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.