Surgery For Advanced Ovarian Cancer Research Articles

Effectiveness and safety of niraparib as neoadjuvant therapy in advanced ovarian cancer with homologous recombination deficiency: NANT study protocol for a prospective, multicenter, exploratory, phase 2, single-arm study (041)

Objectives: Neoadjuvant chemotherapy followed by interval debulking surgery did not achieve survival benefits compared to primary debulking surgery in advanced ovarian cancer. Niraparib is the only approved poly (ADP-ribose) polymerase inhibitor by the FDA to treat homologous recombination deficiency (HRD)-positive ovarian cancer patients with platinum-sensitive relapse after ≥ 3 lines of chemotherapy hitherto. We aimed to assess the efficacy and safety of neoadjuvant niraparib monotherapy in BRCAmut/HRD-positive patients with advanced unresectable ovarian cancer. Methods: This multi-center phase II single-arm study followed Simon’s two-stage design. We planned to recruit 53 patients (aged 18-75 years) with newly diagnosed BRCAmut/HRD positive, unresectable (Fagotti score ≥ 8 or upper abdominal computed tomography score ≥ 3), FIGO stage III-IV high-grade serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Enrolled patients received two cycles (four weeks per cycle) of individualized starting dose of neoadjuvant niraparib (200mg or 300mg per day), interval debulking surgery, and at least four cycles of platinum-based chemotherapy. Maintenance therapy of niraparib was dosed (200mg or 300mg per day) within 12 weeks up to three years or disease progression or patient withdrawal. The dual primary objectives were objective response rate (ORR) and R0 resection rate. Both progression-free survival and overall survival were secondary objectives. The data manager will record adverse events (AEs). If more than five patients achieved OR in the first stage, the study would enter the second stage. Results: Since February 2021, 16 patients have been enrolled. By September 20, 2021, six patients had completed neoadjuvant niraparib monotherapy, and four had completed interval debulking surgery. Their baseline characteristics are shown in Table 1. The ORR was 100% (CR n=0; PR n=6) and R0 reduction rate was 75% (R0, n=3; R1, n=1). CA-125 began to decline since day-14 after the first dose of niraparib, significantly decreased after the first cycle of neoadjuvant niraparib (median decrease, 70.8% [min, 23.8%; max, 97.4%] of baseline concentration), and continued to decline thereafter. Treatment-emergent adverse events (TEAEs) could be analyzed in nine patients, and the most common TEAEs were hematological AEs, including any grade leukopenia (66.7%), anemia (66.7%), and thrombocytopenia (55.6%). No treatment-related death was recorded. The grade ≥3 TEAEs were anemia (n=1) and thrombocytopenia (n=5). Thrombocytopenia mainly occurred after the first cycle of neoadjuvant niraparib, which synchronized with the decline of CA-125. Objectives: Neoadjuvant chemotherapy followed by interval debulking surgery did not achieve survival benefits compared to primary debulking surgery in advanced ovarian cancer. Niraparib is the only approved poly (ADP-ribose) polymerase inhibitor by the FDA to treat homologous recombination deficiency (HRD)-positive ovarian cancer patients with platinum-sensitive relapse after ≥ 3 lines of chemotherapy hitherto. We aimed to assess the efficacy and safety of neoadjuvant niraparib monotherapy in BRCAmut/HRD-positive patients with advanced unresectable ovarian cancer. Methods: This multi-center phase II single-arm study followed Simon’s two-stage design. We planned to recruit 53 patients (aged 18-75 years) with newly diagnosed BRCAmut/HRD positive, unresectable (Fagotti score ≥ 8 or upper abdominal computed tomography score ≥ 3), FIGO stage III-IV high-grade serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Enrolled patients received two cycles (four weeks per cycle) of individualized starting dose of neoadjuvant niraparib (200mg or 300mg per day), interval debulking surgery, and at least four cycles of platinum-based chemotherapy. Maintenance therapy of niraparib was dosed (200mg or 300mg per day) within 12 weeks up to three years or disease progression or patient withdrawal. The dual primary objectives were objective response rate (ORR) and R0 resection rate. Both progression-free survival and overall survival were secondary objectives. The data manager will record adverse events (AEs). If more than five patients achieved OR in the first stage, the study would enter the second stage. Results: Since February 2021, 16 patients have been enrolled. By September 20, 2021, six patients had completed neoadjuvant niraparib monotherapy, and four had completed interval debulking surgery. Their baseline characteristics are shown in Table 1. The ORR was 100% (CR n=0; PR n=6) and R0 reduction rate was 75% (R0, n=3; R1, n=1). CA-125 began to decline since day-14 after the first dose of niraparib, significantly decreased after the first cycle of neoadjuvant niraparib (median decrease, 70.8% [min, 23.8%; max, 97.4%] of baseline concentration), and continued to decline thereafter. Treatment-emergent adverse events (TEAEs) could be analyzed in nine patients, and the most common TEAEs were hematological AEs, including any grade leukopenia (66.7%), anemia (66.7%), and thrombocytopenia (55.6%). No treatment-related death was recorded. The grade ≥3 TEAEs were anemia (n=1) and thrombocytopenia (n=5). Thrombocytopenia mainly occurred after the first cycle of neoadjuvant niraparib, which synchronized with the decline of CA-125.

