Pre-operative kinetic parameter determination of colorectal adenocarcinomas. Prognostic significance.

Abstract

The aim of this study was to test the prognostic value of pre-operative assessment of tumour kinetics in colorectal adenocarcinoma. The study of tumour kinetics was performed using an in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed using flow cytometry. This procedure enables calculation of the in vivo S-phase fraction labelling index (LI), the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). Disease-free survival curves were calculated by a Kaplan-Meier method. The statistical significance between curves was tested by the log rank test. A multivariate analysis was performed using the Cox's proportional hazards model to determine the effect of pathological staging (lymph node involvement), ploidy and kinetic parameters. Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy. In univariate analysis, lymph node involvement, labelling index > 10% and Tpot < 5 days were associated with poor prognosis, with P= 0.0006, 0.049 and 0.029 respectively; no significant differences were found in Ts (P = 0.214), and ploidy (P= 0.095). In multivariate analysis, lymph node involvement, ploidy and Tpot were found to be independent factors of colorectal cancer prognosis (P= 0.028, 0.032 and 0.035 respectively) in all tumours. Tpot was considered a independent prognostic factor in diploid tumours (P= 0.047) but not in aneuploid tumours (P= 0.345). These results suggest that kinetic parameters determined by pre-operative biopsies of colorectal adenocarcinoma represent a prognosis factor, independent of pathological staging, particularly in diploid tumours.