We discovered a single case of comprehensive compliance out of 4,790 eligible patients. We did not anticipate that the considerable discordance between established guidelines and routine practice would yield a single case to report. Moreover, those who received at minimum ≥ 4 cystoscopies, ≥ 4 cytologies and initiation of BCG within 90 days of diagnosis had improved survival when compared with those who did not.
Factors that may explain the inadequacy of compliance with guideline-recommended care include: 1) the dearth of evidence-based medicine for surveillance strategies, 2) the surveillance and treatment strategies are too stringent, 3) patient preferences and treatment-related toxicities, 4) publication of practice guidelines after 1997, and 5) meta-analyses documenting the benefits of perioperative chemotherapy in 2004. With regard to the first three factors, a surveillance schedule that is too stringent with the attendant patient discomfort that is based on expert opinion will undoubtedly yield low compliance. In the absence of validation of surveillance strategies, we anticipate that compliance will remain low. Our study is especially timely, since it is among the first in bladder cancer to examine the relationship between process-of-care surveillance measures and an outcome that matters to cancer patients—survival. We hope our findings demonstrating a process-outcomes link will improve utilization of surveillance and treatment services. With regard to point 4, although the guidelines were first published in 1997, by limiting our cohort to those with high-risk disease, we expected preference-sensitive variation in this high-risk group to err on overutilization, not underutilization. Moreover, the benefits of BCG were well known prior to 1992. In fact, Southwest Oncology Group 8795 was closed prematurely in 1991 after accruing half of the projected number of subjects (349 in lieu of 720) as evidenced by the superiority of BCG over mitomycin C in recurrence-free survival (let alone placebo). With regard to the point 5—meta-analysis demonstrating an advantage of a single perioperative intravesical dose of chemotherapy was first reported in 2004—multiple studies published in the 1980s and 1990s demonstrated the benefits of perioperative intravesical chemotherapy. 7, 15–21
Some contend that with time, compliance with practice guidelines will be sufficient. Notwithstanding the statistically significant increase of compliance with at ≥ 4 cystoscopies, ≥ 4 cytologies and an induction course of BCG, we anticipate only 25% compliance by the year 2024. This anticipated 25% rate of compliance with recommended care (in 2024) is congruent with the deficit seen in patients with atrial fibrillation and hip fractures in 2003.3
Not coincidentally, atrial fibrillation and hip fractures have since been prioritized in the Initial National Priorities for Comparative Effectiveness Research.22
Our findings are commensurate with others depicting the underutilization of effective care in patients with bladder cancer, spanning extent of disease, from the underuse of definitive treatment and neoadjuvant chemotherapy for patients with at least stage II disease, 37% and 1%, respectively,23
to endoscopic surveillance and perioperative instillation of mitomycin in patients with non-muscle-invasive disease, 40% and 0.3%, respectively.4–6
Our findings may appear at odds with those of Strope et al.
, who have queried a similar cohort and discovered increased utilization of intravesical therapy and physician office visits.24
While office visits was not a process metric in our analysis, our findings echoed theirs with regard to intravesical therapy (post-operative immunotherapy). Moreover, while we also demonstrate increased mean utilization of most services over time we note that the compliance rate did not increase; hence the increased utilization may be as a result of non-coordinated care. With regard to treatment intensity and survival, our findings are at odds with 1) Hollingsworth et al.,
who demonstrated that while increasing treatment intensity was associated with major interventions (radical cystectomy, radiotherapy, and systemic chemotherapy), it was not significantly associated with median cancer-specific survival (albeit there was a trend with p=0.07); 25
and 2) the Hollenbeck et al.
analysis that demonstrated that increasing treatment intensity was actually associated with a significantly higher hazard for cause-specific mortality (HR 1.43). 26
In fact, based on Hollingsworth et al.
analysis, if provider treatment intensity was modified to reflect the 25th
percentile, the authors anticipate Medicare savings of $18.7 million without detriment to oncologic outcomes. Our analysis differed from the Michigan’s group in that we excluded individuals who 1) underwent definitive treatment (cystectomy, radiotherapy or systemic chemotherapy) within the initial two-year period, or 2) did not survive during the initial two years, since a significant proportion of individuals with non-muscle-invasive bladder cancer on the initial transurethral resection may have been understaged. Therefore, this may in part explain why in their analyses, they discovered that the upper quartile of treatment intensity may not benefit from more services, 25, 26
since more intense surveillance and intravesical treatment strategies are unlikely to rescue a patient who has progressed to myoinvasion.27–30
While our sample size is large, our study has methodological limitations. As with any observational study, omitted-variable bias may impact adherence rates with established-clinical guidelines and the propensity score model. Patient preferences for surveillance and treatment strategies may have also confounded our findings of significant non-compliance. While the discomfort associated with endoscopic evaluation and intravesical therapy, may have contributed to noncompliance, we attempted to minimize confounding by limiting our cohort to those with high-grade tumors—a disease state that warrants higher intensity of surveillance and treatment—and to those who survived at least two years without undergoing definitive treatment (thus excluding those with competing causes of death and those who were understaged and quickly progressed). Last, while the surveillance strategies were statistically significant predictors of lower mortality, they may be a proxy for improved access to care. However, in the absence of an association between education and median income with the quality measures, this is not likely to be a significant cause.
Despite these limitations, our findings serve to alert patients and providers to the wide gap between guideline-recommended care and routine practice. So, how do we bridge the chasm between clinical practice guidelines and routine care? One approach relies on restructuring payment policies through performance-based incentive programs to explicitly promote improvements in quality of care. Pay-for-performance
incentives and alternative payment models (e.g., PROMETHIUS® and accountable care organizations) have been integrated into most commercial and public health plans (e.g., the Centers for Medicare & Medicaid Services sponsors the Hospital Quality Improvement Demonstration Project).31
By linking incentives with physician adherence to clinically effective measures, facilitating positive patient outcomes and avoiding complications, we hope to bend the arc of the care trajectory for bladder cancer by implementing adequate cystoscopies and cytologies and initiation of BCG. These measures are feasible and effective in minimizing the morbidity and mortality associated with bladder cancer. Alternative strategies such as clinical reminders, electronic health records and development of scorecards not tied to financial incentives, may improve quality of care without the unintended consequences—gaming the system for financial incentives, stifling innovation and hindering development of creative solutions to improving quality and the potential to paradoxically penalize providers caring for underserved, non-compliant patients who are at high risk for progression.
Irrespective of the approach, in the absence of a broad quality-improvement initiative, the diffusion of clinically effective care will be slow, and many more unnecessary recurrences, procedures and deaths will be realized. This is an especially critical point since progress in preventing bladder cancer-related mortality lags behind other diseases—a 5% relative reduction in mortality rate over the last 15 years.32
This contribution is slight when one considers that bladder cancer is the fifth most common cancer contrasts starkly with prostate, breast, lung and colon cancers where we have seen greater reductions in mortality during the same period.33