Trends in specific procedures performed at the time of cytoreduction for ovarian cancer: Is interval debulking surgery truly less radical? A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVES: To evaluate procedures performed during primary debulking surgery (PDS) and interval debulking surgery (IDS) for ovarian cancer. METHODS: Patients surgically treated at our institution for newly diagnosed stage IIIC/IV epithelial ovarian cancer between 6/1/2015-12/31/2021 were identified using a prospectively collected database. Patients were triaged to PDS or neoadjuvant chemotherapy (NACT) followed by IDS using an institutional algorithm. Data on specific procedures performed, including consultants called, were collected from operative and pathology reports. Appropriate statistical analyses were applied. RESULTS: Overall, 467 patients underwent PDS and 434 underwent IDS; 76% (PDS) and 71% (IDS) of cases achieved complete gross resection. Comparing PDS vs IDS cohorts, median age was 63 years (range, 23-86) vs 67 years (range, 35-95), 79% vs 86% of patients had high-grade serous histology, and 38% vs 70% had stage IV disease. Most procedures (except ostomy, distal pancreatectomy) were more common during PDS (P < .05). Bowel surgery was performed during 65% of PDS and 33% of IDS, and upper abdominal surgery during 72% of PDS and 52% of IDS; both were more common during PDS (P < .001). Estimated blood loss (median, 500 mL [PDS] vs 300 mL [IDS]) and operative time (median, 362 min [PDS] vs 267 min [IDS]) were higher for PDS (P < .001). A consulting surgeon was utilized during 31% of PDS and 18% of IDS, with hepatopancreaticobiliary as the most commonly called service (61% and 65%, respectively). CONCLUSIONS: In our study of patients with advanced-stage ovarian cancer, while most procedures were more often performed during PDS, NACT did not obviate the need for radical surgical resection. Thus, advanced surgical skills remain essential.

Salpingectomy for ovarian cancer prevention: Video education for the surgeon.

Given the unremitting obstacles to effectively screen for and treat ovarian cancer (OC), prevention is a necessary countermeasure. The recent discovery of the fallopian tube as the origin of the most common and deadly type of OC, high grade serous cancer (HGSC), makes prevention through salpingectomy possible (Madsen et al., 2015). Opportunistic salpingectomy (OS) is the practice of removing the post-reproductive fallopian tubes at the time of other intraperitoneal surgery, or for sterilization in lieu of tubal ligation, to decrease OC risk (Falconer et al., 2015). The safety, effectiveness, and reach of OS as a primary prevention strategy depends on the knowledge mobilization of a standard surgical approach for surgeons (Hanley et al., 2017, Morelli et al., 2013). Resources for accomplishing this knowledge mobilization activity are needed. We therefore aim to create a peer-reviewed, publicly available surgical instructional video that facilitates standardization of the practice of salpingectomy for the purpose of OC prevention. Content creation was generated by a team of surgeon stakeholders, medical illustrators, instructional designers, and health education specialists. Expert gynecologic surgeons were filmed performing salpingectomy in order to build a video library. Accurate illustration and editing of live video footage was executed to support surgeons in visualizing key anatomic landmarks to ensure safe and complete fallopian tube excision. Review of eligibility criteria, fundamentals of preoperative counseling, and strategic and technical points were prioritized. This endeavor is strictly educational, with no commercial benefit. Publicly available, peer-reviewed surgical education tools will help us collaborate to safely and equitably expand OS within and beyond the current scope of surgical practice.

Secondary cytoreductive surgery and oncologic outcomes in the era of targeted maintenance therapy for recurrent, platinum-sensitive ovarian cancer.

