What question did this study set out to answer?

This research aims to evaluate the clinical impact of first-line chemotherapy and immune checkpoint inhibitors in metastatic urothelial carcinoma with variant histology.

June 11, 2026

Clinical impact of immune checkpoint inhibitors and Chemotherapy in the first-line treatment of metastatic urothelial carcinoma with variant histology

Key Points

This research aims to evaluate the clinical impact of first-line chemotherapy and immune checkpoint inhibitors in metastatic urothelial carcinoma with variant histology.
Retrospective analysis of patients treated with first-line palliative chemotherapy or immune checkpoint inhibitors at a single center from 2006 to 2024.
Assessment of primary endpoint as objective response rate and secondary endpoints as progression-free and overall survival using Kaplan-Meier analysis and descriptive statistics.
Inclusion of 42 patients, with treatment allocation reflecting real-world clinical decisions.
Objective response rate was 52.7% for immune checkpoint inhibitors compared to 39.1% for chemotherapy.
Median progression-free survival was 7.8 months (ICI) versus 6.3 months (CT) with 95% CI provided, but no significant differences (p=0.316).
Median overall survival was 12.4 months (ICI) compared to 10.4 months (CT) with 95% CI, but no significant differences (p=0.318).

Abstract

Introduction: Treatment of metastatic urothelial carcinoma (mUC) has evolved. The efficacy of chemotherapy (CT) and immune checkpoint inhibitors (ICI) against UC with Variant Differentiation (UC-VD) or pure variant histology (PVH) is rarely reported. This study assessed the clinical impact of first-line (1L) CT and/or ICI in patients with UC-VD or PVH. Methods: This retrospective study included patients treated with 1L palliative CT or ICI at the West German Tumor Center Essen (2006–2024). Treatment allocation reflected real-world clinical decision-making and was not randomized. Primary endpoint was objective response rate (ORR); secondary endpoints were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier analysis, log-rank tests, and descriptive statistics were used. Results: 42 patients were analyzed: 45.2% received ICI (73.6% monotherapy, 26.4% combination/maintenance), 54.8% CT. Median age was 67.7 years in ICI group und 61.2 in CT group. PVH was predominant in CT group (65.2%), while UC-VD with squamous differentiation was common in ICI group (42.1%). ORR of ICI was 52.7%. As secondary endpoints, median PFS and OS were 7.8 months (95% CI: 4.3–19.0) and 12.4 months in ICI group; for CT group, 6.3 months (95% CI: 4.5–11.6) and 10.4 months (95% CI: 1.9–58.2), respectively. ORR was 52.7% (ICI) vs. 39.1% (CT). No significant differences were observed in PFS (p = 0.316), OS (p = 0.318), or ORR (p = 0.515). Conclusions: 1L ICI demonstrated numerically higher response rates compared to 1L CT, however, these results are purely descriptive and serve only to inform hypothesis-building, without reaching statistical significance. Survival outcomes were also better in ICI group, albeit without statistical significance, however these should be interpreted cautiously given the retrospective design and limited sample size. Given emerging combination strategies involving ICI or targeted agents, these findings support further investigation of ICI in this diverse and underrepresented population. Limitations: small sample size and retrospective design.

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Cite This Study

Isgandarov et al. (Tue,) studied this question.

synapsesocial.com/papers/6a2a515980c8f91e7f39d990 https://doi.org/https://doi.org/10.1159/000552945

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