- PURPOSE: Early tumor shrinkage (eTS) has prognostic value in metastatic renal cell carcinoma (mRCC). We aimed to validate the role of eTS in first line treatment from the COMPARZ study (NCT00720941). METHODS: 1100 patients treated with sunitinib or pazopanib were analyzed for tumor response according to RECIST 1.0. eTS was defined as tumor shrinkage by ≥ 10%. A landmark analysis was performed on day (d) 42 and 90 and Cox proportional hazards regression was computed for the prognostic effect of eTS. RESULTS: In patients with eTS median OS was 34.1 [CI 95% 28.4; not reached (NR)] and 33.6 (CI 95% 30.1; NR) months (mo) at d 42 and 90, respectively, compared to 19.6 (CI 95% 14.0; 28.9) and 15.1 (CI 95% 12.4; 18.7) mo for patients without eTS. There was no interaction between type of treatment and eTS (d 42 p = 0.79; d 90 p = 0.37). eTS ≥ 10% remained an independent prognostic marker in multivariable analyses at both d 42 and 90. CONCLUSIONS: Similar results were found for eTS at the 42 and 90 days landmarks. eTS ≥ 10% has prognostic relevance in mRCC and reflects a putative tool to guide future clinical treatment.