Metastatic renal carcinoma comprehensive prognostic system

Abstract

The purpose of the study was to identify a comprehensive prognostic system of pretreatment clinical parameters in 425 patients (pts) with metastatic renal-cell carcinoma treated with different subcutaneous (s.c.) recombinant cytokine-based home therapies in consecutive trials. Treatment consisted of (A) s.c. interferon-alpha 2a (INF-alpha), s.c. interleukin-2 (IL-2) (n=102 pts), (B) s.c. IFN-alpha 2a, s.c. IL-2, and i.v. 5-fluorouracil (5-FU) (n=235 pts) or (C) s.c. IFN-alpha 2a, s.c. IL-2, and i.v. 5-FU combined with p.o. 13-cis-retinoic acid (13cRA) (n=88 pts). Kaplan-Meier survival analysis, log-rank statistics, and Cox regression analysis were employed to identify risk factors and to create a multiple risk factor model. The following pretreatment risk factors were identified by univariate analysis: (1) three and more metastatic sites, (2) presence of liver, lymph node or bone metastases, (3) neutrophil count > or = 6500 cells microl(-1), (4) serum lactate dehydrogenase level (LDH) > or = 220 U l(-1), and (5) serum C-reactive protein level (CRP) > or = 11 mg l(-1). Cox regression analysis with forward stepwise variable selection identified neutrophil count as the major prognostic factor (hazard ratio=1.9, P<0.001), while serum levels of LDH and CRP, time between diagnosis of tumour and onset of metastatic disease, number of metastatic sites, and bone metastases were significant but somewhat less important prognostic variables within the multiple risk factor model (hazard ratio < or = 1.5). Patients were assigned to one of the three risk groups according to cumulative risk defined as the sum of simplified risk s.c.ores for six pretreatment variables. Low-, intermediate-, and high-risk patients achieved a median overall survival of 32+ months (95% CI 24, 43; 5-year survival of 27%), 18+ months (95% CI 15, 20; 5-year survival of 11%), and 8+ months (95% CI 6, 10; 5-year survival of 5%), respectively. These prognostic categories are helpful both in individual patient care and in the assessment of patients entering prospective clinical trials.

Figure 3

Overall survival of 425 advanced renal-cell carcinoma patients treated with outpatient s.c. IL-2/INF-α2a therapy (A). Overall survival of 163 low-risk patients, 197 intermediate-risk patients, and 65 high-risk patients treated with outpatient subcutaneous interleukin-2/interferon-α2a therapy (B). Survival was calculated from the start of therapy using Kaplan–Meier method.

Figure 1

Overall survival of 362 patients with neutrophil counts <6500 cells μl⁻¹ and 63 patients with neutrophil counts ⩾6500 cells μl⁻¹ (A). Overall survival of 330 patients with LDH levels <220 U l⁻¹ and 95 patients with LDH levels ⩾220 U l⁻¹ (B). All patients were treated with outpatient s.c. IL-2/IL-α2a therapy. Survival was calculated from the start of therapy using Kaplan–Meier method.

Figure 2

Overall survival of 222 patients with CRP levels <11 mg l⁻¹ and 203 patients with CRP levels ⩾11 mg l⁻¹ (A). Overall survival of 350 patients with <3 metastatic sites and 75 patients with ⩾3 metastatic sites (B). All patients were treated with outpatient s.c. IL-2/INF-α2a therapy. Survival was calculated from the start of therapy using Kaplan–Meier method.