Prognostic value of whole lymph node molecular analysis in colorectal cancer: a prospective multicenter study.

Lymph node (LN)-negative colorectal cancer (CRC) patients may be understaged by conventional hematoxylin and eosin for its low sensitivity for detecting LN micrometastasis (LNM). The one-step nucleic acid amplification assay (OSNA) has shown superior performance in detecting LNM. To date, OSNA studies in CRC have analyzed part of the LN tissue with OSNA and part with H&E, introducing a tissue allocation bias for LNM detection. We aimed to evaluate the prognostic significance of the whole LN molecular analysis using OSNA in CRC patients. This prospective multicenter study analyzed LNs from stage I-III CRC by both cytology smears (CS) and OSNA, the latter analyzing the whole LN tissue and reported as the Total Tumor Load (TTL). X-tile software was used to determine the optimal TTL threshold. Cox proportional hazard and Kaplan-Meier estimation were used to assess the prognostic significance of TTL for both cancer-specific survival (CSS) and recurrence-free survival (RFS). 158 CRC patients were included, with 156 eligible for survival analysis. A TTL of 15,000 copies/µL was identified as the optimal cut-off, stratifying CRC patients into low and high risk for both CSS and RFS (P < 0.05). Conversely, CS pN-positive patients with TTL ≤ 15,000 copies/μL had comparable long-term outcomes to CS pN-negative patients (P > 0.05). A TTL threshold of > 15,000 copies/μL has prognostic value as it identifies CRC patients with significantly reduced CSS and RFS. The clinical implementation of the whole LN analysis by OSNA allows accurate patient risk stratification and optimizes postsurgical management.