Biomolecular and Genetic Prognostic Factors That Can Facilitate Fertility-Sparing Treatment (FST) Decision Making in Early Stage Endometrial Cancer (ES-EC): A Systematic Review.

Panayiotis Tanos,Giuseppe Gullo,Savvas Dimitriou,Vasilios Tanos

doi:10.3390/ijms23052653

Abstract

Endometrial cancer occurs in up to 29% of women before 40 years of age. Seventy percent of these patients are nulliparous at the time. Decision making regarding fertility preservation in early stage endometrial cancer (ES-EC) is, therefore, a big challenge since the decision between the risk of cancer progression and a chance to parenthood needs to be made. Sixty-two percent of women with complete remission of ES-EC after fertility-sparing treatment (FST) report to have a pregnancy wish which, if not for FST, they would not be able to fulfil. The aim of this review was to identify and summarise the currently established biomolecular and genetic prognostic factors that can facilitate decision making for FST in ES-EC. A comprehensive search strategy was carried out across four databases; Cochrane, Embase, MEDLINE, and PubMed; they were searched between March 1946 and 22nd December 2022. Thirty-four studies were included in this study which was conducted in line with the PRISMA criteria checklist. The final 34 articles encompassed 9165 patients. The studies were assessed using the Critical Appraisal Skills Program (CASP). PTEN and POLE alterations we found to be good prognostic factors of ES-EC, favouring FST. MSI, CTNNB1, and K-RAS alterations were found to be fair prognostic factors of ES-EC, favouring FST but carrying a risk of recurrence. PIK3CA, HER2, ARID1A, P53, L1CAM, and FGFR2 were found to be poor prognostic factors of ES-EC and therefore do not favour FST. Clinical trials with bigger cohorts are needed to further validate the fair genetic prognostic factors. Using the aforementioned good and poor genetic prognostic factors, we can make more confident decisions on FST in ES-EC.

Highlights

The aim of this review is to identify and summarise the currently established biomolecular and genetic prognostic factors that can facilitate the decision for fertility-sparing treatment (FST) in cases of early stage endometrial cancer (ES-endometrial carcinoma (EC))
L1CAM expression is, significantly, but not universally, associated with mutant P53. It may be strong enough for clinical implementation as a prognostic marker in combination with P53 as well as a promising therapeutic target [70]. This is the first thorough systematic review that identifies and summarises the most well-established biomolecular and genetic prognostic factors that facilitate FST decisionmaking in cases of ES-EC
PTEN, PIK3CA, Kirsten rat sarcoma viral oncogene homolog (KRAS), FGFR2, CTNNB1, microsatellite instability (MSI), and ARIDIA mutations are linked to good five-year survival (85%) for EC, and tumour protein 53 (TP53) is labelled as a poor prognostic factor with 55% five-year survival for EC [78]

Summary

Introduction

Temporal preservation of the uterus in early stage endometrial cancer (ES-EC) is an available option for women who have a strong will to preserve fertility and achieve spontaneous pregnancy. This raises primarily medical and ethical and social dilemmas since fertility-sparing treatment (FST) consists of compromising radical care in the effort of allowing them to reproduce. Sometimes, these patients will need to preserve their fertility by assisted reproductive technology (ART) [4]

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