New data from a phase 3 randomised clinical trial published in JAMA Network Open has shown that neoadjuvant chemoradiotherapy (NCRT) followed by surgery does not significantly improve long-term survival compared with surgery followed by adjuvant therapy (AT) in patients with locally advanced oesophageal squamous cell carcinoma (ESCC).
The prospective trial recruited 254 patients with resectable locally advanced thoracic ESCC at the Sichuan Cancer Hospital in China between 2018 and 2020. Eligible participants were aged 18–75 years with histologically confirmed disease, staged as cT1N+M0 or cT2–4aNxM0, and were fit for multimodality therapy. They were randomly allocated to receive NCRT with concurrent paclitaxel and carboplatin followed by surgery, or surgery followed by adjuvant chemoradiotherapy, determined by multidisciplinary teams.
CLINICAL SUMMARY
What was examined
A prospective phase 3 randomised clinical trial comparing long-term survival outcomes of neoadjuvant chemoradiotherapy (NCRT) followed by surgery versus surgery followed by adjuvant therapy (AT) in patients with locally advanced oesophageal squamous cell carcinoma (ESCC).
Key findings
- There were no statistically significant differences in overall survival (OS) or disease-free survival (DFS) between the NCRT and AT groups at long-term follow-up (~59 months).
- The 5-year OS was 59.2 % in the NCRT group vs 59.6 % in the AT group (hazard ratio [HR] 1.01; P = .97).
- The 5-year DFS was 53.1 % vs 56.5 % for NCRT vs AT, respectively (HR 1.13; P = .53)
Pathological response insights
- Patients within the NCRT group who achieved pathologic complete response (pCR) had significantly better survival than those who did not, with a 5-year OS of 76.5 % vs 52.1 % (HR 0.39; P = .01).
Clinical implications
- Both NCRT followed by surgery and surgery with AT can be reasonable strategies for resectable locally advanced ESCC, with similar long-term outcomes.
- pCR after NCRT may identify a subgroup with substantially improved prognosis, supporting its use where achievable.
- Patient selection and multidisciplinary evaluation remain essential in tailoring treatment sequencing.
After a median follow-up of approximately 59 months, there were no statistically significant differences in long-term outcomes between the two treatment strategies. The 5-year overall survival (OS) rates were 59.2 per cent (95 % CI, 51.0 %–68.8 %) in the NCRT group and 59.6 per cent (95 % CI, 51.2 %–69.5 %) in the AT group, with a hazard ratio (HR) of 1.01 (95 % CI, 0.67–1.51; P = .97). Disease-free survival (DFS) at 5 years was also similar between groups (53.1 % vs 56.5 %; HR, 1.13; 95 % CI, 0.77–1.68; P = .53).
While the overall comparison did not favour one approach over the other, subgroup analysis in the NCRT arm revealed that patients who achieved pathologic complete response (pCR) after NCRT had significantly better survival outcomes. The 5-year OS for the pCR subgroup was 76.5 per cent compared with 52.1 per cent for those without pCR (HR, 0.39; 95 % CI, 0.18–0.82; P = .01), suggesting that pCR status may help identify patients most likely to benefit from neoadjuvant treatment.
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The trial’s findings underscore that although NCRT can produce excellent pathological responses in some patients, routine use does not confer a clear survival advantage over surgery with AT for all comers with locally advanced ESCC. Given the overlapping survival curves observed in this study, both multimodality strategies remain reasonable options, depending on individual patient factors and multidisciplinary assessment.
The authors highlight that identifying clinical and biological predictors of response to neoadjuvant therapy will be important in personalising treatment and optimising outcomes for patients with ESCC, particularly in settings where the balance of benefits and risks must be carefully weighed.
Paper: He W, Li Z, Xie Q, et al. Long-Term Survival Outcomes of NCRT With Surgery vs Surgery With Adjuvant Therapy for ESCC: A Single-Center Prospective Phase 3 Randomized Clinical Trial. JAMA Netw Open. 2026;9(1):e2550307. Access online here.