Residual disease after primary surgery for advanced epithelial ovarian cancer: expert elicitation exercise to explore opinions about potential impact of publication bias in a planned systematic review and meta-analysis

ObjectivesWe consider expert opinion and its incorporation into a planned meta-analysis as a way of adjusting for anticipated publication bias. We conduct an elicitation exercise among eligible British Gynaecological Cancer...

FDG PET/CT parameters and CA-125 levels to predict optimal cytoreduction at primary cytoreductive surgery for advanced ovarian cancer (149)

Objectives: To develop models predicting optimal cytoreduction in primary cytoreductive surgery (CRS) using clinical-pathologic characteristics and FDG PET/CT-derived parameters in advanced ovarian cancer. Methods: We retrospectively identified patients with stage III-IV ovarian cancer who underwent primary CRS between June 2013 and February 2020 at our center. We calculated the following 18 parameters: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), visual grade, and the number of lesions in three divided areas of the abdominal cavity. Optimal cytoreduction was defined as grossly no residual tumor after CRS. We constructed various predictive models for optimal cytoreduction by combining clinical-pathologic characteristics and FDG PET/CT-derived parameters. The predictive performance of each model was assessed based on the area under the receiver operating characteristic curve (AUC). Results: In total, 159 patients were included in the study. The median age was 55 years. The most common histologic subtype was serous (74.2%). Stage III and stage IV were 73.6% and 26.4%, respectively. Optimal cytoreduction was achieved in 104 patients (65.4%). The median CA-125 was 764 IU/ml. As a single variable, MTV, TLG, number of lesions above the renal vein showed high AUC for optimal cytoreduction, at 0.749, 0.748, and 0.748, respectively. The best predictive multivariable model consisted of CA-125 (<750 or ≥750 IU/ml), the number of lesions above the renal vein (<2 or ≥2), and MTV above the renal vein with an AUC of 0.770 for optimal cytoreduction. Conclusions: We successfully developed FDG PET/CT-based predictive model for optimal cytoreduction. This result may help determine patients’ treatment plans. Objectives: To develop models predicting optimal cytoreduction in primary cytoreductive surgery (CRS) using clinical-pathologic characteristics and FDG PET/CT-derived parameters in advanced ovarian cancer. Methods: We retrospectively identified patients with stage III-IV ovarian cancer who underwent primary CRS between June 2013 and February 2020 at our center. We calculated the following 18 parameters: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), visual grade, and the number of lesions in three divided areas of the abdominal cavity. Optimal cytoreduction was defined as grossly no residual tumor after CRS. We constructed various predictive models for optimal cytoreduction by combining clinical-pathologic characteristics and FDG PET/CT-derived parameters. The predictive performance of each model was assessed based on the area under the receiver operating characteristic curve (AUC). Results: In total, 159 patients were included in the study. The median age was 55 years. The most common histologic subtype was serous (74.2%). Stage III and stage IV were 73.6% and 26.4%, respectively. Optimal cytoreduction was achieved in 104 patients (65.4%). The median CA-125 was 764 IU/ml. As a single variable, MTV, TLG, number of lesions above the renal vein showed high AUC for optimal cytoreduction, at 0.749, 0.748, and 0.748, respectively. The best predictive multivariable model consisted of CA-125 (<750 or ≥750 IU/ml), the number of lesions above the renal vein (<2 or ≥2), and MTV above the renal vein with an AUC of 0.770 for optimal cytoreduction. Conclusions: We successfully developed FDG PET/CT-based predictive model for optimal cytoreduction. This result may help determine patients’ treatment plans.

