Adjuvant vs. progression-triggered treatment with gemcitabine in platinum-ineligible high-risk bladder cancer patients: Long-term follow-up of a randomized phase 3 trial

•No statistically significant difference in OS for platinum-ineligible high risk UCUB patients treated with adjuvant Gemcitabine chemotherapy compared to patients treated at progression.•No statistically significant difference in PFS.•Deterioration in QoL in patients treated with adjuvant Gemcitabine chemotherapy. Cisplatin-based chemotherapy (ChT) is the preferred perioperative treatment in muscle-invasive urothelial carcinoma of the urinary bladder (UCUB). Nevertheless, a certain number of patients are ineligible for platinum-based ChT. This trial compared immediate adjuvant vs. delayed gemcitabine ChT at progression in platinum-ineligible patients with high-risk UCUB. High-risk platinum-ineligible UCUB patients (n = 115) were randomized 1:1 to adjuvant gemcitabine (n = 59) or gemcitabine at progression (n = 56). Overall survival was analyzed. Additionally, we analyzed progression-free survival (PFS), toxicity and quality of life (QoL). After a median follow-up of 3.0 years (inter quartile range [IQR]: 1.3–11.6), adjuvant ChT did not significantly prolong overall survival (OS) (HR: 0.84; 95% CI: 0.57–1.24; P = 0.375), with 5-year OS of 44.1% (95% CI: 31.2–56.2) and 30.4% (95% CI: 19.0–42.5), respectively. We noted no significant difference in PFS (HR: 0.76; 95% CI: 0.49–1.18; P = 0.218), with 5-year PFS of 36.2% (95% CI: 22.8–49.7) in the adjuvant group and 22.2% (95% CI: 11.5%–35.1%) when treated at progression. Patients with adjuvant treatment showed a significantly worse QoL. The trial was prematurely closed after recruitment of 115 of the planned 178 patients. There was no statistically significant difference in terms of OS and PFS for patients with platinum-ineligible high-risk UCUB receiving adjuvant gemcitabine compared to patients treated at progression. These findings underline the importance of implementing and developing new perioperative treatments for platinum-ineligible UCUB patients.