Cliby, William A.

PURPOSE To compare mortality risk among long-term survivors of high-grade serous ovarian cancer (HGSOC) with that of the general US population and to examine how mortality and recurrence trends have evolved under changing treatment approaches. MATERIALS AND METHODS This is a retrospective cohort study including patients with histologically confirmed HGSOC treated at a single referral cancer center from 1991 to 2022. Mortality risk, expressed as standardized mortality ratios (SMRs, ratio of observed deaths in the study population to expected deaths in an age-matched US population), was assessed at diagnosis and yearly on patients without events (disease persistence, recurrence, or death from any cause). RESULTS A total of 2,074 consecutive patients were included. The median follow-up was 12.5 years (IQR, 11.7-13.8). Most patients were stage III (1,396, 69.2%), 1,299 (62.8%) underwent primary cytoreductive surgery, and 1,688 (87.4%) received platinum-taxane as first-line therapy. At diagnosis, the mortality rate was 7.40 times higher than that in the general population (95% CI, 7.04 to 7.77). By 7 event-free years, the 95% CI for the SMR included 1 for the first time, and at 10 years, the SMR was 1.05 (95% CI, 0.72 to 1.49), indicating no statistically significant excess mortality compared with the general population. In those event-free at 10 years, the 5-year cumulative incidence of ovarian cancer–related deaths (8.2% [95% CI, 4.2 to 16.0]) was comparable with that of non–ovarian cancer–related deaths (6.3% [95% CI, 2.9 to 13.8]). CONCLUSION In this cohort, mortality risk steadily declined for patients who remained event-free, approaching that of the general population by 7 years after diagnosis. These results emphasize the importance of individualized, long-term follow-up to address both recurrence risk and survivorship needs.