OBJECTIVES: To compare oncologic outcomes of secondary cytoreductive surgery (SCS) before and after FDA approval of Poly(ADP-ribose) polymerase inhibitor (PARPi) and bevacizumab maintenance therapies for platinum-sensitive recurrent ovarian cancer (PS-ROC). METHODS: Patients who underwent SCS for first recurrence of PS-ROC from 1/1/2013-1/1/2020 were identified. Exclusion criteria included prior chemotherapy for recurrence, bowel obstruction procedures, and palliative surgery. Data were dichotomized pre/post 1/2017, relative to FDA approval of PARPi and bevacizumab maintenance for ROC. Second progression-free survival (PFS2), the primary endpoint, was estimated using Kaplan-Meier method. RESULTS: Overall, 245 patients underwent SCS-131 (53%) pre- and 114 (47%) post-approval. Most patients had high-grade serous tumors (83% and 90%, respectively; p = 0.13). Deleterious BRCA1/2 alterations were identified in 27% (32/120) and 28% (32/113) of tested patients, respectively (p = 0.88). Disease-free intervals pre- and post-approval were: 6-12 months, 16% and 18%; 12-30 months, 56% and 59%; and >30 months, 28% and 24%, respectively (p = 0.73). Overall, 85% and 86% of patients, respectively, achieved complete gross resection (CGR; p > 0.99). PARPi maintenance use increased from 3.8% to 27% (p < 0.001) following approval, and bevacizumab from 1.5% to 12% (p < 0.001). Median PFS2 was 19 and 20.1 months, respectively. In the post group, 1-year PFS2 rate was 84.5% (95% CI, 75.7-90.4%) for patients with CGR vs 56.2% (95% CI, 29.5-76.2%) for those with residual disease; 3-year PFS2 rates were 31.3% (95% CI, 21.6-41.4%) and 12.5% (95% CI, 2.1-32.8%), respectively (p = 0.001). CONCLUSIONS: CGR during SCS is associated with improved PFS2 compared to suboptimal resection. Prospective randomized trials are warranted to elucidate the role of SCS as more therapeutics become available.

ARIA II: a randomized controlled trial of near-infrared Angiography during RectosIgmoid resection and Anastomosis in women with ovarian cancer.

BACKGROUND: Ovarian cancer with extensive metastatic disease involving pelvic structures often requires rectosigmoid resection for complete gross resection; however, it is associated with increased surgical morbidity. There are limited data, and none in ovarian cancer, on near-infrared assessment of perfusion in rectosigmoid resections with anastomosis. PRIMARY OBJECTIVE: To compare the rate of pelvic complications (pelvic abscesses, anastomotic leaks, and infections) within 30 days of surgery with and without near-infrared assessment of perfusion at time of rectosigmoid resection and re-anastomosis in patients undergoing cytoreductive surgery for ovarian cancer. STUDY HYPOTHESIS: We hypothesize the use of near-infrared technology (intravenous indocyanine green and endoscopic near-infrared fluorescence imaging), compared with standard intra-operative assessment, to evaluate anastomotic perfusion at time of rectosigmoid resection and re-anastomosis will result in lower rates of post-operative pelvic complications. TRIAL DESIGN: This is a planned multicenter randomized controlled trial. Patients who undergo rectosigmoid resection as part of their ovarian cytoreductive surgery will be randomized 1:1 to standard assessment of anastomosis with the surgeon's usual technique (control arm) or assessment with near-infrared angiography using indocyanine green and endoscopic fluorescence imaging (experimental arm). Randomization will occur after rectosigmoid resection has been completed and the surgeon declares their plan to create a diverting ostomy. Randomization will be stratified by plan for diverting ostomy. MAJOR INCLUSION/EXCLUSION CRITERIA: Main inclusion criteria include patients with primary or recurrent ovarian, fallopian tube, or primary peritoneal cancer who are scheduled for cytoreductive surgery with suspected need for low-anterior rectosigmoid resection. PRIMARY ENDPOINT: Rate of 30-day post-operative pelvic complications. SAMPLE SIZE: 310 (155 per arm) ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Q2 2027 and Q4 2027, respectively. TRIAL REGISTRATION: NCT04878094.

Uterine washings as a novel method for early detection of ovarian cancer: Trials and tribulations.

Given the tubal origin of high-grade serous ovarian cancer (HGSC), we sought to investigate intrauterine lavage (IUL) as a novel method of biomarker detection. IUL and serum samples were collected from patients with HGSC or benign pathology. Although CA-125 and HE4 concentrations were significantly higher in IUL samples compared to serum, they were similar between IUL samples from patients with HGSC vs benign conditions. In contrast, CA-125 and HE4 serum concentrations differed between HGSC and benign pathology (P =.002 for both). IUL and tumor samples from patients with HGSC were subjected to targeted panel sequencing and droplet digital PCR (ddPCR). Tumor mutations were found in 75 % of matched IUL samples. Serum CA-125 and HE4 biomarker levels allowed for better differentiation of HGSC and benign pathology compared to IUL samples. We believe using IUL for early detection of HGSC requires optimization, and current strategies should focus on prevention until early detection strategies improve.

