Immunotherapy in radical surgery of colorectal carcinoma

Cancer-associated immunodeficiency is seriously worsened by surgical trauma. Short-term preoperative interleukin-2 (IL-2) immunotherapy abolishes postoperative immunodeficiency and can induce immunological control of the growth of minimal residual disease. Growth factors play an important role in oncological practice in treating neutropenia (G-CSF) or associated anaemia during chemotherapy (erythropoietin). Unfortunately, lymphocytopenia is not considered a biological marker with regard to survival. On the other hand, the role of the immune response to surgical trauma has been emphasised by many surgeons, and to counteract it immune nutrition (omega 3 fatty acid, mRNA, arginine) or thymic hormone have been tried. We believe that the obvious method of counteracting postoperative lymphocytopenia is the administration of the specific growth factor for T lymphocytes, i.e. IL-2. The aim of this study was to report on our experience with IL-2 preoperative immunoactivation in colorectal cancer and the long-term outcome of patients treated in comparison with a control group operated on without immunotherapy. In order to obtain activated lymphocytosis at the time of operation administration of IL-2 (6 million I.U. twice daily subcutaneously) for 3 preoperative days is sufficient, starting 4 days before surgery. The inclusion/exclusion criteria were histologically documented colorectal cancer, elective surgery, laparotomic surgery, no second tumour, age 20-80 years, no cardiovascular, hepatic or renal failure. From June 1992 to December 2005, 67 patients were treated (Dukes B/C: 46/21) with IL-2 immunotherapy. The clinical and biological results were compared with those of a control group of 173 patients (Dukes B/C 114/59) operated on in the same period and recruited with the same criteria. Dukes stage-C patients in both groups underwent adjuvant chemotherapy plus radiotherapy for rectal cancer. Data were statistically analysed using Fisher's exact test, Student's T-test and analysis of variance, as appropriate. The overall survival curves were plotted with the Kaplan-Mayer method. After a median follow-up of 69 months (range: 12-169) the progression rate was 15/67 (22%) vs 68/173 (39%) in controls (p = 0.02). Important results were obtained in Dukes-B patients: progression rate 7/46 (15%) vs 37/114 (32,4%) in controls (p = 0.03). We can conclude that immunotherapy is well tolerated. IL-2 is capable of counteracting surgery-induced immunodeficiency. The amplification of the immune response in the post-operative period is capable of controlling minimal residual disease after radical surgery, of reducing the progression rate, and of improving the prognosis and overall survival.