Quality of bladder cancer care in the USA

Keywords::

• bladder cancer
• guideline adherence
• quality of care
• survival

Significant progress has been made in improving the care of patients with bladder cancer over the past 25 years. Notable advances include an enhanced understanding of neoadjuvant chemotherapy [1], perioperative intravesical chemotherapy [2], postoperative intravesical immunotherapy [3], a better understanding of the importance of surgical quality [4] and the establishment of clinical practice guidelines [5]. In this context, we summarize the literature on compliance with the aforementioned metrics of quality of care from population-level observational studies.

Delay in diagnosis & treatment

Timely diagnosis is foundational to improving cancer-specific survival. However, using linked Surveillance, Epidemiology and End Results (SEER)–Medicare data, Hollenbeck et al. reported that approximately 24% of 29,740 patients with hematuria and bladder cancer had a delay in their diagnosis of longer than 3 months [6]. Patients with a delay in their diagnosis longer than 9 months had a 34% higher risk of dying of bladder cancer compared with those diagnosed within 3 months. The authors note that advancing age and more comorbid illnesses were associated with statistically significant delays.

Similarly, prompt treatment – radical cystectomy or chemoradiotherapy within 3 months of diagnosis of myoinvasive disease – is generally a well-accepted quality-of-care metric. Using linked SEER–Medicare data, Gore et al. reported that of the 442 patients with stage II bladder cancer who underwent radical cystectomy, 35% had a delay in their treatment beyond 3 months [7]. Moreover, the authors note that a delay of treatment beyond 3 months, when compared with those treated within 3 months, was associated with twice the risk of cancer-specific mortality. Patients who are not married as well as those diagnosed in the south or northeast were more likely to have a delay in treatment than those who were married or diagnosed in the west or midwest, respectively.

Surveillance & treatment for non-muscle-invasive bladder cancer

The National Comprehensive Cancer Network, American Urological Association and European Association of Urology developed clinical guidelines that detail a surveillance schedule and treatment strategy in hopes of minimizing morbidity from non-muscle-invasive bladder cancer. The surveillance and treatment strategies embodied within these guidelines have been infused into education, specialty certification and reimbursement models. Nonetheless, using a relaxed definition for a single quality-of-care measure (cystoscopy every 6 months instead of every 3 months), Schrag et al. reported that 40% of a SEER–Medicare cohort underwent the recommended number of endoscopic procedures [8]. Using MEDSTAT claims data, Madeb et al. discovered that of 14,677 subjects with non-muscle-invasive bladder cancer who underwent resection of their bladder tumor, only 49 (0.3%) received perioperative intravesical instillation of chemotherapy [9]. In addition, Huang et al. found that only 42% of patients with high-grade, non-muscle-invasive bladder cancer received a single intravesical instillation of immunotherapy or chemotherapy within 1 year of diagnosis [10].

Using linked SEER–Medicare data, we reported that 5%, 5% and 50% of patients with high-grade disease underwent the recommended number of cystoscopies, cytologies and radiographic imaging, respectively [11]. Approximately 3% and 26% received a single dose of perioperative intravesical chemotherapy and postoperative intravesical immunotherapy, respectively. In fact, we found only a single case of comprehensive compliance out of 4545 patients with high-grade disease. With the exception of age (lower odds of compliance with cytology, imaging and postoperative intravesical instillation of immunotherapy with advancing age) and stage (higher odds of compliance with cytology, imaging and postoperative intravesical instillation of immunotherapy with higher stage), we did not find any consistent associations between sociodemographics or tumor characteristics and receipt of cancer care. Additionally, with the exception of radiographic imaging, unexplained surgeon variance contributed significantly to the low-compliance rate: 25% for cystoscopy, 26% for postoperative instillation of intravesical immunotherapy, 45% for perioperative intravesical instillation of chemotherapy and 59% for cytology.

Some contend that the surveillance and treatment strategies may be too stringent, thus explaining the 99.6% noncompliance rate. This contention is fitting since most of the surveillance measures are based on expert opinion. Against this backdrop, we then examined the relative association of individual and comprehensive surveillance and treatment strategies with cancer-specific survival [12]. Patients who underwent at least four cystoscopies, four cytologies, or a single intravesical instillation of postoperative immunotherapy had a 39%, 45% and a 29% lower risk for bladder cancer mortality, respectively. We then measured the relative association of a comprehensive regimen with survival [12]. Patients who underwent at least four cystoscopies, four cytologies and early initiation of intravesical instillation of immunotherapy had a 59% lower risk of dying of bladder cancer than those who received less than four cystoscopies, four cytologies and no postoperative immunotherapy. To our surprise, less frequent surveillance or delay in postoperative immunotherapy did not yield a statistically significant survival advantage over the referent. Unfortunately, only 14% of patients in our cohort received the level of care that was associated with a survival advantage.