Importance Ovarian cancer is the eighth most common cause of cancer and cancer death in women worldwide. In 2022, ovarian cancer was diagnosed in approximately 324 398 individuals, and 206 839 died of ovarian cancer worldwide. In 2025, it is estimated that 20 890 US women will be diagnosed with ovarian cancer and 12 730 patients will die of ovarian cancer. Observations Approximately 90% of ovarian cancers are epithelial malignancies, of which 70% to 80% are high-grade serous ovarian cancers. Less common epithelial subtypes include endometrioid, clear cell, low-grade serous, mucinous, and carcinosarcoma. The median age at diagnosis of ovarian cancer is 63 years. Risk factors include older age, family history of breast or ovarian cancer, endometriosis, and nulliparity. Hereditary factors are associated with 25% of cases, predominantly linked to BRCA1 / 2 gene variants. At diagnosis, approximately 95% of patients experience nonspecific symptoms, such as abdominal pain, bloating, and urinary urgency and frequency, and about 80% have advanced-stage disease (stage III-IV), including extrapelvic disease, ascites, and abdominal masses. Diagnostic and staging evaluation includes pelvic ultrasound; computed tomography of the chest, abdomen, and pelvis; and serum tumor markers such as carbohydrate antigen 125, carbohydrate antigen 19-9, and carcinoembryonic antigen. First-line treatment for early-stage ovarian cancer, defined as limited to the ovary or fallopian tube (stage I) or confined to the pelvis (stage II), is surgery (hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymphadenectomy), followed by adjuvant chemotherapy (carboplatin and paclitaxel). With treatment, early-stage ovarian cancer has a 5-year overall survival of 70% to 95%. Advanced-stage ovarian cancer may be treated with primary cytoreductive surgery (removal of all visible cancer in the abdominal cavity) and adjuvant chemotherapy (carboplatin and paclitaxel) or with neoadjuvant chemotherapy followed by cytoreductive surgery and adjuvant chemotherapy. Most patients with advanced-stage ovarian cancer receive maintenance therapy with bevacizumab (a monoclonal antibody that blocks angiogenesis) and/or poly–adenosine diphosphate ribose polymerase (PARP) inhibitors. With treatment, the 5-year overall survival rate for advanced-stage ovarian cancer is 10% to 40%. However, individuals with BRCA -related gene variants have a 5-year overall survival rate of approximately 70% with PARP inhibitor treatment. Despite an initial remission rate of 80%, approximately 75% of patients with advanced-stage disease have ovarian cancer relapse within 2 years. Conclusions and Relevance Approximately 21 000 women are diagnosed with ovarian cancer annually in the US, and approximately 80% have advanced-stage ovarian cancer at diagnosis. First-line treatment of early-stage ovarian cancer is surgery and adjuvant platinum-based chemotherapy. Treatment of advanced-stage ovarian cancer includes cytoreductive surgery, platinum-based chemotherapy, and targeted maintenance therapies such as bevacizumab and/or PARP inhibitors.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide updated guidance regarding neoadjuvant chemotherapy (NACT) and primary cytoreductive surgery (PCS) among patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (epithelial ovarian cancer [EOC]). METHODS A multidisciplinary Expert Panel convened and updated the systematic review. RESULTS Sixty-one studies form the evidence base. RECOMMENDATIONS Patients with suspected stage III-IV EOC should be evaluated by a gynecologic oncologist, with cancer antigen 125, computed tomography of the abdomen and pelvis, and chest imaging included. All patients with EOC should be offered germline genetic and somatic testing at diagnosis. For patients with newly diagnosed advanced EOC who are fit for surgery and have a high likelihood of achieving complete cytoreduction, PCS is recommended. For patients fit for PCS but deemed unlikely to have complete cytoreduction, NACT is recommended. Patients with newly diagnosed advanced EOC and a high perioperative risk profile should receive NACT. Before NACT, patients should have histologic confirmation of invasive ovarian cancer. For NACT, a platinum-taxane doublet is recommended. Interval cytoreductive surgery (ICS) should be performed after ≤four cycles of NACT for patients with a response to chemotherapy or stable disease. For patients with stage III disease, good performance status, and adequate renal function treated with NACT, hyperthermic intraperitoneal chemotherapy may be offered during ICS. After ICS, chemotherapy should continue to complete a six-cycle treatment plan with the optional addition of bevacizumab. Patients with EOC should be offered US Food and Drug Administration–approved maintenance treatments. Patients with progressive disease on NACT should have diagnosis reconfirmed via tissue biopsy. Patients without previous comprehensive genetic or molecular profiling should be offered testing. Treatment options include alternative chemotherapy regimens, clinical trials, and/or initiation of end-of-life care. Additional information is available at www.asco.org/gynecologic-cancer-guidelines . This guideline has been endorsed by the Society of Gynecologic Oncology.

Objective: Using a triage algorithm for primary cytoreductive surgery (PCS) reduces perioperative mortality, however, nonlethal complications are common. This study identified procedures associated with postoperative complications in triage-appropriate women, with the aim of guiding the next steps to foster surgical quality improvement. Materials and Methods: Consecutive triage-appropriate women with stage IIIC/IV ovarian cancer undergoing PCS, from January 2012 to April 2018, were included. The expanded Accordion scale was used to grade complications. Adjusted risk ratios ( RRs ) were calculated to quantify the association between concomitant procedures and risk of 30-day grade 3+ (G3+) complications by fitting Poisson regression models adjusted for performance status and age. Population-attributable risk (PAR) was calculated based on the adjusted RR s and prevalence of each procedure. Results: Of 214 women, 82.7% had intermediate- or high-complexity surgery, 68.7% had complete gross resection, 3.7% had residual disease >1 cm, and 18.7% experienced G3+ complications. In univariate analysis, operative time, surgical complexity, splenectomy, and bowel resection (any and extent of) were associated with G3+ complications. Operative time, bowel resection (any, extent of, and large) were associated with G4+ complications. In the adjusted analysis for G4+ complications, bowel resection (any, extent of, and large) had statistically significant PAR values of 60.7%, 54.7%, and 50.8%, respectively. PAR values associated with G3+ complications were 27.4% and 26.8% for any and multiple bowel resections, respectively. Conclusions: Bowel resection, upper abdominal procedures, and longer operative times are essential for PCS, but each contributes to the relatively constant rates of postoperative morbidity despite triage to prevent frail patients from undergoing PCS. Surgical-improvement research should focus on improving the safety of these procedures. (J GYNECOL SURG 39:123)

