JAMA Surgery

Prophylactic Salpingo-Oophorectomy and Survival After BRCA1/2 Breast Cancer Resection

ImportanceFew studies have investigated whether prophylactic salpingo-oophorectomy (PSO) for patients with previously resected breast cancer who carry pathogenic germline BRCA1 or BRCA2 variants is associated with a reduced risk of cancer-specific death.ObjectiveTo assess the association of PSO and prophylactic mastectomy (PM) with prognosis after quadrantectomy or mastectomy as primary treatment for patients with BRCA1 or BRCA2 breast cancer.Design, Setting, and ParticipantsThis retrospective cohort study was performed in a single-institution, tertiary referral center. Consecutive patients with invasive breast cancer treated surgically between 1972 and 2019 were recruited and followed up prospectively after they were found to carry the BRCA1 or BRCA2 gene variant. The data analysis was performed between April 2022 and July 2023.ExposureFollowing breast surgery, some patients underwent PSO, PM, or both, whereas others did not.Main Outcomes and MeasuresThe primary study end point was overall survival as measured by the Kaplan-Meier method. Secondary end points were crude cumulative incidence of breast cancer–specific mortality, ipsilateral breast tumor recurrence (IBTR), contralateral breast cancer, ovarian cancer, and ovarian cancer–specific mortality.ResultsOf 480 patients included in the cohort (median age at initial surgery, 40.0 years; IQR, 34.0-46.0 years), PSO was associated with a significantly reduced risk of death (hazard ratio [HR], 0.40; 95% CI, 0.25-0.64; P < .001). This reduction was most evident for patients carrying the BRCA1 variant (HR, 0.35; 95% CI, 0.20-0.63; P = .001), those with triple-negative disease (HR, 0.21; 95% CI, 0.09-0.46; P = .002), and those with invasive ductal carcinoma (HR, 0.51; 95% CI, 0.31-0.84; P = .008). Prophylactic salpingo-oophorectomy was not associated with risk of contralateral breast cancer or IBTR. Initial or delayed PM was associated with a reduced risk of IBTR but not with overall survival or breast cancer–specific mortality.ConclusionsThe study findings suggest that PSO should be offered to all patients with BRCA1/2 breast cancer who undergo surgery with curative intent to reduce risk of death. In particular, PSO should be offered to patients with the BRCA1 variant at the time of breast surgery.

Salpingectomy for the Primary Prevention of Ovarian Cancer

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.

Hyperthermic Intraperitoneal Chemotherapy After Interval Cytoreductive Surgery for Patients With Advanced-Stage Ovarian Cancer Who Had Received Neoadjuvant Chemotherapy

ImportanceHyperthermic intraperitoneal chemotherapy (HIPEC) followed by interval cytoreductive surgery (ICS) has shown survival benefits for patients with advanced-stage ovarian cancer. However, there is still a lack of consensus regarding the integration of HIPEC into clinical practice.ObjectiveTo evaluate the safety and effectiveness of ICS with HIPEC compared with ICS alone in clinical practice for patients with advanced-stage ovarian cancer.Design, Setting, and ParticipantsThis prospective, multicenter, comparative effectiveness cohort study enrolled 205 patients with stage III or IV ovarian cancer who had received at least 3 cycles of neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC at 7 Korean Gynecologic Oncology Group institutions between September 1, 2017, and April 22, 2022. Nine patients were excluded because they did not meet the inclusion criteria.ExposuresNeoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC.Main Outcomes and MeasuresThe primary end point was progression-free survival (PFS). Overall survival (OS) and the safety profile were the key secondary end points.ResultsThis study included 196 patients (median age, 58.0 years [range, 38-82 years]), of whom 109 underwent ICS with HIPEC and 87 underwent ICS without HIPEC. The median duration of follow-up was 28.2 months (range, 3.5-58.6 months). Disease recurrence occurred in 128 patients (65.3%), and 30 patients (15.3%) died. Interval cytoreductive surgery with HIPEC was associated with a significant improvement in median PFS compared with ICS without HIPEC (22.9 months [95% CI, 3.5-58.6 months] vs 14.2 months [95% CI, 4.0-56.2 months]; P = .005) and median OS (not reached [95% CI, 3.5 months to not reached] vs 53.0 [95% CI, 4.6-56.2 months]; P = .002). The frequency of grade 3 or 4 postoperative complications was similar in both groups (ICS with HIPEC, 3 of 109 [2.8%] vs ICS without HIPEC, 3 of 87 [3.4%]; P > .99). Among patients with recurrence, the frequency of peritoneal recurrence was lower in the ICS with HIPEC group than in the ICS without HIPEC group (21 of 64 [32.8%] vs 41 of 64 [64.1%]; P = .001).Conclusions and RelevanceThis study suggests that ICS in conjunction with HIPEC was associated with longer PFS and OS than ICS without HIPEC for patients with advanced-stage ovarian cancer and was not associated with higher rates of postoperative complications. The lower rate of peritoneal recurrence after HIPEC may be associated with improved OS.

