Neoadjuvant chemotherapy and individualized de-escalation surgery for fertility preservation in stage IB1-IIA2 cervical cancer: A multicenter prospective study (FIND study).

Abstract

5533 Background: Radical trachelectomy (RT) has long been the standard fertility-sparing surgery (FSS) for early-stage cervical cancer (most validated for tumor<2cm), produced satisfied oncologic outcomes but adverse pregnancy outcomes. Neoadjuvant chemotherapy (NACT) offers a potential pathway for tumor downstaging, which may further expand the population eligible for FSS. Based on this, this study aimed to evaluate the oncologic and reproductive outcomes of an individualized, NACT-based fertility-preserving strategy in patients with early-stage cervical cancer (FIGO 2018 IB1–IIA2) (CSEM009, NCT02624531). Methods: This prospective, non-randomized clinical study enrolled patients aged 18–40 years with pathologically confirmed stage IB1–IIA2 squamous, adenocarcinoma, or adenosquamous carcinoma and a strong desire for fertility preservation. All patients underwent pretreatment pelvic MRI. Patients with a baseline tumor diameter <1 cm proceeded directly to simple trachelectomy (ST). Those with tumors ≥1 cm received 2–3 cycles of platinum-based NACT. Individualized surgery was performed based on Post-NACT MRI: cervical conization (CON) for complete response, ST for residual disease ≤2 cm, and RT for residual disease 2–4 cm. Lymph node assessment involved sentinel lymph node biopsy (SLNB) or systematic lymphadenectomy. Primary endpoints were 5-year overall survival (OS), 5-year progression free survival (PFS), and reproductive outcomes. Results: From June 2015 to June 2023, 99 eligible patients were enrolled. Among them, 84 received NACT, and 80 ultimately underwent FSS. Median follow-up duration was 67 months (range: 7–122). For the entire cohort of 99 patients, 5-year PFS and OS were 88.9% and 93.9%, respectively. In the FSS group (n=80), 5-year PFS and OS were 91.3% and 96.3%. In FSS patients, univariate analysis identified lymphovascular space invasion (LVSI) as significantly associated with recurrence and mortality (p<0.05). Patients with initial tumors ≤2 cm (n=42), 2–4 cm (n=29), and ≥4 cm (n=9) had 5-year PFS rates of 95.2%, 86.2%, and 88.9%, and 5-year OS rates of 97.6%, 93.1%, and 100%, respectively. Nineteen patients failed to undergo FSS with 5-year PFS 78.9% and 5-year OS 84.2%. Of 40 FSS patients attempting pregnancy, 19 (47.5%) achieved at least one pregnancy, resulting in 17 cumulative deliveries: 3 after conization and 14 after ST. No successful pregnancies occurred after RT. Conclusions: This prospective study demonstrates that fertility-sparing strategy involving NACT and individual less radical FSS provides favorable long-term oncologic safety and meaningful reproductive potential in patients with FIGO 2018 IB1-IIA2 cervical cancer. Clinical trial information: NCT02624531 .