Is There a Role for Adjuvant Immunochemotherapy after Radical Nephrectomy in pT_2-3N₀M₀ Renal Cell Carcinoma?

Abstract

Five-year overall survival after radical surgery in N₀M₀ renal cell carcinoma varies from 45-80% in pT₂ to 35-50% in pT₃ categories. In view of the alpha interfer-on and vinblastine combination which has shown some activity in advanced disease with increasing efficacy in limited metastatic invasion, we decided to explore the theoretical advantage of adjuvant chemo-immunotherapy in radically resected stage II, III renal cell carcinoma.

A single-institution phase II study was undertaken to evaluate the efficacy and tolerability of α2a-interferon (α2a-INF) in combination with vinblastine in 30 patients with pT₂-T₃ N₀M₀ renal cell carcinoma (RCC). Thirty-two patients who received only radical nephrectomy and extended lymphadenectomy were analyzed and results were compared with the first group.

Twenty-three of 30 (76.6%) patients in the first group are alive with no evidence of disease. The median follow-up for the 23 patients still alive was 67 months (range 60 to 72). Metastases were documented in 5 patients (16.6%) with a median interval to progression of 24 months. Four of them (13.6%) died of tumor. In the control group, 16 out of 32 patients (50%) are still alive, with a median follow-up for the patients still alive of 62 months (range 60 to 68). Fifteen patients developed distant metastases and 2 of them had a local recurrence. All of them (46.8%) died of tumor. Median progression interval was 24 months. After stratification by pathological grade, site, laterality and number of nodes found at lymphadenectomy there were no statistical differences in risk of progression or death in the two groups. Patients who received the adjuvant treatment were characterized by a significantly better survival curve (p = 0.003) than those treated with surgery alone. The 5-year standardized mortality ratio (SMR) was 0.33 (I.C. 95% = 0.15-0.52). Side effects in the group receiving adjuvant treatment were mild, although the accumulation of several adverse reactions was responsible for treatment discontinuation in 4 patients.

Our results cannot demonstrate conclusively the superiority of α2a-INF/vinblastine over surgery alone but the low SMR and the better survival curves seen in the pT_2/3N₀M₀ category treated with immunochemotherapy deserve further randomized studies with a higher number of patients and longer follow-up period.