Search Results (70)

Objectives: Platinum resistance remains a critical bottleneck in ovarian cancer management, yet reliable pre-treatment predictive tools are lacking. Existing markers like the platinum-free interval are retrospective, while genomic profiling is often cost-prohibitive. This study aimed to develop an accessible, machine learning-based dynamic weighted fusion (DWF) model using routine laboratory data to provide bidirectional risk stratification, particularly to reliably rule out platinum resistance before treatment initiation. Methods: In this retrospective study (2019–2023), seventy baseline clinical features were collected to differentiate platinum-resistant from platinum-sensitive ovarian cancer patients. We developed a DWF framework that dynamically integrates the top-performing classifiers from a library of 168 algorithms (combining 14 feature selection and 12 machine learning methods). Class imbalance was addressed via oversampling, and model efficacy was evaluated using area under the curve (AUC), accuracy, sensitivity, and specificity. Results: The DWF model achieved a robust AUC of 0.760 (95% CI: 0.683–0.837), outperforming all individual base classifiers. Subgroup analysis demonstrated highly consistent overall discrimination across initial treatment strategies (AUC of 0.755 for primary debulking surgery and 0.761 for neoadjuvant chemotherapy). Feature interpretation highlighted that resistance is driven by synergistic dysregulation of systemic inflammation and hypercoagulability, rather than single biomarkers. Conclusions: The proposed DWF model effectively leverages low-cost, standardized clinical data to serve as a robust bidirectional stratification tool. Its exceptional ability to rule out resistance provides clinicians with the evidence-based confidence to proceed with standard therapies, while its high-risk alerts identify candidates for early therapeutic adjustments and enhanced surveillance in ovarian cancer care. Full article

Background: With an ongoing debate concerning the optimal timing of advanced ovarian cancer surgical treatment, primary debulking surgery (PDS) versus neoadjuvant chemotherapy followed by interval debulking surgery (IDS), this study aimed to compare survival outcomes between PDS and IDS populations and evaluate prognostic factors in a real-world cohort of patients treated with first-line chemotherapy and bevacizumab. Methods: A retrospective multi-center study was conducted involving 369 patients with newly diagnosed advanced ovarian cancer. Patient data included demographics, histology, treatment details, chemotherapy response, and survival outcomes. Kaplan–Meier estimates with log-rank tests were used for univariate analyses, as well as Cox proportional hazard models for multivariate analyses. Results: Patients undergoing IDS were older (62.5 vs. 60.0 years), had higher pretreatment CA-125 (1846 vs. 395.6 IU/mL), an increased proportion were at with stage IV (36.25% vs. 21.10%), and they received fewer bevacizumab cycles (12 vs. 18) compared to those undergoing PDS. Median progression-free survival (PFS) was 18.6 months (95% CI: 17.3–20.2) and overall survival (OS) was 45.4 months (95% CI: 41.1–52.1). Multivariate analysis confirmed poor chemotherapy response (HR 1.80, 95% CI: 1.36–2.37; p < 0.0001) and IDS (HR 1.65, 95% CI: 1.37–2.39; p < 0.0001) as independent predictors of shorter PFS. For OS, independent risk factors were age > 70 (HR 1.62; p = 0.0202), poor response (HR 2.03; p < 0.0001), and IDS (HR 1.75; p = 0.0006). Conclusions: In this real-world cohort treated with first-line chemotherapy and bevacizumab, interval debulking surgery was associated with inferior progression-free and overall survival compared with primary debulking surgery. However, these findings reflect a high-risk population and are strongly influenced by patient selection and treatment pathways, underscoring the need for cautious interpretation. Full article

