Patient-Reported Outcome Instruments in Non-Muscle-Invasive Bladder Cancer (NMIBC): A Systematic Review

Non-muscle-invasive bladder cancer (NMIBC) is a chronic and recurrent condition requiring repeated intravesical treatments and lifelong surveillance, imposing a substantial burden on patients. Patient-reported outcomes (PROs) are increasingly required by regulatory bodies and HTA bodies to capture treatment impact from the patient perspective, yet no consensus on the optimal PRO instruments for use in NMIBC trials exists. This systematic review evaluated PRO instruments used in NMIBC and appraised their psychometric evidence using a structured evidence-maturity framework informed by the consensus-based standards for the selection of health measurement instruments (COSMIN) methodology.

Six electronic databases (MEDLINE, CENTRAL, Embase, Scopus, Web of Science, and APA PsycINFO) were searched from January 2000 to 31 December 2024. Studies reporting the development, validation, or application of PRO instruments in adult NMIBC populations were eligible. Eligible instruments were required to be multi-item measures with psychometric validation, evidence of interpretability, or documented use in clinical trials. No language restrictions were applied. Conference abstracts and grey literature without peer-reviewed full texts were excluded. Data were extracted using Covidence, synthesized by instrument, and mapped against an NMIBC conceptual model. Evidence maturity was classified as tier 1 (well-established evidence base), tier 2 (moderate evidence base or context-specific validation), or tier 3 (preliminary evidence or under active development), on the basis of prespecified criteria. The COSMIN risk of bias checklist was used to appraise the methodological quality of included measurement property studies. Single-item measures were excluded from the main synthesis but are discussed in the context of future use.

A total of 39 studies covering eight PRO instruments met the inclusion criteria. The European organization for research and treatment of cancer quality of life questionnaire-non-muscle-invasive bladder cancer 24-item module (EORTC QLQ-NMIBC24) and bladder cancer index (BCI) demonstrated strong validity, reliability, and responsiveness in NMIBC, covering urinary, sexual, and recurrence-related domains, and were classified as tier 1 (well-established evidence base). The European organisation for the research and treatment of cancer quality of life questionnaire core 30 (EORTC QLQ-C30), functional assessment of cancer therapy-general (FACT-G), and FACT-Bladder were classified as tier 2, having been validated across broader cancer populations but with limited NMIBC-specific evidence. The NMIBC-symptom index (SI), PRO-common terminology criteria for adverse events (CTCAE), and M.D. Anderson symptom inventory (MDASI) were classified as tier 3, as conceptually relevant instruments with promising early validation but insufficient NMIBC-specific psychometric evidence for regulatory-grade use. A new structured psychometric comparison facilitates direct cross-instrument comparison of internal consistency, test-retest reliability, construct validity, responsiveness, and minimally important difference estimates. Conceptual mapping revealed persistent gaps in the coverage of recurrence anxiety, cumulative treatment burden, and long-term survivorship domains. Single-item burden measures (FACT-GP5 and EORTC item library Q168) may serve as pragmatic complements to multi-item instruments in regulatory submissions.

On the basis of the available evidence, the EORTC QLQ-NMIBC24 and BCI currently provide the strongest psychometric foundation for use as primary PRO instruments in NMIBC clinical trials, though this recommendation should be interpreted in light of the methodological limitations noted above. Core measures (QLQ-C30 and FACT-G) remain valuable when used in combination with disease-specific modules. Persistent gaps in the measurement of recurrence anxiety and treatment burden highlight the need for complementary instruments and targeted single items to achieve fully regulatory-aligned PRO assessment in future NMIBC trials. TRIAL REGISTRATION: This systematic review was registered in International Prospective Register of Systematic Reviews (PROSPERO) [CRD420251076486].