Provider Treatment Intensity and Outcomes For Patients With Early-Stage Bladder Cancer
Provider Treatment Intensity and Outcomes For Patients With Early-Stage Bladder Cancer
Provider Treatment Intensity and Outcomes For Patients With Early-Stage Bladder Cancer
Background Bladder cancer is among the most prevalent and expensive to treat cancers in the United States. In the
absence of high-level evidence to guide the optimal management of bladder cancer, urologists may vary
widely in how aggressively they treat early-stage disease. We examined associations between initial treat-
ment intensity and subsequent outcomes.
Methods We used the Surveillance, Epidemiology, and End Results–Medicare database to identify patients who
were diagnosed with early-stage bladder cancer from January 1, 1992, through December 31, 2002 (n = 20
713), and the physician primarily responsible for providing care to each patient (n = 940). We ranked the
Results The average Medicare expenditure per patient for providers in the highest quartile of treatment intensity
was more than twice that for providers in the lowest quartile of treatment intensity ($7131 vs $2830,
respectively). High–treatment intensity providers more commonly performed endoscopic surveillance and
used more intravesical therapy and imaging studies than low–treatment intensity providers. However, the
intensity of initial treatment was not associated with a lower risk of mortality (adjusted hazard ratio of
death from any cause for patients of low– vs high–treatment intensity providers = 1.03, 95% confidence
interval 0.97 to 1.09). Initial intensive management did not obviate the need for later interventions. In fact,
a higher proportion of patients treated by high–treatment intensity providers than by low–treatment inten-
sity providers subsequently underwent a major medical intervention (11.0% vs 6.4%, P = .02).
Conclusions Providers vary widely in how aggressively they manage early-stage bladder cancer. Patients treated by
high–treatment intensity providers do not appear to benefit in terms of survival or in avoidance of subse-
quent major medical interventions.
Bladder cancer is the fifth most common new cancer diagnosis the optimal approaches to bladder cancer surveillance and treat-
and among the most expensive cancers to treat in the United States ment is largely lacking. Rather, current guidelines for the surveil-
(1). Nearly three-quarters of incident cases of bladder cancer are lance and treatment of early-stage bladder cancer are most
non–muscle-invasive (ie, early-stage) tumors (2), which are removed
endoscopically. In up to half of these patients, the disease will
progress to muscle-invasive cancer (3–6). Because mortality from Affiliations of authors: Division of Oncology, Department of Urology
muscle-invasive disease is common (7,8) and often requires a major (BKH, JEM), Division of Health Services Research, Department of Urology
(BKH, ZY, RLD, JEM), Department of Surgery (JDB), and Michigan Surgical
medical intervention (radical cystectomy, systemic chemotherapy, Collaborative for Outcomes Research and Evaluation (BKH, JDB), University
and/or radiation therapy), effective strategies for the prevention of Michigan Health System, Ann Arbor, MI.
and early detection of disease progression are of paramount Correspondence to: Brent K. Hollenbeck, MD, MS, Division of Oncology,
importance. Department of Urology, University of Michigan Health System, 1500 East
Medical Center Dr, TC 3875, Ann Arbor, MI 48109 (e-mail: bhollen@umich.
How best to achieve this goal remains unclear. Common strat- edu).
egies for bladder cancer surveillance and treatment that may be See “Funding” and “Notes” following “References.”
useful include intensive intravesical therapy, repeat endoscopic re- DOI: 10.1093/jnci/djp039
section after diagnosis, and frequent endoscopic surveillance (9,10). © The Author 2009. Published by Oxford University Press. All rights reserved.
However, evidence from randomized clinical trials establishing For Permissions, please e-mail: journals.permissions@oxfordjournals.org.
the lowest quartile of treatment intensity). Compared with died from any cause between January 1, 1992, and December 31,
patients who were treated by low–treatment intensity providers, 2005. Patients treated by low–treatment intensity providers had a
those treated by high–treatment intensity providers were, on similar risk of death as those who were treated by high–treatment
average, followed up more rigorously with bladder endoscopy intensity providers (adjusted hazard ratio [HR] of death = 1.03,
(8.3 vs 7.3 procedures, P < .001), urine cytology (2.3 vs 1.3 tests, 95% confidence interval [CI] = 0.97 to 1.09) after adjusting for
P < .001), and radiographic imaging (6.0 vs 5.1 studies, P < .001). differences in demographics and cancer severity (ie, tumor grade
Treatment-related processes of care followed similar trends. and stage). When the patients were stratified by tumor grade and
Patients who were treated by high–treatment intensity providers stage, we observed the anticipated effects of these markers of
received statistically significantly more instillations (5.0 vs 2.6, P disease severity on survival, that is, patients with high-grade or T1
< .001) and induction courses (0.6 vs 0.5, P < .001) of intravesical disease had generally lower survival than their counterparts with
therapy than patients who were treated by low–treatment inten- low-grade or Ta disease, respectively, at all levels of provider treat-
sity providers. ment intensity. However, as with the primary analysis, we observed
Despite these differences in provider practice style, the median no survival benefit associated with more intensive care. For exam-
survival of patients was similar across all four quartiles of provider ple, among patients with T1 disease—a population with the high-
treatment intensity (Table 3) and ranged from 76.5 months for est risk of disease progression—those treated by low–treatment
those whose providers were in the second highest quartile to 79.8 intensity providers had a similar risk of death as those treated by
months for those whose providers were in the second lowest high–treatment intensity providers (adjusted HR of death = 0.98,
quartile (P = .50). Overall, 11 485 (55.4%) of the 20 713 patients 95% CI = 0.88 to 1.09).
