First-Line Immune Checkpoint Inhibitors in Older Patients with Advanced Urothelial Carcinoma: A Systematic Review and Meta-Analysis
In brief
First-line combinations lowered death hazard 21% in older bladder cancer patients
In phase 3 trial data, first-line immune-based combinations were associated with a 21% lower death hazard than platinum chemotherapy among patients aged 65 and older with advanced urothelial cancer. Results varied substantially across regimens, and the pooled benefit weakened when antibody-drug conjugate combinations were excluded; monotherapy did not improve survival. Safety data and whether age changes treatment benefit remain unclear.
- Journal
- Cancers (Q1)
- Published
- 9 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Dalila Incognito, Andrea D'Arienzo, Sergio Facchini, Chiara Barraco, Antonio Picone, Antonella Nicastro, et al.
- PMID
- 42794891
- DOI
- 10.3390/cancers18182924
Why clinicians should know about it
- Picked for Nephrology (top studies of the week, 27 September 2026): Immune checkpoint inhibitors in urothelial carcinoma
- Picked for Oncology and Radiation Oncology (top studies of the week, 27 September 2026): Combination strategies improved OS versus chemotherapy
- Picked for Radiation Oncology (top studies of the week, 27 September 2026): ICI urothelial meta‑analysis, no RT
- Picked for Surgical Oncology (top studies of the week, 27 September 2026): High-quality evidence in a top journal
Abstract
Urothelial carcinoma predominantly affects older patients, who often exhibit frailty, comorbidities, renal impairment, and reduced physiological reserve. We evaluated overall survival (OS) and progression-free survival (PFS) with first-line immune-based strategies in patients aged ≥65 years with advanced or metastatic urothelial carcinoma. The aim was to characterize treatment effects within this age-defined subgroup, not to determine whether age modifies treatment efficacy compared with younger patients. Methods: We conducted a systematic review and meta-analysis of phase 3 randomized trials published from January 2015 to May 2026 reporting age-specific survival outcomes. Combination regimens were compared with platinum-based chemotherapy using random-effects models. Results: Combination strategies improved OS versus chemotherapy (HR 0.79, 95% CI 0.64-0.96), although heterogeneity was substantial (I2 = 69.7%) and the prediction interval crossed the null (0.48-1.27). Class-specific HRs were 0.56 (95% CI 0.26-1.20) for ADC plus ICI, 0.85 (0.77-0.95) for ICI plus chemotherapy, and 0.91 (0.34-2.42) for dual-checkpoint inhibition. PFS favoured experimental treatment but remained imprecise (HR 0.54, 95% CI 0.27-1.08; I2 = 89.5%). Excluding ADC plus ICI trials attenuated the OS effect (HR 0.88, 95% CI 0.80-0.96), indicating that the pooled estimate was influenced by these trials. ICI monotherapy did not improve OS. Conclusions: First-line immune-based combinations improved survival in selected patients aged ≥65 years, but benefit varied across treatment classes and should not be considered uniform across regimens. These findings do not establish whether age modifies treatment efficacy. Age-specific safety data were insufficient to define the benefit-risk profile of individual strategies.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.