Epithelial ovarian cancer is predominantly characterized by peritoneal dissemination, providing a strong biological rationale for intraperitoneal (IP) chemotherapy. Although IP cisplatin-based regimens have demonstrated substantial survival benefits in pivotal randomized trials, toxicity and catheter-related complications limit their widespread adoption. IP carboplatin has emerged as a pragmatic alternative with improved tolerability while preserving its pharmacokinetic advantages. This review summarizes the biological and pharmacological rationale for IP carboplatin and critically examines the clinical evidence, with a particular emphasis on the Intraperitoneal Carboplatin for Ovarian Cancer (iPocc) trial and its divergence from Gynecologic Oncology Group (GOG)-252. We further discuss the potential applicability of IP carboplatin beyond the traditional setting of minimal residual disease, including patients undergoing neoadjuvant chemotherapy and interval debulking surgery, as well as its possible use in the contemporary era of maintenance therapy. Collectively, the accumulated evidence supports renewed consideration of IP carboplatin as a versatile component in modern ovarian cancer management. Full article

Although standard chemotherapy for three to four cycles followed by surgery is considered safe and effective in the management of advanced ovarian cancer, the impact of extending treatment beyond this period remains uncertain. Some authors suggest that the number of neoadjuvant chemotherapy cycles does not directly affect prognosis and may reflect a confounding bias. Others, however, indicate that a prolonged exposure to chemotherapy can promote the selection of resistant tumor clones, negatively influencing patient survival and disease progression. This review aims to summarize the current evidence on the topic, evaluating the effect of prolonged chemotherapy on surgical cytoreduction and survival. To achieve this, we conducted an analysis of the English-language literature available in PubMed, focusing on treatment duration, achievement of complete surgical resection, survival outcomes, and prognostic factors. Full article

(1) Background: Hudson first described the procedure that includes en-block removal of an ovarian tumor fixed in the pelvis with the whole pelvic peritoneum and invaded surrounding structures. However, sometimes pelvic peritonectomy (PP) with or without shaving of the bowel serosa is not enough to achieve complete cytoreduction, and en-block rectosigmoid resection (RR) is necessary. This study aims to investigate the impact of bowel surgery on survival rates and morbidity of patients with advanced ovarian cancer. (2) Methods: We retrospectively analyzed patients with advanced ovarian cancer with cul-de-sac involvement that underwent debulking surgery at the 1st Department of Obstetrics—Gynecology of “Papageorgiou” General Hospital, from 2017–2022. The primary outcomes were the survival rates and morbidity between PP and RR. (3) Results: A total of 93 patients met the inclusion criteria. Patients were categorized into two groups: Group A (34 patients) with RR and Group B (59 patients) with PP. There was no statistically significant difference in the majority of patients’ characteristics and oncological outcomes. On the other hand, patients with RR had a significantly higher surgical complexity score (SCS), peritoneal cancer index (PCI), ICU admission, rate of postoperative complications, longer surgery duration and hospital stay. When comparing the duration of surgery, the RR group has significantly higher operation time during primary compared to interval debulking surgery. Concerning survival rates, there was no significant difference in progression-free (PFS) (p = 0.22) and overall survival (OS) (p = 0.85) between the two groups, while residual disease and postoperative complications were identified as independent prognostic factors for PFS and OS; (4) Conclusions: The modified Hudson procedure with RR is a safe and reproductible technique, but when complete gross resection can be achieved with PP, this technique is preferred in order to avoid increased patient’s morbidity. Full article

Background: The optimal timing of cytoreductive surgery for advanced high-grade serous carcinoma (HGSC) remains a critical unmet question in the modern era of platinum-based chemotherapy and PARP inhibitor (PARPi) maintenance. To address this gap, we compared outcomes following primary debulking surgery (PDS) versus interval debulking surgery (IDS) in a uniformly treated, contemporary cohort. Methods: Patients with FIGO stage IIIB–IVB HGSC treated between 2019 and 2023 were retrospectively analyzed. Baseline tumor burden was assessed using detailed radiologic and laparoscopic evaluations, including both presurgical and intraoperative assessments. Progression-free survival (PFS) and overall survival (OS) were examined using multivariable Cox proportional hazards models and reported as adjusted hazard ratios (aHRs). Subgroup analyses were rigorously conducted according to residual disease status and BRCA mutation status. Results: Among 221 patients (PDS, n = 60; IDS, n = 151), the median follow-up was 40 months. In the overall cohort, adjusted PFS and OS did not differ significantly between the PDS and IDS groups (PFS: aHR, 1.15; 95%CI, 0.67–1.98; OS: aHR, 1.24; 95%CI, 0.54–2.83). Outcomes were comparable among patients achieving R0 resection. Notably, BRCA-mutated patients demonstrated a substantial survival advantage with PDS (BRCA-mutated PFS: aHR, 3.34; 95%CI, 1.06–16.67; OS: aHR, 6.07; 95%CI, 2.13–∞), whereas BRCA wild-type patients showed no significant difference between surgical strategies. Conclusions: The findings suggest that BRCA-mutated patients may derive a survival benefit from PDS, whereas surgical timing had a limited impact on BRCA wild-type disease. This result underscores the importance of integrating molecular profiling, particularly BRCA mutation status, with surgical assessment to guide optimal and personalized treatment strategies in the PARPi era. Full article

