C-reactive protein at pembrolizumab initiation and its trajectory from first-line chemotherapy as prognostic markers in metastatic urothelial carcinoma (YUSHIMA study).

PURPOSE: To evaluate C-reactive protein (CRP) at pembrolizumab initiation and paired CRP measurements before first-line chemotherapy and at pembrolizumab initiation as prognostic markers of overall survival (OS) in metastatic urothelial carcinoma (mUC). METHODS: We retrospectively analyzed 346 patients treated with pembrolizumab after platinum chemotherapy. Pre-immunotherapy (pre-IO) CRP was categorized as < 5, 5 to < 20, or ≥ 20 mg/L. Among 333 patients with paired measurements, four joint categories were defined at 5 mg/L. OS was evaluated using Kaplan-Meier methods, restricted mean survival time (RMST), and multivariable Cox regression. Up to 58 patients may overlap an earlier network report. RESULTS: Median OS was 19.1, 12.2, and 4.9 months across increasing CRP categories (p < 0.0001). At 24 months, unadjusted RMST was 4.9 months longer below versus at or above 10 mg/L (95% confidence interval [CI] 2.9-6.8). In 322 complete cases, the adjusted hazard ratio was 1.98 for high versus low CRP (95% CI 1.40-2.79) and 1.14 per approximate doubling (95% CI 1.07-1.21). The proportional hazards assumption was not met. Albumin adjustment attenuated the high versus low estimate to 1.26 (95% CI 0.79-2.00). Paired categories separated OS descriptively. CONCLUSION: Higher pre-IO CRP was associated with shorter OS after clinical adjustment, but shared prognostic information with albumin. Paired categories were descriptive. Because the cohort partly overlaps previous work, external validation is required.