DR.

ANGELA SMITH (Orcid ID : 0000-0003-3930-9817)

Accepted Article
Article type : Original Article

Corresponding Author Email Id : angela_smith@med.unc.edu

Article category: Urological Oncology

The impact of bladder cancer on health-related quality of life

Angela B. Smith1,2,MD,MS, Byron Jaeger3,PhD, Laura C. Pinheiro,PhD, MPH4, Lloyd J. Edwards,

PhD,3 Hung-Jui Tan1,2,MD,MSHPM, Matthew E. Nielsen1,2,5,MD,MS, Bryce B. Reeve,PhD2,4
1
Department of Urology, UNC, Chapel Hill, NC
2
Lineberger Comprehensive Cancer Center, Multidisciplinary Genitourinary Oncology, Chapel
Hill, NC
3
Department of Biostatistics, Gillings School of Global Public Health, UNC
4
Department of Health Policy and Management, Gillings School of Global Public Health, UNC
5
Department of Epidemiology, Gillings School of Global Public Health, UNC

Running Title: HRQOL in older adults with bladder cancer

Corresponding Author:

Angela B. Smith, MD, MS

UNC Department of Urology
2115 Physicians Office Building
Chapel Hill, NC 27599-7235

Funding Sources: BJ is supported by a Big Data to Knowledge training grant under the
supervision of Drs. Kosorok and Ferris. AS is supported by an AHRQ K08 grant.

Disclosures/ Conflicts of Interest: None

Keywords: urinary bladder neoplasms, health-related quality of life, treatment outcome,

urologic surgery, patient reported outcomes

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/bju.14047
This article is protected by copyright. All rights reserved.
 Abstract
Accepted Article
Objectives: To identify HRQOL changes before to after diagnosis in older adults with bladder
cancer and to compare their changes to non-cancer controls.

Patients and Methods: Data from the Surveillance, Epidemiology, and End Results registries
were linked with Medicare Health Outcomes Survey (MHOS) data. Medicare beneficiaries >= 65
years from 1998-2013 who were diagnosed with bladder cancer between baseline and follow-
up MHOS were matched with non-cancer controls using propensity scores. Linear mixed models
were used to estimate predictors of HRQOL changes.

Results: After matching, 535 bladder cancer patients (458 non-invasive and 77 invasive) and
2770 non-cancer controls were identified. Both non-invasive and invasive cases (respectively)
reported significant declines in HRQOL over time when compared to controls: Physical
Component Summary (-2 and -5.3 vs. -0.4), Bodily Pain (-1.9 and -3.6 vs. -0.7), Role Physical (-
2.7 and -4.7 vs. -0.7), General Health (-2.4 and -6.1 vs. 0), Vitality (-1.2 and -3.5 vs. -0.1) and
Social Functioning (-2.1 and -5.7 vs. -0.8). All scores range from 0 to 100. When stratified by
time since diagnosis, HRQOL improved over 1 year for some domains (Role Physical) but
remained lower across most domains.

Conclusions: After diagnosis, bladder cancer patients experienced significant declines in

physical, mental, and social HRQOL relative to controls. Decrements were most pronounced
among individuals with invasive disease. Identifying methods to better understand and address
HRQOL decrements among bladder cancer patients is needed.

Introduction

Bladder cancer is the 5th most common cancer, with 77,000 new cases in 2016, and an
estimated 587,426 living with the disease in the United States.1 Invasive disease requires radical
surgical treatment or chemo-radiation with intensive surveillance. Though less severe, non-
invasive disease requires long-term surveillance with periodic cystoscopy and intravesical
therapy. Intense treatment and surveillance may negatively impact health-related quality of life
(HRQOL).

To date, bladder cancer HRQOL research has been limited, with retrospective studies
investigating treatment differences within cohorts of patients with non-invasive and invasive
disease. Among patients with muscle invasive bladder cancer (MIBC) undergoing cystectomy,
HRQOL has been compared between diversion types2,3 while HRQOL for non-muscle invasive
bladder cancer (NMIBC) patients has been studied between various intravesical treatments.4 A
limitation in the current understanding of HRQOL among patients with bladder cancer is how
patients’ HRQOL changes following diagnosis. This is critical for patients with bladder cancer
given that it is prevalent in older adults that face other threats (i.e. comorbidities) to HRQOL. A
prior study investigating the impact of cancer diagnosis on HRQOL in several cancers reported

This article is protected by copyright. All rights reserved.

 significant declines in physical health compared with control subjects among patients with
bladder cancer.5 However, the impact of treatment, disease stage, and time since diagnosis on
Accepted Article
HRQOL specific to bladder cancer patients was not reported.

