Abstract Introduction Although several studies in esophageal squamous cell carcinoma (ESCC) have reported no definitive overall survival (OS) differences between neoadjuvant chemoradiotherapy (NACRT) and neoadjuvant chemotherapy (NAC), the higher pathological complete response (pCR) rate with NACRT has been viewed as a potential advantage. Beyond ongoing concerns about the validity of pCR as a surrogate endpoint, it remains uncertain whether survival differs between these modalities among patients with ESCC who achieve pCR. Methods An integrated individual patient data (IPD) analysis of phase III trials evaluating perioperative therapies for resectable ESCC was conducted, emphasizing prognostic differences between NAC and NACRT, particularly among patients who achieved pCR. Results IPD from 7 phase III randomized controlled trials across 6 countries included 1,044 patients with ESCC (83.5% male; mean age 62.3 years). Of these, 605 (58.0%) received NAC and 439 (42.0%) received NACRT, with R0 resection rates of 89.6% vs. 84.7% and pCR rates of 6.9% vs. 34.2%, respectively. Among patients who achieved pCR (n=192), the 5-year OS was 97.5% in the NAC group and 70.4% in the NACRT group, while 5-year recurrence-free survival was 80.8% and 63.7%, respectively. Multivariable analysis demonstrated a significant survival advantage for NAC among patients who achieved pCR. Conclusion Among patients who achieved pCR, postoperative outcomes varied considerably by neoadjuvant treatment modality. The markedly favourable prognosis associated with pCR after NAC suggests that these patients may represent an optimal candidate cohort for future evaluation of surgery avoidance and watch-and-wait strategies.
Okui et al. (Mon,) studied this question.
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