Rethinking Endpoints in NMIBC Clinical Trials

Although the high risk of recurrence and progression has historically challenged standard non-muscle-invasive bladder cancer (NMIBC) treatment regimens, the field is entering an exciting period of therapeutic innovation.1-3 A growing pipeline of novel agents aims to improve the depth and durability of response while extending the disease-free interval.2 As these therapies emerge, clinical trials are increasingly designed with diverse and complementary endpoints, underscoring the importance of understanding the nuances of each study to fully appreciate their potential impact on patient care.4

Why Durability Matters in NMIBC Treatment Evaluation

Select a category to learn more.

Icon of bladder cancer patient with arrows pointing to a checkmark or x, indicating a positive or negative treatment response

Initial Response Is Foundational in Disease Management

Understand what comes next

Icon of diamond, reflecting guidance on the importance of durability in NMIBC treatment

Guidance Reflects the Importance of Durability

See the guidance

Icon featuring magnifying glasses examining an extended timeline of life with non-muscle-invasive bladder cancer

Evaluation Should Reflect NMIBC as a Long-term Disease

Understand how outcomes evolve

Icon featuring a diamond bladder within a shield, indicating the preservation of a bladder despite NMIBC

Durable Outcomes Support Bladder Preservation

See impact of lasting outcomes

Durable endpoints are not replacing complete response (CR)—they are contextualizing it

Not all endpoints are created equal—and the differences may impact your NMIBC treatment decisions

Table 1. Key Clinical Trial Endpoints in NMIBC
Select a category to view the associated example endpoints below.
Example Endpoint:What It Measures:Why It Matters to Urologists & Patients
Complete Response (CR)6
Whether a patient is disease-free at a particular moment (eg, 3 months, 12 months)
Demonstrates clearance of the tumor at first surveillance
CR at any time7-8
Whether a patient ever achieved a CR during treatment even if the response was not durable and the disease later returned
Demonstrates clearance of the tumor at any surveillance point
Example Endpoint:What It Measures:Why It Matters to Urologists & Patients
Duration of Response (DoR)6
Time from CR to recurrence or progression
Indicates how long a patient can expect to remain disease-free after an initial response
Progression-Free Survival (PFS)6
Time to worsening grade or stage of muscle-invasive or metastatic disease
Indicates how long a therapy prevents biologic worsening
Cystectomy-Free Survival (CFS)6
[a surrogate for event-free-survival (EFS)]
Time to radical cystectomy
Indicates how long a therapy preserves the bladder
Example Endpoint:What It Measures:Why It Matters to Urologists & Patients
Kaplan–Meier (KM) Curves9
Probability of remaining event-free over time
Visualizes the probability of experiencing an event over the duration of follow-up, allowing providers to model the expected time of an event and compare this between treatments
Landmark Analyses (6, 12, 18 mo)6
Durability of an event at fixed surveillance intervals
Indicates how an outcome will align with real-world cystoscopy schedule
Median Follow-ups9
Length of time that half of the patients were observed for
Ensures late recurrences captured (≥2 years in many trials)
Example Endpoint:
Complete Response (CR)6
What It Measures:
Whether a patient is disease-free at a particular moment (eg, 3 months, 12 months)
Why It Matters to Urologists & Patients
Demonstrates clearance of the tumor at first surveillance
Example Endpoint:
CR at any time7-8
What It Measures:
Whether a patient ever achieved a CR during treatment even if the response was not durable and the disease later returned
Why It Matters to Urologists & Patients
Demonstrates clearance of the tumor at any surveillance point
Example Endpoint:
Duration of Response (DoR)6
What It Measures:
Time from CR to recurrence or progression
Why It Matters to Urologists & Patients
Indicates how long a patient can expect to remain disease-free after an initial response
Example Endpoint:
Progression-Free Survival (PFS)6
What It Measures:
Time to worsening grade or stage of muscle-invasive or metastatic disease
Why It Matters to Urologists & Patients
Indicates how long a therapy prevents biologic worsening
Example Endpoint:
Cystectomy-Free Survival (CFS)6
[a surrogate for event-free-survival (EFS)]
What It Measures:
Time to radical cystectomy
Why It Matters to Urologists & Patients
Indicates how long a therapy preserves the bladder
Example Endpoint:
Kaplan–Meier (KM) Curves9
What It Measures:
Probability of remaining event-free over time
Why It Matters to Urologists & Patients
Visualizes the probability of experiencing an event over the duration of follow-up, allowing providers to model the expected time of an event and compare this between treatments
Example Endpoint:
Landmark Analyses
(6, 12, 18 mo)6
What It Measures:
Durability of an event at fixed surveillance intervals
Why It Matters to Urologists & Patients
Indicates how an outcome will align with real-world cystoscopy schedule
Example Endpoint:
Median Follow-ups9
What It Measures:
Length of time that half of the patients were observed for
Why It Matters to Urologists & Patients
Ensures late recurrences captured (≥2 years in many trials)