Regionalizing ovarian cancer cytoreduction to high-volume centers and the impact on patient travel in New York State.

OBJECTIVE: To evaluate the theoretical impact of regionalizing cytoreductive surgery for ovarian cancer (OC) to high-volume facilities on patient travel. METHODS: We retrospectively identified patients with OC who underwent cytoreduction between 1/1/2004-12/31/2018 from the New York State Cancer Registry and Statewide Planning and Research Cooperative System. Hospitals were stratified by low-volume (<21 cytoreductive surgical procedures for OC annually) and high-volume centers (≥21 procedures annually). A simulation was performed; outcomes of interest were driving distance and time between the centroid of the patient's residence zip code and the treating facility zip code. RESULTS: Overall, 60,493 patients met inclusion criteria. Between 2004 and 2018, 210 facilities were performing cytoreductive surgery for OC in New York; 159 facilities (75.7%) met low-volume and 51 (24.3%) met high-volume criteria. Overall, 10,514 patients (17.4%) were treated at low-volume and 49,979 (82.6%) at high-volume facilities. In 2004, 78.2% of patients were treated at high-volume facilities, which increased to 84.6% in 2018 (P < .0001). Median travel distance and time for patients treated at high-volume centers was 12.2 miles (IQR, 5.6-25.5) and 23.0 min (IQR, 15.2-37.0), and 8.2 miles (IQR, 3.7-15.9) and 16.8 min (IQR, 12.4-26.0) for patients treated at low-volume centers. If cytoreductive surgery was centralized to high-volume centers, median distance and time traveled for patients originally treated at low-volume centers would be 11.2 miles (IQR, 3.8-32.3; P < .001) and 20.2 min (IQR, 13.6-43.0; P < .001). CONCLUSIONS: Centralizing cytoreductive surgery for OC to high-volume centers in New York would increase patient travel burden by negligible amounts of distance and time for most patients.

Procedural interventions for oligoprogression during treatment with immune checkpoint blockade in gynecologic malignancies: a case series.

OBJECTIVE: To evaluate the feasibility and outcomes of performing procedural interventions, defined as surgical resection, tumor ablation, or targeted radiation therapy, for oligoprogressive disease among patients with gynecologic malignancies who are treated with immune checkpoint blockade. METHODS: Patients with gynecologic cancers treated with immune checkpoint blockade between January 2013 and October 2021 who underwent procedural interventions including surgical resection, interventional radiology ablation, or radiation therapy for oligoprogressive disease were identified. Procedures performed before immune checkpoint therapy initiation or ≥6 months after therapy completion were excluded. Long immunotherapy duration prior to intervention was defined as ≥6 months. Progression-free survival and overall survival were calculated from procedure date until disease progression or death, respectively. RESULTS: During the study period, 886 patients met inclusion criteria and received immune checkpoint blockade therapy. Of these, 34 patients underwent procedural interventions for oligoprogressive disease; 7 underwent surgical resection, 3 underwent interventional radiology ablation, and 24 underwent radiation therapy interventions. Primary disease sites included uterus (71%), ovary (24%), and cervix (6%). Sites of oligoprogression included abdomen/pelvis (26%), bone (21%), lung (18%), distant lymph node (18%), brain (9%), liver (6%), and vagina (3%). Most tumors (76%) did not exhibit microsatellite instability or mismatch repair deficiency. Approximately half (53%) of the patients had long immune checkpoint therapy duration prior to intervention. Median progression-free survival following the procedure was 5.3 months (95% CI, 3.1-9.9), and median overall survival was 21.7 months (95% CI, 14.9-not estimable). Long versus short immune checkpoint therapy duration prior to procedure and length of immune checkpoint therapy had no effect on progression-free or overall survival. CONCLUSIONS: Procedural interventions for patients with oligoprogression on immune checkpoint blockade therapy are feasible and demonstrate favorable outcomes. With expanding use of immune checkpoint therapy, it is important to investigate combined modalities to maximize therapeutic benefit for patients with gynecologic cancers.