Median survival in months by quartiles of Adjusted HR of death (95% CI) for patients of
provider treatment intensity low– vs high–treatment intensity providers
Bladder cancer–
Patient stratification 1 (low) 2 3 4 (high) All-cause mortality specific mortality
All patients 76.8 79.8 76.5 78.0 1.03 (0.97 to 1.09)† 0.70 (0.59 to 0.83)†
Stratified by grade
Low 85.1 86.6 83.4 85.9 1.03 (0.96 to 1.11)‡ 0.66 (0.52 to 0.85)‡
High 62.0 64.0 62.5 63.3 1.03 (0.92 to 1.15)‡ 0.81 (0.63 to 1.03)‡
Unknown 71.1 80.7 72.8 71.3 0.96 (0.78 to 1.19)‡ 0.39 (0.20 to 0.75)‡
Stratified by stage
Ta 85.3 87.4 84.3 89.9 1.06 (0.98 to 1.14)§ 0.74 (0.57 to 0.97)§
Tis 76.8 72.0 74.9 72.4 0.91 (0.74 to 1.11)§ 0.49 (0.27 to 0.89)§
T1 75.8 76.6 76.7 78.9 0.98 (0.88 to 1.09)§ 0.68 (0.54 to 0.86)§
Ta or T1 64.4 64.8 63.7 61.7 1.06 (0.89 to 1.27)§ 0.72 (0.44 to 1.18)§
groups. In particular, patients treated by high–treatment inten- would require systematic variation in unmeasured risk factors
sity urologists might have more aggressive disease than those across providers, which is probably less likely than variation in
treated by low–treatment intensity urologists, which could such risks across patients. Finally, our sensitivity analysis to assess
explain the apparent lack of benefit associated with treatment treatment intensity and survival in separate patient populations
intensity. We addressed this well-described limitation of observa- also failed to demonstrate a survival advantage of more aggressive
tional data (35,36) in several ways. First, we used a clinical regis- treatment.
try to ascertain patients’ bladder cancer stage and grade, which Although more aggressive early treatment intensity was not
are, arguably, the most important determinants of death in the associated with survival, it was associated with higher rates of
bladder cancer patient population (7,37). Patients in the different major medical interventions, including radical cystectomy, sys-
treatment intensity groups were similar with respect to age, sex, temic chemotherapy, and radiation therapy. There are several
and comorbidity. Second, we assessed treatment intensity at potential explanations for this finding. First, as discussed above,
the level of the provider. Relative to a patient-level analysis, this high–treatment intensity providers may have been treating sicker
approach is less susceptible to selection bias to the extent that it patients who, ultimately, required such interventions. However,
unmeasured confounding seems unlikely given our approach of
measuring treatment intensity at the level of the provider and the
large differences in the rates of major intervention. Second, it is
possible that more intensive therapy could, paradoxically, increase
the risk of disease progression and thus the need for major medi-
cal interventions. However, we know of no biological mechanism
to support this possibility. Third and perhaps most likely, pro-
vider practice styles with regard to the management of early-
stage bladder cancer, as measured by their initial treatment
intensity, may be consistent with those for more advanced dis-
ease. Simply put, urologists who treat aggressively early are likely
to provide aggressive treatment in all aspects of bladder cancer
care, and vice versa.
A second limitation of our findings relates to their applica-
bility to the broader population of patients with early-stage
Figure 1. Use of major medical interventions among patients with bladder cancer. Because we relied on SEER–Medicare data, our
early-stage bladder cancer by quartiles of provider treatment intensity, findings may not be generalizable to patients younger than 65 years.
expressed as the percentage of patients adjusted for age, sex, race, However, it is important to note that nearly three-quarters of
comorbidity, socioeconomic status, and tumor grade and stage. The
adjusted percentages were obtained by back-transforming data from bladder cancer cases in the United States occur annually within
the logistic models. Statistical inference was based on the Wald chi- the Medicare population (12). In early-stage bladder cancer,
square statistic obtained from the Cox proportional hazards models for unlike in prostate cancer, treatment decisions generally are
comparisons between the highest and lowest treatment intensity
quartiles within interventions, adjusting for the above covariates. All not made on the basis of the patient’s age. Thus, extrapolation
P values are two-sided. of our findings to the broader cohort (ie, all patients with
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* ICD-9 = International Classification of Diseases, 9th Revision; MEDPAR = Medicare Provider Analysis and Review file; HCPCS = Healthcare Common
Procedure Coding System; CT = computed tomography; MRI = magnetic resonance imaging; PET = positron emission tomography.
† Induction intravesical therapy: at least five unique claims for instillation of any anticarcinogenic agent within a 45-day period.