Clinical and fertility outcomes in lynch syndrome patients with endometrial carcinoma or endometrial Intraepthelial neoplasia treated with fertility sparing management

Abstract

Objectives

Provide evidence on fertility-sparing treatment for patients with Lynch Syndrome (LS) and early-stage low grade endometrioid endometrial cancer (EC) or endometrial intraepithelial neoplasia (EIN).

Methods

We conducted a retrospective chart review of patients with EC or EIN, LS pathogenic germline variant, and treatment with progestin therapy without upfront hysterectomy due to desire to preserve fertility. Demographic, clinical, and reproductive variables were collected.

Results

Of the 273 patients who met criteria for LS with EIN (38) or EC (235) there were seven patients, three with an initial diagnosis of EIN and four with an initial diagnosis of EC who underwent fertility sparing treatment. The median age was 36 (range 31–44) at diagnosis with the following mutations MLH1 (2), PMS2 (1), MSH2 (1) and MSH6 (3). Four out of 7 (53%) patients responded to progestin therapy with a 33% (1/3) and 75% (3/4) regression rate for EIN and EC respectively. Two out of 4 patients (50%) subsequently recurred. There were three pregnancies and two live births. Five patients ultimately underwent hysterectomy. Two patients, both with mutant p53 expression on immunohistochemistry, had higher grade or stage pathology, one with stage 1A grade 2 EC and one with stage 1B grade 3 EC.

Conclusion

Fertility sparing management for LS patients with an EIN or EC diagnosis is uncommon. Progesterone response rates appear to be lower than those in sporadic cases, though similar clinical and histologic factors (age, BMI, and p53 expression pattern) may predict disease regression and fertility outcomes. A larger sample and standardized treatment paradigm are needed to provide more evidence on fertility sparing management for LS patients.