Abstract Data evaluating change in body composition during treatment of advanced cancer are limited. Here we evaluated computed tomography (CT)–based changes in muscle mass during treatment for advanced ovarian cancer (OC) and association with outcomes. We analyzed the preoperative and posttreatment skeletal muscle index (SMI), skeletal muscle area normalized for height of 109 patients with advanced OC who underwent primary surgery and platinum-based chemotherapy from 2006 to 2016. Based on an SMI less than 39 cm2/m2, 54.1% of patients were never sarcopenic, 24.8% were sarcopenic on both CT scans, and 21.1% were newly sarcopenic upon treatment completion. Patients who lost muscle during treatment had the worst survival of the 3 groups identified: median survival 2.6 years vs 4.6 years if sarcopenic on both CT scans and 4.8 years if never sarcopenic. Loss of muscle portends a poor prognosis among patients with OC. Additional research is needed to better understand and best mitigate these changes.

307 Background: In the US, more than 12,000 people die from ovarian cancer annually. Although new treatments have recently become available, ovarian cancer care delivery remains suboptimal. The Association of Community Cancer Centers (ACCC) developed a series of initiatives to improve the quality of care for patients with ovarian cancer. In Phase I, ACCC evaluated the needs of cancer programs, conducted 3 quality improvement (QI) workshops, and developed expert-driven Quality of Care recommendations to aid cancer programs in self-assessment and quality improvement. In Phase II, ACCC invited programs to self-assess their level of care using the Quality of Care recommendations. Methods: In 2022, ACCC surveyed 7 ovarian cancer programs across the US. Developed by a multidisciplinary expert steering committee, the 26-question survey assessed the patient populations served, services provided, diagnostic evaluations performed, access to molecular testing, and a self-assessment of quality care delivery and interest in conducting QI projects related to self-identified needs. The survey was administered in Qualtrics and summarized using descriptive statistics. Results: Surveys were completed by 1 community, 2 comprehensive community, 2 hospital-associated, 1 academic comprehensive, and 1 NCI-designated comprehensive cancer programs. The median annual ovarian cases was 40 [range: 2 to 68]. The 7 programs serve diverse racial/ethnic distribution of patients with ovarian cancer ranging from 55% Black to 60% Asian and 30% Pacific Islander. Five programs have a multidisciplinary team for ovarian cancer. All 5 multidisciplinary teams included gynecologic oncology and pathology; 3 teams also included medical oncology and or radiology colleague(s). Sites assessed their level of care for 7 domains of quality care from 1 (lowest) to 5 (highest). The average score was 4.0 for Care Coordination and Patient Education, Treatment Planning, and Disease Surveillance. Diagnosis and Initial Management scored on average 3.8, Equity in Care 3.25, Prevention and Screening 3.25, and Quality of Life 3.2. Sites ranked areas of interest for future QI projects (1 = area of most interest, 7 = area of least interest). The highest ranked domains were Care Coordination and Patient Education as well as Diagnosis and Initial management (average rankings 2.8). These were followed by Quality of Life (average 3.0), Prevention and Screening (Average 3.8), Treatment Planning (Average 4.4), Equity in Care (Average 5.0), and Disease Surveillance (Average 6.2). Conclusions: This assessment will be used to identify 4 additional sites for Phase II QI workshops. Findings from these projects will be combined, summarized, and disseminated to inform future education opportunities and QI initiatives. This initiative aims to help organize and standardize the care of patients with ovarian cancer and improve patient care coordination.

