Comparison of proton-based definitive chemoradiotherapy and surgery-based therapy for esophageal squamous cell carcinoma: a multi-center retrospective Japanese cohort study

Background Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study. Methods Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I–IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used. Results The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61–1.25). Although, the 3-year P-CRT group progression–free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04–1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38–0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1–2 (HR 0.61, 95% CI 0.29–1.26) and cStage I–II (HR 0.50, 95% CI 0.24–1.07) subgroups, although this trend was not evident in other populations, such as cT3–4 and cStage III–IVA. Conclusions Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1–2 and cStage I–II disease, proton-based CRT has the potential to serve as a first-line treatment.