Frailty associated with failure to recover from grade 3 complications after surgery for advanced ovarian cancer (560)

<b>Objectives:</b> Frailty is characterized by vulnerability to stressors and lack of reserve. Frailty is emerging as an important predictor of tolerance to treatment in gynecologic malignancy and is associated with poor outcomes in advanced ovarian cancer (OC). An important stressor is the experience of severe complications at debulking surgery. We aimed to assess the impact of frailty on short-term survival after surgical cytoreduction and a severe complication in advanced OC. <b>Methods:</b> Patients with stage IIIC/IV OC who underwent curativeintent primary debulking surgery (PDS) from January 2, 2003, to April 30, 2018 at a single institution were identified from a prospectively maintained surgical database of OC patients. Patient's clinical, surgical, and outcomes data were collected from the medical record. Frailty was defined by a frailty index (FI). The FI included 30 items scored at 0, 0.5, or 1 and was calculated by summing across all the item scores and dividing by the total (range: 0-1). Those without frailty index or lack of follow-up data were excluded. Surgical complications were collected for 30 days post-surgery and graded by the modified Accordion scale. All patients who experienced a grade 3 complication were included. Cox regression models were fit to evaluate associations with death within six months after surgery. <b>Results:</b> Of the 922 patients who had PDS in this time period, 142 met the inclusion criteria. The average age of the cohort was 64.6 years, and the majority had serous histology (92.3%), stage IIIC disease (64.1%), and grade 3 disease (97.9%). Nearly half underwent high complexity surgery (47.2%), and most had resection to no gross residual disease (40.1%) or ≤1 cm of disease (43.7%). FI was ≥0.15 in 36 (25.4%) patients. There were 27 (19%) deaths within the first six months after PDS. Univariate factors associated with death by six months after surgery included age (HR: 1.6 per 10-year increase, 95% CI: 1.1-2.4), ASA score >3 (HR: 4.8, 95% CI: 1.6-13.8), body mass index (HR: 1.3 per 5 kg/m² increase, 95% CI: 1.0-1.6), FI >0.15 (HR: 2.5, 95% CI: 1.3-5.4, Figure), and residual disease (HR: 4.2, 95% CI: 1.8-12.1 for > 1 cm disease compared to no gross residual disease). <b>Conclusions:</b> Since surgical complications are non-avoidable, it is important to identify the patients who will not be able to recover from a complication. Identifying frailty prior to surgery is important to determine patients who may be better suited for neoadjuvant chemotherapy and prehabilitation efforts.

Circulating tumor-derived small extracellular vesicles micro RNAs plus CA-125 objectively tests residual tumor prior to debulking surgery in advanced ovarian cancer (525)

<b>Objectives:</b> No residual disease after debulking surgery (R0 resection) is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models, such as CA-125, CT, PET-CT, or laparoscopy. Therefore, it is of paramount importance to preoperatively estimate the likelihood of R0 resection for choosing the best therapeutic strategy. In this study, we sought to develop a novel, non-invasive, and objective detection method. <b>Methods:</b> Differentially expressed microRNAs (miRNA) in circulating small extracellular vesicles (sEVs) between any residual disease (R0) and no residual disease (non-R0) AOC patients were revealed using small RNA sequencing. miRNA expression of plasma samples was measured by TaqMan qRT-PCR. The prediction model of residual disease risk was established via LASSO and logistic regression analysis based on the discovery-validation set. Tissue sEVs were extracted from primary tumor tissue, metastatic tumor tissue, adjacent tissue, or non-tumor tissue by differential ultracentrifugation and size exclusion chromatography (SEC). Cell-type-specific markers (EpCAM, FAP, CD45, CD31) in tumor sEVs pool were evaluated by western blot analysis. Plasma sEVs were captured by the magnetic bead sorting system (MACS) using specific surface proteins as markers (EpCAM, CD45, CD235a). <b>Results:</b> A total of 270 subjects were recruited in this study from four clinical centers. According to the comprehensive plasma sEVs miRNAs profile in AOC patients, we identified and optimized a risk model consisting of plasma sEVs 5-miRNA and CA-125 for predicting residual disease (AUC:0.912; sensitivity:0.964; specificity:0.884; PPV:0.911; NPV:0.905;). Moreover, there were significant differences in model index scores between AOC patients and patients with benign ovarian tumors, early-stage ovarian cancer with FIGO I or II, and advanced colorectal cancer. Our data showed that EpCAM-positive sEVs accounted for the highest in tumor sEVs pool. Besides, these 5-miRNAs were a high concentration horizontal packaging in plasma EpCAM-sEVs. By further comparing the sEVs 5-miRNA expression in paired tumor and non-tumor tissue as well as plasma, we found that they were mainly originated from epithelial ovarian cancer cells and their tumor microenvironment. These results indicated that plasma sEVs 5-miRNA in AOC patients was associated with residual disease. <b>Conclusions:</b> Collectively, our study demonstrated a distinct profile of circulating sEVs miRNAs between R0 and non-R0 patients and obtained a robust model of circulating tumor-derived sEVs 5-miRNA combined with CA-125 to preoperatively anticipate a high risk of residual disease for optimizing clinical treatment and guiding differential diagnosis. This prediction panel, as a tool of non-invasive liquid biopsy, can be part of a standard monitoring strategy for screening high-risk patients who are allowed for neoadjuvant chemotherapy.

