The 2012 NCCN Bladder Cancer Guidelines
The NCCN is a nonprofit collaboration of 21 participating National Cancer Institute (NCI)-designated cancer centers. The NCCN publishes clinical practice guidelines on the management of 35 cancers, which are commonly accepted as standards by the Center for Medicare Services (CMS) and private insurers.15,24
Like the AUA and EAU guidelines, the NCCN guidelines incorporate both scientific evidence and consensus opinion into their recommendations. Unlike the AUA and EAU guidelines, the method and extent of literature review for each NCCN guideline update are not well described. The NCCN grades recommendations based upon the relevant levels of evidence and consensus.
Evidence is graded as high-level (referring to large randomized clinical trials or meta-analyses) or lower level (which is broad in scope and ranges from well-performed observational studies to case series). The NCCN grades recommendations from category 1 to category 3, with category 1 representing high-level evidence and uniform opinion, categories 2A and 2B representing variable levels of evidence and consensus, and category 3 representing major disagreement amongst panel members.25
Within the 2010 NCCN Bladder Cancer Guidelines, 86% of recommendations were graded category 2A and 14% 2B, with no category 1 or category 3 recommendations.15 Interestingly, the most recent update to the NCCN Bladder Cancer Guidelines does contain category 1 recommendations that will be discussed below.
Similar to the EAU guidelines, the NCCN provides recommendations for diagnosis, treatment, and follow-up. The NCCN guidelines advocate for cystoscopy, urinary cytology, and the routine application of upper tract imaging upon suspicion of NMIBC. Similar to both the AUA and EAU guidelines, the NCCN recommends as an option the administration of a single dose of perioperative, intravesical chemotherapy. Additionally, the guidelines offer as an option the administration of induction immunotherapy or chemotherapy.
For patients with high-grade noninvasive disease, the NCCN guidelines recommend re-resection in the context of incomplete index resection or the absence of muscle in the initial specimen. For patients with high-grade T1 disease, the guidelines strongly advise re-resection and offer, as an alternative, consideration of radical cystectomy. The 2012 NCCN guidelines assign a category 1 recommendation to the administration of intravesical BCG to patients with T1 disease, either low- or high-grade, and recommend the administration of BCG to patients with CIS.
While the most recent guidelines do state that there are data to support the use of maintenance BCG, there is no specific recommendation regarding the application of maintenance BCG in the absence of cytologic or cystoscopic disease recurrence. The guidelines provide a comprehensive framework for the treatment of bladder cancer patients with recurrent disease and offer as an option the administration of intravesical valrubicin for BCG-refractory CIS.
Like the EAU guidelines, the NCCN uses a risk-adapted follow-up paradigm. For patients with low-grade noninvasive disease the guidelines recommend cystoscopy at three months, then increasing intervals as appropriate. For patients with invasive disease, high-grade disease, or CIS, the guidelines recommend cystoscopy every three to six months for two years then at increasing intervals as appropriate. Furthermore, surveillance upper tract imaging is recommended every one to two years for patients with high-grade disease.
Variations in adherence
Despite the potential population-level and patient-level benefits to the dissemination and widespread application of clinical practice guidelines, there remains a considerable variation in practice patterns among urologists who treat NMIBC. Hollingsworth and colleagues evaluated variation in treatment intensity among a Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort of patients with NMIBC and found substantial variation in patterns of care.26
Indeed, these investigators documented a greater than twofold difference in bladder cancer expenditures among patients treated by high-intensity providers when compared to low-intensity providers.26,27
Furthermore, provider factors accounted for more of the observed variation in care intensity than any measureable patient characteristics.
While patients treated by high-intensity providers were more likely to undergo radical therapy for bladder cancer, treatment by a high-intensity provider did not confer any cancer-specific survival benefit.26
The same investigators also then specifically evaluated variation in the use of cystoscopy, urine cytology, and intravesical therapy and, again, found considerable variation in the use of these services among treatment providers. Neither increasing utilization of cystoscopic surveillance nor increasing utilization of intravesical therapy was associated with a patient-level survival benefit. Interestingly, maximal use of urine cytology was associated with a reduction in bladder cancer death when compared to the lowest level of utilization.27
These data underscore the considerable degree of provider-level variation in treatment patterns among urologists caring for patients with NMIBC. Furthermore, these data may ultimately be used in future guidelines to identify optimal population-based care intensity paradigms.