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

• Main Authors: Haifeng Li, Xin An, Riqing Huang, Lu Li, Chengbiao Chu, Wei Yang, Zike Qin, Zhuowei Liu, Fangjian Zhou, Cong Xue, Yanxia Shi
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-08-01
• Series: Frontiers in Molecular Biosciences
• Subjects: PD-1 inhibitor; LDH; NLR; urothelial carcinoma; mUIPI
• Online Access: https://www.frontiersin.org/articles/10.3389/fmolb.2021.621883/full

Introduction: The use of antibodies against programmed death receptor-1 (PD-1) and its ligand (PD-L1) has 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 mUIPI. Major observations were progression-free survival (PFS), overall 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, 26.3–53.2). 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 was 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, 18.11, 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 received anti–PD-1/PD-L1–based therapy.