Surgery versus definitive radiotherapy in the management of stage I-II small cell neuroendocrine carcinoma of the cervix: A systematic review and meta-analysis.

[BACKGROUND] Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare malignancy with poor prognosis. Optimal management of stage I-II disease remains uncertain, with guidelines variably recommending primary surgery or definitive radiotherapy. This study aimed to compare overall survival (OS) in patients with stage I-II SCNECC treated with primary surgery versus definitive radiotherapy through a systematic review and meta-analysis of the current literature.

[METHODS] Medline and Embase were searched for English-language studies reporting OS for stage I-II SCNECC treated with either primary surgery or definitive radiotherapy. Studies with ≥5 patients per treatment group were included. Hazard ratios (HR) for OS were pooled using a random-effects meta-analysis. Heterogeneity was assessed with I. The impact of including stage IIB patients was evaluated using a Likelihood Ratio Test comparing Cox proportional hazards models.

[RESULTS] Of 621 unique records, five studies met the inclusion criteria, encompassing 650 patients treated for stage I-II SCNECC between 1987 and 2012 in 38 hospitals across three countries. Among these patients, 474 underwent primary surgery and 176 received definitive radiotherapy. Of all patients, 84 % received chemotherapy. Median follow-up ranged from 31 to 83 months, and median OS ranged from 21 to 111 months. The pooled HR for OS favoured primary surgery compared to definitive radiotherapy (HR 0.53; 95 % CI 0.31-0.91; p = 0.021). Inter-study heterogeneity was substantial (I = 64 %, p = 0.024). Inclusion of stage IIB patients did not significantly affect the overall HR (p = 0.914).

[CONCLUSIONS] In stage I-II SCNECC, primary surgery is associated with longer OS compared to definitive radiotherapy. While findings are limited by the retrospective nature of included studies and potential selection bias, these results support consideration of surgical consultation for eligible patients as part of a multidisciplinary decision-making process. Prospective studies and inter-institutional collaboration are urgently needed to define optimal treatment strategies in this rare malignancy.