To our knowledge, no prospective study has investigated the impact of bladder cancer
diagnosis on HRQOL, using health status assessments before cancer diagnosis and assessing the
impact of time since diagnosis, treatment type, and stage. The objective of this study was to
compare prospective HRQOL changes for a group of patients diagnosed with bladder cancer
with changes among matched non-cancer control individuals drawn from the same population.
We hypothesized that bladder cancer patients, regardless of disease stage or treatment, would
self-report HRQOL declines, most pronounced among those with invasive disease receiving
aggressive treatment.

Materials and Methods

Study participants
This study included new incident bladder cancer patients 65 years and older who were enrolled
in Medicare Advantage managed care plans. Survey data from the Centers for Medicare and
Medicaid Services’ (CMS’) Medicare Health Outcomes Survey (MHOS) were linked with the
Surveillance, Epidemiology, and End Results (SEER) cancer registries provided by the National
Cancer Institute. The MHOS is an annual survey administered to a random sample of 1000-
1,200 Medicare beneficiaries from each managed care plan.6 Each participant is asked to
complete a baseline survey and a follow-up survey 2 years later if they are enrolled in the same
plan. Cancer-specific information is collected on patients with newly diagnosed cancer within
specified geographic regions through the SEER program. The SEER-MHOS linkage is described
elsewhere.7 We obtained Institutional Review Board permission for secondary data analysis
from the University of North Carolina at Chapel Hill.

Our study included 14 MHOS cohorts with baseline assessments from 1998-2011 and follow-up
assessments from 2000-2013.8 We identified 535 individuals who completed both baseline and
follow-up MHOS and were diagnosed with bladder cancer between assessments. To
prospectively evaluate the impact of a bladder cancer diagnosis on HRQOL, we selected non-
cancer controls who responded to both baseline and follow-up MHOS, resided in the same SEER
region, and participated in the same managed care plans as the cancer patients. Using
propensity scores, we matched 5 controls to each case to balance the proportion of patient and
survey characteristics between the groups. Propensity score matching was performed using
baseline age, race, education, region, marital status, proxy status, assessment mode, smoking
status, high blood pressure, heart disease, stroke, COPD, inflammatory bowel disease, arthritis,
sciatica, diabetes, and depression.9 This resulted in selection of 2,770 controls matched to 535
bladder cancer patients.

Data Collection
The MHOS provides self-reported data on demographics (age, gender, race, smoking status,
marital status), survey characteristics (self-report, proxy status, mail or telephone report),

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 HRQOL, chronic medical conditions, and health status.8 HRQOL was self-reported using the
Medical Outcomes Study Short Form-36 questionnaire (SF-36) on the MHOS from 1998-2005.
Accepted Article
Subsequently, the MHOS changed to the Veterans RAND – 12 (VR-12) from 2006-2013. The SF-
36/VR-12 includes 8 subscales: Physical Functioning, Role Physical, General Health, Vitality
(representing energy level and fatigue), Social Functioning, Role Emotional, and Mental
Health.10 Each subscale produces a Physical Component Summary (PCS) score and a Mental
Component Summary (MCS) score. SF-36/VR-12 scores were normalized to the general US
population (mean + SD is 50 +/- 10) with scores ranging from 0 to 100 and higher scores
indicating better HRQOL. A clinically meaningful difference is noted of at least one-half
standard deviation (5 points).11 However, a prior study in this area has defined a minimally
important difference of 2 for summary measures (e.g. PCS and MCS) and 4 for subscales (e.g.
Vitality, Social Functioning).12

Definitions for treatment, stage, time since diagnosis

Staging was defined using historic stage, given longitudinal changes in AJCC and incomplete
data for the AJCC staging variable. Historic stage was dichotomized as localized or muscle
invasive disease. Treatment was defined using codes to differentiate between conservative
treatment (bladder biopsy, transurethral resection of bladder tumor, partial cystectomy) and
radical treatment (radical cystectomy, pelvic exenteration). Patients were stratified by time
since diagnosis, 0-6, 6-12, or >12 months. These time periods were chosen to reflect early post-
treatment effects, intermediate recovery following treatment, and post-treatment baseline. A
sensitivity analysis using 3 month increments was also conducted, with no appreciable
differences in results (Supplemental Figure 1). Given the low frequency of individuals who were
missing pathologic data (<20), patients with missing stage and treatment were excluded from
analyses.