Background/Objectives: This pilot study investigates the feasibility of using patient-derived microtumors (PDMs) to assess chemotherapy response in epithelial ovarian cancer. Methods: Fresh tissue from 10 patients was used to develop PDMs, which were then tested against carboplatin/paclitaxel, carboplatin/docetaxel, and carboplatin/pegylated liposomal doxorubicin (PLD). Of the 10 PDMs, 3 were obtained from primary debulking surgery (PDS), and 7 were obtained at the time of interval debulking surgery following neoadjuvant chemotherapy. Results: When looking at PDMs derived from tissue collected at the time of PDS, we found that 100% of PDMs demonstrated a full response to carboplatin/PLD, while 30% showed a full response to all regimens, all of which were derived from high-grade serous carcinoma during PDS. The remaining PDMs showed moderate responses to carbo/taxol and carbo/doce. Conclusions: This study suggests that PDMs can be used to assess the efficacy of chemotherapy regimens, as a hypothesis-generating step toward future predictive validation. Full article

Background and Objectives: Advanced epithelial ovarian cancer (AEOC) often requires extensive cytoreductive surgery. Minimally invasive surgery (MIS), especially diagnostic laparoscopy, is increasingly used to assess resectability and guide treatment. This review aimed to evaluate the evidence on MIS in AEOC, focusing on its diagnostic and therapeutic roles in primary and interval debulking surgery (PDS and IDS), and its impact on perioperative and oncologic outcomes. Materials and Methods: A structured literature review was performed using PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library, including studies published between January 2000 and June 2025. Eligible studies involved laparoscopic or minimally invasive cytoreduction in PDS or IDS, reporting surgical feasibility, perioperative results, and oncologic outcomes. Data were synthesized qualitatively due to heterogeneity across studies. Results: Observational studies indicate that diagnostic laparoscopy predicts resectability, reduces futile laparotomies, and improves patient selection for primary surgery. In selected patients, non-randomized cohorts of laparoscopic PDS report R0 resection rates up to 95%, with low morbidity and short hospital stays. In IDS after neoadjuvant chemotherapy, MIS has been associated with reduced blood loss, fewer complications, and faster postoperative recovery, while showing progression-free and overall survival comparable to laparotomy in retrospective series. Conversion to open surgery was generally reported in fewer than 10% of cases when stringent selection criteria were applied. Conclusions: Diagnostic laparoscopy is a valuable tool for accurate preoperative evaluation and surgical planning in EOC. MIS, particularly for IDS, appears to offer reduced morbidity and equivalent survival outcomes when performed in experienced centers, whereas its application in PDS remains investigational and should be reserved for highly selected cases. These conclusions are limited by the predominance of retrospective evidence and the heterogeneity in patient selection and surgical expertise. Full article

