effect in the complete gross resection cohort. Timing of initial cytoreduction did not significantly affect the benefit of secondary cytoreduction. Median overall survival without previous maintenance therapy was 73 months (95% confidence interval 65 to 79) versus 55 months (95% confidence interval 47 to 63) after previous bevacizumab versus 44 months (95% confidence interval 32 to 56) after previous poly(adenosine diphosphate-ribose) polymerase inhibitors (p =.0056). Unifocal relapse, platinum-free interval > 16 months, age < 75 years, CA125 < 105 U/mL, Eastern Cooperative Oncology Group performance status 0, initial International Federation of Gynecology and Obstetrics-stage I/II, <500 mL ascites, non-mucinous histologies, and complete gross resection were associated with significantly improved overall survival post-secondary cytoreduction. CONCLUSIONS:Secondary cytoreductive surgery performed at specialized high-volume centers was associated with substantially prolonged overall survival compared with chemotherapy alone, particularly when complete gross resection was achieved. Neither BRCA status nor timing of initial cytoreduction significantly influenced this benefit, whereas prior maintenance therapy with poly(adenosine diphosphate-ribose) polymerase inhibitors and/or bevacizumab was associated with shorter overall survival after surgery.

OBJECTIVE:To evaluate whether the use of indocyanine green fluorescence angiography was associated with a reduced risk of anastomotic leak after rectosigmoid resection in patients undergoing cytoreductive surgery for International Federation of Gynecology and Obstetrics stage III to IV epithelial ovarian cancer. METHODS:We performed a single-center retrospective cohort study of consecutive patients with stage III to IV epithelial ovarian, fallopian tube, or primary peritoneal cancer who underwent primary or interval cytoreductive surgery with rectosigmoid resection and anastomosis between January 2009 and December 2023. Patients treated from 2020-2023 underwent indocyanine green fluorescence angiography in addition to conventional perfusion assessment; those treated from 2009-2019 underwent conventional perfusion assessment (visual inspection of anastomotic tension and intraoperative air leak testing) alone. Multivariable logistic regressions were used to identify predictors of anastomotic leak. RESULTS:Among 795 patients included, 556 (70.0%) underwent surgery before indocyanine green fluorescence angiography adoption and 239 (30.0%) after. Overall, 45 patients (5.7%) developed an anastomotic leak. Leak rates were significantly lower in the indocyanine green fluorescence angiography group compared with the group without indocyanine green fluorescence angiography (2.5% vs 7.0%; p =.01). In multivariable analysis, use of indocyanine green fluorescence angiography was independently associated with a lower risk of anastomotic leak (odds ratio 0.37, 95% confidence interval 0.14 to 0.83, p =.03). CONCLUSIONS:In this retrospective cohort study of patients undergoing cytoreductive surgery for stage III to IV ovarian cancer, use of indocyanine green fluorescence angiography was independently associated with a significantly lower rate of rectosigmoid anastomotic leak compared with conventional assessment. These findings support the use of indocyanine green fluorescence angiography as an adjunct intraoperative tool to reduce the risk of anastomotic leak.

OBJECTIVE:Homologous recombination deficiency predicts response to platinum-based chemotherapy and poly(adenosine diphosphate-ribose) polymerase inhibitors in advanced high-grade serous ovarian carcinoma. However, the optimal timing of homologous recombination deficiency testing remains unclear for patients receiving neoadjuvant chemotherapy, as it may affect test informativity and results. We evaluated the concordance of genomic and functional homologous recombination deficiency testing before and after neoadjuvant chemotherapy in patients with high-grade serous ovarian carcinoma. METHODS:Matched tumor samples collected before and after neoadjuvant chemotherapy from patients with high-grade serous ovarian carcinoma treated at the European Institute of Oncology (Milan, Italy, July 2018-December 2021) were analyzed. Genomic homologous recombination deficiency assessment included the Genomic Instability Score and tumor BRCA1/2 mutation testing using SOPHiA DDM Homologous Recombination Deficiency Solution. Functional homologous recombination deficiency assessment was performed through RAD51 foci formation immunofluorescence. Cohen's kappa coefficients (κ) assessed genomic and functional homologous recombination deficiency testing concordance for matched pre- versus post-neoadjuvant chemotherapy results, and functional versus genomic homologous recombination deficiency testing concordance at all time points. RESULTS:Samples collected before and after neoadjuvant chemotherapy from 23 patients with high-grade serous ovarian carcinoma were analyzed. Homologous recombination deficiency informativity was higher before neoadjuvant chemotherapy (87%, 20/23) than in samples collected afterward (65%, 15/23), whereas Genomic Instability Score informativity was 91% (21/23) and 78% (18/23), respectively. Concordance of the Genomic Instability Score was moderate (κ = 0.52), while homologous recombination deficiency concordance was substantial (κ = 0.67) in matched samples collected before and after neoadjuvant chemotherapy. Two of 15 matched informative samples (13%) lost Genomic Instability Score positivity after chemotherapy, but their homologous recombination deficiency test remained positive due to BRCA mutations. Functional homologous recombination deficiency assessment showed poor concordance between time points and with homologous recombination deficiency testing at each time point. CONCLUSIONS:Genomic homologous recombination deficiency tests were concordant in matched tumor samples collected before and after neoadjuvant chemotherapy for high-grade serous ovarian carcinoma, but tissue collection before chemotherapy should be prioritized due to higher informativity. Loss of informativity may result in missed opportunities for poly(adenosine diphosphate-ribose) polymerase inhibitor therapy.