Neoadjuvant immuno-chemotherapy versus neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Abstract OBJECTIVES The CROSS regimen has been the standard neoadjuvant treatment for oesophageal squamous cell carcinoma (ESCC) over the last decade. However, the emerging Neoadjuvant Immuno-Chemotherapy followed by Esophagectomy (NICE) regimen has shown promising potential. This study compares the treatment response and long-term outcomes of NICE versus CROSS for ESCC. METHODS We retrospectively analyzed patients who underwent NICE or CROSS between January 2018 and April 2022. NICE consisted of camrelizumab with carboplatin and paclitaxel over two 21-day cycles. CROSS included carboplatin and paclitaxel chemotherapy with concurrent radiotherapy (41.4 Gy) per protocol. After matching, 177 patients were included in each group for analysis. RESULTS The pathological complete remission (pCR) rates were similar between NICE and CROSS (20.9% vs 25.4%, P = 0.314). NICE demonstrated superior 3-year overall survival (OS) (73.5% vs 58.4%, P = 0.003) and cancer-specific survival (77.3% vs 64.3%, P = 0.006). Recurrence rates, including local and distant recurrences, were comparable. Subgroup analysis revealed no survival differences in pCR patients (HR 1.65, 95% CI 0.56–4.84), but non-pCR patients in NICE group showed improved OS compared to CROSS (HR 1.86, 95% CI 1.24–2.77). Patients following NICE reported higher proportions of adjuvant therapy than CROSS (P < 0.001), and largely driven by immunotherapy (OR 5.45). Furthermore, in multivariable analysis receipt of adjuvant therapy was identified as a significant promoter for improving long-term prognosis after NICE. CONCLUSIONS NICE offers better survival than CROSS with similar recurrence patterns. Adjuvant immunotherapy might be an important factor for long-term benefits in residual pathological disease after NICE.