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Background <p>While multimodality therapy for locally advanced esophageal cancer evolves, neoadjuvant chemoradiation has been a longstanding treatment paradigm. Pathologic complete response (pCR) rates vary by histology: 25% for adenocarcinoma (AC) and up to 50% for squamous cell carcinoma (SCC). Long-term outcomes after pCR remain poorly understood but important to define as multiple treatment options emerge.</p> Patients and Methods <p>We analyzed patients with cT2+/N+M0 esophageal AC or SCC treated with neoadjuvant chemoradiation and resection from an institutional database. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan–Meier and multivariable Cox models. A risk score for recurrence was developed and validated using National Cancer Data Base data.</p> Results <p>Of 830 patients, 37.1% achieved pCR (<i>n</i> = 250/720, 34.2% for AC and <i>n</i> = 58/100, 58.0% for SCC). pCR was associated with prolonged OS (5-year OS: 56.2% versus 35.0% for residual disease,<i> p</i> &lt; 0.001). pCR remained an independent predictor of OS after adjustment for known predictors of OS (HR 0.58, <i>p</i> &lt; 0.001). Recurrence typically occurred within 2 years then plateaued, with 5-year RFS of 72.6% for AC and 83.0% for SCC. Clinical T3/T4, cN+, fewer lymph nodes examined, and AC histology were independently associated with worse RFS. A weighted risk score for recurrence was developed, which externally predicted OS after pCR in the NCDB (HR 1.12 per point, <i>p</i> &lt; 0.001). Median OS was 7.8 years for cases with score 0–3 versus 5.7 years for cases with score 4–5.</p> Conclusions <p>pCR after neoadjuvant chemoradiotherapy is a strong predictor of survival, but recurrence remains common. Further investigation into adjuvant therapies for high-risk pCR patients is needed.</p>

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Long-term Oncologic Outcomes Following Pathologic Complete Response for Esophageal Cancer

  • 期刊论文

  • 发表日期：

    2025年11月5日

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  • Andrew J. Sinnamon,
  • Samir H. Saeed,
  • Allan A. Lima Pereira,
  • Rutika Mehta,
  • Justin A. Drake,
  • Shaffer R. S. Mok,
  • Gregory Y. Lauwers,
  • Jessica M. Frakes,
  • Sarah E. Hoffe,
  • Jobelle J. Baldonado,
  • Jacques P. Fontaine,
  • Jose M. Pimiento

摘要

Background

While multimodality therapy for locally advanced esophageal cancer evolves, neoadjuvant chemoradiation has been a longstanding treatment paradigm. Pathologic complete response (pCR) rates vary by histology: 25% for adenocarcinoma (AC) and up to 50% for squamous cell carcinoma (SCC). Long-term outcomes after pCR remain poorly understood but important to define as multiple treatment options emerge.

Patients and Methods

We analyzed patients with cT2+/N+M0 esophageal AC or SCC treated with neoadjuvant chemoradiation and resection from an institutional database. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan–Meier and multivariable Cox models. A risk score for recurrence was developed and validated using National Cancer Data Base data.

Results

Of 830 patients, 37.1% achieved pCR (n = 250/720, 34.2% for AC and n = 58/100, 58.0% for SCC). pCR was associated with prolonged OS (5-year OS: 56.2% versus 35.0% for residual disease, p < 0.001). pCR remained an independent predictor of OS after adjustment for known predictors of OS (HR 0.58, p < 0.001). Recurrence typically occurred within 2 years then plateaued, with 5-year RFS of 72.6% for AC and 83.0% for SCC. Clinical T3/T4, cN+, fewer lymph nodes examined, and AC histology were independently associated with worse RFS. A weighted risk score for recurrence was developed, which externally predicted OS after pCR in the NCDB (HR 1.12 per point, p < 0.001). Median OS was 7.8 years for cases with score 0–3 versus 5.7 years for cases with score 4–5.

Conclusions

pCR after neoadjuvant chemoradiotherapy is a strong predictor of survival, but recurrence remains common. Further investigation into adjuvant therapies for high-risk pCR patients is needed.