Statistical Analysis

Analyses were conducted in R version 3.3.0.13 Numeric variables were scaled14 using sample
estimates. Bivariate associations were evaluated using t-test for continuous variables and chi-
square for categorical variables. Using HRQOL before and after diagnosis for each subject as
longitudinal outcomes necessitated a statistical approach accounting for within-subject
correlation and heterogeneity amongst subjects. Hence, the linear mixed model15,16 for
longitudinal data was employed using restricted maximum likelihood estimation.17 Variable
interactions with time allowed estimation of both synchronous and lagged effects18 (e.g. the
effect of comorbidities at baseline on HRQOL at follow-up). Model selection was facilitated by
information criteria19 and several measures of multivariate association.20 Least-squares mean21
estimates facilitated group-wise comparison of HRQOL domains. Confounding effects were
minimized by propensity matching using a five-to-one control to case ratio based on patient
demographics and preexisting conditions. Sensitivity analyses were conducted by separately
fitting a model using the full data (i.e. without propensity matching) and comparing conclusions
drawn. Results from the full data model were in complete agreement with inferences made by
the propensity score model (Supplemental Table 1 and Figures 2-4). Additional logistic

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 regression models were constructed to evaluate predictors of a meaningful decrease in MCS or
PCS (defined as a decrease of 2 points or more).
Accepted Article
Results

Study Sample
Patients were stratified by non-invasive (n=458) and invasive (n=77) disease and compared to
matched controls (n=2,770). After propensity score matching, no statistically significant
differences between cases and controls were observed based on demographic characteristics,
survey characteristics, or pre-existing comorbidities (Table 1). Mean time (and standard
deviation) between surveys was 2.7 years (1.9) for cases and 2.1 years (0.1) for matched
controls.

Changes in Physical Health

Adjusted HRQOL measures for physical health were compared between controls and cases
based on disease stage (Table 2). PCS scores ranged from 0 to 100, with higher scores
representing better HRQOL. Changes over time in PCS scores were significantly worse in both
non-invasive (∆=-2.0; p=0.01) and invasive (∆=-5.3; p<0.01) cases compared to controls (∆=-0.4).
Similar decrements in Bodily Pain, Role Physical, and General Health were identified for cases
regardless of stage (Figure 1). However, changes over time in Physical Functioning diminished
only in invasive cases (∆=-5.8) compared to controls (∆=-0.3) (p<0.01).

Physical HRQOL was evaluated by treatment and time since diagnosis. Patients undergoing
cystectomy reported significant HRQOL decrements across nearly all physical domains,
including PCS, Physical Functioning, Role Physical and General Health (Figure 2). Role Physical
scores improved over time whereas Physical Functioning deteriorated (Figure 3). PCS and
General Health also appeared to decline after diagnosis and did not return to baseline.

Predictors of a significant decrease in PCS included living in the South (OR 2.6; p=0.02) and a
diagnosis of recent depression (OR 4.2; p<0.0001) (Table 3). Patients with hypertension and
atherosclerosis appeared to be less likely to experience significant decreases in PCS.

Changes in Mental Health

Adjusted mental HRQOL measures were compared between controls and cases based on
disease stage (Table 2). MCS scores ranged from 0 to 100, with higher scores representing
better HRQOL. Mean MCS change over time did not significantly differ between non-invasive
(∆=-1.4; p=0.08) or invasive (∆=-2.5; p=0.29) cases compared to controls (∆=-0.3) (Figure 1).
However, Social Functioning decrements over time were noted between non-invasive (∆=-2.1;
p=0.01) and invasive (∆=-5.7; p<0.01) cases compared to controls (∆=-0.8). Similar decrements
were notable for Vitality, with non-invasive (∆=-1.2; p<0.01) and invasive (∆=-3.5; p<0.01) cases
reporting greater declines in Vitality than controls (∆=-0.1). No significant differences in Mental
Health or Role Emotional were observed between cases and controls.

