Off-label use of adjuvant targeted therapy (TT) for high-risk locoregional renal cell carcinoma (RCC) is associated with decreased overall survival, new study findings suggest.

The study included 41,127 patients who underwent nephrectomy for either stage pT3a or greater or pN+ clear cell RCC. Of these, 2071 received off-label adjuvant TT. Investigators assembled a propensity matched cohort of 1604 patients—802 who received off-label adjuvant TT and 802 who did not. Median overall survival (OS) time was significantly shorter among patients who received adjuvant TT than those who did not (52 vs 79 months), Nicholas H. Chakiryan, MD, of Oregon Health & Sciences University in Portland, and colleagues reported in Urologic Oncology.

The investigators also demonstrated decreased survival among adjuvant TT recipients in 2 pathologic subgroups (pT3/4N0/x and pTanyN+). Median survival times were 75 vs 86 months in the pT3/4N0/x subgroup and 17 vs 21 months in the pTanyN+ subgroup.

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The investigators defined adjuvant TT as receipt of single or multiple-agent chemotherapy within 3 months of nephrectomy. All patients in the study who received adjuvant TT did so prior to FDA approval of adjuvant sunitinib in 2017, so they were categorized as having received off-label adjuvant TT, the investigators noted.

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The authors analyzed 2006 to 2015 data obtained from the National Cancer Database. For the overall study population, the adjuvant TT group was significantly younger than the patients who did not receive adjuvant TT (mean age 59.1 vs 63.9 years). In the propensity matched cohort, patients in both groups had a mean age of 60.3 years.

“The finding of decreased survival for patients receiving adjuvant TT was not identified in any of the randomized controlled trials (RCTs) on this topic, Dr Chakiryan and colleagues pointed out. A possible reason for this discrepancy could be that the RCTs used disease-free survival as the primary end point, not OS, they noted.

“For example, receipt of adjuvant TT could delay radiographic progression, but result in enough toxicity to decrease OS,” the authors explained. “Additionally, it is well described that patients enrolled in RCTs tend to be younger and have fewer comorbidities than those encountered in real-world clinical practice.”


Chakiryan NH, Acevedo AM, Garzotto MA, et al. Survival outcomes and practice trends for off-label use of adjuvant targeted therapy in high-risk locoregional renal cell carcinoma [published online March 30, 2020]. Urol Oncol. doi: 10.1016/j.urolonc.2020.02.028