Molecular Prognosticators Guiding Fertility-Sparing Surgery in Early-Stage Endometrial Cancer: A Comprehensive Review

Endometrial cancer (EC) is a common malignancy found among women. It is ranked as the 6th most common cancer among women and the 15th most common cancer globally. Increasing prevalence of several factors like obesity and other metabolic disorders have caused a growing trend of prevalence of endometrial cancer. The standard approach of treatment with excellent prognosis is total hysterectomy with bilateral salpingo-oophorectomy (TH/BSO). However, due to its drawback of complete infertility, newer approaches of fertility-sparing approaches are emerging to combat this challenge. Clinicians must choose the most suitable candidates for fertility-sparing surgery (FSS) using the present existing conventional criteria with regard to the patient's age, tumor characteristics, and fertility goals. The limitations using the conventional criteria can be eliminated by refining the criteria with molecular prognostic factors to ease the candidate selection process for FSS.

Relevant literature regarding molecular subtypes, hormone therapy sensitivity, clinical assessment, and guidelines pertaining to fertility preservation in EC were retrieved from several electronic databases and articles addressing the role of molecular profiling in predicting patient response, guiding patient selection, and/or informing the development of therapies for fertility preservation in early-stage EC, particularly in women of reproductive age were included. Primary focus was on areas of consensus, emerging trends, and evidence gaps that warrant further investigation. This review will assess the integration of molecular prognostic factors to refine the patient selection criteria and guide FSS in early-stage EC. We will present existing clinical criteria, ongoing clinical trials, limitations, and the advantages of integrating molecular data on patient selection, treatment safety, and fertility outcomes.

Four distinct molecular subtypes have been classified which includes POLE-mut, MMR-d, p53-abn and NSMP. POLE-mut subtype had excellent prognosis with >95% patients achieving complete remission with <2% recurrence rate followed by MMRd and NSMP with intermediate prognosis and lastly p53-abn with poor prognosis of 60-70% achieving complete remission and 30-40% having recurrence. The data highlights the clinical value of molecular classification in selecting appropriate candidates for fertility sparing surgery (FSS).

There is a lack of integration of molecular subtypes for clinicians to choose candidates for FSS and this gap should be addressed. Further research must be performed to follow personalized medicine to refine their treatment plan.