QUEST: Quality of Life and Evaluation of Survival in Treatment of Bladder Cancer – A Prospective Study on Quality of Life and Survival of Bladder Cancer Patients Using Patient-Reported Outcome Measurements (PROMs)

Background

Bladder cancer is one of the most prevalent genitourinary malignancies globally, with MIBC accounting for approximately 25-30% of newly diagnosed cases.¹ MIBC, defined as clinical stage cT2-T4a, necessitates aggressive treatment to achieve oncological control while striving to maintain patients’ quality of life (QoL).² Historically, radical cystectomy (RC) combined with neoadjuvant chemotherapy has been the standard of care, offering 5-year survival rates of approximately 50-60%.³ RC entails complete bladder removal, pelvic lymphadenectomy, and urinary diversion, often resulting in significant QoL impairments across urinary, bowel, and sexual domains due to the creation of an ileal conduit or neobladder.⁴ In recent decades, bladder preservation strategies, particularly trimodal therapy (TMT)—comprising maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy—have gained traction as an alternative, with studies reporting comparable survival outcomes to RC in well-selected patients.^5,6

Randomized controlled trials (RCTs) directly comparing RC and TMT are limited, but observational studies and meta-analyses suggest that TMT achieves equivalent oncological efficacy for appropriately selected patients, with 5-year overall survival rates ranging from 50-70%.^7,8 The potential QoL advantages of TMT, primarily due to retention of the native bladder, have been highlighted in studies using validated Patient-Reported Outcome Measures (PROMs) like the Bladder Cancer Index (BCI) and EORTC QLQ-C30, which demonstrate better urinary and sexual function compared to RC.^9,10 However, TMT is not without drawbacks, as long-term radiation toxicities may affect bowel and bladder function.¹¹

Despite these insights, most QoL data originate from Western populations, which may not fully reflect the experiences of patients in resource-constrained settings like India, where socioeconomic, cultural, and logistical factors influence treatment decisions.¹² At our tertiary cancer center in eastern India, we manage a high volume of MIBC patients annually, yet institution-specific data comparing RC and TMT outcomes are lacking. The QUEST study aims to address this gap by prospectively evaluating QoL and survival in our patient population, contributing to tailored treatment decision-making.

Sample size calculation

The design is of a prospective trial comparing quality of life (QoL) outcomes in muscle-invasive bladder cancer (MIBC) patients undergoing: Bladder preservation (BP) with chemoradiotherapy vs. Radical cystectomy (RC); with the primary endpoint being superiority in the QoL domain of patients opting for bladder preservation.

As per findings from Murthy et al.,⁷

In the sexual bother domain of the BCI, which was found to be significantly superior for BP arm, compared to RC arm:

BP mean score = 81

RC mean score = 62

Mean difference = 19 points; p = 0.02, indicating statistical significance

Standard deviations (SD): BP = 24.8; RC = 36.6

Effect size (Δ): 19 (mean difference in sexual bother score)

Pooled SD (σ):

$$\mathrm{\sigma }=\surd \{({{\mathrm{SD}}_{\mathrm{RC}}}^2+{{\mathrm{SD}}_{\mathrm{BP}}}^2)/2\}=\surd \{({36.6}^2+{24.8}^2)/2\}=31.27$$

α (Type I error) = 0.05

Power (1 - β) = 0.80

Sample size formula (for equal group sizes): n = [{2*(Z_α/2+Z_β)²}*σ²]/Δ²; Z_α/2 = critical value for a two-sided test at significance level α; Z_β = critical value corresponding to the power of the test (1 - β), i.e. 0.20.

$$\mathrm{n}=[\{2\ast {(1.96+0.84)}^2\ast {31.27}^2\}/{19}^2]=42.5\approx 43\text{patients}$$

Accounting for approximately 10% attrition, sample size comes to 47 patients in each arm. Hence, a total 94 patients need to be recruited; 47 patients in each arm.

Figure 1. CONSORT (Consolidated Standards of Reporting Trials) diagram depicting workflow of the study.

Discussion

The QUEST study is designed to address an essential knowledge gap regarding the comparative quality of life (QoL) and survival outcomes between bladder preservation (BP) and radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC) within the Indian context. This is particularly important given the significant cultural, economic, and systemic differences that influence patient care in low- and middle-income countries (LMICs).

