TUMOR PROLIFERATION IN RECTAL-CANCER FOLLOWING PREOPERATIVE IRRADIATION

Purpose: This study examines the effect of preoperative irradiation on tumor proliferation in rectal cancer. Patients and Methods: One hundr ed twenty-two patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation followed by surgery, Pretreatmen t tumor biopsies and postirradiation surgical specimens were scored fo r proliferative activity by assaying the extent of Ki-67 and prolifera ting-cell nuclear antigen (PCNA) immunostaining and the number of mito ses per 10 high-power fields (hpf), Preirradiation and postirradiation proliferative activity was determined and correlated to clinical outc ome. Results: There was an overall reduction in the tumor proliferativ e activity of rectal cancer after irradiation compared with its preirr adiation state. Decreases in the activity of all three markers of tumo r proliferation (Ki-67 and PCNA immunostaining, and mitotic counts) we re observed in irradiated tumors compared with pretreatment biopsies, postirradiation tumor proliferative activity was associated with patho logic tumor stage. A high level of proliferative activity was observed in tumors downstaged to the rectal wall (T1-2) compared with tumors t hat retained transmural penetration (T3-4), Multivariate analysis indi cated that postirradiation proliferative activity and stage were indep endently associated with survival following surgery. patients with tum ors that exhibited elevated proliferative activity postirradiation had improved survival compared with patients with tumors that showed less proliferative activity. Conclusion: Moderate- to high-dose preoperati ve irradiation decreases both the tumor size and proliferative activit y of rectal cancers, Elevated postirradiation tumor proliferative acti vity correlates strongly with improved survival. This may aid in ident ifying high-risk patients following preoperative irradiation and surge ry. (C) 1995 by American Society of Clinical Oncology.