Quality of Life and Health State Utilities in Bladder Cancer

INTRODUCTION

Bladder cancer ranges from low-risk non-muscle-invasive bladder cancer (NMIBC) which behaves like a chronic disease but requires frequent invasive monitoring, to metastatic bladder cancer which is largely incurable, with 5-year survival rates of 5%[1]. Approximately 75%of patients present with NMIBC; 20%of patients present with muscle-invasive bladder cancer (MIBC); and 5%present with metastatic disease. Patients with bladder cancer experience an array of potential cancer trajectories including some who never had a recurrence and those who progress to MIBC and metastatic bladder cancer. Various bladder cancer treatments include intravesical therapies like Bacillus Calmette-Guerin (BCG) for NMIBC, radical cystectomy or chemoradiation for MIBC, and systemic chemotherapy or immunotherapy for metastatic bladder cancer. These treatments may variably impact health-related quality of life (QOL). Beyond treatment, the surveillance of patients with NMIBC or some patients with MIBC who undergo chemoradiation requires periodic invasive monitoring with office cystoscopy which may further impact QOL.

Understanding the expected QOL outcomes for patients of various stages of bladder cancer can inform the clinical care of patients by enunciating expected outcomes at various time points in the trajectory of a patient’s bladder cancer. Understanding the impact of bladder cancer treatments on patient-centered outcomes beyond cancer recurrence and survival would inform treatment decision-making, could be used to populate health economic models that evaluate the cost utility of different bladder cancer treatment and surveillance strategies, and could inform clinical trial design. Finally, by assessing QOL across the spectrum of bladder cancer care, these results may elucidate gaps in our knowledge of bladder cancer care. This might inform novel patient-centered outcomes research to improve the care and outcomes of men and women with bladder cancer.

Therefore, our primary objective was to obtain estimates for bladder cancer-specific QOL for patients with NMIBC, MIBC, and metastatic bladder cancer. Secondary objectives for this study were to evaluate the impact of stage of bladder cancer on financial burden and work disability of patients and to characterize patient-reported health state utilities for various bladder cancer health states. We hypothesized that QOL and health state utilities would decrease among patients with more advanced bladder cancer.

METHODS

RESULTS

Sample characteristics

Across the US, 972 self-identified bladder cancer patients completed the survey, 911 of whom indicated their bladder cancer health state. Among respondents, 243 responded from the PSN and 903 responded from Inspire. Survey respondents were more likely to be male, white, non-Hispanic, well educated, privately insured and married (Appendix Table 1). No clinically significant differences in sociodemographic characteristics were noted across bladder cancer health states with the exception of education, for which patients with advanced disease were more likely to report lower education levels (p = 0.03). Among patients with MIBC and metastatic cancer, 19%and 27%, respectively, presented with NMIBC and subsequently progressed to more advanced bladder cancer. Patients across disease states underwent a variety of treatments ranging from intravesical treatments to radical cystectomy (of whom 12%underwent neobladder) and chemotherapy, all of which varied by time since treatment and recurrence (Appendix Table 2).

To gain a better understanding of disease and treatment patterns, we evaluated time since first diagnosis (Figure 1) and time since last treatment (Fig. 2). For most respondents across each disease state, time since first diagnosis was within the first 5 years. A higher proportion of patients with recurrent NMIBC and MIBC reported a time since first diagnosis between 1–5 years (rather than 0–12 months) when compared to patients with non-recurrent NMIBC and metastatic disease.

Fig. 1

Time since first diagnosis by bladder cancer health state.

Fig. 2

Time since last treatment by bladder cancer health state.

DISCUSSION

We characterized QOL and health state utilities across bladder cancer health states ranging from non-recurrent NMIBC to metastatic bladder cancer. We found that cancer- and disease-specific QOL, including urinary, bowel and sexual function worsened among patients with more advanced stages of bladder cancer, such as MIBC and metastatic bladder cancer. To some extent, this varied by QOL domain. Similarly, work and activity impairment worsened as we examined patients with later stages of bladder cancer. Health state utilities were also worst among metastatic bladder cancer patients.

Our study is unique by measuring disease states across the bladder cancer spectrum, while also including multiple instruments to compare and contrast the impact of disease on various aspects of QOL (e.g. general cancer, bladder cancer-specific, financial toxicity, and work/activity impairment). Most studies have narrowly focused on specific bladder cancer states and QOL domains, such as the impact of intravesical therapy on urinary QOL [10], or bladder cancer-specific QOL differences between men and women undergoing radical cystectomy [11]. Nonetheless, a few large studies have evaluated QOL across the spectrum of bladder cancer. In a sample of approximately 800 bladder cancer patients undergoing inpatient rehabilitation, EORTC QLQ-C30 was measured and compared with a representative community sample [12]. Patients with both NMIBC and MIBC had similar QOL, but were found to have significantly more problems and worse functioning than the general population. Another cross-sectional study of 1,796 patients with bladder cancer in the UK was recently published, demonstrating worse function and symptom scores with age [13].

