Fertility-sparing vs hysterectomy for uterine STUMP: A pragmatic clinical study

Background: Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are rare neoplasms with unpredictable clinical behavior. Optimal management, particularly in reproductive-aged women, remains controversial, with limited data comparing the safety of fertility-sparing versus hysterectomy. Methods: This multicentre retrospective cohort study included women aged 18-85 with histologically confirmed STUMP treated at 17 Italian gynecologic oncology centers from 2010 to 2023. Patients underwent either fertility-sparing surgery (myomectomy or hysteroscopic resection) or definitive surgery (hysterectomy ± salpingo-oophorectomy). Kaplan-Meier and Cox models were used to compare recurrence-free survival (RFS) and overall survival (OS). Results: Median (range) follow-up was 51 (1-291) months. Among 401 women, 106 (26.4 %) received fertility-sparing treatment (mean [± SD] age: 35.3 ± 6.8 years) and 295 (73.6 %) underwent definitive surgery (mean [± SD] age: 47.7 ± 9.2). At total follow-up, recurrence occurred in 12.5 % of patients, predominantly within the pelvis. Median RFS was longer after definitive surgery than after fertility-sparing procedures (50.0 vs 42.5 months; HR 2.39 [95 % CI 1.36-4.19]), although this difference disappeared when benign (leiomyoma) recurrences were excluded (HR 1.74 [95 % CI 0.90-3.34]). At last available follow-up, 97.5 % of patients were alive, with no significant OS difference between treatment groups (HR 0.22 [95 % CI 0.27-1.79]). Outcomes were comparable across menopausal status and concurrent adnexal removal. Conclusion: Definitive surgery reduces recurrence risk, but long-term survival is similarly excellent after fertility-sparing surgery in appropriately selected women with STUMP. Conservative management represents a reasonable option for patients desiring fertility, provided they receive counseling regarding recurrence risk, diagnostic uncertainty, and the need for long-term surveillance.