Exploratory Subgroup Analyses of Renal Function and Overall Survival in European Organization for Research and Treatment of Cancer randomized trial of Nephron-sparing Surgery Versus Radical Nephrectomy.

Background: In the European Organization for Research and Treatment of Cancer (EORTC) randomized trial 30904, nephron-sparing surgery (NSS) reduced the risk of renal dysfunction compared with radical nephrectomy (RN); however, overall survival was better in the RN arm.

Objective: To determine whether treatment effect on the risk of renal dysfunction and all-cause mortality differed in magnitude across levels of baseline variables.

Design, Setting, And Participants: This was an exploratory subgroup analysis of EORTC 30904, a phase 3 randomized trial conducted in patients with a small (≤5cm) renal mass and normal contralateral kidney.

Intervention: Patients were randomized to RN (n=273) or NSS (n=268).

Outcome Measurements And Statistical Analysis: End points included follow-up estimated glomerular filtration rate (eGFR) <60ml/min/1.73m, eGFR <45ml/min/1.73m, eGFR <30ml/min/1.73m, and all-cause mortality. Treatment effect was examined within baseline variables: age (<62 vs ≥62 yr), sex, chronic disease (any vs none), performance status (0 vs≥1), and serum creatinine ≤1.25 vs >1.25×upper limit of normal (ULN). Logistic and Cox regression models were used for analysis of renal dysfunction and all-cause mortality, respectively.

Results And Limitations: The median follow-up periods were 6.7 yr for eGFR and 9.3 yr for survival. No variable-by-treatment interactions were significant at alpha=0.05. For patients with baseline creatinine >1.25×ULN (n=36), estimated mortality hazard ratio (HR) for NSS versus RN reversed its direction (HR=0.76, 95% confidence interval [CI]: 0.17-3.39) relative to the rest of the study cohort (HR=1.56, 95% CI: 1.06-2.29), although this reversal was not statistically significant (interaction p=0.25). This analysis was limited by low power.

Conclusions: This exploratory analysis did not reveal strong evidence of treatment effect modification in EORTC 30904, but it was limited by low power.

Patient Summary: We aimed to determine whether the effect of partial versus radical nephrectomy on kidney function and overall survival depended on age, sex, and baseline health of patients enrolled in a large clinical trial. Such dependence could not be demonstrated in this analysis.