High- or Intermediate-Risk Histologic Features in Patients with Clinical Early-Stage Cervical Cancer Planned for Fertility-Sparing Surgery: A Systematic Review

SIMPLE SUMMARY: Fertility-sparing surgery (FSS) is a viable option for young women with early-stage cervical cancer, with the success of preserving fertility rate exceeding 90%. However, certain high-risk histologic features such as positive lymph nodes, positive surgical margins, parametrial invasion or intermediate-risk factors may require additional treatments that can negatively affect fertility. This review provides an overview of the occurrence of these high- or intermediate-risk histologic features, the available treatment options and the variations in approaches among different treatment centers worldwide. Parametrial invasion in tumors less than 2 cm was found to be rare, supporting the rationale for omitting parametrectomy in small tumors. In cases of positive lymph nodes at frozen section analysis, a hysterectomy is not recommended prior to adjuvant (chemo)radiation, as leaving the uterus in place reduces the risk of complications during surgery and radiation therapy. Adjuvant chemotherapy after FSS could be an alternative treatment option considering its effectiveness, safety and potential for fertility preservation. ABSTRACT: Background: Fertility-sparing surgery (FSS) is a viable option for young women with early-stage cervical cancer (ECC); however, certain risk factors may necessitate additional treatments and impact fertility. This review examines the prevalence of these risk factors and available treatment options. Methods: A systematic search was conducted of studies including patients with ECC (IA1 with LVSI, IA2, IB1 (FIGO 2009)) who underwent FSS. Results: Sixty-four articles, comprising a total of 4118 women planned for FSS, were included. High- or intermediate-risk histologic features were found in 638 (15.5%) women: 5.1% had positive lymph node(s), 4.1% had positive resection margins, 0.3% had parametrial involvement, 1.0% had unspecified high-risk features, and 5.1% had intermediate-risk histology (primarily based on the Sedlis criteria). Adjuvant treatment impaired fertility in all women with adjuvant hysterectomy and/or (chemo)radiation (58.7%). Adjuvant chemotherapy was given to 1351 (32.8%) patients, which may reduce fertility. Conclusions: Fertility preservation could be achieved in most women; but high- or intermediate-risk factors necessitate more extensive surgery or radiotherapy leading to infertility. Adjuvant chemotherapy could be an alternative treatment option considering its effectiveness, safety and higher change in fertility preservation. The low incidence of parametrial involvement justifies waiving parametrectomy in tumors < 2 cm.