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The Cancer Genome Atlas recently identified a genomic-based molecular classification of endometrial carcinomas, with 4 molecular categories: (1) ultramutated (polymerase epsilon [POLE] mutated), (2) hypermutated (microsatellite instability), (3) copy number abnormalities-low, and (4) copy number abnormalities-high. Two studies have since proposed models to classify endometrial carcinomas into 4 molecular subgroups, modeled after The Cancer Genome Atlas, using simplified and more clinically applicable surrogate methodologies. In our study, 151 endometrial carcinomas were molecularly categorized using sequencing for the exonuclease domain mutations (EDM) of POLE, and immunohistochemistry for p53 and mismatch repair (MMR) proteins. This separated cases into 1 of 4 groups: (1) POLE EDM, (2) MMR-D, (3) p53 wildtype (p53 wt), or (4) p53 abnormal (p53 abn). Seven gynecologic pathologists were asked to assign each case to one of the following categories: grade 1 to 2 endometrioid carcinoma (EC), grade 3 EC, mucinous, serous carcinoma (SC), clear cell, dedifferentiated, carcinosarcoma, mixed, and other. Consensus diagnosis among all 7 pathologists was highest in the p53 wt group (37/41, 90%), lowest in the p53 abn group (14/36, 39%), and intermediate in the POLE EDM (22/34, 65%) and MMR-D groups (23/40, 58%). Although the majority of p53 wt endometrial carcinomas are grade 1 to 2 EC (sensitivity: 90%), fewer than half of grade 1 to 2 EC fell into the p53 wt category (positive predictive value: 42%). Pure SC almost always resided in the p53 abn group (positive predictive value: 96%), but it was insensitive as a marker of p53 abn (sensitivity 64%) and the reproducibility of diagnosing SC was suboptimal. The limitations in the precise histologic classification of endometrial carcinomas highlights the importance of an ancillary molecular-based classification scheme.

To conduct a cost-effectiveness analysis of opportunistic salpingectomy (elective salpingectomy at hysterectomy or instead of tubal ligation).A Markov Monte Carlo simulation model estimated the costs and benefits of opportunistic salpingectomy in a hypothetical cohort of women undergoing hysterectomy for benign gynecologic conditions or surgical sterilization. The primary outcome measure was the incremental cost-effectiveness ratio. Effectiveness was measured in terms of life expectancy gain. Sensitivity analyses accounted for uncertainty around various parameters. Monte Carlo simulation estimated the number of ovarian cancer cases associated with each strategy in the Canadian population.Salpingectomy with hysterectomy was less costly ($11,044.32 ± $1.56) than hysterectomy alone ($11,206.52 ± $29.81) or with bilateral salpingo-oophorectomy ($12,626.84 ± $13.11) but more effective at 21.12 ± 0.02 years compared with 21.10 ± 0.03 and 20.94 ± 0.03 years, representing average gains of 1 week and 2 months, respectively. For surgical sterilization, salpingectomy was more costly ($9,719.52 ± $3.74) than tubal ligation ($9,339.48 ± $26.74) but more effective at 22.45 ± 0.02 years compared with 22.43 ± 0.02 years (average gain of 1 week) with an incremental cost-effectiveness ratio of $27,278 per year of life gained. Our results were stable over a wide range of costs and risk estimates. Monte Carlo simulation predicted that salpingectomy would reduce ovarian cancer risk by 38.1% (95% confidence interval [CI] 36.5-41.3%) and 29.2% (95% CI 28.0-31.4%) compared with hysterectomy alone or tubal ligation, respectively.Salpingectomy with hysterectomy for benign conditions will reduce ovarian cancer risk at acceptable cost and is a cost-effective alternative to tubal ligation for sterilization. Opportunistic salpingectomy should be considered for all women undergoing these surgical procedures.

Prophylactic bilateral salpingo-oophorectomy is advised for women with BRCA mutations, but there are adverse consequences of premature menopause. The majority of BRCA-associated ovarian cancers appear to arise in the fallopian tube; therefore, salpingectomy may be an alternative to bilateral salpingo-oophorectomy. We compared the costs and benefits of salpingectomy with bilateral salpingo-oophorectomy among BRCA mutation carriers.We developed a Markov Monte Carlo simulation model to compare three strategies for risk reduction in women with BRCA mutations: 1) bilateral salpingo-oophorectomy; 2) bilateral salpingectomy; and 3) bilateral salpingectomy with delayed oophorectomy. Net health benefits were measured in years-of-life expectancy and quality-adjusted life-year expectancy, and the primary outcome was the incremental cost-effectiveness ratio. The model estimated the number of future breast and ovarian cancers and cardiovascular deaths attributed to premature menopause with each strategy.Bilateral salpingo-oophorectomy was associated with the lowest cost and highest life expectancy compared with the other two strategies. When quality-of-life measures were included, salpingectomy followed by delayed oophorectomy yielded the highest quality-adjusted life expectancy with incremental cost-effectiveness ratios of $37,805 and $89,680 per quality-adjusted life-year for BRCA1 and BRCA2, respectively, relative to salpingectomy alone. Bilateral salpingo-oophorectomy yielded the lowest number of future breast and ovarian cancers compared with the other two strategies.Bilateral salpingo-oophorectomy offers the greatest risk reduction for breast and ovarian cancer among BRCA mutation carriers. However, when considering quality-adjusted life expectancy, bilateral salpingectomy with delayed oophorectomy is a cost-effective strategy and may be an acceptable alternative for those unwilling to undergo bilateral salpingo-oophorectomy.