Is postoperative adjuvant therapy necessary for esophageal cancer patients with pathological complete response after...

Current National Comprehensive Cancer Network (NCCN) guidelines recommend omission of adjuvant therapy in esophageal cancer patients achieving pathological complete response (pCR) following neoadjuvant treatment. However, 20-40% of these patients experience disease recurrence, potentially indicative of residual micrometastatic disease. This retrospective study evaluates survival outcomes between adjuvant therapy and observation in pCR populations.

We analyzed 184 esophageal cancer patients with confirmed pCR after completed neoadjuvant therapy at Hebei Medical University Fourth Hospital (2012-2024). All patients completed at least two cycles of neoadjuvant chemotherapy or chemoimmunotherapy, or full-dose neoadjuvant chemoradiotherapy (40-50.4 Gy). Patients were stratified into adjuvant therapy (n = 66) and observation (n = 118) cohorts. The comparison between the two groups was performed using inverse probability of treatment weighting (IPTW) to adjust for confounding factors. Kaplan-Meier methodology with log-rank testing and Cox proportional hazards models evaluated disease-free survival (DFS) and overall survival (OS). Based on the identified high-risk prognostic factors from survival analyses, we proposed a risk-adapted clinical decision-making algorithm for postoperative adjuvant therapy selection among pCR patients.

Multivariate analysis identified clinical T4a stage as an independent prognostic risk factor (P = 0.001). With median follow-up of 37.1 months, adjuvant therapy demonstrated superior 3-year DFS (P = 0.0027) and marginal OS improvement (P = 0.057). Significant OS benefits emerged in cT4a-stage (P = 0.034) and clinical lymph node-positive subgroups (P = 0.048). Adjuvant therapy recipients experienced prolonged median recurrence-free interval (35.50 vs 12.79 months, P < 0.001) and reduced recurrence incidence (1.51% vs 15.25%, P < 0.001). In the adenocarcinoma subgroup (n = 26), all recurrent events were distant metastases (7.69%) without local locoregional failure. Proposed risk-adapted algorithm for pCR esophageal cancer after neoadjuvant therapy: adjuvant therapy recommended for high-risk (cT4a any cN) and moderate-risk (cN ⁺ cT2-3) subgroups; shared decision-making for standard-risk (cT2-3N0) balancing benefit and toxicity.

Clinical T4a stage predicts adverse outcomes in pCR patients. Adjuvant therapy reduces and delays recurrence in pCR esophageal cancer patients, improving survival, especially in high-risk subgroups (cT4a, cN⁺). These findings challenge current guideline recommendations and support risk-adapted adjuvant strategies in esophageal cancer.