Clinical Trial Intelligence

Which Endpoints Are Measured Most Often in European Bladder and Urothelial Cancer Phase II & III Trials?

9 July 2026

Across 92 European CTIS-authorized Phase II and Phase III bladder/urothelial cancer trials, safety and tolerability endpoints are the most frequently measured overall, appearing in 70 trials (76.1%). Overall survival (OS) follows in 58 trials (63.0%), while response and time-to-event endpoints cluster closely: duration of response (DOR) and progression-free survival (PFS) each appear in 39 trials (42.4%), and objective response rate (ORR) appears in 38 trials (41.3%). Primary endpoints are less dominated by one measure: recurrence/event-free survival leads at 25 trials (27.2%), followed by ORR in 24 trials (26.1%) and safety in 23 trials (25.0%).

92
EU CTIS Phase II–III trials analyzed
76.1%
measured safety / tolerability
63.0%
measured overall survival
27.2%
used recurrence/EFS as a primary endpoint

Safety and survival dominate the endpoint landscape

The most common endpoint family is safety/tolerability, measured in 70 of 92 trials (76.1%). Overall survival is measured in 58 trials (63.0%), while DOR, PFS, ORR and recurrence/event-free survival each appear in roughly 38–39 trials (41.3%–42.4%).

Endpoint families measured in any role
Safety / tolerability76.1%
Overall survival (OS)63.0%
Duration of response (DOR)42.4%
Progression-free survival (PFS)42.4%
Objective response / ORR41.3%
Recurrence / event-free survival41.3%
Quality of life / PRO37.0%
Pharmacokinetics / exposure29.3%
Measure: trial-level presence of endpoint family in primary, secondary, or other endpoint fields; denominator = 92 trials.
Interpretation

European bladder/urothelial cancer protocols remain safety-heavy even in Phase III, but the core efficacy language is clearly oncology-standard: OS, PFS, ORR, DOR and recurrence/EFS together form the dominant endpoint backbone.

Primary endpoints are split between recurrence/EFS, ORR and safety; secondary endpoints concentrate OS and safety

Primary endpoint fields were non-empty in 88 of 92 trials (95.7%), secondary endpoint fields in 73 trials (79.3%), and other/exploratory endpoint fields in 2 trials (2.2%). The most frequent primary endpoint family was recurrence/event-free survival in 25 trials (27.2%), followed by ORR in 24 trials (26.1%) and safety in 23 trials (25.0%).

Top endpoint families by endpoint role
Primary endpoints
Recurrence / EFS25 / 92 · 27.2%
Objective response / ORR24 / 92 · 26.1%
Safety / tolerability23 / 92 · 25.0%
Overall survival19 / 92 · 20.7%
PFS14 / 92 · 15.2%
Complete response / clearance14 / 92 · 15.2%
Secondary endpoints
Safety / tolerability55 / 92 · 59.8%
Overall survival55 / 92 · 59.8%
DOR39 / 92 · 42.4%
Quality of life / PRO34 / 92 · 37.0%
PFS33 / 92 · 35.9%
Objective response / ORR32 / 92 · 34.8%
Other / exploratory endpoints

Other or exploratory endpoint fields were rare: 2 of 92 trials (2.2%) had non-empty other-endpoint lists. Within that small subset, immunogenicity, biomarker/molecular, QoL/PRO, recurrence/EFS, time to response and complete-response/local-clearance measures each appeared in 1 trial (1.1%).

Measure: trial-level endpoint family presence by endpoint role; denominator = 92 trials.
Interpretation

The primary endpoint strategy is not uniform across bladder/urothelial trials: it splits between local-control/time-to-event endpoints, response endpoints and safety. Secondary endpoint packages are much more standardized, with OS and safety each appearing in 55 trials (59.8%).

Phase II emphasizes safety and response; Phase III increases recurrence/EFS and patient-reported outcomes

The dataset includes 56 Phase II and 36 Phase III trials. Safety/tolerability appears in 48 Phase II trials (85.7%) versus 22 Phase III trials (61.1%). ORR appears in 28 Phase II trials (50.0%) but only 10 Phase III trials (27.8%), while QoL/PRO appears more often in Phase III: 18 of 36 trials (50.0%) versus 16 of 56 Phase II trials (28.6%).

Endpoint prevalence by phase
Endpoint family Phase II Phase III
Safety / tolerability48 / 56 · 85.7%22 / 36 · 61.1%
Overall survival38 / 56 · 67.9%20 / 36 · 55.6%
Objective response / ORR28 / 56 · 50.0%10 / 36 · 27.8%
DOR26 / 56 · 46.4%13 / 36 · 36.1%
PFS25 / 56 · 44.6%14 / 36 · 38.9%
Recurrence / EFS20 / 56 · 35.7%18 / 36 · 50.0%
Quality of life / PRO16 / 56 · 28.6%18 / 36 · 50.0%
Pharmacokinetics / exposure18 / 56 · 32.1%9 / 36 · 25.0%
Measure: trial-level endpoint family presence; Phase II n=56, Phase III n=36.
Interpretation

Phase II protocols carry heavier safety, response and PK packages, consistent with dose-optimization and early efficacy screening. Phase III protocols shift toward confirmatory durability and patient-benefit measures, with recurrence/EFS and QoL/PRO each present in 18 of 36 trials (50.0%).

Endpoint choice changes sharply by bladder/urothelial disease setting

The largest disease-setting groups were non-muscle-invasive bladder cancer (20 trials), muscle-invasive bladder cancer (19), broad/unspecified bladder or urothelial cancer (18), advanced/metastatic urothelial cancer (16), solid-tumour basket studies including urothelial cancer (15), and upper tract urothelial carcinoma (4). Recurrence/EFS dominates NMIBC and MIBC, while ORR dominates advanced/metastatic and basket studies.

Most characteristic endpoint families by disease setting