Safety and feasibility of therapeutic anticoagulation for newly diagnosed venous thromboembolism in women who undergo neoadjuvant chemotherapy for advanced ovarian cancer.

OBJECTIVE: We sought to investigate the safety and feasibility of therapeutic anticoagulation for newly diagnosed venous thromboembolism among women who undergo neoadjuvant chemotherapy for the treatment of advanced ovarian cancer. METHODS: A retrospective study using data extrapolated from a prospectively maintained institutional database was used to identify all patients with ovarian cancer who underwent neoadjuvant chemotherapy from April 2015 through September 2018 at our institution. All patients who received therapeutic anticoagulation for newly diagnosed venous thromboembolism at initial diagnosis or during neoadjuvant chemotherapy were included. RESULTS: Of 290 patients who underwent neoadjuvant chemotherapy for advanced ovarian cancer during the study period, 67 (23%) had newly diagnosed venous thromboembolism at the time of initial diagnosis or developed venous thromboembolism during neoadjuvant chemotherapy. Of these 67 patients, 64 (96%) received therapeutic anticoagulation. A total of 13 (20%) of 64 patients who underwent therapeutic anticoagulation experienced a bleeding episode while on anticoagulation; 4 (31%) of the 13 events were of major severity. Three patients developed major internal bleeding in the peritoneal cavity, and one patient suffered from a major vaginal bleeding episode. All four patients were hospitalized (range, 5-11 days) and received ≥2 units of red blood cells for anemia. None of these patients died from fatal bleeding or had to delay starting chemotherapy. Of note, all four patients received low-molecular-weight heparin via subcutaneous injection. Overall, 13 (20%) of 64 patients required an anticoagulant dose reduction, mostly due to weight loss or new bleeding episodes. CONCLUSION: Therapeutic anticoagulation in this setting appeared safe, with a low risk of major bleeding complications. Furthermore, anticoagulation did not result in delay of chemotherapy or cytoreductive surgery.

Impact of postoperative morbidity on outcomes in patients with advanced epithelial ovarian cancer undergoing intestinal surgery at the time of primary or interval cytoreductive surgery: A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVE: To assess the impact of short-term postoperative complications on oncologic outcomes for patients with epithelial ovarian cancer undergoing primary cytoreductive surgery (PCS) or interval cytoreductive surgery (ICS) with intestinal resection. METHODS: A retrospective chart review was performed for patients with ovarian cancer who underwent PCS or ICS with at least one intestinal resection at our institution from 1/1/2015 to 12/31/2020. Progression-free survival (PFS) and overall survival (OS) were analyzed for the PCS and ICS cohorts separately. Short-term complications within 30 days of surgery (surgical secondary events [SSEs]) were graded by a validated institutional SSE system. RESULTS: Among 437 patients who underwent intestinal resections during PCS (n = 289) or ICS (n = 148), 183 (42%) had one, 180 (41%) had two, and 74 (17%) had three intestinal resections. Six (1.4%) of 437 patients experienced an anastomotic leak postoperatively. There were no perioperative deaths. There was no difference in PFS and OS for patients who underwent PCS with any SSE vs. no SSE within 30 days of surgery (HR, 1.05; 95% CI: 0.76-1.47; p = 0.75 and HR, 0.79; 95% CI: 0.49-1.26; p = 0.32, respectively). There was no difference in PFS and OS for patients who underwent ICS with any SSE vs. no SSE within 30 days of surgery (HR, 1.43; 95% CI: 0.99-2.07; p = 0.055 and HR. 1.18; 95% CI: 0.72-1.93; p = 0.52, respectively. CONCLUSION: Short-term postoperative morbidity for patients who underwent intestinal surgery during primary surgical management for advanced ovarian cancer did not impact oncologic outcomes.

Salpingectomy for the Primary Prevention of Ovarian Cancer: A Systematic Review.

