Risk Reducing Gynaecological Surgery for Lynch Syndrome

Lynch Syndrome is caused by germline mutations in the DNA mismatch repair genes (MMR) namely MLH1, MSH2, MSH6, PMS2. The lifetime risk of endometrial cancer is 40-60% compared with a risk of 3% in the general population. For ovarian cancer, the lifetime risk is 10-12% compared with a general population risk of 1.4%. Women with Lynch also have a greater likelihood of synchronous endometrial cancer than other ovarian cancer patients.

Definition

• Removal of uterus, both tubes and ovaries with washings to prevent cancer
• Implies that all organs are normal at the time of surgery

Why Surgery?
The efficacy of endometrial cancer surveillance is still unproven. However, there are proven benefits of risk reducing surgery.

Prophylactic total laparoscopic hysterectomy should be offered to female patients whose childbearing is complete unless contraindicated. A study showed that no endometrial cancer developed in women with RRS where 33% of women developed endometrial cancer and 5.5% developed ovarian cancer when surgery was not performed.

Salpingo- Oophorectomy should also be performed because of the high incidence of ovarian cancer in HNPCC (10%), and the frequent coexistence of endometrial and ovarian cancer.

Some advocate that endometrial sampling should be done prior to prophylactic surgery as because not all women who harbor endometrial cancers have symptomatic uterine bleeding. This could then affect the surgical management at the time.

When is the Optimal Timing?
Optimal timing of the surgery is unclear. However, endometrial cancer has been reported in HNPCC patients younger than age 35. At present, it seems reasonable to delay prophylactic surgery until childbearing is complete. Consensus opinion is that it should be done before the age of 50 at the latest.

Some centers recommend individualized approach related to the particular gene mutation, the age of onset of colorectal cancer or 10 years prior to the earliest onset of EC in known relatives.

Risk vs Benefit
Pros and cons of prophylactic hysterectomy with and without salpingo-oophorectomy

What Surgery?

• Inspection of pelvis
• Peritoneal washings for cytology
• Removal of uterus, tubes and ovaries
• Preferably laparoscopic – no morcellation
• Avoid subtotal hysterectomy
• If a pre-operative endometrial biopsy has not been performed then the uterus should be bivalved after removal and the endometrium thoroughly inspected; frozen section evaluation should also be strongly considered.

Role of HRT after Surgery
Estrogen replacement therapy after RRSO is not contraindicated in women with HNPCC, as there is no evidence that this adversely affects the incidence of other cancers.