This article is protected by copyright. All rights reserved.

 Mental HRQOL was also compared by treatment and time since diagnosis. Individuals
undergoing cystectomy reported statistically significant decrements in HRQOL across several
Accepted Article
mental health domains, including Role Emotional, Vitality and Social Functioning scores (Figure
2). With regard to time since diagnosis, several mental HRQOL domains remained stable over
time, including Vitality and MCS (Figure 3). Changes in Social Functioning were small among
cases diagnosed between 6-12 months and worse in the first 6 months since diagnosis and 12
months after diagnosis.

Predictors of a significant decrease in MCS included recent depression (OR 2.8; p=0.002), being
a former or never smoker (OR 2.9, p=0.009; OR 2.2, p=0.02) (Table 3). Patients with distant
depression (OR 0.2; p=0.001) or chronic sciatica (OR 0.59; p=0.04) appeared to be less likely to
experience significant decreases in MCS.

Discussion

In this prospective population-based study, we evaluated the burden of bladder cancer

diagnosis and treatment on the lives of older Americans. We found that physical HRQOL was
significantly impacted by diagnosis/treatment (regardless of stage) and worse among
individuals with invasive disease. Significant decrements in Social Functioning were also noted
among invasive bladder cancer patients compared to non-cancer controls. To our knowledge,
this is the first study to report HRQOL changes from before to after bladder cancer diagnosis as
they relate to treatment and disease stage, compared with a matched control group of older
adults without cancer.

Until recently, our understanding of HRQOL in bladder cancer patients has been limited. A
systematic review evaluating HRQOL in patients with bladder cancer concluded that most
studies were retrospective, cross-sectional, and with methodologic limitations such as lack of
pre-diagnosis data, insufficient follow-up duration, and small sample size.22 While specific
HRQOL differences between urinary diversion were evaluated, differences by time since
diagnosis and management strategies were not considered.23 Since publication of the
systematic review, additional studies have emerged, which shed light on general and cancer-
specific HRQOL among bladder cancer patients.5,24 Notably, HRQOL of bladder cancer patients
was previously evaluated using SEER-MHOS, but in a limited capacity.5 These studies
investigated 9-12 cancer sites (including bladder) and compared cancer patients with non-
cancer controls, with limited detail regarding specific cancer types.5,25 Results were similar in
that physical health status decreased more than mental health across all cancer domains;5 and
physical health status following diagnosis was worse among cancer patients.25 In another study
which evaluated bladder cancer specifically in the SEER-MHOS, differences in PCS and MCS
scores were investigated comparing two cohorts—patients who completed a MHOS before
diagnosis and individuals who completed the survey after diagnosis.24 Although significant
declines in PCS and MCS were observed, a limitation of this cross-sectional study was potential
confounding through comparison of two independent cohorts (pre-diagnosis and post-
diagnosis).24

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 We expanded upon these studies by performing a detailed analysis of bladder cancer patients,
including pre- and post-diagnosis HRQOL assessments for each patient, and evaluating more
Accepted Article
granular data regarding disease stage, treatment, and time since diagnosis. Furthermore, we
were able to compare these patients with matched controls, in a population that has numerous
competing comorbidities (that could negatively impact HRQOL and ADLs). With this rigorously
defined cohort, we conducted a thorough investigation into disease-specific characteristics that
may impact HRQOL. Similar to Reeve et al and Kent et al,5,25 but in contrast to Fung et al,24 we
observed a significant decline in HRQOL in PCS, but not MCS scores. Deficits were most
pronounced in specific sub-domains of Bodily Pain, Role Physical, and General Health, with the
largest declines were among cases with invasive disease in Physical Health (all with >2 point
changes (clinically meaningful difference)). These deficits compare similarly to a variety of
other cancer conditions, including colorectal cancer, lung cancer, kidney cancer, and Non-
Hodgkins Lymphoma (although treatment/stage was not included in these analyses).

We also investigated predictors of significant declines in mental and physical HRQOL.

