The Prognostic Value of a Pathologic Complete Response After Neoadjuvant Therapy for Digestive Cancer: Systematic Review and Meta-Analysis of 21 Studies

Background. Neoadjuvant therapy (NAT) before radical excision has become the preferred initial option for locally advanced digestive cancers such as esophageal cancer (EC), esophagogastric junction adenocarcinoma (EGJAC), gastric adenocarcinoma (GAC), rectal cancer (RC), and pancreatic cancer (PC). Although some patients reportedly achieve a pathologic complete response (pCR) after neoadjuvant therapy, the published data are inconsistent regarding whether pCR yields a survival benefit. The current meta-analysis was performed to assess the potential prognostic value of pCR after preoperative therapy for patients with digestive cancers. Methods. An extensive electronic search in PubMed, Web of Science, and the Cochrane Library was performed for relevant articles, from which data relative to independent correlations of pCR with overall survival (OS) and disease-free survival (DFS) were extracted for analysis. A random-effects model was used to calculate the pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs). Results. The study identified 6780 patients who met the inclusion and exclusion criteria. The results showed that pCR was significantly correlated with better OS (HR, 0.50; 95% CI, 0.43-0.58; P<0.001) and DFS (HR, 0.49; 95% CI, 0.40-0.60; P<0.001) for the digestive cancer patients who achieved pCR than for those who did not achieve pCR. Subgroup analysis showed that the correlation of pCR with OS was significant in EC (HR, 0.57; 95% CI, 0.47-0.69; P<0.001), EGJAC/GAC (HR, 0.38; 95% CI, 0.17-0.86; P=0.02), RC (HR, 0.48; 95% CI, 0.28-0.81; P=0.006), and PC (HR, 0.41; 95% CI, 0.17-0.97; P=0.04). In addition, the survival benefit for pCR patients was of similar magnitude, irrespective of the type of study, type of NAT, or ethnicity. Conclusions. A pCR is correlated with favorable survival outcomes compared with a non-pCR for digestive cancer patients after NAT.