Optimal adjuvant strategy in intermediate-risk cervical cancer: a systematic review and meta-analysis

Objective To evaluate the efficacy and safety of adjuvant treatment strategies following radical hysterectomy for intermediate-risk, early-stage cervical cancer using a reconstructed HR Hazard ratio (HR) meta-analysis. Methods A systematic review and meta-analysis was conducted by the Japan Society of Gynecologic Oncology Cervical Cancer Committee. PubMed/MEDLINE, Cochrane, and Ichushi were searched on July 29, 2025, using “cervical cancer,” “intermediate-risk,” and “adjuvant therapy.” Studies comparing adjuvant radiotherapy alone (RT) with no further treatment (NFT), concurrent chemoradiotherapy (CCRT), or systemic chemotherapy (CT) after conventional radical hysterectomy were independently reviewed by two reviewers. Primary outcomes were survival and grade ≥ 3 treatment-related toxicities. Results Of 402 screened articles, 24 studies comprising 9278 patients were included: RT ( n = 4167), NFT ( n = 2057), CCRT ( n = 2118), and CT ( n = 936). The majority of studies enrolled patients with ≥ 2 Sedlis risk factors (median 84.2%, interquartile range 44.7–100%). Compared with NFT, RT significantly improved recurrence-free survival (HR 0.61, P < 0.01) but did not confer a significant overall survival benefit (HR 0.77, P = 0.09). RT also reduced recurrence in patients with a single risk factor (HR 0.55, P < 0.01). RT showed no survival disadvantage compared with CCRT (recurrence-free survival: HR 1.26; overall survival: HR 1.07), and survival outcomes were comparable between RT and CT (recurrence-free survival: HR 0.86; overall survival: HR 1.16) (all P > 0.05). Grade ≥ 3 toxicities were significantly lower with RT than with CCRT (odds ratio 0.25; P < 0.001). Conclusion Adjuvant RT represents an effective and well-tolerated postoperative strategy for intermediate-risk, early-stage cervical cancer. Adjuvant CT may represent a potential alternative option.