Depression appeared to be a strong predictor of decline in both domains, an expected finding
given the strong link between depression and mental/physical health.26 Additional predictors of
MCS decline included former or never smoker (with a stronger effect noted among former
smokers) while a diagnosis of chronic sciatica and distant depression appeared to be protective.
These findings may reflect coping mechanisms that impact mental HRQOL. For example,
patients with distant depression or chronic sciatica may have developed strong coping
mechanisms which dampen the impact of a cancer diagnosis on mental health. Protective
mechanisms for physical HRQOL decline included hypertension and atherosclerosis. These
conditions may predispose to worse physical HRQOL at baseline, which diminish the impact of a
cancer diagnosis on further physical decline.

Other prospective studies have investigated HRQOL differences between bladder cancer cases
and representative community samples of non-cancer controls. Among 823 cases and 2,037
controls, patients with NMIBC and MIBC disease reported similar worse functioning than
controls across all domains using the EORTC QLQ-C30 cancer-specific instrument.27 This is in
contrast to our findings, which revealed significant differences between non-invasive and
invasive disease for physical function, with non-invasive patients having a 2-point decrement
and invasive a 5-point decrement between baseline and follow-up. Differences between our
findings may be due to similar of treatment strategies in the EORTC QLQ-C30 study, with the
majority of patients in that study undergoing cystectomy. In our study, non-invasive patients
were more likely to undergo non-cystectomy treatment, which likely influence HRQOL.

Certainly, treatment can negatively impact HRQOL. In a meta-analysis of 29 studies evaluating

cystectomy, HRQOL remained similar or improved compared to pre-cystectomy.2 In contrast,
HRQOL among NMIBC patients showed that mental health was significantly worse than SF-36
US norms at diagnosis, but PCS was unchanged over a 1-year period. 4 Lack of differences in
HRQOL following treatment may be related to the pre-treatment baseline (which was not
included). Understanding HRQOL changes before and after treatment may represent a more
realistic depiction of the impact of cancer on overall HRQOL. Our study was able to address this

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 concern and investigated the role of treatment on HRQOL by stratifying patients into two
groups: cystectomy or no cystectomy. In contrast to prior studies, which demonstrated minimal
Accepted Article
impact on HRQOL, our study revealed significant decrements in Physical Functioning as well as
Vitality and Social Functioning compared to controls and patients undergoing non-cystectomy
treatment. The negative impact on HRQOL among cases treated with cystectomy is often
understated. Specifically, cystectomy patients have higher suicide rates compared to the
general population; in particular, patients 80 years and older are at increased risk for suicide,
which may be related to worse mental HRQOL.28 An increased risk of suicide may be related to
the striking decrease in social functioning noted in our study. In contrast to cystectomy,
patients undergoing non-cystectomy treatment had decrements in several physical domains
(General Health, Role Physical) but minimal impact on mental health domains. Changes in
HRQOL among NMIBC patients paralleled these findings.

Aside from disease stage and treatments, HRQOL can be impacted by time since diagnosis given
the potential for adaptation and coping. A comparison between 259 patients who underwent
cystectomy or non-cystectomy treatment revealed no differences in long-term (>2 year) HRQOL
using the cancer and disease-specific FACT-Bl questionnaire.29 Given that our study evaluated
short-term HRQOL (within 2 years of diagnosis), the impact of diagnosis and treatment on
HRQOL may differ if follow-up was extended. The majority of domains did not differ based on
time since diagnosis, although Role Physical appeared to improve by 1 year. This domain
involves role limitations due to physical health such as limiting time at work, difficulty
performing work, or accomplishing less than you would like. Recovery may be prolonged after
surgery (or intravesical treatments/intense surveillance), and therefore improvements to
baseline may not occur until one year post-diagnosis in this specific subdomain. To further
investigate longitudinal trends, future research should investigate long-term HRQOL in bladder
cancer patients. Finally, an additional consideration is the presence or absence of prior cancer
diagnoses. A subset of patients with non-invasive disease had an additional cancer diagnosis,
which may impact their HRQOL when compared to new cancer patients. Although this subset of
patients was too small to compare, this consideration should be acknowledged.