Background/Objectives: Epithelial ovarian cancer (EOC) is a leading cause of death among forms of gynecologic cancer. Significant causes of mortality include high recurrence rates and the development of resistance to platinum-based chemotherapy. This highlights the need for reliable prognostic biomarkers to improve patient stratification and inform treatment decisions. Claudin-4, a tight junction protein frequently overexpressed in epithelial tumors, has been associated with tumor progression and resistance to chemotherapy. Methods: We retrospectively analyzed 83 patients with EOC who underwent debulking surgery. Claudin-4 expression was assessed by immunohistochemistry and categorized as high or low based on a semi-quantitative scoring system. Survival outcomes were evaluated using Kaplan–Meier analysis and Cox regression. Predictors of platinum resistance were examined using logistic regression. Results: High Claudin-4 expression was observed in 55.4% of cases and was associated with significantly shorter disease-free survival (DFS) (23 vs. 66 months, p = 0.00024) and overall survival (OS) (85 months vs. NR, p = 0.0031). In multivariable analysis, platinum resistance (DFS; HR 4.99, OS; HR 4.27) and high Claudin-4 expression (DFS; HR 2.46, OS; HR 3.59) were independent predictors of poor outcomes. Logistic regression further demonstrated that high Claudin-4 expression and interval debulking surgery were independent predictors of platinum resistance. Conclusions: High Claudin-4 expression was associated with inferior survival and an increased risk of platinum resistance in EOC. Our findings suggest that Claudin-4 may serve as a negative prognostic biomarker and a potential therapeutic target. Future prospective studies are warranted to further elucidate the underlying mechanisms and validate Claudin-4’s clinical utility. Full article

Background/Objectives: This systematic review and meta-analysis evaluates the oncological safety and outcomes of minimally invasive versus open interval debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer, addressing whether laparoscopy represents a safe alternative to the standard open procedure. Methods: The Ovid/Medline, Pubmed, and Cochrane databases were systematically screened for studies investigating surgical resection status and/or patient survival after laparotomy compared to minimally invasive interval debulking surgery for FIGO stage III-IV ovarian cancer. A meta-analysis was performed using a random-effects model and risk of bias was assessed. Results: Overall, 14 observational and randomized studies published between 2015 and 2024 with a total of 16,578 patients (4310 laparoscopy and 12,268 laparotomy) were included. A complete cytoreduction to no visible tumour was achieved significantly more often after minimally invasive surgery compared to laparotomy (RR = 1.12; 95% CI [1.01, 1.23]; p = 0.03). Overall survival showed no significant difference between the two groups (HR = 0.81; 95%CI [0.64, 1.04]); progression-free survival was significantly more common after laparoscopy (HR = 0.67; 95% CI [0.48, 0.94]; p = 0.02; I² = 55%; p = 0.07). Patients undergoing minimally invasive surgery experienced significantly fewer postoperative complications (RR = 0.50; 95% CI [0.33, 0.76]; p ≤ 0.001), a lower mean blood loss (165 mL vs. 325 mL; SMD −0.58, 95% CI [−0.82, −0.35]; p ≤ 0.001), a shorter mean hospital stay (3 days vs. 5 days; SMD −0.79, 95% CI [−1.06, −0.52], p ≤ 0.001), and a faster initiation of adjuvant chemotherapy (mean 25 ± 32 days vs. 33 ± 28 days). Conclusions: This study indicates that laparoscopic interval debulking surgery is an oncologically safe alternative in selected patients with advanced-stage ovarian cancer. However, randomized controlled trials should confirm these findings as certainty of evidence is low and residual confounding cannot be excluded. Trial registration: PROSPERO Identifier CRD42024524725. Full article

Background: Pivotal clinical trials have led to the routine clinical use of PARP inhibitor (PARPi) (olaparib, niraparib, or rucaparib) maintenance therapy in high-grade serous tubo-ovarian and peritoneal cancers. Whether various PARPis have comparable clinical impact in the real-world is an area of ongoing investigation. Methods: We conducted a retrospective study of all patients who received PARPi maintenance therapy at Nottingham Cancer Centre from October 2017 to April 2025. Clinical data were extracted from multidisciplinary team electronic health records, including age, BRCA mutation status, HRD status, treatment history, type of PARP inhibitor received, progression-free survival (PFS), and overall survival (OS). Results: A total of 177 patients had received PARPi therapy with a mean age of 63 years at diagnosis. In all, 94/177 (53.1%) had received PARPi as primary maintenance, while 83/177 (46.9%) were treated in the recurrent setting. All together, 25/177 (14.1%) had BRCA1 germline mutation and 21/177 (11.9%) had BRCA2 germline mutation. In the primary olaparib setting, PFS was significantly better in BRCA2 germline-mutated patients compared to BRCA1 germline-mutated patients [median PFS was not reached vs. 29.0 months, respectively, p = 0.002]. In BRCA, wild-type patients receiving primary niraparib, median PFS was 11 months. Median PFS for patients with upfront surgery was 37 months compared to 19 months in the interval debulking group but not significant (p = 0.49). In the recurrent setting, there was no significant difference in median PFS between niraparib and rucaparib [10 months vs. 9 months, p = 0.594]. Conclusions: BRCA2 germline-mutated patients obtained significantly greater benefit from olaparib compared to BRCA1-mutated patients. PFS benefit from niraparib (primary or recurrent setting) is comparable to clinical trials. There was no difference in benefit between niraparib and rucaparib in the recurrent setting. Full article

