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

Abstract

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.

Epidemiology, treatments, and related biomarkers of locally advanced or metastatic urothelial carcinoma in Chinese population: A scoping review

“…For treatment-naive and treatment-experienced patients, ORR ranged from 24% to 54.5% and median OS ranged from 9.8 to 20.53 months. 15,61,62,64,65 One currently published realworld retrospective study among patients receiving different line of therapy, revealed an ORR of 28% in patients receiving PD-1 inhibitors or PD-1 inhibitors plus chemotherapy. 76 However, given the reported outcomes were from studies with different sample size, inclusion of population with mixed treatment sequences and study designs, there is an apparent heterogeneity existing in this wide range of results and should be interpreted with caution.…”

“…64 One study with no specific PD1/ L1 treatment reported median PFS as 6.2 months and OS as 20.53 months in 52 treatment-naive and treatmentexperienced mUC patients. 65 The other study found that immunotherapy might be beneficial for UC patients with ESRD. 62 In terms of safety, treatment-related adverse events (TRAE) and immune-related adverse events (irAE) were reported.…”

“…Immunotherapies were reported in six studies, two of which were single-arm trials and four of which were retrospective cohort studies. 15,[61][62][63][64][65] Study details are provided in Table 4. Treatment-specific data were reported in single-arm trials for tislelizumab and toripalimab respectively, while the remaining four studies reported data for multiple immunotherapies.…”

“…In four studies reporting PD-L1 expression, positive rates of PD-L1 ranged from 33.33% to 100% among those tested via IHC due to different enrollment criteria of patients dependent on studies. 15,61,62,65 One study only included PD-L1+ patients 61 whereas other three studies included PD-L1 status-negative or -unknown patients. 15,62,65 In addition, one study investigated RC48-ADC in HER2-positive patients evaluated by IHC and further confirmed by FISH.…”

“…15,61,62,65 One study only included PD-L1+ patients 61 whereas other three studies included PD-L1 status-negative or -unknown patients. 15,62,65 In addition, one study investigated RC48-ADC in HER2-positive patients evaluated by IHC and further confirmed by FISH. 11 In seven studies related to FGFR, five reported FGFR3 alterations, [68][69][70][71][72] one explored FGFR family alterations in UC patients, 73 and one investigated the landscape of FGF/ FGFR alterations in a large cohort of 12,737 cancer patients with a high prevalence of FGF/FGFR mutations | 15397 occurring in urinary tract cancer (52.7%, 145/275).…”