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.

Abstract

BACKGROUND:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Julia Heinzelbecker, Natalie Spieler, Michael Kuehn, Claus Fischer, Björn Volkmer, Friedrich von Rundstedt, Peter Albers, Eduard Becht, Andreas Bannowsky, H Matthias Weber, Rainer Hofmann, Markus Müller, Sigrun Langbein, Gabriel Steiner, Margitta Retz, Jörn Kamradt, Gudrun Wagenpfeil, Stefan Wellek, Jan Lehmann, Michael Stoeckle
• Journal: Urologic oncology (Urol Oncol) Vol. 41 Issue 8 Pg. 356.e19-356.e30 (08 2023) ISSN: 1873-2496 [Electronic] United States
• PMID: 37198025 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Cisplatin
• Gemcitabine
• Platinum

Topics

• Humans
• Adjuvants, Immunologic (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Transitional Cell (pathology)
• Cisplatin
• Follow-Up Studies
• Gemcitabine
• Platinum (therapeutic use)
• Quality of Life
• Urinary Bladder (pathology)
• Urinary Bladder Neoplasms (pathology)