AUTHOR=Li Haifeng , An Xin , Huang Riqing , Li Lu , Chu Chengbiao , Yang Wei , Qin Zike , Liu Zhuowei , Zhou Fangjian , Xue Cong , Shi Yanxia 

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

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.621883

DOI=10.3389/fmolb.2021.621883

ISSN=2296-889X

ABSTRACT=<p><bold>Introduction:</bold> 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.</p><p><bold>Materials and Methods:</bold> 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).</p><p><bold>Results:</bold> 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 (<italic>p</italic> &lt; 0.001). The median OS for the poor, intermediate, and good mUIPI was 12.82, 18.11, and 34.87 months, respectively (<italic>p</italic> = 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.</p><p><bold>Conclusions:</bold> mUIPI predicts early responses in mUC patients who received anti–PD-1/PD-L1–based therapy.</p>