Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial

Clin Cancer Res. 2016 Jul 1;22(13):3201-8. doi: 10.1158/1078-0432.CCR-15-2199. Epub 2016 Feb 1.

Abstract

Purpose: We reported in a retrospective study that the presence of micrometastasis in lymph nodes, when assessed by carcinoembryonic antigen (CEA)-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer. The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial.

Experimental design: From November 2001 to December 2005, a total of 419 colorectal cancer cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II colorectal cancer cases were enrolled. After RNA quality check, 304 colorectal cancer cases were analyzed for CEA mRNA in lymph nodes by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method.

Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Postoperative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-fluorouracil derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for 1 year, whereas chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (high MMV, n = 95) was an independent poor prognostic factor for 5-year disease-free survival (DFS; P = 0.001) and 5-year overall survival (OS; P = 0.016).

Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II colorectal cancer. Clin Cancer Res; 22(13); 3201-8. ©2016 AACR.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Carcinoembryonic Antigen / analysis*
  • Carcinoembryonic Antigen / genetics
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Fluorouracil / analogs & derivatives*
  • Fluorouracil / therapeutic use
  • Humans
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • Neoplasm Micrometastasis / pathology*
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Prospective Studies
  • RNA, Messenger / analysis

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • RNA, Messenger
  • carmofur
  • Fluorouracil