Importance: Most ovarian cancers originate in the fimbriated end of the fallopian tube. This has led to the hypothesis that surgical resection of the fallopian tubes at the time of gynecologic and nongynecologic surgical procedures-referred to as an opportunistic salpingectomy-may prevent the development of epithelial ovarian cancer for women at an average risk of developing the disease. Objective: To compile a comprehensive, state-of-the-science review examining the current landscape of performing bilateral salpingectomy for ovarian cancer prevention. Evidence Review: A systematic review of the literature was performed on March 4, 2022, to identify studies examining salpingectomy for ovarian cancer prevention. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 statement. Four databases were selected: PubMed via the National Library of Medicine's PubMed.gov, Embase via Elsevier's Embase.com, Cochrane Central Register of Controlled Trials (CENTRAL) via Wiley's Cochrane Library, and Northern Light Life Sciences Conference Abstracts via Ovid. A total of 20 gray literature sources, including 1 database, 2 registers, 1 repository, 1 index, 1 archive, 1 preprint server, 1 agency, and 12 organizations, were also searched. Findings: The initial search produced 1089 results; a total of 158 publications were included in the final review. Salpingectomy has been associated with ovarian cancer risk reduction of approximately 80%. Studies have demonstrated that salpingectomy was safe, cost-effective, and was not associated with an earlier age of menopause onset. With widespread implementation, salpingectomy has the potential to reduce ovarian cancer mortality in the US by an estimated 15%. Both physician and patient awareness regarding the adnexa as the origin for most ovarian cancers, as well as the existence of salpingectomy and its potential benefits in reducing ovarian cancer risk, has increased during the past decade. Raising awareness and developing effective implementation strategies are essential. Conclusions and Relevance: The results of this systematic review suggest that bilateral salpingectomy for ovarian cancer prevention was safe and feasible and has the potential to be a cost-effective and cost-saving strategy across the population. Prospective studies to demonstrate long-term survival outcomes and feasibility in nongynecologic surgical procedures are warranted.

Leave it in the past - primary treatment modality for high-grade epithelial ovarian cancer is not associated with secondary cytoreduction outcomes: A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVES: To compare outcomes of patients with high-grade epithelial ovarian cancer (EOC) who underwent secondary cytoreduction surgery (SCS) after up-front treatment with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) versus primary debulking surgery (PDS). METHODS: Patients with high-grade EOC who underwent SCS from 2/1/2004-10/31/2021 were classified by up-front treatment. Clinical and treatment characteristics were compared between cohorts. Progression-free survival (PFS2) and overall survival (OS2) following SCS were compared using a Cox model adjusted for stage, age at SCS, and number of years between end of chemotherapy and SCS. RESULTS: Of 374 patients, 62 (17%) underwent NACT-IDS and 312 (83%) PDS. Justification for NACT was disease extent (n = 57, 92%), comorbidities (n = 3, 5%), and thromboembolism (n = 2, 3%). The NACT-IDS cohort had a higher median age at SCS (64 years [IQR: 56-70] vs 59 years [IQR: 53-66]; P = .03), higher proportion of stage III/IV disease (100% vs 81%; P < .001), and shorter median interval between end of chemotherapy and SCS (1.5 years [IQR: 1.1-2.3] vs 1.9 years [IQR: 1.3-3.1]; P = .01). Achievement of complete gross resection at SCS did not differ between NACT-IDS and PDS (84% vs 88%; P = .18). PFS2 (HR: 1.19, 95% CI: 0.83-1.71) and OS2 (HR: 0.96, 95% CI: 0.57-1.63) did not vary by primary treatment modality after adjusting for clinically relevant covariates. CONCLUSIONS: Despite more extensive disease at presentation, patients with high-grade EOC who recur after NACT-IDS seem to have similar surgical and survival outcomes after SCS compared to patients who recur after PDS, suggesting that prior NACT-IDS should not preclude SCS.

Salpingectomy in Ovarian Cancer Prevention.

This Viewpoint explains the use of opportunistic salpingectomy, removal of the fallopian tubes for the primary prevention of ovarian cancer in a woman already undergoing pelvic surgery for another indication.

Chemotherapy response in low-grade serous ovarian carcinoma at a comprehensive cancer center: Readdressing the roles of platinum and cytotoxic therapies.

