Survival Outcome and Treatment Response of Patients with Late Relapse from Renal Cell Carcinoma in the Era of Targeted Therapy

Abstract Background A subset of primarily localized renal cell carcinoma (RCC) patients will experience disease recurrence ≥5 yr after initial nephrectomy. Objective To characterize the clinical outcome of patients with late recurrence beyond 5 yr. Design, setting, and participants Patients with metastatic RCC (mRCC) treated with targeted therapy were retrospectively characterized according to time to relapse. Relapse was defined as the diagnosis of recurrent metastatic disease >3 mo after initial curative-intent nephrectomy. Patients with synchronous metastatic disease at presentation were excluded. Patients were classified as early relapsers (ERs) if they recurred within 5 yr; late relapsers (LRs) recurred after 5 yr. Outcome measurements and statistical analysis Demographics were compared with the Student t test, the chi-square test, or the Fisher exact test. The survival time was estimated with the Kaplan-Meier method, and associations with survival outcome were assessed with univariable and multivariable Cox regression analyses. Results and limitations Among 1210 mRCC patients treated with targeted therapy after surgery for localized disease, 897 (74%) relapsed within the first 5 yr and 313 (26%) (range: 5–35 yr) after 5 yr. LRs presented with younger age ( p < 0.0001), fewer with sarcomatoid features ( p < 0.0001), more clear cell histology ( p = 0.001), and lower Fuhrman grade ( p < 0.0001). Overall objective response rates to targeted therapy were better in LRs versus ERs (31.8% vs 26.5%; p = 0.004). LRs had significantly longer progression-free survival (10.7 mo vs 8.5 mo; p = 0.005) and overall survival (OS; 34.0 mo vs 27.4 mo; p = 0.004). The study is limited by its retrospective design, noncentralized imaging and pathology review, missing information on metastatectomy, and nonstandardized follow-up protocols. Conclusions A quarter of patients who eventually developed metastatic disease and were treated with targeted therapy relapsed over 5 yr from initial nephrectomy. LRs have more favorable prognostic features and consequently better treatment response and OS.