Furthermore, differences in QOL across health states appeared to be related to the burdens of the treatments received and time since treatment more than bladder cancer health state, with patients undergoing radical cystectomy reporting more fatigue, appetite loss and decreased role functioning, detriments in QOL that appeared to improve with time.

On multivariable analysis, differences in QOL were not demonstrated between non-recurrent and recurrent NMIBC. A prior study evaluating QOL among patients with NMIBC characterized pain levels among NMIBC patients but did not differentiate by recurrence status. Our study suggests that pain levels may differ between these different and important subgroups and are important to better understand when patients and providers engage in shared decision-making for treatment choices, particularly those who are choosing between radical cystectomy and bladder-conserving therapy for BCG-refractory NMIBC, for which treatment may also be driven by symptomatology.

Interestingly, treatment type had a less substantial impact on cancer-specific QOL. The lone exception was our finding that patients who have undergone radical cystectomy experienced improved emotional functioning compared with those who underwent bladder-conserving therapy. These findings differ from prior studies, wherein radical cystectomy appears to drive worse emotional functioning. Differences in our study conclusions may stem from differences in study populations, including prior studies that evaluated patients in rehabilitation centers which may be related to recovery from surgical complications [12]. Worse emotional functioning among patients undergoing bladder-conserving therapy may relate to fear and/or anxiety regarding disease recurrence and frequent surveillance for patients with NMIBC.

Although cancer-specific QOL did not appear to be largely influenced by bladder cancer health state, our study did demonstrate that patients with metastatic disease were more likely to have significantly diminished urinary and sexual function scores. Treatment was associated with urinary and sexual (but not bowel) function, both diminished among patients who underwent radical cystectomy. These findings align with prior studies, including the original study describing the BCI in which disease-specific HRQOL decrements were noted among those undergoing radical cystectomy compared with those who retained their bladders [14]. That study acknowledged the limitation that they did not assess the impact of time since treatment, which we found impacted cancer-specific QOL. Those who were more than a year out from treatment experienced improved urinary and sexual summary scores, representing an improvement in either function, bother, or both. Interestingly, a sub-analysis of multivariable analyses separately evaluating urinary function and bother domains revealed that these findings are largely driven by improvements in urinary bother and sexual function.

In addition to QOL, we also investigated financial toxicity and work/activity impairment. We found that health state did not significantly impact COST scores. Unfortunately, financial toxicity has not yet been widely studied among bladder cancer patients. A small single institution study of 138 patients found that patients with NMIBC were more likely to report financial toxicity, but this was not significant on multivariable analysis, aligning with the conclusions of our study [15]. In a large cross-sectional cohort, Catto et al did not a higher rate of financial toxicity among younger patients [13]. Work and activity impairments have been even less studied. The only known study evaluating WPAI among urological patients assessed the work impairment of overactive bladder and included a small sample of those with bladder cancer [16]. In this study, more severe lower urinary tract symptoms were associated with significant worsening of work impairment due to health. We found that patients with metastatic disease reported significantly worse work and activity impairment than those with localized bladder cancer. However, these results are limited by a disproportionate number of respondents (30%) reporting full time work. Regardless, a better understanding of these productive impacts can be useful for expectation setting by providers during counseling sessions.

Finally, our study was designed to derive health-state utilities that could be used for future cost-utility analyses. Utilities can be used to estimate quality-adjusted life expectancy, with a utility of 1 representing perfect health and death assigned a value of 0. Prior decision analytic studies in bladder cancer have extrapolated utilities from other disease states such as breast cancer [17]. The utilities calculated from our study derived from the EORTC QLQ-C30 [9]. As hypothesized, cancer-specific utilities were lower among patients with more advanced stages of bladder cancer.

The findings of our study should be interpreted within the context of several limitations. First, the cross-sectional study design does not allow assessment of longitudinal changes in QOL among bladder cancer patients. Second, the survey was conducted using the BCAN Patient Survey Network and Inspire, a selective group of engaged patients with bladder cancer with higher levels of education and income, and which lacks racial and ethnic diversity. The selective sample population may limit the generalizability of our findings. Third, our study survey had missing data that did vary by patient characteristics and which may influence analytic findings. However, the degree of missingness was small and the impact of these missing data on our overall study findings is likely small.

Despite these limitations, our study provides a cross-sectional view of bladder cancer patients with varying health states and contributes informative health state utilities. Generic cancer and bladder cancer-specific QOL diminishes as we assess patients with NMIBC, MIBC, and metastatic bladder cancer. Time is an important modifier, as these QOL detriments diminish with time. These QOL and health state utility estimates can inform shared decision-making with patients and may be used to populate future cost-utility analyses. Novel data on financial toxicity and work impairment can inform discussions that potentially focus on more patient-centered considerations.