Impact of neoadjuvant chemotherapy on fitness for surgery in high-risk patients with advanced ovarian cancer (566)

<b>Objectives:</b> Using a validated surgical triage algorithm, we identified women who are at high risk of postoperative morbidity & mortality (M/M) after surgery for advanced ovarian cancer (OC). We sought to determine the impact of neoadjuvant chemotherapy (NACT) on variables used to determine fitness for surgery and the resultant perioperative outcomes. <b>Methods:</b> Women who underwent primary (PDS) or interval (IDS) debulking surgery for stage IIIC/IV OC (institution 1: From January 2012 to July 2016; institution 2: From October 2011 to November 2019) were classified as high-risk or triage-appropriate retrospectively using a validated triage algorithm. A woman was considered high-risk if at least one of the following high-risk criteria were present: <i>(i)</i> Albumin <3.5g/dL, <i>(ii)</i> age ≥80 years, or <i>(iii)</i> age 75-79 and at least one of the following: ECOG (Eastern Cooperative Oncology Group) performance status >1, stage IV disease, or complex surgery required (more than hysterectomy, salpingo-oophorectomy, and omentectomy). For the NACT/IDS group, we compared serum albumin (normal: >3.5g/dL, low: <3.5g/dL) and triage risk classification before and after NACT, including only women who had data available at both time points. Outcomes were compared between groups using the Wilcoxon rank-sum test, Chi-square test, or Fisher's exact test. <b>Results:</b> Among 959 included women, 65.3% (626/959) underwent PDS, and 34.7% (333/959) underwent NACT/IDS. Among 97 women in the NACT/IDS group who had low albumin before NACT, 90.7% (88/97) improved to normal, and a minority (9.3%, 9/97) remained low after NACT. A small proportion (2%, 3/148) of women who had normal albumin before NACT worsened to low albumin after NACT. Similarly, 66.1% (76/115) of women who were high-risk before NACT improved to triage-appropriate after NACT, and 33.9% (39/115) remained highrisk. A minority (2.2%, 3/136) of women who were triage-appropriate before NACT worsened to high-risk after NACT. When compared to the high-risk group who underwent PDS, the group who underwent NACT and improved to triage-appropriate before IDS had a significantly shorter median operative time, a lower proportion with high surgical complexity, a higher proportion with complete cytoreduction (no gross residual disease), and shorter median hospital stay (Table). The 90-day mortality for high-risk women who improved to triage-appropriate after NACT was five times lower than that of the high-risk group who underwent PDS (1.3% vs 6.5%; p=0.11), although this difference was not statistically significant due to low numbers. <b>Conclusions:</b> For women with advanced OC who are poor surgical candidates, NACT is an effective prehabilitation strategy for improving serum albumin levels, changing triage risk classification, and improving perioperative outcomes.

