First, Seth Strope and colleagues from Michigan queried Medicare beneficiaries with NMIBC and evaluated treatment intensity with respect to risk groups.2 They found that healthcare resource utilization for NMIBC is increasing, primarily through greater use of intravesical therapy. In a completely separate analysis, we found that compliance with established guidelines for NMIBC is embarrassingly poor.3 In 4790 eligible patients, only one single patient received documented care in accordance with our established guidelines, including intravesical therapy, cystoscopy, and cytology. A discrepancy then became clear: How were we utilizing more resources yet not complying with established, evidence-based guidelines? How was there a dissociation between treatment intensity and compliance? Given our previous work, our intuition was that intravesical therapy, specifically intravesical Bacillus Calmette-Guérin (BCG), was used inappropriately and/or underutilized. Our hypothesis was that up-front BCG therapy was underutilized and that BCG was given as a reaction to recurrences, thereby “spending the money without getting the goods.”
Utilizing linked SEER-Medicare, and limiting the cohort to patients with high-grade NMIBC (Tis, Ta, T1), we found a disturbing pattern of BCG utilization. As others have demonstrated, two-thirds of patients did not undergo a restaging transurethral resection, 60% of patients did not receive any BCG after a single resection, and BCG continued to be given (albeit in low numbers) even after multiple endoscopic resections. If we can assume that the third and fourth resections are not restaging procedures then patients are apparently continuing to get BCG despite a failure to respond. In combination with the fact that (at best) only 54% of patients received any BCG after two endoscopic resections led us to formulate the concept that BCG is utilized in a reactionary manner in response to recurrences rather than as a proactive therapy to reduce recurrences and prevent progression.
Ultimately, NMIBC is a chronic disease that is challenging for both the physician and the patient. Especially in high-risk patients, such as those analyzed in our study, urologists must strike a balance between disease control and bladder-sparing therapies. In an attempt to explain the findings of our study, we feel that urologists may forgo intravesical therapy in the case of a small tumor completely resected, despite a high-grade pathology. This is likely secondary to the known local and systemic side effects of BCG. Urologists may also “give BCG another shot” for patients with refractory, resistant, or recurrent disease who may refuse cystectomy or who may not be ideal surgical candidates. BCG therapy, despite its position as the gold standard for over 30 years, must be improved upon. Checkpoint inhibitors have recently demonstrated remarkable benefit and clinically meaningful improvements in overall survival in the metastatic space.4 In an effort to extend this success to the NMIBC realm, many clinical trials are underway that combine BCG with these agents, including systemic anti-Programmed Cell Death Ligand-1 (NCT02792192), systemic anti-Cytotoxic T-Lymphocyte Antigen-4 (NCT01838200 and NCT00880854), and intravesical anti-Programmed Cell Death-1 (NCT02808143). Hopefully more targeted, less toxic, and better-tolerated, local therapy will change the landscape of NMIBC in the future.
Written by: Andrew T. Lenis, Nicholas M. Donin, Karim Chamie
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1. James AC and Gore JL: The costs of non-muscle invasive bladder cancer. Urol. Clin. North Am. 2013; 40: 261–269. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23540783.
2. Strope SA, Ye Z, Hollingsworth JM, et al: Patterns of care for early stage bladder cancer. Cancer 2010; 116: 2604–2611. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2876213&tool=pmcentrez&rendertype=abstract.
3. Chamie K, Saigal CS, Lai J, et al: Quality of care in patients with bladder cancer: a case report? Cancer 2012; 118: 1412–1421.
4. Donin NM, Lenis AT, Holden S, et al: Immunotherapy in the Treatment of Urothelial Carcinoma. The Journal of Urology 2016; 0.