BACKGROUND: Data on platinum sensitivity of low-grade serous ovarian carcinoma (LGSOC) in the upfront setting is lacking, and there is limited and contradictory information on chemotherapy responses in recurrent disease. METHODS: Patients with LGSOC seen at a comprehensive cancer center from January 1, 1998 to September 30, 2021 were identified from institutional databases. Response to neoadjuvant chemotherapy (NACT) or adjuvant platinum-based chemotherapy and to second- to fifth-line regimens was retrospectively characterized by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Wilcoxon rank-sum and two-tailed Fisher exact tests were employed. RESULTS: Of 50 patients, 12 received platinum doublets for suboptimal residual disease and 11 as NACT. Of 12 patients with suboptimal residual disease, seven (58%) achieved objective responses (five partial responses [PRs] and two complete responses); of the 11 patients who underwent NACT, one (9%) achieved a PR (p = .027). The 15 remaining patients had stable disease on first-line platinum chemotherapy. Of 44 patients who recurred, 20 had RECIST-evaluable responses to second-line and 27 to third-line chemotherapy. Objective response rates to platinum-based chemotherapy were 22% (two of nine) in the second line and 10% (one of 10) in the third. In second and third lines, highest response rates were observed with nonplatinum chemotherapy with bevacizumab, at 100% (two of two) and 30% (three of 10), respectively. CONCLUSIONS: Primary platinum-based chemotherapy has moderate activity in LGSOC and minimal activity in the recurrent setting, suggesting standard definitions of platinum sensitivity may not apply in LGSOC. In the second and third lines, nonplatinum chemotherapy/bevacizumab elicited the highest response rates.

Intrathoracic surgery as part of primary cytoreduction for advanced ovarian cancer: Going to the next level - A Memorial Sloan Kettering Cancer Center study.

OBJECTIVE: We investigated the feasibility, safety, and survival outcomes of intrathoracic cytoreduction during primary debulking surgery (PDS) for advanced ovarian cancer. METHODS: We conducted a database review of patients with stage IIIB-IV ovarian (including fallopian tube and primary peritoneal) carcinoma who underwent PDS at our institution from 01/01/2006-9/30/2021. Patients who underwent intrathoracic cytoreduction as part of primary treatment were included. Patients who received neoadjuvant chemotherapy or surgery for reasons other than cytoreduction were excluded. RESULTS: Among 178 patients identified for inclusion, complete gross resection (CGR) in the abdomen and thorax was achieved in 131 (74%); 45 (25%) had optimal cytoreduction, and 2 (1%) had suboptimal cytoreduction. Thirty-one patients (17%) had at least one grade ≥ 3 complication; 8 were possibly related to intrathoracic cytoreduction. There were no deaths within 30 days following surgery. Median length of follow-up among survivors was 53.4 months. Among all patients, the median PFS was 33.6 months (95% CI: 24.7-61.9) and the 3-year PFS rate was 48.9% (95% CI: 41.2%-56.2%). Median OS was 81.3 months (95% CI: 68.9-103). When stratified by residual disease status, median PFS was 51.8 months when CGR was achieved versus 16.7 months with residual disease (HR: 2.17; P < .001) and median OS was 97.6 months when CGR was achieved versus 65.9 months with residual disease (HR: 2.05; P = .003). CONCLUSIONS: Intrathoracic cytoreduction during PDS for advanced ovarian cancer is both safe and feasible. CGR can be achieved in patients with intrathoracic disease if properly selected, and could significantly improve both PFS and OS.

Ten-year conditional probability of survival for patients with ovarian cancer: A new metric tailored to Long-term survivors.