Assessing Breast and Ovarian Cancer Risk Prior to Gender-Affirming Surgery

This Viewpoint discusses the need for assessing the risk of hereditary breast and ovarian cancer in individuals seeking gender-affirming surgery and referring eligible patients to genetic counseling and testing services before surgery.

Assessment of Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging

Whether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy for surgical staging in patients with high-grade endometrial cancer (EC) is unclear. To examine the diagnostic accuracy of, performance characteristics of, and morbidity associated with SLNB using indocyanine green in patients with intermediate- and high-grade EC. In this prospective, multicenter cohort study (Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging [SENTOR] study), accrual occurred from July 1, 2015, to June 30, 2019, with early stoppage because of prespecified accuracy criteria. The study included patients with clinical stage I grade 2 endometrioid or high-grade EC scheduled to undergo laparoscopic or robotic hysterectomy with an intent to complete staging at 3 designated cancer centers in Toronto, Ontario, Canada. All patients underwent SLNB followed by lymphadenectomy as the reference standard. Patients with grade 2 endometrioid EC underwent pelvic lymphadenectomy (PLND) alone, and patients with high-grade EC underwent PLND and para-aortic lymphadenectomy (PALND). The primary outcome was sensitivity of the SLNB algorithm. Secondary outcomes were additional measures of diagnostic accuracy, sentinel lymph node detection rates, and adverse events. The study enrolled 156 patients (median age, 65.5 years; range, 40-86 years; median body mass index [calculated as weight in kilograms divided by height in meters squared], 27.5; range, 17.6-49.3), including 126 with high-grade EC. All patients underwent SLNB and PLND, and 101 patients (80%) with high-grade EC also underwent PALND. Sentinel lymph node detection rates were 97.4% per patient (95% CI, 93.6%-99.3%), 87.5% per hemipelvis (95% CI, 83.3%-91.0%), and 77.6% bilaterally (95% CI, 70.2%-83.8%). Of 27 patients (17%) with nodal metastases, 26 patients were correctly identified by the SLNB algorithm, yielding a sensitivity of 96% (95% CI, 81%-100%), a false-negative rate of 4% (95% CI, 0%-19%), and a negative predictive value of 99% (95% CI, 96%-100%). Only 1 patient (0.6%) was misclassified by the SLNB algorithm. Seven of 27 patients with node-positive cancer (26%) were identified outside traditional PLND boundaries or required immunohistochemistry for diagnosis. In this prospective cohort study, SLNB had acceptable diagnostic accuracy for patients with high-grade EC at increased risk of nodal metastases and improved the detection of node-positive cases compared with lymphadenectomy. The findings suggest that SLNB is a viable option for the surgical staging of EC.

Sentinel Lymph Node Concept in High–Risk Profile Endometrial Cancer

Perspectives on Hyperthermic Intraperitoneal Chemotherapy for Advanced Ovarian Cancer

Perspectives on Hyperthermic Intraperitoneal Chemotherapy for Advanced Ovarian Cancer—Reply

Perspectives on Hyperthermic Intraperitoneal Chemotherapy for Advanced Ovarian Cancer

Survival After Hyperthermic Intraperitoneal Chemotherapy and Primary or Interval Cytoreductive Surgery in Ovarian Cancer

