Neoadjuvant chemotherapy enables fertility preservation without compromising oncologic outcomes in early cervical cancer ≥2 cm: A systematic review and meta-analysis

INTRODUCTION: Early-stage cervical cancer tumours ≥2 cm present a dilemma for fertility preservation, as guidelines generally discourage fertility-sparing surgery (FSS) due to oncologic risks. Neoadjuvant chemotherapy (NACT) followed by FSS has emerged as an alternative to downstage tumours. This study evaluated recurrence and pregnancy outcomes of NACT + FSS versus upfront FSS. METHODS: A PROSPERO-registered (CRD42024605906) meta-analysis was conducted using PubMed, EMBASE, and Cochrane (updated Feb 26, 2025). Eligible studies included women with early-stage cervical cancer (FIGO 2018 IB2-IIA1; ≥2 cm) undergoing upfront FSS or NACT + FSS. Pooled proportions with 95% confidence intervals (CIs) were calculated using a random effects model. RESULTS: Nineteen observational studies (n = 1453) were analysed. Indirect comparison indicated significantly higher pooled pregnancy rate for NACT + FSS (31%; 95% CI: 23-41%) compared to upfront FSS (8%; CI: 1-43%; p = 0.002). Pooled recurrence rate was statistically similar: 10% (CI: 5-20%) for upfront FSS and 13% (CI: 9-20%) for NACT + FSS (p = 0.415). Studies generally exhibited a moderate-to-high risk of bias. CONCLUSION: NACT followed by FSS appears to enhance fertility outcomes without increasing oncologic risk compared to upfront FSS in patients with tumours ≥2 cm. These findings support the personalized extension of fertility-sparing indications, though prospective validation remains necessary.