While our study represents the first comprehensive evaluation of HRQOL from before bladder
cancer diagnosis to after treatment, some limitations should be noted. First, our cohort was
limited to cancer patients who were enrolled in Medicare Advantage managed care plans.
MHOS participants may not be representative of all older adults residing in SEER areas. While
some studies indicate that managed care enrollees are healthier than fee-for-service
beneficiaries,30,31 another study indicated similarities between the groups.32 Second, the sample
size was relatively small among bladder cancer patients, which may reduce our ability to detect
statistically significant HRQOL differences between treatment groups. Third, different HRQOL
instruments were used during the study period (SF-36 from 1998-2005 and VR-12 from 2006-
2013). Furthermore, these data do not capture cancer patients or controls who dis-enroll from
their plan or die before follow-up HRQOL survey.33 HRQOL instruments were not cancer-specific
and may lack sensitivity with respect to bladder cancer specific treatment effects. Furthermore,
limited health literacy may be a potential barrier to collecting HRQOL from all patients. Fourth,

This article is protected by copyright. All rights reserved.

 we were unable to capture unknown confounders in the propensity score model which may
influence our results. Finally, we were unable to incorporate detailed information on treatment
Accepted Article
(e.g. neoadjuvant chemotherapy) and AJCC stage given constraints of coding and definition
changes from 1998-2013. The number of patients with MIBC undergoing cystectomy was
relatively small, limiting interpretation in this population.

Our current understanding of HRQOL among bladder cancer patients has several implications
for clinical practice. First, clinicians should inform patients who receive treatment that their
short-term HRQOL in several domains is likely to decrease, even among those undergoing non-
cystectomy procedures. HRQOL decrements are expected for patients with NMIBC and MIBC.
Setting appropriate expectations is critical to improving patient satisfaction, which has been
shown to be linked in a variety of conditions including joint replacement.34-36 Second, shared
decision making should incorporate an honest discussion regarding the impact of HRQOL when
comparing non-cystectomy treatment with cystectomy. A large study investigating patient
participation in shared decision-making showed that the majority of patients wished to engage
directly if quality of life was incorporated into the decision-making process.37 Multidisciplinary
clinics should provide all possible options in an unbiased and straightforward manner. Finally,
understanding that physical HRQOL is most impacted by the diagnosis and treatment of bladder
cancer irrespective of stage informs future interventions wishing to address and optimize
physical health in bladder cancer patients. Physical health decrements may be addressed
through judicious use of physical therapy and other supportive care interventions, even among
NMIBC patients.

In conclusion, our study is the first to report treatment and stage-specific HRQOL changes by
bladder cancer stage and treatment. Our results provide valuable information for researchers
interested in future interventions aimed at improving HRQOL in older adults with bladder
cancer.

Table 1: Propensity score adjusted bladder cancer cases and controls in SEER-MHOS cohort

Table 2: Adjusted HRQOL measures of baseline and follow-up of non-cancer controls and
bladder cancer patients

Table 3: Multivariable model with predictors of meaningful decrease in MCS or PCS among
patients with bladder cancer

Figure 1: Adjusted HRQOL changes from baseline to follow-up of controls and bladder cancer
patients stratified by stage

Figure 2: Adjusted HRQOL changes from baseline to follow-up of controls and bladder cancer
patients stratified by treatment

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 Figure 3: Adjusted HRQOL changes from baseline to follow-up of controls and bladder cancer
patients stratified by time since diagnosis
Accepted Article
Supplemental Table 1: Full Model for bladder cancer cases and controls in SEER-MHOS cohort
(non-propensity score adjusted)

Supplemental Figure 1: Adjusted HRQOL changes from baseline to follow-up of controls and
bladder cancer patients stratified by time since diagnosis (3 month increments)

Supplemental Figure 2: Adjusted HRQOL changes from baseline to follow-up of controls and
bladder cancer patients stratified by stage – full, non-propensity matched model

Supplemental Figure 3: Adjusted HRQOL changes from baseline to follow-up of controls and
bladder cancer patients stratified by treatment- full, non-propensity matched model

Supplemental Figure 4: Adjusted HRQOL changes from baseline to follow-up of controls and
bladder cancer patients stratified by time since diagnosis- full, non-propensity matched model