Ovarian cancer has the highest mortality rate among gynecologic malignant tumors. Data are lacking on the survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with ovarian cancer who underwent primary or interval cytoreductive surgery. To assess the clinical benefit of HIPEC after primary or interval maximal cytoreductive surgery in women with stage III or IV primary advanced ovarian cancer. In this single-blind randomized clinical trial performed at 2 institutions in South Korea from March 2, 2010, to January 22, 2016, a total of 184 patients with stage III or IV ovarian cancer with residual tumor size less than 1 cm were randomized (1:1) to a HIPEC (41.5 °C, 75 mg/m2 of cisplatin, 90 minutes) or control group. The primary end point was progression-free survival. Overall survival and adverse events were key secondary end points. The date of the last follow-up was January 10, 2020, and the data were locked on February 17, 2020. Hyperthermic intraperitoneal chemotherapy after cytoreductive surgery. Progression-free and overall survival. Of the 184 Korean women who underwent randomization, 92 were randomized to the HIPEC group (median age, 52.0 years; IQR, 46.0-59.5 years) and 92 to the control group (median age, 53.5 years; IQR, 47.5-61.0 years). After a median follow-up of 69.4 months (IQR, 54.4-86.3 months), median progression-free survival was 18.8 months (IQR, 13.0-43.2 months) in the control group and 19.8 months (IQR, 13.7-55.4 months) in the HIPEC group (P = .43), and median overall survival was 61.3 months (IQR, 34.3 months to not reported) in the control group and 69.5 months (IQR, 45.6 months to not reported) in the HIPEC group (P = .52). In the subgroup of interval cytoreductive surgery after neoadjuvant chemotherapy, the median progression-free survival was 15.4 months (IQR, 10.6-21.1 months) in the control group and 17.4 months (IQR, 13.8-31.5 months) in the HIPEC group (hazard ratio for disease progression or death, 0.60; 95% CI, 0.37-0.99; P = .04), and the median overall survival was 48.2 months (IQR, 33.8-61.3 months) in the control group and 61.8 months (IQR, 46.7 months to not reported) in the HIPEC group (hazard ratio, 0.53; 95% CI, 0.29-0.96; P = .04). In the subgroup of primary cytoreductive surgery, median progression-free survival was 29.7 (IQR, 17.2-90.1 months) in the control group and 23.9 months (IQR, 12.3-71.5 months) in the HIPEC group, and the median overall survival was not reached in the control group and 71.3 months (IQR, 45.6 months to not reported) in the HIPEC group. The addition of HIPEC to cytoreductive surgery did not improve progression-free and overall survival in patients with advanced epithelial ovarian cancer. Although the results are from a subgroup analysis, the addition of HIPEC to interval cytoreductive surgery provided an improvement of progression-free and overall survival. ClinicalTrials.gov Identifier: NCT01091636.

Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Epithelial Ovarian Cancer

The Intersection of Endometriosis and Ovarian Cancer Prevention

Surgeon Type and Anastomotic Leaks in Ovarian Cancer

Bowel Resection Outcomes in Ovarian Cancer Cytoreductive Surgery by Surgeon Specialty

ImportanceExtensive bowel surgery is often necessary to achieve complete cytoreduction in patients with epithelial ovarian cancer. Regardless of who performs the surgery, it has been well documented that bowel resections are a high-risk procedure and an anastomotic leak is a severe complication that can occur. There are few studies addressing whether surgeon type impacts surgical outcomes in this patient population.ObjectiveTo compare surgical outcomes between gynecologic oncologist, general surgeons, and a 2-surgeon team approach for patients with advanced epithelial ovarian cancer who underwent bowel surgery during cytoreductive debulking.Design, Setting, ParticipantsThis retrospective cohort study used the American College of Surgeons’ National Surgical Quality Improvement Program datasets from 2012 through 2020. The aforementioned years of the dataset were analyzed from March 2022 to March 2023 and reanalyzed in May 2024 for quality assurance. Analysis of cytoreductive surgeries performed by a gynecologic oncologist, a general surgeon, or a 2-surgeon team approach for patients with ovarian cancer recorded in National Surgical Quality Improvement Program datasets was included. The 2-surgeon team approach included any combination of the aforementioned surgical specialties.Main outcome and measureThe primary outcome of interest was anastomotic leak after bowel surgery during ovarian cancer debulking.ResultsA total of 1810 patients were included in the study; in the general surgery cohort, mean (SD) patient age was 65.1 (11.1) years and mean (SD) body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) was 26.9 (7.4); in the gynecologic oncology cohort, mean (SD) patient age was 63.5 (11.7) years and mean BMI (SD) was 27.7 (6.5); and in the 2-surgeon team cohort, mean (SD) patient age 62.4 (12.1) years and mean (SD) BMI was 28.1 (7.0). Gynecologic oncologists performed 1217 cases (67.2%), general surgery performed 97 cases (5.4%), and 496 cases had 2-surgeon teams involved (27.4%). Bivariate analysis revealed an anastomotic leak rate of 3.6% for gynecologic oncologists, 5.2% for general surgeons, and 0.4% for cases that had 2 surgical teams involved (P < .001). By multivariable analysis, the adjusted odds ratio for anastomotic leak was 1.53 (95% CI, 0.59-3.96) for the general surgeon group (P = .38) vs an adjusted odds ratio of 0.11 (95% CI, 0.03-0.47) for the 2-surgeon team approach (P = .003) with the referent being gynecologic oncology.Conclusion and RelevanceIn this study, the anastomotic leak rate was found to be lower when 2 surgeons participated in the case, regardless of the surgical specialty. These results suggest that team-based care improves surgical outcomes.

