Impact of adjuvant sequential chemoradiotherapy on long-term overall survival in early-stage cervical cancer: Final analysis of the STARS phase III randomized trial.

5527 Background: The STARS trial (NCT00806117) previously demonstrated that adjuvant sequential chemoradiotherapy (SCRT) significantly improved disease-free survival (DFS) compared with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) in early-stage cervical cancer patients with pathological risk factors. This pre-specified analysis reports the mature overall survival (OS) results. Methods: In this open-label, phase III trial, 1,048 cervical cancer patients with FIGO stage IB1–IIA2 and postoperative pathological risk factors were randomized (1:1:1) to receive RT alone, CCRT (RT with weekly cisplatin), or SCRT (paclitaxel-cisplatin chemotherapy before and after RT). The second endpoint was OS, analyzed by intention-to-treat. Subgroup analyses were performed based on risk stratification: intermediate-risk (deep stromal invasion or lymphovascular space invasion) and high-risk (node-positive or parametrial involvement). Results: With a median follow-up of 90 months, SCRT significantly improved OS compared to both RT (10-year OS 89.0% vs 81.0%; HR 0.54, 95% CI 0.35-0.83; P=0.005) and CCRT (89.0% vs 83.0%; HR 0.64, 0.41-0.98; P=0.040) in intention to treat population. No significant difference was observed in OS between CCRT and RT (HR 0.85, 0.58-1.24; P=0.404). The survival benefit of SCRT was consistent across key subgroups: it was most pronounced in intermediate-risk patients (HR 0.54 vs RT, 95% CI 0.31-0.93; P=0.027) and showed a clinically meaningful trend in high-risk patients (HR 0.61, 95% CI 0.30-1.24). However, CCRT showed no overall benefit in these risk-based populations but was markedly effective in the subgroup with deep stromal invasion without lymphovascular invasion (HR 0.20 vs RT, 95% CI 0.05-0.85; P=0.029) in per-protocol population. SCRT achieved higher protocol completion than CCRT (73.4% vs 62.3%) and was an independent favorable prognostic factor for OS (HR 0.54) in multivariable analysis, along with lymph node metastasis and adenocarcinoma histology. Conclusions: The long-term STARS trial update confirms adjuvant SCRT as the optimal strategy, demonstrating both DFS and OS superiority in early-stage cervical cancer with postoperative risk factors. The significant 10-year survival benefit strongly supports adopting SCRT where radiotherapy access is limited. Clinical trial information: NCT00806117 .