Purpose <p>Evidence for adjuvant immunotherapy after neoadjuvant chemoimmunotherapy (NCIT) remains limited. This study aims to assess survival benefits of adjuvant immunotherapy in esophageal squamous cell carcinoma (ESCC) patients treated with NCIT.</p> Methods <p>This multicenter retrospective study analyzed 398 esophageal cancer patients who underwent NCIT followed by R0 resection (2019–2023). Postoperatively, 147 received immunotherapy (ICIs group) and 251 did not (non-ICIs group). After propensity score matching (PSM), 143 patients were included in each group. The primary endpoints were 2-year overall survival (OS) and disease-free (DFS) rates.</p> Results <p>Before matching, adjuvant immunotherapy showed no significant OS (hazard ratio [HR] 0.68, <i>p</i> = 0.14) or DFS (HR = 0.75, <i>p</i> = 0.161) benefit versus non-ICIs in ESCC patients. Post-PSM, however, ICIs demonstrated significantly improved 2-year DFS (HR = 0.57, <i>p</i> = 0.013) and OS (HR = 0.47, <i>p</i> = 0.008). Subgroup analyses revealed that ≤65 years, male, lower location, cT3-4, cN1, ypT3-4, ypN2-3, ypIIIB-IVA stage, non-pCR, and non-MPR were significantly associated with survival benefits from adjuvant immunotherapy. Both before and after matching, pCR patients did not benefit from immunotherapy, whereas non-pCR patients exhibited significantly improved DFS (HR = 0.54, <i>p</i> = 0.007) and OS (HR = 0.48, <i>p</i> = 0.01) after matching. Multivariate Cox analysis showed that adjuvant chemoimmunotherapy was the only regimen independently improving both DFS and OS compared to no adjuvant therapy, while immunotherapy alone did not demonstrate significant survival improvement.</p> Conclusions <p>Adjuvant immunotherapy enhanced survival in NCIT-treated ESCC patients overall, although no survival benefit was observed with adjuvant immunotherapy in pCR patients. Whereas non-pCR patients may benefit from adjuvant immunotherapy, with chemoimmunotherapy may be the optimal strategy. These findings are exploratory. Further validation in longer follow-up time, larger cohorts or prospective studies are needed.</p>

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Adjuvant Immunotherapy Improves Esophageal Squamous Cell Carcinoma Survival After Neoadjuvant Chemoimmunotherapy: A Multicenter Real-World Study

  • Zhuolun Xie,
  • Zhiping Xiu,
  • Yiping Lin,
  • Ning Gong,
  • Fang Peng,
  • Wencheng Zhang,
  • Rong Wang,
  • Wei Wang

摘要

Purpose

Evidence for adjuvant immunotherapy after neoadjuvant chemoimmunotherapy (NCIT) remains limited. This study aims to assess survival benefits of adjuvant immunotherapy in esophageal squamous cell carcinoma (ESCC) patients treated with NCIT.

Methods

This multicenter retrospective study analyzed 398 esophageal cancer patients who underwent NCIT followed by R0 resection (2019–2023). Postoperatively, 147 received immunotherapy (ICIs group) and 251 did not (non-ICIs group). After propensity score matching (PSM), 143 patients were included in each group. The primary endpoints were 2-year overall survival (OS) and disease-free (DFS) rates.

Results

Before matching, adjuvant immunotherapy showed no significant OS (hazard ratio [HR] 0.68, p = 0.14) or DFS (HR = 0.75, p = 0.161) benefit versus non-ICIs in ESCC patients. Post-PSM, however, ICIs demonstrated significantly improved 2-year DFS (HR = 0.57, p = 0.013) and OS (HR = 0.47, p = 0.008). Subgroup analyses revealed that ≤65 years, male, lower location, cT3-4, cN1, ypT3-4, ypN2-3, ypIIIB-IVA stage, non-pCR, and non-MPR were significantly associated with survival benefits from adjuvant immunotherapy. Both before and after matching, pCR patients did not benefit from immunotherapy, whereas non-pCR patients exhibited significantly improved DFS (HR = 0.54, p = 0.007) and OS (HR = 0.48, p = 0.01) after matching. Multivariate Cox analysis showed that adjuvant chemoimmunotherapy was the only regimen independently improving both DFS and OS compared to no adjuvant therapy, while immunotherapy alone did not demonstrate significant survival improvement.

Conclusions

Adjuvant immunotherapy enhanced survival in NCIT-treated ESCC patients overall, although no survival benefit was observed with adjuvant immunotherapy in pCR patients. Whereas non-pCR patients may benefit from adjuvant immunotherapy, with chemoimmunotherapy may be the optimal strategy. These findings are exploratory. Further validation in longer follow-up time, larger cohorts or prospective studies are needed.