5510 Background: Transcriptional profiling of ovarian cancers has proven to be complex. As such it has been difficult to validate existing signatures across studies. Cancer Genome Atlas (TCGA) researchers have identified four molecular subtypes of high-grade serous ovarian cancer (HGSOC). However, survival duration did not differ significantly for the TCGA subtypes. Potential limitations of the TCGA data include short clinical follow-up (45% were alive at the time of last follow-up) and the need to unify gene expression measures from multiple platforms. Methods: Clinically annotated stage-II–IV HGSOC samples (n = 175) with >70% tumor cell content were profiled using the Agilent Whole Human Genome 4 x 44K chip. To identify subtypes non-negative matrix factorization (NMF) of mRNA expression was performed using ~2000 genes with the highest variability across patients. In parallel differentially expressed genes were identified using the Rosetta Similarity Search Tool as well as analysis of variance based on genes known to be involved in epithelial to mesenchymal transition. Results: Median follow-up time was 35 months (range, 0–202 months, 12% were alive at the time of last follow-up). NMF clustering confirmed four HGSOC subtypes (immunoreactive, differentiated, proliferative, and mesenchymal) on the basis of gene content in the clusters. Pathway signatures with therapeutic potential were identified for individual or multiple subtypes. Survival differed significantly between the four molecular subgroups in univariate (Hazard Ratio [HR] 2.4, 95% CI 1.5-4.1, p = 0.007) and multivariate (HR 2.3, 95% CI 1.3-4.0, p = 0.003) analyses when accounting for age, stage, grade, and postoperative residual tumor. Using the supervised clustering approach two distinct molecular subtypes of HGSOC based on epithelial and mesenchymal gene expression signatures were identified with significantly different survival outcomes. Conclusions: Here we independently validate and expand upon the molecular TCGA classification of HGSOC. The potential of these two prognostic classifiers may lie in their ability to recognize categories of patients that are more likely to respond to particular therapies.

5076 Background: Advanced OVCA should be managed aggressively, and extensive surgery has been the most accepted initial treatment. Medically unfit patients or those with extensive disease, in which complete cytoreduction is unlikely, may not benefit from upfront radical surgery, and neoadjuvant chemotherapy might be an appropriate alternative. Thus, reliable preoperative indicators of surgical outcome are necessary for considering primary surgery vs. neoadjuvant chemotherapy. Our aim is to determine if C-reactive protein (CRP), IL-6, albumin and Glasgow Prognostic Score (GPS – score based on CRP and albumin) correlate with overall survival (OS), length of hospital stay (LOS), surgical morbidity, and suboptimal cytoreduction. Methods: We randomly selected 50 stages III/IV OVCA who underwent surgery as a primary treatment between July 2002 and June 2009 at Mayo Clinic with serum albumin levels and frozen serum available. CRP and IL-6 were measured in stored serum. Univariate and multivariate regression models were fit to evaluate associations with each of the outcomes. Results: Among the 50 patients, the mean age was 67.7 years. 34% had pretreatment albumin <3.5 g/ml, 22.4% had CRP level ≥10 mg/l, 26.5% had IL-6 ≥24 pg/ml and 45% had abnormal GPS score. At 1, 3 and 5 years following surgery, the OS was 75.6%, 49.8% and 36.9%, respectively. RD (0, <1, ≥1cm; p<0.001) was the only independent predictor of OS. Also, IL-6 (p=0.028) and stage (p=0.046) were independently associated with LOS, but no inflammatory or nutritional markers were significant associated with post surgical complications. Stage IV (p=0.019) and elevated CRP (p=0.044) were independent predictors of suboptimal surgery (RD ≥ 1cm). Conclusions: One-third of the patients in our series had low serum albumin at the time of the OVCA diagnosis, and at least one-fourth had elevated inflammatory markers. Advanced stage and elevated inflammatory markers (CRP and IL-6) were independent predictors of longer hospital stay and suboptimal debulking. These pilot data, if confirmed in a larger population, may help in the selection of candidates for neoadjuvant chemotherapy.