Does prophylactic surgery reduce the risk of gynecologic cancers arising from the Lynch syndrome?

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Abstract

BACKGROUND

Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) is associated with an early onset of cancer, including colorectal, ovarian and endometrial cancers, and cancers of the small bowel, renal pelvis and ureter. Women with the Lynch syndrome have lifetime risks for endometrial and colorectal cancer of 40-60%, and for ovarian cancer of 10-12%. It has been suggested that prophylactic total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) is a sensible preventive strategy in women with the Lynch syndrome once childbearing has been completed, but clear evidence for the utility of this method is lacking.

OBJECTIVES

To assess whether risk of gynecologic cancers can be reduced by prophylactic TAH or BSO in women with the Lynch syndrome.

DESIGN AND INTERVENTION

In this retrospective cohort study, the records of patients enrolled in three registries of hereditary cancers from 1973 to 2004 were reviewed to identify women who had Lynch syndrome (MLH1, MSH2 or MSH6 germline mutations). Women who had undergone TAH with or without BSO for prevention of cancer or treatment of benign conditions (cases) were matched against individuals of similar age who had been treated at the same institution but did not undergo TAH with or without BSO (controls). Women who had undergone BSO and controls were compared in a similar manner.

OUTCOME MEASURES

The primary endpoint was occurrence of endometrial, ovarian or primary peritoneal cancer.

RESULTS

Among the 315 women with germline mutations associated with the Lynch syndrome for whom follow-up data were available, 61 (19%) underwent TAH, and 47 (15%) also underwent BSO. Endometrial cancer was diagnosed in 69 women (33%) in the control group, whereas none who had undergone prophylactic TAH developed this malignancy. Incidence density was zero for the women who had undergone hysterectomy versus 0.045 per woman-year for controls (P < 0.001). Prevented fraction was 100% (95% CI 90-100%). Median age when endometrial cancer was diagnosed was 46 years (range 30-69 years) whereas median age at TAH was 41 years (range 20-63 years). There were no cases of ovarian carcinoma among the 47 women who had undergone BSO, but 12 cases (5%) were diagnosed in the control group. Incidence density was zero for women who had undergone BSO, but 0.005 per woman-year for controls (P = 0.09). Prevented fraction was 100% (95% CI 62-100%). A nonsignificant trend towards reduced risk of ovarian cancer with BSO was demonstrated. Median age when ovarian cancer was diagnosed was 42 years (range 31-48 years) whereas median age at surgery was 41 years (range 20-58 years). Surgical complications occurred in one woman undergoing prophylactic surgery (1.6%).

CONCLUSION

Prophylactic surgery is effective in reducing risk of gynecologic cancers in women with Lynch syndrome, but studies with longer follow-up are required to assess long-term survival.

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