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 Table 1: Propensity score adjusteda bladder cancer cases and controls in SEER-MHOS cohort
Non-cancer Bladder Bladder
Accepted Article controls, Cancer, Non- Cancer,
Characteristic p-value
n=2770 (83%) invasive, n=458 invasive, n=77
(14%) (2.3%)
Female 1518 (54.8%) 118 (25.8%) 23 (29.9%)
Gender 1.0
Male 1252 (45.2%) 340 (74.2%) 54 (70.1%)
<High school 767 (27.7%) 119 (26.0%) 23 (29.9%)
High school graduate or GED 867 (31.3%) 141 (30.8%) 24 (31.2%)
Education 0.96
Some college or 2-yr degree 667 (24.1%) 116 (25.3%) 19 (24.7%)
>= college graduate 469 (16.9%) 82 (17.9%) 11 (14.3%)
Age Mean +- SD, yr 75.8 +- 0.1 75.4 +- 0.3 76.9 +- 0.8 0.13
White 2324 (83.9%) 383 (83.6%) 65 (84.4%)
African American 115 (4.2%) 17 (3.7%) **
Race Asian or Pacific Islander 155 (5.6%) 29 (6.3%) ** 0.45
Hispanic 165 (6.0%) 27 (5.9%) **
Other ** ** **
Midwest 271 (9.8%) 41 (9.0%) **
Northeast 475 (17.1%) 76 (16.6%) 13 (16.9%)
Region 0.99
South 513 (18.5%) 82 (17.9%) 15 (19.5%)
West 1511 (54.5%) 259 (56.6%) 42 (54.5%)
Married 1806 (65.2%) 307 (67.0%) 42 (54.5%)
Marital status at Never Married 114 (4.1%) 17 (3.7%) **
0.22
baseline Divorced/separated/widowed 850 (30.7%) 134 (29.3%) 29 (37.7%)
Marital status changeb 152 (5.5%) 24 (5.2%) **
Never 1699 (61.3%) 288 (62.9%) 42 (54.5%)
Smoking status Former 619 (22.3%) 103 (22.5%) 17 (22.1%) 0.42
Current 452 (16.3%) 67 (14.6%) 18 (23.4%)
Assessment Mailed 2485 (89.7%) 415 (90.6%) 67 (87.0%)
0.61
mode Telephone 285 (10.3%) 43 (9.4%) **
Yes 391 (14.1%) 64 (14.0%) 14 (18.2%)
Proxy 0.60
No 2379 (85.9%) 394 (86.0%) 63 (81.8%)
Hypertension 1592 (57.5%) 258 (56.3%) 44 (57.1%)
0.90

Heart disease 1027 (37.1%) 180 (39.3%) 23 (29.9%) 0.27

Stroke 261 (9.4%) 42 (9.2%) 13 (16.9%) 0.09
Emphysema, asthma or COPD 420 (15.2%) 71 (15.5%) 13 (16.9%) 0.91
Pre-existing
conditions Crohn disease, ulcerative colitis 150 (5.4%) 22 (4.8%) ** 0.78
or IBD
Arthritis 1361 (49.1%) 226 (49.3%) 40 (51.9%) 0.89
Sciatica 661 (23.9%) 109 (23.8%) 26 (33.8%) 0.13
Diabetes 636 (23.0%) 97 (21.2%) 23 (29.9%) 0.24
Depressionc 637 (23.0%) 102 (22.3%) 25 (32.5%) 0.14

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 0-6 106 (23.1%) 21 (27.3%)
Time since 6-12 118 (25.8%) 16 (20.8%)
Accepted Article
diagnosis, 12-18 88 (19.2%) 23 (29.9%)
months >=18 145 (31.7%) 17 (22.1%)
Additional 0 288 (62.9%) 53 (68.8%)
cancer(s) before 1 99 (21.6%) **
bladder ca >=2 71 (15.5%) 14 (18.2%)
diagnosis
Abbreviations:IBD,inflammatory bowel disease; COPD,chronic obstructive pulmonary disease; GED,General Educational
Degree; SD,standard deviation.
**suppressed due to small samples (<11) to protect identity;
a
Propensity scores are matched using age, gender, race, education, region, marital status, proxy status, assessment mode, smoking
status, high blood pressure, heart disease, stroke, COPD, gastrointestinal disorders such as Crohn’s, ulcerative colitis, IBD,
arthritis, sciatica, diabetes, and depression.
b
Widowed, divorced,or separated between baseline/follow-up.
c
Depression risk as defined by answering yes to 1 or more depression questions #36-38 of MHOS