OBJECTIVES: We assessed a conditional probability of survival (CPS) model to determine the probability of living 10 years after ovarian cancer diagnosis after having already survived 5 years. METHODS: We identified patients newly diagnosed with high-grade epithelial ovarian cancer from 1/1/2001-12/31/2009 and treated at our institution. Patients with <3 years follow-up were excluded. CPS was defined as the probability of surviving additional years (y) based on the condition a patient had already survived a given time (x): S(x + y)/S(x). Confidence intervals were estimated using a variation of Greenwood's formula. RESULTS: Of 916 patients meeting inclusion criteria, 473 (52%) were diagnosed from 2001 to 2005 and 443 (48%) from 2006 to 2009. Median age at diagnosis was 60 years (range, 25-95). The conventional 10-year OS rate for all patients was 29% (95% CI: 26%-32%)-75% (95% CI: 68%-82%) for stage I/II disease, 22% (95% CI: 19%-26%) for stage III, and 6.9% (95% CI: 3.9%-12%) for stage IV. For patients <65 years, the 10-year CPS for 5-year survivors was 65% (95% CI: 59%-70%); for those ≥65 years, it was 48% (95% CI: 38%-57%). For patients <65 years, the 10-year CPS for 5-year survivors by stage was: stage I/II, 89% (95% CI: 81%-94%); stage III, 58% (95% CI: 50%-66%); and stage IV, 26% (95% CI: 12%-42%). For patients ≥65 years, rates by stage were 78% (95% CI: 53%-91%), 42% (95% CI: 30%-53%), and 29% (95% CI: 7%-56%), respectively. CONCLUSIONS: For long-term survivors with high-grade epithelial ovarian cancer, CPS provides better prediction of survival than conventional methods.

Association of bowel preparation with surgical-site infection in gynecologic oncology surgery: Post-hoc analysis of a randomized controlled trial.

OBJECTIVE: To determine the relationship between bowel preparation and surgical-site infection (SSI) incidence following colorectal resection during gynecologic oncology surgery. METHODS: This post-hoc analysis used data from a randomized controlled trial of patients enrolled from 03/01/2016-08/20/2019 with presumed gynecologic malignancy investigating negative-pressure wound therapy among those requiring laparotomy. Patients were treated preoperatively without bowel preparation, oral antibiotic bowel preparation (OABP), or OABP plus mechanical bowel preparation (MBP) per surgeon preference. Univariate and multivariable analyses with stepwise model selection for SSI were performed for confirmed gynecologic malignancies requiring colorectal resection. RESULTS: Of 161 cases, 15 (9%) had no preparation, 39 (24%) OABP only, and 107 (66%) OABP+MBP. The overall SSI rate was 19% (n = 31)-53% (n = 8/15) in the no preparation, 21% (n = 8/39) in the OABP alone, and 14% (n = 15/107) in the OABP+MBP groups (P = 0.003). The difference between OABP and OABP+MBP was non-significant (P = 0.44). The median length of stay was 9 (range, 6-12), 6 (range, 5-8), and 7 days (range, 6-10), respectively (P = 0.045). The overall complication rate (34%; n = 54) did not significantly vary by preparation type (P = 0.23). On univariate logistic regression analysis, OABP (OR, 0.23; 95% CI: 0.06-0.80) and OABP+MBP (OR, 0.14; 95% CI: 0.04-0.45) were associated with decreased SSI risk compared to no preparation (P = 0.004). On multivariate analysis, both methods of preparation retained a significant impact on SSI rates (P = 0.004). CONCLUSION: Bowel preparation is associated with reduced SSI incidence and is beneficial for patients undergoing gynecologic oncology surgery with anticipated colorectal resection. Further investigation is needed to determine whether OABP alone is sufficient.

Outcomes and long-term follow-up by treatment type for patients with advanced-stage ovarian cancer managed at a tertiary cancer center: A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVE: To assess long-term outcomes of patients with advanced-stage ovarian cancer by treatment type. METHODS: Patients with newly diagnosed stage III-IV ovarian cancer who underwent primary treatment at our tertiary cancer center from 01/01/2015-12/31/2015 were included. We reviewed electronic medical records for clinicopathological, treatment, and survival characteristics. RESULTS: Of 153 patients, 88 (58%) had stage III and 65 (42%) stage IV disease. Median follow-up was 65.8 months (range, 3.6-75.3). Eighty-nine patients (58%) underwent primary debulking surgery (PDS), 50 (33%) received neoadjuvant chemotherapy followed by interval debulking surgery (IDS), and 14 (9%) received chemotherapy alone, without surgery (NSx). Median PFS to first recurrence was 26.2 months (range, 20.1-36.2), 13.5 months (range, 12-15.1), and 4.2 months (range, 1.1-5.8) in the PDS, IDS, and NSx groups, respectively (P < .001). At first recurrence/progression, 80 patients (72.7%) were treated with chemotherapy, 28 (25.5%) underwent secondary cytoreductive surgery (CRS) followed by chemotherapy, and 2 (1.8%) received no treatment. Seven patients (4.6%) underwent palliative surgery for malignant bowel obstruction. Overall, 62.7% received 1-3 lines of chemotherapy. The 5-year OS rates were 53.2% (95% CI: 44.7%-61%) for the entire cohort, 71.5% (95% CI: 60.2%-80%) for the PDS group, 35.2% (95% CI: 22.2-48.5%) for the IDS group, and 7.9% (95% CI: 0.5%-29.9%) for the NSx group. CONCLUSION: The longitudinal treatment modalities and outcomes of patients with advanced ovarian cancer described here can be useful for patient counseling, long-term planning, and future comparison studies.

