Chronological transition in outcome of second-line treatment in patients with metastatic urothelial cancer after pembrolizumab approval: a multicenter retrospective analysis.

After first-line chemotherapy failure, metastatic urothelial carcinoma (mUC) patients undergo pembrolizumab (PEM) or gemcitabine and docetaxel (GD) therapy. We retrospectively investigated outcomes of second-line GD or PEM for mUC patients. A total of 198 mUC patients from Nagoya City University and affiliated hospitals who received second-line treatment were grouped according to immune check point inhibitor (ICI) availability: Groups A (pre-ICI: n = 104) and B (post-ICI: n = 94). We compared clinical outcomes using Kaplan–Meier curves. Univariate and multivariate Cox regression analyses assessed potential prognostic factors for overall survival (OS). Median OS was significantly longer for Group B [median 13.6 months, 95% confidence interval (CI): 7.6–17.6] than A (7.6 months, 5.3–8.8). By sub-group analysis, patients received no additional treatment (Naive, n = 70), or PEM or GD (Salvage, n = 24) in Group B, with median OS of Naive and A groups similar. Compared to the Salvage group, significant differences in OS were observed (median 7.6 months, 95% CI 5.3–8.8; Group A, 7.6 months, 4.7–13.8; Naive, 25.7 months, 14.0–31.0; p < 0.01). For the Salvage group, OS for sequential treatment of GD–salvage PEM and PEM–salvage GD patients was similar (p = 0.10). Multivariate analysis showed a low neutrophil-to-lymphocyte ratio (NLR) and high geriatric nutritional risk index (GNRI) as significant prognostic factors affecting long OS [95% CI 1.12–3.45, hazard ratio (HR): 1.97; 95% CI 0.24–0.71, 0.41, respectively]. Second-line GD or PEM therapy for mUC patients showed equivalent survival benefits. GNRI and NLR are prognostic biomarkers for survival outcome.