Our study builds upon and aims to enhance insights from prior prospective evaluations, notably the recently published BMJ Oncology study by Murthy et al.,⁷ which compared QoL in 104 Indian patients undergoing either RC with ileal conduit or BP with radiotherapy. While that study found better outcomes in sexual domains with BP, it reported no significant differences in urinary, bowel, or global health-related QoL. These findings, although valuable, are limited by several methodological caveats that QUEST seeks to address.

Firstly, the cross-sectional design of Murthy et al.’s study inherently restricts temporal understanding of QoL evolution post-treatment. In contrast, QUEST employs a prospective, longitudinal design, allowing for the assessment of QoL trajectories over time—a more robust approach given the dynamic nature of recovery and adaptation.

Secondly, while the BMJ study reported comparable urinary and bowel outcomes, the potential for response shift bias (i.e., patients recalibrating their internal QoL standards over time) was not formally accounted for. Moreover, non-responder bias, especially in the sexual domain (response rate: 53%), likely affected the accuracy of findings, as patients with worse outcomes may have opted out of sensitive questionnaires. QUEST aims to mitigate this through repeated PROM administration, greater cultural sensitization, and patient counselling to encourage honest and complete reporting.

Another key limitation of the Murthy study was heterogeneity in follow-up durations (median 31 months for RC vs. 18 months for BP), which introduces bias in QoL interpretation due to differential late toxicities or psychological adaptation. Our study enforces a uniform minimum 36-month follow-up, ensuring comparability across arms.

Additionally, the Murthy study excluded neo-bladder reconstructions—an increasingly relevant option with better cosmetic and continence outcomes than ileal conduits. In contrast, QUEST includes all RC modalities and stratifies analysis accordingly, offering a broader generalizability.

In summary, while previous evidence—including that from Murthy et al.—supports bladder preservation as a viable alternative to RC in terms of QoL and survival, their findings should be interpreted cautiously due to design limitations. The QUEST study is poised to provide complementary and enhanced insights through rigorous methodology, extended follow-up, and nuanced interpretation tailored to real-world Indian patients. These results are expected to inform not only clinical practice but also shared decision-making, patient counselling, and potentially, policy guidelines for MIBC management in LMICs. The use of validated PROMs ensures robust QoL assessment,⁴ while the longitudinal follow-up strengthens survival analyses.¹⁵

Limitations include potential selection bias due to non-randomization, which will be mitigated through statistical adjustments.¹⁶ Results are expected to inform personalized treatment strategies and enhance patient counseling, contributing to the growing body of evidence supporting tailored approaches in MIBC management.

Ultimately, the results of QUEST will inform shared decision-making between patients and clinicians. Understanding the trade-offs in QoL and survival associated with each treatment modality in our local context is critical for personalized care. We anticipate that publishing this protocol and its extended data (SPIRIT checklist, consent materials) under open licenses will promote transparency and facilitate future research collaborations. The use of a CC0 license on Zenodo ensures that the protocol and related documents are immediately available for reuse by other researchers.

Conclusion

The QUEST study will generate institution-specific data on the comparative effectiveness of bladder preservation and RC for MIBC, focusing on QoL and survival. By addressing the unique needs of Indian patients, it aims to support shared decision-making and potentially influence clinical practice guidelines in similar settings. These findings may pave the way for future research to refine treatment protocols and optimize patient-centered outcomes in bladder cancer care.

Ethical considerations and timeline

The study protocol was approved by the Institutional Ethics Committee of Chittaranjan National Cancer Institute (CNCI-IEC-JC-2025-03), Kolkata, India. The study will be conducted in accordance with the ethical principles of the World Medical Association Declaration of Helsinki.¹⁴ Written informed consent will be obtained from all participants before enrollment, and patient data will be anonymized and securely stored. The patient-reported outcome measures have been translated into local vernacular languages and culturally validated, with permissions obtained from the developers (e.g., University of Michigan for the BCI; EORTC for the QLQ-C30). The study is registered in the Clinical Trials Registry of India (CTRI/2025/03/083504).