High-Sensitivity Mutation Analysis of Cell-Free DNA for Disease Monitoring in Endometrial Cancer.

PURPOSE: We sought to determine whether sequencing analysis of circulating cell-free DNA (cfDNA) in patients with prospectively accrued endometrial cancer captures the mutational repertoire of the primary lesion and allows for disease monitoring. EXPERIMENTAL DESIGN: Peripheral blood was prospectively collected from 44 newly diagnosed patients with endometrial cancer over a 24-month period (i.e., baseline, postsurgery, every 6 months after). DNA from the primary endometrial cancers was subjected to targeted next-generation sequencing (NGS) of 468 cancer-related genes, and cfDNA to a high-depth NGS assay of 129 genes with molecular barcoding. Sequencing data were analyzed using validated bioinformatics methods. RESULTS: cfDNA levels correlated with surgical stage in endometrial cancers, with higher levels of cfDNA being present in advanced-stage disease. Mutations in cfDNA at baseline were detected preoperatively in 8 of 36 (22%) patients with sequencing data, all of whom were diagnosed with advanced-stage disease, high tumor volume, and/or aggressive histologic type. Of the 38 somatic mutations identified in the primary tumors also present in the cfDNA assay, 35 (92%) and 38 (100%) were detected at baseline and follow-up, respectively. In 6 patients with recurrent disease, changes in circulating tumor DNA (ctDNA) fraction/variant allele fractions in cfDNA during follow-up closely mirrored disease progression and therapy response, with a lead time over clinically detected recurrence in two cases. The presence of ctDNA at baseline (P < 0.001) or postsurgery (P = 0.014) was significantly associated with reduced progression-free survival. CONCLUSIONS: cfDNA sequencing analysis in patients with endometrial cancer at diagnosis has prognostic value, and serial postsurgery cfDNA analysis enables disease and treatment response monitoring. See related commentary by Grant et al., p. 305.

Ovarian cancer mutational processes drive site-specific immune evasion.

High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability1-4 patterned by distinct mutational processes5,6, tumour heterogeneity7-9 and intraperitoneal spread7,8,10. Immunotherapies have had limited efficacy in HGSOC11-13, highlighting an unmet need to assess how mutational processes and the anatomical sites of tumour foci determine the immunological states of the tumour microenvironment. Here we carried out an integrative analysis of whole-genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumour sites from 42 treatment-naive patients with HGSOC. Homologous recombination-deficient HRD-Dup (BRCA1 mutant-like) and HRD-Del (BRCA2 mutant-like) tumours harboured inflammatory signalling and ongoing immunoediting, reflected in loss of HLA diversity and tumour infiltration with highly differentiated dysfunctional CD8+ T cells. By contrast, foldback-inversion-bearing tumours exhibited elevated immunosuppressive TGFß signalling and immune exclusion, with predominantly naive/stem-like and memory T cells. Phenotypic state associations were specific to anatomical sites, highlighting compositional, topological and functional differences between adnexal tumours and distal peritoneal foci. Our findings implicate anatomical sites and mutational processes as determinants of evolutionary phenotypic divergence and immune resistance mechanisms in HGSOC. Our study provides a multi-omic cellular phenotype data substrate from which to develop and interpret future personalized immunotherapeutic approaches and early detection research.