Adjuvant chemotherapy following trimodality therapy for esophageal carcinoma—Is the evidence sufficient?

The preferred management of localized esophageal carcinoma consists of multi-modality therapy (chemotherapy, radiation, and surgery). The ideal timing, treatment sequence, and dose of therapy remain active areas of investigation and controversy. Following publication of favorable outcomes for neoadjuvant chemoradiation prior to definitive resection, tri-modality therapy has become the standard approach in the United States for patients with local/regionally advanced disease (1-5). As the experience with trimodality therapy has grown, adjuvant treatment following completion of all planned therapy has become an area of interest. For those 15–30% of patients with a pathologic complete response (pathCR), the decision to reserve further therapy until the time of recurrence appears straightforward, with no clear evidence of significant clinical benefit for either adjuvant chemotherapy or radiation. However, even for patients with pathCR, recurrence rates remain high with approximately >33% of patients developing distant metastases. In patients with residual disease burden following trimodality therapy, the question of adjuvant chemotherapy becomes more relevant (6-8). This group of patients (pT+ and/or N+) remains at highrisk for both local and/or distant failure. The addition of adjuvant systemic therapy is hoped to provide superior outcomes compared to observation alone (9). Taken together, the evidence would suggest a potential role for adjuvant systemic therapy regardless of pathologic response; the challenge becomes identifying those patients in whom further systemic therapy, with its inherent risks, will offer a relevant clinical benefit.