Clinical Pearls & Morning Reports
The role of nephrectomy in treating metastatic renal-cell carcinoma in the era of targeted therapy has been brought into question, since there is limited level 1 evidence directly comparing the benefit of nephrectomy with targeted therapy. Méjean et al. assessed the benefit of initial nephrectomy followed by sunitinib in patients with metastatic clear-cell renal-cell carcinoma compared to the benefits provided by sunitinib alone. Read the NEJM original article here.
Q: What percentage of cases of kidney cancer are metastatic at diagnosis?
A: Kidney cancer accounts for 5% of all cancers in men and 3% of all cancers in women, and approximately 15% of these are metastatic at diagnosis.
Q: What treatment options have become available in recent years for renal-cell carcinoma?
A: Since 2005, the treatment options have rapidly expanded owing to the introduction of therapies targeted to the molecular mechanisms underlying renal-cancer carcinogenesis. Inhibitors of vascular endothelial growth factor (VEGF) signaling, including the VEGF receptor tyrosine kinase inhibitors sunitinib and pazopanib and the anti-VEGF monoclonal antibody bevacizumab, are now standard first-line treatment options for favorable-risk and intermediate-risk metastatic renal-cell carcinoma, whereas the mammalian target of rapamycin (mTOR) inhibitor temsirolimus is widely recommended for patients who have renal-cell carcinoma and poor prognostic risk. Several other agents targeting the VEGF receptor, mTOR, c-MET, or the interaction of the immune checkpoint inhibitor programmed death 1 receptor with its ligand have shown efficacy and are current treatment options for patients with renal-cell carcinoma.
A: In the trial by Méjean et al., sunitinib alone was not inferior to nephrectomy followed by sunitinib. In both the intermediate-risk and poor-risk groups of patients, the median overall survival was longer in the sunitinib-alone group than in the nephrectomy–sunitinib group (23.4 vs. 19.0 months in the intermediate-risk subgroup and 13.3 vs. 10.2 months in the poor-risk group). The median progression-free survival was longer among patients in the sunitinib-alone group than among those in the nephrectomy–sunitinib group (8.3 months [95% CI, 6.2 to 9.9] vs. 7.2 months [95% CI, 6.7 to 8.5]). The objective response rate was similar in the two trial groups (29.1% in the sunitinib-alone group and 27.4% in the nephrectomy–sunitinib group), although the rate of disease control was nonsignificantly higher in the sunitinib-alone group than in the nephrectomy–sunitinib group (74.6% vs. 61.8%).
A: A potential limitation of the trial is that enrolled patients were appropriate candidates for nephrectomy in the opinion of the treating urologist; therefore, the results are not generally applicable to patients with a poor performance status, minimal primary tumor burden, and high volumes of metastatic disease, because these patients are not generally recommended to undergo nephrectomy. Because this was a noninferiority trial, the results may underestimate the benefit of nephrectomy. Another limitation of the trial is the recruitment of fewer patients than planned (450 patients rather than 576), which reduced the statistical power.