Role of a Modified Urothelium Immune Prognostic Index in Patients With Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1-Based Therapy.

Introduction: The use of antibodies against programmed death receptor-1 (PD-1) and its ligand (PD-L1) have improved survival in metastatic urothelial carcinoma (mUC) patients. However, reliable and convenient biomarkers of early responses and outcomes are still lacking. Materials and Methods: We retrospectively screened mUC patients who received anti-PD-1/PD-L1-based therapy at our institute. A modified urothelium immune prognostic index (mUIPI) based on the neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) was developed to characterize the three groups as good, intermediate, and poor UIPI. Major observations were progression-free survival (PFS), over survival (OS), and disease control rate (DCR). Results: We identified 52 mUC patients with a median follow-up time of 29.8 months (95% CI, 26.3 to 53.2). Low NLR was with improved PFS and OS (hazard ratio [HR] 0.40, 95% CI 0.18-0.92; HR 0.27, 95% CI 0.11-0.69, respectively). Normal LDH were associated with improved PFS but not OS (HR 0.22,95% CI 0.10-0.52; HR 0.86,95% CI 0.34-2.13, respectively). The median PFS for the poor, intermediate, and good mUIPI groups was 1.97 months (95% CI, 1.15 to NR), 3.48 months (95% CI, 1.58 to NR), and 14.52 months (95% CI, 5.75 to NR), respectively (P < 0.001). The median OS for the poor, intermediate, and good mUIPI was 12.82 months, 18.11 months, and 34.87 months, respectively (P = 0.28). A good mUIPI was associated with a higher DCR compared to intermediate and poor mUIPI (odds ratio [OR], 7.58, 95% CI, 1.73-43.69; OR, 6.49, 95% CI, 0.14-295.42, respectively). In the subgroup analysis, a good mUIPI was associated with improved PFS in the subgroups of male patients and patients with low urinary tract primary tumors, liver metastases, non-first line treatment, and monotherapy. Conclusions: mUIPI predicts early responses in mUC patients who receive anti-PD-1/PD-L1-based therapy.