Cost analysis of the enhanced recovery after surgery protocol applied in advanced ovarian cancer: A secondary outcome of the PROFAST trial

IntroductionA randomised trial implementing Enhanced Recovery After Surgery (ERAS) for high complexity advanced ovarian cancer (AOC) surgery (PROFAST) demonstrated a reduction of median length of stay and hospital readmissions when compared to patients managed conventionally. One secondary objective was to determine if an ERAS pathway in the perioperative management of advanced ovarian cancer patients led to cost savings. Material and methodsSecondary objective of a prospective randomised trial of patients with suspected or diagnosed advanced ovarian cancer allocated to conventional or ERAS perioperative management, carried out at a referral centre from June 2014 to March 2018. Treatment was determined by a computer-generated random allocation system. MethodsGross counting was employed to estimate the cost of hospitalisation in wards, intensive care unit (ICU) and surgical care, while micro-costing was used to obtain image and laboratory test costs. Mean costs between trial arms were considered. Sensitivity analyses were performed. ResultsNinety-nine patients (n = 50 ERAS group, n = 49 Conventional group) were included. Mean costs per patient were 10,719€ in the ERAS group and 11,028€ in the conventional group, leading to an average saving of 309€ per patient. These results were based on 96 patients, excluding 3 extreme outliers mainly related with very high ICU costs. Savings, which were significant for hospital ward costs (−33% total; 759€ per patient in first hospitalisation, and 914€ per partient/day of readmission) were found as robust in the sensitivity analysis. ConclusionsImplementation of an ERAS pathway leads to cost savings when compared to conventional management after AOC surgery.

A multimodal prehabilitation program for the reduction of post-operative complications after surgery in advanced ovarian cancer under an ERAS pathway: a randomized multicenter trial (SOPHIE)

BackgroundMultimodal prehabilitation programs that combine exercise training, nutritional support, and optimize psychological status have demonstrated efficacy in reducing post-operative complications in non-gynecological abdominal surgeries; however, the benefit in advanced ovarian...

Use of Laparoscopic and Laparotomic J-Plasma Handpiece in Gynecological Malignancies: Results From A Pilot Study in A Tertiary Care Center

IntroductionThe J-Plasma has recently been introduced into the surgical community with different intrinsic characteristics aimed to further reduce the thermal effect and enhance precision when compared to standard radiofrequency. This study aimed to investigate the role of this new technology in different conditions of gynecological carcinomatosis characterized by the indication for regional peritonectomy and/or ablation, either in laparotomy (LPT) or in laparoscopy (LPS), in the context of a modern personalized approach to the surgical management of gynecological malignancies.Material and MethodsFrom January 2019 to April 2019, 12 patients were selected for this prospective pilot study at the Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. In this single surgeon experience, the inclusion criteria were: histologically proven advanced ovarian/endometrial cancer, primary or interval debulking surgery, and intraoperative indication for regional peritonectomy. Six patients were treated by LPS (Group 1) and 6 by LPT (Group 2).ResultsIn Group 1 the indication for debulking surgery was in 4 cases an interval debulking surgery and 2 advanced endometrial cancer. All patients in Group 2 underwent primary debulking surgery for advanced ovarian cancer. The whole cohort achieved a complete tumor excision after surgery. The median OT and median EBL were 195 min and 100 ml in Group 1, and 420 min and 500 ml in Group 2. The median hospital stay was 4 days in Group 1 and 13 days in Group 2, respectively. No intra and postoperative complications were registered within 60 days after surgery.ConclusionsJ-Plasma allows to approach delicate maneuvers on viscera, mesentery, and blood vessels with a high degree of safety and precision thanks to its limited vertical and lateral thermal spread, favoring the surgeon to push ever higher the cytoreduction/morbidity tradeoff. The use of J-Plasma in cytoreductive surgery could also increase the range of possible minimally invasive procedures, narrowing the technical distance with the open technique and thus contributing to designing a personalized surgical strategy for each patient in different scenarios of peritoneal carcinomatosis.

Distal gastrectomy as part of debulking surgery for advanced stage ovarian cancer

Ovarian cancer is characterized through a high capacity of spread via multiple pathways such as peritoneal, hematogenous or lymphatic route. Therefore, upper abdominal involvement might be encountered; in such cases extended visceral resections might be needed in order to achieve radical cytoreductive surgery. The aim of the current paper is to report the cases of three patients diagnosed with extended upper abdominal lesions and in which distal gastrectomy was successfully associated. Postoperatively a single case developed a postoperative leak which was successfully treated in a conservative manner. In all cases the histopathological studies demonstrated the presence of tumoral involvement of the gastric wall. In conclusion, gastrectomy can be safely associated as part of debulking surgery for advanced stage ovarian cancer in order to increase the chances to obtain long term survival.

