Molecular classification in fertility-sparing treatment of early-stage endometrial cancer: A potential tool for optimizing patient selection.

OBJECTIVE

To investigate the prognostic significance of molecular classification on treatment outcomes of fertility-sparing treatment (FST) in early-stage endometrial cancer (EC), and its potential in optimizing fertility-sparing management.

METHODS

Patients with early-stage EC who received FST with ProMisE classification were investigated. Oncological and reproductive outcomes were compared across four molecular subtypes. Factors influencing complete response (CR) were analyzed.

RESULTS

Among 116 molecularly classified patients, 80 were evaluated for therapeutic effects, including 64 (80.0 %) p53wt, 7 (8.7 %) MMR-D, 5 (6.3 %) POLE EDM, and 4 (5.0 %) p53abn. Overall CR rates were comparable across four molecular subtypes, with 92.2 % of p53wt, 71.4 % of MMR-D, 100.0 % of POLE EDM, and 75.0 % of p53abn (P = 0.145). MMR-D patients needed the longest median treatment time to achieve CR (7.9 months, range 3.5-15.9), while POLE EDM required the shortest (3.0 months, range 2.8-6.4), followed by p53abn (3.5 months, range 3.0-3.7) and p53wt (3.7 months, range 2.2-22.8) (P = 0.049). Among 14 p53wt patients with superficial myometrial invasion (MI) or G2 histology, 13 (92.9 %) achieved CR, and of 8 who attempted to conceive,4 delivered. Multivariable analysis identified MMR-D, superficial MI and insulin resistance negatively predicted CR, while POLE EDM was a positive factor.

CONCLUSIONS

Molecular classification of EC may serve as a tool for predicting response to FST and assist in identifying candidates for FST. POLE EDM patients tended to obtain promising outcomes. MMR-D cases should be cautiously administrated for FST with close surveillance. Patients with p53wt demonstrated favorable outcomes, including those with superficial MI or G2 EC. Patients with endometrium-confined p53abn tumors may benefit from FST. However, given the small sample sizes of certain subtypes, further investigation is necessary to validate these findings.