Background/Objectives: Patients with advanced ovarian cancer with a high tumor burden typically undergo neoadjuvant chemotherapy (NACT) followed by interval debulking surgery. The optimal number of NACT cycles remains undefined: although three to four cycles are considered gold-standard, in real-world practice, five or more cycles are frequently administrated. This study aims to evaluate the impact of delayed interval debulking surgery (DIDS) after ≥5 cycles of NACT on the survival rates. Methods: We conducted a retrospective analysis of women with advanced ovarian cancer that underwent surgery in the 1st Department of Obstetrics–Gynecology Clinic from 2012 to 2022. Patient characteristics, oncological, and follow-up information were collected. Results: A total of 125 patients met the inclusion criteria and were divided into two groups: Group A (77 patients) received 3–4 of NACT cycles, and Group B (48 patients) ≥5 cycles. No statistically significant difference was observed between the groups concerning age, BMI, comorbidities, Aletti score, FIGO stage, pre-operative CA-125 values, surgery duration, rate of postoperative complications, hospital stay, ICU admittance, and complete gross resection (RD = 0). However, patients undergoing DIDS experienced significantly greater intraoperative blood loss. Progression-free survival did not differ between groups (IDS: 17 vs. DIDS: 18 months, p = 0.561), whereas overall survival was significantly lower in the DIDS group (IDS: 52 vs. DIDS: 36 months, p = 0.00873). This statistical significance persisted after controlling for residual disease, but was lost after adjusting for FIGO stage. Conclusions: DIDS may be considered for advanced ovarian cancer patients with a high tumor burden, when complete gross resection (RD = 0) cannot be achieved during IDS. Further prospective randomized trials are necessary to evaluate its oncological safety and morbidity. Full article

Background/Objectives: To compare oncologic outcomes of second-line chemotherapy regimens in relapsed high-grade serous ovarian cancer (HGSOC) by platinum sensitivity. Methods: We retrospectively reviewed HGSOC patients treated at two centers (June 2003–December 2020), classified by platinum-free interval (6- and 12-month cut-offs). Outcomes were progression-free survival (PFS, primary) and objective response and disease control rates (secondary). Regimens administered to ≥10% of patients or with favorable outcomes were compared using multivariable Cox analyses. Results: Among 468 patients (41.2% sensitive, 32.9% partially sensitive, 25.9% resistant), platinum-sensitive patients were younger (p = 0.024), diagnosed earlier, and more likely to undergo primary debulking surgery (both p < 0.001), achieving best outcomes after second-line chemotherapy (median PFS 14.8 vs. 10.5 and 5.2 months, p < 0.001). In both sensitive groups, the most common regimens were taxane + platinum ± bevacizumab, followed by pegylated liposomal doxorubicin + carboplatin, which was associated with shorter PFS in platinum-sensitive patients (hazard ratio (HR) 1.67, p = 0.016). Second-line maintenance with bevacizumab or poly(ADP-ribose) polymerase inhibitors was associated with improved PFS in both groups (p < 0.001). In platinum-resistant patients, the omission of bevacizumab (HR 2.01, p < 0.001) and a primary treatment history without cytoreduction (HR 4.43, p = 0.044) were associated with inferior outcomes. Conclusions: In platinum-sensitive patients with a favorable prognosis, taxane + platinum regimens were most commonly used and outperformed PLD + carboplatin. Maintenance therapy also conferred a meaningful benefit. In platinum-resistant disease, bevacizumab use and prior cytoreductive surgery may improve outcomes, underscoring the importance of treatment selection and surgical approach. Full article