Postoperative embolic complications after cytoreductive surgery for advanced stage ovarian cancer

Postoperative embolism after pelvic surgery for ovarian malignancies represents a serious adverse event which might be fatal and should be carefully prevented. In such cases multiple risk factors have been incriminated such as the presence of the malignancy, particularly in cases in which an ovarian primary is suspected, the necessity of performing extended pelvic resections, the length of the surgical procedure, the position of the patient on the operating table or the difficult and late postoperative mobilization of the patient. The aim of the current paper is to report the cases of six patients who developed severe postoperative embolic complications after surgery for advanced stage ovarian cancer and to analyze the risk factors which seem to increase the risk of developing such adverse effects.

A narrative review of the role of anaesthesia and peri-operative medicine in improving outcomes after surgery for advanced ovarian cancer

A narrative review of the role of anaesthesia and peri-operative medicine in improving outcomes after surgery for advanced ovarian cancer

Cytoreductive surgery plus HIPEC for advanced epithelial ovarian cancer: Analysis from a multicentric national Indian HIPEC registry of 1,470 patients—An ISPSM Collaborative study.

5525 Background: Improved long-term results can be achieved in advanced epithelial ovarian cancer (EOC) patients using optimal cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: Indian society of peritoneal surface malignancy (ISPSM) is a registered body which maintains prospective data of 26 centers across India who perform CRS –HIPEC. From February 2017 until January 2022, 1470 patients with advanced EOC were treated with CRS-HIPEC. He general practice patterns and the oncological outcomes in terms of progression free survival (PFS) and overall survival (OS) &amp; post-operative morbidity and mortality is reported. Results: Upfront (n = 156), interval (n = 645) and recurrent (n = 669) cytoreductions were performed based on the timeline at presentation. Mean age 54.5±10.74, PCI 13. 6±5.2, duration of surgery 10.6±1.h hrs. 36.4% had total peritonectomy, 12.7% had multivisceral resection, 41.8%had bowel resections and stoma rate was 7.4%. 60.3% had semiopen HIPEC, 83.1% used cisplatin for HIPEC and 83.1 % had HIPEC for 90 minutes. Overall G3-G5 morbidity was 25.4% with major ones being post-operative intra-abdominal collection (21.8%), electrolyte imbalance (16.4%), pulmonary (16.4%) followed by hematological (12.7%). Surgical morbidity was more in upfront cytoreduction group compared to interval group (20% versus 13.5%) and recurrent group (20% versus 15%), respectively. The 30 day mortality was 3.8%. With a median follow-up of 46 months, median PFS was 33 months in primary (upfront plus interval) group and 16 months in recurrent cytoreduction group. Median OS was not achieved in both primary and recurrent groups (4 year OS rates: 60 and 55%, respectively). Conclusions: This prospective database provides a collation and audit of the management of advanced epithelial ovarian cancer with CRS HIPEC in multiple centers registered under ISPSM. In advanced EOC patients, CRS plus HIPEC offers potential benefits in PFS and OS rates, with acceptable rates of morbidity and mortality and can be practiced even in resource constrained setting.

Wedge liver resection as part of cytoreductive surgery in advanced ovarian cancer – a safe and feasible procedure for a gynecologic oncologist

Objective: In this study, we aimed to determine the learning curve for liver wedge resection performed as part of cytoreductive surgery in advanced ovarian malignant tumors. Materials and methods: This was a retrospective analysis of 120 women diagnosed with stage IIIC ovarian cancer according to the International Federation of Gynecology and Obstetrics (FIGO) classification: 22 underwent liver wedge resection as part of cytoreductive surgery (Group A), while 98 did not require liver surgery (Group B). In the study, the t-Student test was used for variables with normal distribution and the Mann−Whitney U test was utilized for increment and abnormally distributed variables. The variables categorized were shown as a number of cases (n) and a percentage (%), and compared using the chi-square test, with a p-value &lt;0.05 considered significant. A cumulative sum control chart (CUSUM) method was used to investigate the learning curves in both groups and the entire cohort. Results: There were no significant differences in the operating time, intraoperative blood loss, postoperative hospitalization or minor and severe adverse effects between the Groups A and B. The operative time, total blood loss, and incidence of adverse effects showed a similar learning curve for Group B and the entire cohort. Conclusion: It is safe and feasible for gynecologic oncologists to perform wedge liver resections as part of cytoreductive surgery in women with advanced ovarian tumors.

