Prognostic significance of early tumor shrinkage in metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based combination therapy

Abstract Background Immune checkpoint inhibitor (ICI)-based combination therapies have become the standard first-line treatment for metastatic renal cell carcinoma (mRCC). This study evaluated the prognostic significance of early tumor shrinkage in patients with mRCC treated with first-line ICI-based combination therapies. Methods We retrospectively reviewed 169 mRCC patients who received nivolumab plus ipilimumab, pembrolizumab (or avelumab) plus axitinib, pembrolizumab plus lenvatinib, or nivolumab plus cabozantinib at Kobe University Hospital and its affiliated institutions. Patients were stratified into four groups according to early tumor shrinkage at the first imaging assessment after therapy initiation. The association between early tumor shrinkage and the overall survival (OS) was analyzed. Results The median early tumor shrinkage rate was 17.8%. Twenty-one patients (12.4%) had 50%–100% shrinkage, 31 (18.3%) had 30%–<50% shrinkage, 81 (47.9%) had 0%–<30% shrinkage, and 36 (21.3%) showed progression. The median OS was 42.4 months. The corresponding median OS by shrinkage category above was not reached (NR), NR, 34.7 months, and 30.8 months, respectively (p = 0.023), with 2-year OS rates of 86.7%, 75.1%, 66.1%, and 60.5%, respectively. A univariate analysis identified a prior nephrectomy, International mRCC Database Consortium risk group, bone or liver metastasis, C-reactive protein level, histological subtype, and early tumor shrinkage as predictors of the OS. In the multivariate analysis, prior nephrectomy, bone or liver metastasis, histological subtype, and early tumor shrinkage remained independent. Conclusion Early tumor shrinkage was independently associated with the OS, suggesting its potential as a prognostic indicator in patients with mRCC treated with first-line ICI-based combination therapy.