Given the rising use of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in advanced epithelial ovarian cancer (EOC), we sought to assess practice trends in overall survival (OS), complete gross resection (R0), and postoperative mortality following debulking surgery. The National Cancer Database (NCDB) was used to identify 34,982 stage IIIC and IV EOC patients between 2010 and 2017 who underwent surgery. Annual proportions of patients receiving IDS and PDS were calculated. Median OS was estimated using the Kaplan–Meier method. Joinpoint models were fitted to evaluate surgical trends. Statistics were performed using SPSS and Joinpoint. Of 34,982 patients, 10,460 (29.9%) underwent IDS. IDS patients were older, more likely to have stage IV disease, and more likely to be non-White. Median OS was higher in the PDS group (54 vs. 38.8 months, p < 0.001). Postoperative 90-day mortality was lower in the PDS group (1.7% vs. 2.4%, p < 0.001), though IDS patients had a lower 30-day readmission rate (6.2% vs. 3.1%, p < 0.001). IDS patients were less likely to undergo extensive surgery (27.4% vs. 36.7%, p < 0.001) and more likely to achieve R0 resection (42% vs. 38.6%, p < 0.001). The IDS rate increased from 18.9% to 40.6% (annual percentage change (APC): 11.8%, p < 0.05) from 2010 to 2017. Median OS improved from 46.6 to 51 months (APC: 1.9%, p < 0.05), driven by the PDS cohort. The R0 resection rate rose from 34.8 to 41% (APC: 2.65%, p < 0.01), driven by the PDS cohort (APC: 2.83%, p < 0.01). Postoperative 90-day mortality decreased from 2.4% to 1.5% (APC: −4.64%, p < 0.05), due to a reduction in PDS patients (APC: −6.83%, p < 0.05). There was no change in the rate of extensive surgery over time. In conclusion, from 2010 to 2017, increased triage of patients to NACT was accompanied by a higher R0 resection rate and reduced postoperative mortality in PDS patients, with no observed detriment to OS. This data suggests improvement in case selection between IDS and PDS. Full article

Objective: This study aimed to evaluate the association between the Peritoneal Cancer Index (PCI) and the completeness of cytoreductive surgery (CRS) in patients undergoing surgery for advanced ovarian cancer (AOC). Secondary objectives included identifying a PCI cut-off predictive of incomplete cytoreduction, assessing the relationship between PCI and surgical complexity via the Aletti Surgical Complexity Score (SCS), and exploring disease distribution to better understand ovarian cancer distribution. Methods: A retrospective review of 227 patients undergoing primary or interval debulking surgery for AOC from January 2017 to September 2024 at University Hospitals of Derby and Burton was conducted. PCI was recorded intra-operatively, and procedures were classified using the SCS. ROC analysis identified PCI thresholds for incomplete CRS, logistic regression predicted CRS outcomes, and heat mapping visualised disease distribution. Results: Complete CRS of visible disease (R0) was achieved in 90.75% of patients, while 9.25% had incomplete CRS. Median PCI was significantly higher in incomplete CRS cases (28, IQR 21–32) compared to complete CRS (15, IQR 8–23, p < 0.001). ROC analysis identified a PCI threshold of 25.5 with 71.4% sensitivity and 83.5% specificity for predicting incomplete CRS. PCI > 25.5 increased the odds of incomplete cytoreduction by 12.65 times (p < 0.001). Higher PCI scores correlated with increased surgical complexity, operative time, and blood loss, though complication rates were similar. Heat maps showed stepwise disease distribution from pelvis to upper abdomen. Conclusions: PCI is a reliable predictor of CRS completeness in AOC, with a threshold of >25.5 indicating a high risk of incomplete cytoreduction. The study underscores PCI’s role in surgical planning and calls for multi-centre studies to validate these findings and further examine disease distribution. Full article