A Promising Approach for Primary Cytoreductive Surgery for Advanced Ovarian Cancer: Survival Outcomes and Step-by-Step Description of Total Retroperitoneal en-Bloc Resection of Multivisceral-Peritoneal Packet (TROMP).

(1) Background: A complete tumor resection during primary cytoreductive surgery has been reported to be the most important and perhaps the only independent prognostic factor in advanced ovarian cancers. The goal of complete cytoreduction needs to be weighed against the potential morbidities and long-term survival outcomes. (2) Methods: in this retrospective analysis of a prospectively obtained database, 208 consecutive patients with advanced ovarian cancer who underwent a conventional primary cytoreductive surgery (150 patients) or TROMP technique (58 patients) were included. Progression-free and overall survival rates were calculated using Kaplan–Meier analysis as well as the 95% confidence interval of the hazard ratio between treatment groups. (3) Results: After a median follow-up phase of more than 3 years (range 1–72 months), there are no statistically significant differences between both groups in progression-free and overall survival rates. Albeit, the TROMP group included statistically significant more advanced-stage cases compared to the conventional surgery group. (4) Conclusions: the TROMP technique is a promising tool for successful primary cytoreductive surgery in a selected group of patients with high tumor burdens in order to achieve optimal surgical results and survival outcomes without introducing any additional risks or complications.

Safety and Efficacy of Supradiaphragmatic Lymph Node Dissection in Advanced Ovarian Cancer.

Postoperative gross residual disease after cytoreductive surgery for advanced ovarian cancer impacts patient survival negatively. Specifically, unresected enlarged, metastatic supradiaphragmatic lymph nodes (SDLNs) may worsen progression-free survival (PFS) and overall survival (OS). Multiple studies have shown that upper abdominal debulking during primary cytoreductive surgery improves survival outcomes, but the evidence for resection of SDLN metastasis is less definitive. This review focuses on the feasibility, safety, and efficacy of SDLN resection for metastatic disease in advanced-stage ovarian cancer and explores emerging data on survival outcomes. A literature review from January 2004 to December 2021 identified 4 relevant studies, all published after 2016. Eligible studies included patients with advanced ovarian, tubal, or peritoneal cancer who had undergone SDLN resection using a transdiaphragmatic approach or video-assisted thorascopy, and had evaluated SDLN dissection for diagnoses and treatment or assessed the benefits of SDLN resection as it relates to prognosis. All 4 studies demonstrated the feasibility and safety of SDLN resection. Three of the studies reported a low intrathoracic recurrence rate after intrathoracic debulking. Cowan et al. described an impressive median PFS and OS of 17.2 months and 70.1 months, respectively, in patients who had undergone SDLN resection. Resection of enlarged SDLNs in carefully selected patients has the potential to confirm intrathoracic disease spread, help achieve maximal cytoreduction without delaying adjuvant treatment, and improve survival. More studies are needed to quantify the survival benefit of SDLN resection. (J GYNECOL SURG 38:202).

Risks and benefits of systematic lymphadenectomy during interval debulking surgery for advanced high-grade serous ovarian cancer

Recent findings have suggested that lymphadenectomy during primary cytoreductive surgery (CRS) in patients with ovarian cancer was not associated with an improve in survival, at the expense of a high morbidity. The aim of our study was to evaluate the impact of lymphadenectomy in patients with high-grade serous ovarian cancer benefitting from neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). A retrospective, unicentric study including all patients undergoing NACT and IDS was carried out from 2005–2018. Patients with and without lymphadenectomy were compared in terms of recurrence free survival (RFS), overall survival (OS), and complication rates. Survival was assessed using a Cox regression model and Kaplan–Meyer curves. We included 203 patients. Of these, 133 had a lymphadenectomy (65.5%) and 77 had involved nodes (57.9%). Patients who did not benefit from a lymphadenectomy were older with a more extensive disease and lesser rate of complete CRS. No differences were noted between the lymphadenectomy and no lymphadenectomy group concerning 2-year RFS (47.4% and 48.6%, P = 0.87, respectively) and 5-year OS (63.2% versus 58.6%, P = 0.41, respectively). Postoperative complications tended to be more frequent in the group with a lymphadenectomy (18.57 versus 31.58, P = 0.09). In the group of patients with lymphadenectomy, survival was significantly altered in patients with involved nodes (positive lymph nodes: 2-year RFS 42.5% and 5-year OS 49.4%, negative nodes: 2-year RFS 60.7% and 5-year OS 82.2%, P = 0.03 and P < 0.001, respectively). Lymphadenectomy during IDS does not improve survival and increases postoperative complications.