Table 2: Adjusted HRQOL measures of baseline and follow-up of non-cancer controls and
bladder cancer patients

Control Non-Invasive Disease Invasive Disease

Baseline Follow- Baseline Follow- p-value Baseline Follow- p-value
up up up
Physical 32.0 31.6 32.0 (30.7, 30.0 0.01 31.1 (28.7, 25.8 <0.01
Component (31.2, (30.7, 33.2) (28.8, 33.4) (23.3,
Score 32.9) 32.5) 31.3) 28.3)
Bodily Pain 39.7 (38.8, 39.0 39.4 (38.2, 37.5 0.01 39.6 (37.3, 36 (33.6, 0.03
40.) (38.1, 40.5) (36.3, 41.8) 38.4)
39.9) 38.7)
Physical 31.4 (30.4, 31.1 31.9 (30.5, 31.1 1.0 31.6 (28.9, 25.8 <0.01
Functioning 32.4) (30.1, 33.2) (29.7, 34.2) (23.0,
32.1) 32.5) 28.5)
Role Physical 37.0 (35.9, 36.3 36.5 (35.1, 33.8 <0.01 35.8 (33.1, 31.1 <0.01
38.0) (35.3, 37.9) (32.4, 38.5) (28.3,
37.3) 35.2) 33.9)
General 37.3 (36.4, 37.3 36.5 (35.4, 34.1 <0.01 36.1 (33.8, 30.0 <0.01
Health 38.1) (36.5, 37.7) (32.9, 38.3) (27.6,
38.2) 35.2) 32.3)
Mental 46.1 (45.4, 45.8 45.6 (44.5, 44.9 0.08 46.8 (44.8, 44.3 0.29
Component 46.9) (45.1, 46.6) (43.9, 48.7) (42.3,
Score 46.6) 46.0) 46.4)
Mental Health 45.2 (44.4, 45.0 44.5 (43.5, 44.2 0.16 45.3 (43.2, 42.7 0.06
46.0) (44.3, 45.6) (43.1, 47.3) (40.6,
45.8) 45.3) 44.8)
Role 43.9 (43.0, 43.5 43.8 (42.5, 42.6 0.16 46.0 (43.7, 43.4 0.62
Emotional 44.8) (42.6, 45.0) (41.3, 48.4) (39.9,
44.4) 43.8) 44.9)
Vitality 40.5 (39.7, 40.4 40.0 (38.8, 38.8 <0.01 39.7 (37.5, 36.2 <0.01
41.3) (39.5, 41.1) (37.6, 42.0) (33.8,
41.2) 40.0) 38.5)

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 Social 40.4 (39.5, 39.6 40.1 (38.8, 38.0 0.01 40.1 (37.7, 34.4 <0.01
Functioning 41.3) (38.6, 41.3) (36.7, 42.6) (31.8,
Accepted Article 40.5) 39.3) 36.9)
*Values represent mean (95% CI)
**p-values<0.05 bolded

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 Table 3: Multivariable Model with Predictors of Meaningful Decrease in MCS or PCS
Accepted Article
Odds of significant decrease Odds of significant
Variable p-value
in MCS decrease in PCS

Southern
--- 2.651 (1.152, 6.267) 0.0235
region

Hypertension --- 0.597 (0.372, 0.953) 0.0314

Atherosclerosis --- 0.556 (0.345, 0.889) 0.0149

Graduate
--- 0.574 (0.297, 1.098) 0.0955
Education

Age (years) --- 1.032 (0.997, 1.069) 0.0784

0.0022 (MCS)
Recent < 0.0001 (PCS)
2.768 (1.461, 5.394) 4.188 (2.136, 8.618)
Depression

Chronic
1.759 (0.963, 3.253) --- 0.0682
Depression

Distant
0.210 (0.073, 0.516) --- 0.0015
Depression

Former
2.900 (1.322, 6.645) --- 0.0094
Smoker

Never Smoked 2.202 (1.053, 4.831) --- 0.0410

Chronic
0.588 (0.348, 0.983) --- 0.0446
Sciatica

Male 1.564 (0.949, 2.598) --- 0.0812

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Accepted Article

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Accepted Article

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