Real-world outcomes and prognostic role of neutrophil-to-lymphocyte ratio (NLR) in patients with advanced urothelial carcinoma treated with enfortumab vedotin plus pembrolizumab (EVP).

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Background: EVP has demonstrated a significant survival benefit in advanced urothelial carcinoma (aUC) in clinical trials. However, real-world data evaluating outcomes and early prognostic biomarkers in this setting is limited. We assessed real-world outcomes and explored the prognostic value of neutrophil-to-lymphocyte ratio (NLR), focusing on NLR prior to cycle 3 (NLR3) and the dynamic change in NLR (dNLR), in aUC patients treated with first-line EVP. Methods: We conducted a retrospective, multicenter analysis of patients with aUC treated with EVP in Alberta, Canada between September 2024 and January 2026, with a minimum follow-up of 3 months. NLR3 and dNLR were evaluated. High NLR3 was defined as ≥ 2.7. dNLR was defined as the relative change from baseline to pre-cycle 3 and categorized as a decrease > 10% versus stable/increase (≤10% decrease or any increase). Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Sixty patients were included (median age 69 years, 82% male). Primary tumor site was bladder in 41 patients and upper genitourinary tract in 14. Histology was pure urothelial carcinoma in 48 patients and mixed histology in 12. 33 patients had visceral metastases; most commonly involving lung (n = 16), bone (n = 12) and liver (n = 12). 15 patients had lymph node–only metastases and 12 had locally advanced unresectable disease. FGFR testing was performed in 31 patients, with alterations identified in 8. Median follow-up was 10.3 months, and the median number of EVP cycles administered was 8. The overall ORR was 62%, and 1-year PFS was 42%. Patients with low NLR3 had higher ORR (82% vs 55%; OR 0.26, 95% CI 0.07–0.96; p = 0.037) and superior survival, including PFS (1-yr 75% vs 27%; HR 0.16, 95% CI 0.04–0.54; p = 0.003) and OS (1-yr 100% vs 50%; p = 0.005) compared to high NLR3. NLR decrease > 10% was associated with better PFS (1-yr 70% vs 26%; HR 0.31; 95% CI 0.12–0.75 p = 0.01). OS difference was numerically higher with NLR decrease > 10% but not statistically significant (1-yr 73% vs 59%; p = 0.11). Conclusions: In this real-world cohort of patients with aUC treated with EVP, low NLR3 and early NLR decline were associated with higher response rates and improved survival. NLR3 and dynamic NLR changes are simple, readily available biomarkers that provide early prognostic information and may support risk stratification in routine clinical practice.

NLR3, dynamic NLR, and impact on patient outcomes.