Prognostic Value of Peritoneal Cancer Index After Complete Cytoreductive Surgery in Advanced Ovarian Cancer.

Residual disease (RD) after primary debulking surgery (PDS) is a prognostic factor for survival in advanced ovarian cancer (AOC). This study aimed to examine whether the tumor extent affects overall survival (OS) and progression-free survival (PFS) in AOC patients treated with PDS. A total of 118 patients treated with PDS were included. Age, ECOG score, AOC International Federation of Gynecology and Obstetrics (FIGO) stage, CA-125, RD, peritoneal cancer index (PCI), preoperative imaging (CT-PCI) and macroscopic visualization at the surgery start (S-PCI) were analyzed. Tumor extent was quantified using the PCI, and by CT-PCI and S-PCI. Cox regression, Kaplan-Meier and receiver operating curves (ROC) were performed for survival analyses. S-PCI correlated with both OS (1.067, 95%CI=1.018-1.119, p<0.007) and PFS. Patients exhibiting S-PCI≥18.5, adjusted to age, performance status, and RD, had a two-fold risk of dying (HR=2.070, 95%CI=1.061-4.038, p=0.033) compared those with PCI<18.5. CT-PCI correlated with OS in crude data (1.037, 95%CI=1.005-1.071, p=0.025), but this was not sustained in multivariate analyses. RD of any size doubled the risk of dying (2.177, 95%CI=1.235-3.838, p=0.007). The tumor extent at the beginning of surgery seemed to affect OS in patients with AOC, regardless of the extent of RD at the end of the surgery. PCI above 18.5 doubled the risk of dying of the disease. No difference in major complications was noted in the two groups of patients. CT-PCI seemed to play a prognostic role for PFS; however, it is still to be investigated as a prognostic factor for OS.

ASO Visual Abstract: Risk Factors for Anastomotic Leakage in Advanced Ovarian Cancer Surgery: A large Single-Center Experience

ASO Visual Abstract: Risk Factors for Anastomotic Leakage in Advanced Ovarian Cancer Surgery: A large Single-Center Experience

Risk Factors for Anastomotic Leakage in Advanced Ovarian Cancer Surgery: A Large Single-Center Experience

BackgroundCytoreductive surgery is currently the main treatment for advanced epithelial ovarian cancer (OC), and several surgical maneuvers, including colorectal resection, are often needed to achieve no residual disease. High surgical complexity carries an inherent risk of postoperative complications, including anastomosis leakage (AL). Albeit rare, AL is a life-threatening condition. The aim of this single-center retrospective study is to assess the AL rate in patients undergoing colorectal resection and anastomosis during primary surgery for advanced epithelial OC through a standardized surgical technique and to evaluate possible pre/intra- and postoperative risk factors to identify the population at greatest risk.MethodsA retrospective analysis of clinical and surgical characteristics of 515 patients undergoing colorectal resection and anastomosis during primary or interval debulking surgery between December 2011 and October 2019 was performed. Several pre/intra- and postoperative variables were evaluated by multivariate analysis as potential risk factors for AL.ResultsThe overall anastomotic leakage rate was 2.9% (15/515) with a significant negative impact on postoperative course. Body mass index < 18 kg/m2, preoperative albumin value lower than 30 mg/dL, section of the inferior mesenteric artery at its origin, and medium–low colorectal anastomosis (< 10 cm from the anal verge) were identified as independent risk factors for AL on multivariate analysis.ConclusionsAL is confirmed to be an extremely rare but severe postoperative complication of OC surgery, being responsible for increased early postoperative mortality. Preoperative nutritional status and surgical characteristics, such as blood supply and anastomosis level, appear to be the most significant risk factors.