Neoadjuvant chemotherapy for muscle-invasive bladder cancer

There is increasing evidence that neoadjuvant chemotherapy followed by cystectomy renders a survival advantage in patients with myoinvasive bladder cancer [1]. Against that backdrop, David et al., using the National Cancer Data Base, examined the incidence of chemotherapy (adjuvant and neoadjuvant) use among patients with stage III bladder cancer [13]. Of the 7161 patients diagnosed with stage III bladder cancer in 1998–2003, 11.6% received chemotherapy, of which 1.2% and 10.4% were in neoadjuvant and adjuvant settings, respectively. In a follow-up analysis using the National Cancer Data Base in 2003–2007, Fedeli et al. noted a significant increase in the use of chemotherapy from 27% in 2003 to 34% in 2007 [14]. There was a corresponding increase in neoadjuvant chemotherapy rate from 6% in 2003 to 13% in 2007. Using linked SEER–Medicare data from 1992–2002, Porter et al. noted that 18%, 22% and 33% of stage II, III and IV bladder cancer patients received chemotherapy, respectively [15]. This is mostly comprised of gemcitabine, paclitaxel and carboplatin. Overall, only 1.4% of patients received the chemotherapy in a neoadjuvant setting. On multivariate analysis, the authors noted a lower risk of utilization of systemic chemotherapy with advancing age, lower grade and stage, and increasing comorbidities.

Radical cystectomy, lymphadenectomy & urinary diversion for muscle-invasive bladder cancer

Evidence-based guidelines recommend radical cystectomy (including a standard pelvic lymphadenectomy) as the standard treatment for patients with muscle-invasive bladder cancer. Bladder-sparing protocols – chemoradiotherapy or radical endoscopic resection with or without systemic chemotherapy – are primarily reserved for the very elderly, those with significant comorbidities or poor performance status, and those who refuse extirpative surgery. Using linked SEER–Medicare data, Gore et al. reported that only 21% of eligible patients underwent radical cystectomy [16]. The authors discovered a lower odds of radical cystectomy with advancing age, increasing comorbidities, lower grade disease and long travel distance to the nearest cystectomy provider. Furthermore, patients who did not undergo radical cystectomy had a 33–46% higher risk of dying of bladder cancer than those who underwent radical cystectomy.

With regard to lymphadenectomy, Hedgepeth et al. utilized linked SEER–Medicare data to address variations in the use of pelvic lymphadenectomy among 4472 patients with muscle-invasive bladder cancer who underwent radical cystectomy [17]. While it is reassuring that approximately 70% of patients underwent a pelvic lymphadenectomy during surgery, only 22% of those patients had at least ten lymph nodes removed – clearly representing substandard pelvic lymph node dissections. Lower odds of undergoing a standard lymph node dissection were found with advancing age, low-grade disease, metastatic bladder cancer, and low-surgical volume. Additionally, unexplained surgeon variance contributed significantly to the low-compliance rate: 54% for performing a lymphadenectomy and 41% for removing at least ten lymph nodes.

Gore et al. also examined factors that modulate the type of urinary diversion (continent versus incontinent urinary diversion) [18]. Using linked SEER–Medicare data, the authors discovered that of the 3611 patients undergoing cystectomy, only 20% had a continent diversion. On multivariate analysis, they discovered that a lower odds of continent diversion was found with advancing age, female gender, African–American race, lower median income, increasing comorbidities, those diagnosed in 1992–1994, those diagnosed in nonacademic institutions or non-National Cancer Institute-designated Comprehensive Cancer Centers, and those diagnosed in low-volume hospitals. Additionally, the authors reported geographical variation in the rate of continent urinary diversion, including lower rates in San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico and Utah.

Conclusion

Despite the notable advances over the last quarter century, the anticipated survival benefits in bladder cancer have not come to fruition. Over the last 15 years, we have seen only a 5% relative reduction in bladder cancer-related mortality, while prostate, breast, lung and colon cancers have had a more precipitous drop in cancer-specific mortality – a 20–40% relative risk reduction [19]. Some contend that this lack of improvement may be attributed to lack of public awareness, inadequate and disproportionate funding, and declining basic science research [20]. Herein, we demonstrate that inadequacies in the quality of care have slowed improvement in bladder cancer-specific survival. This suboptimal care spans the spectrum of disease – from non-muscle-invasive to invasive disease, and from diagnosis to treatment to surveillance.

Financial & competing interests disclosure

This work was supported in part by the Ruth L Kirschstein National Research Service Award Extramural (1 F32 CA144461-01 [principal investigator: K Chamie]); American Cancer Society (117496-PF-09-147-01-CPHPS [principal investigator: K Chamie]); Jonsson Comprehensive Cancer Center Seed Grant [principal investigator: MS Litwin]); and National Institute of Diabetes and Digestive and Kidney Diseases (N01-DK-1-2460 [principal investigator: MS Litwin]). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.