Primary Care Use and 90-Day Mortality Among Older Adults Undergoing Cancer Surgery

ImportanceMultimorbidity and postoperative clinical decompensation are common among older surgical patients with cancer, highlighting the importance of primary care to optimize survival. Little is known about the association between primary care use and survivorship among older adults (aged ≥65 years) undergoing cancer surgery.ObjectiveTo examine primary care use among older surgical patients with cancer and its association with mortality.Design, Setting, and ParticipantsIn this retrospective cohort study, data were abstracted from the electronic health record of a single health care system for older adults undergoing cancer surgery between January 1, 2017, and December 31, 2019. There were 3 tiers of stratification: (1) patients who had a primary care practitioner (PCP) (physician, nurse practitioner, or physician assistant) vs no PCP, (2) those who had a PCP and underwent surgery in the same health system (unfragmented care) vs not (fragmented care), and (3) those who had a primary care visit within 90 postoperative days vs not. Data were analyzed between August 2023 and January 2024.ExposurePrimary care use after surgery for colorectal, head and neck, prostate, ovarian, pancreatic, breast, liver, renal cell, non–small cell lung, endometrial, gastric, or esophageal cancer.Main Outcomes and MeasuresPostoperative 90-day mortality was analyzed using inverse propensity weighted Kaplan-Meier curves, with log-rank tests adjusted for propensity scores.ResultsThe study included 2566 older adults (mean [SEM] age, 72.9 [0.1] years; 1321 men [51.5%]). Although 2404 patients (93.7%) had health insurance coverage, 743 (28.9%) had no PCP at the time of surgery. Compared with the PCP group, the no-PCP group had a higher 90-day postoperative mortality rate (2.0% vs 3.6%, respectively; adjusted P = .03). For the 823 patients with unfragmented care, 400 (48.6%) had a primary care visit within 90 postoperative days (median time to visit, 34 days; IQR, 20-57 days). Patients who had a postoperative primary care visit were more likely to be older, have a higher comorbidity burden, have an emergency department visit, and be readmitted. However, they had a significantly lower 90-day postoperative mortality rate than those who did not have a primary care visit (0.3% vs 3.3%, respectively; adjusted P = .001).Conclusions and RelevanceThese findings suggest that follow-up with primary care within 90 days after cancer surgery is associated with improved survivorship among older adults.

Bariatric Surgery and Longitudinal Cancer Risk

ImportanceCancer is one of the leading causes of death in the United States, with the obesity epidemic contributing to its steady increase every year. Recent cohort studies find an association between bariatric surgery and reduced longitudinal cancer risk, but with heterogeneous findings.ObservationsThis review summarizes how obesity leads to an increased risk of developing cancer and synthesizes current evidence behind the potential for bariatric surgery to reduce longitudinal cancer risk. Overall, bariatric surgery appears to have the strongest and most consistent association with decreased incidence of developing breast, ovarian, and endometrial cancers. The association of bariatric surgery and the development of esophageal, gastric, liver, and pancreas cancer is heterogenous with studies showing either no association or decreased longitudinal incidences. Conversely, there have been preclinical and cohort studies implying an increased risk of developing colon and rectal cancer after bariatric surgery. A review and synthesis of the existing literature reveals epidemiologic shortcomings of cohort studies that potentially explain incongruencies observed between studies.Conclusions and RelevanceStudies examining the association of bariatric surgery and longitudinal cancer risk remain heterogeneous and could be explained by certain epidemiologic considerations. This review provides a framework to better define subgroups of patients at higher risk of developing cancer who would potentially benefit more from bariatric surgery, as well as subgroups where more caution should be exercised.

Salpingectomy and Ovarian Cancer Prevention

Salpingectomy and Ovarian Cancer Prevention—Reply

Sentinel Lymph Node Concept in High–Risk Profile Endometrial Cancer—Reply