Interpreting Clinical Trial Endpoints

Clinical trial endpoints help guide treatment decisions, but their interpretation often depends on the population being analyzed. Regulatory authorities emphasize the importance of clearly defined patient populations and entry criteria so outcomes can be interpreted consistently across NMIBC studies.4,5

One of the most important considerations when reviewing trial results is whether outcomes are reported in the intent-to-treat (ITT) population or among responders only.

Population
What It Includes
What It Helps Urologists Understand
Icon indicating all patients enrolled in a non-muscle-invasive bladder cancer clinical trial
Population
Intent-to-treat (ITT)10
What It Includes
All patients enrolled regardless of whether they respond to treatment
What It Helps Urologists Understand

The overall proportion of patients who may benefit from a therapy

The likelihood a patient will respond

Icon of 3 NMIBC patients held in a hand, indicating patients who achieved a predefined response during a clinical trial
Population
Responder-only11
What It Includes
Subset of patients who achieved predefined response
What It Helps Urologists Understand

The durability and time-to-event outcomes

How long disease control or event-free survival may be expected

Understanding both populations helps place trial results into meaningful clinical context
Connect with an MSL to learn more
References: 1. Sylvester RJ, van der Meijden APM, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006;49:466-477. 2. Holzbeierlein J, Chang SS, James AC, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline: 2024 amendment. J Urol. 2024;1-50. 3. Soria F, Rosazza M, Livoti S, et al. Clinical validation of the intermediate-risk non-muscle-invasive bladder cancer scoring system and substratification model proposed by the International Bladder Cancer Group: a multicenter Young Academic Urologists Urothelial Working Group collaboration. Eur Urol Oncol. 2024;7:1497-1503. 4. U.S. Food & Drug Administration. BCG-unresponsive nonmuscle invasive bladder cancer: developing drug and biological products for treatment: guidance for industry. August 2024. Accessed April 5, 2026. https://www.fda.gov/media/101468/download 5. Kamat AM, Apolo AB, Babjuk M, et al. Definitions, end points, and clinical trial designs for bladder cancer: recommendations from the Society for Immunotherapy of Cancer and the International Bladder Cancer Group. J Clin Oncol. 2023;41:5437-5447. 6. Delgado A, Guddati AK. Clinical endpoints in oncology – a primer. Am J Cancer Res. 2021;11(4):1121-1131. 7. Chakra MA, Boormans J, Hayne, D, O’Donnell MA. Strategic sequencing of bladder-sparing therapies in the management of BCG-unresponsive non-muscle invasive bladder cancer. Ann Med. 2026;58(1):2612387. 8. Joshi SS. Durable 24-month outcomes from BOND-003 Cohort C: phase 3 study of intravesical cretostimogene grenadenorepvec for high-risk BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ: Presented at the Southeast Sectional AUA Meeting; March 18, 2026; Rio Grande, Puerto Rico. 9. Rich JT, Neely JG, Paniello RC, et al. A practical guide to understanding Kaplan-Meier curves. Otolaryngol Head Neck Surg. 2010;143(3):331-336. 10. McCoy E. Understanding the intention-to-treat principle in randomized controlled trials. West J Emerg Med. 2017;18(6):1075-1078. 11. Korn EL, Othus M, Chen T, Freidlin B. Assessing treatment efficacy in the subset of responders in a randomized clinical trial. Ann Oncol. 2017;28:1640-1647.
Contact
an MSL