Gynecologic cancer prevention in Lynch syndrome/hereditary nonpolyposis colorectal cancer families

OBJECTIVE: Women from Lynch syndrome/hereditary nonpolyposis colorectal cancer (Lynch/HNPCC) families have an increased lifetime risk of developing endometrial and ovarian cancer. This study models a comparison of management strategies for women who carry a Lynch/HNPCC mutation. METHODS: A decision analytic model with three arms was designed to compare annual gynecologic examinations with annual screening (ultrasonography, endometrial biopsy, CA 125) and with hysterectomy with bilateral salpingo-oophorectomy at age 30 years The existing literature was searched for studies on the accuracy of endometrial and ovarian cancer screening using endometrial biopsy, transvaginal ultrasonography, and serum CA 125. The Surveillance, Epidemiology and End Results database from 1988 to 2001 was used to estimate cancer mortality outcomes. RESULTS: In the surgical arm, 0.0056% of women were diagnosed with ovarian cancer and 0.0060% of women with endometrial cancer. These numbers increased to 3.7% and 18.4% in women being screened, and 8.3% and 48.7% in women undergoing annual examinations, respectively. Surgical management led to the longest expected survival time at 79.98 years, followed by screening at 79.31 years, and annual examinations at 77.41 years. If starting at age 30 and discounting life years at 3%, surgery still leads to the greatest expected life years. When comparing prophylactic surgery with the screening option, one would need to perform 75 surgeries to save one woman's entire life. For cancer prevention, however, only 28 and 6 prophylactic surgeries would need to be performed to prevent one case of ovarian and endometrial cancer, respectively. CONCLUSION: Risk-reducing hysterectomy and bilateral salpingo-oophorectomy may be considered in women with Lynch/HNPCC to prevent gynecologic cancers and their associated morbidities.