[Skip to Navigation]
Sign In
Invited Commentary
March 31, 2021

Quantifying the Costs of Care Among Patients With High-Risk Non–Muscle-Invasive Bladder Cancer Treated in the Veterans Health Administration

Author Affiliations
  • 1Division of Urology, Department of Surgery, Huntsman Cancer Institute, University of Utah, Salt Lake City
  • 2Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City
JAMA Netw Open. 2021;4(3):e213816. doi:10.1001/jamanetworkopen.2021.3816

Bladder cancer is one of the most expensive malignant neoplasms to manage on a per-patient basis.1 Approximately 70% of patients with newly diagnosed bladder cancer present with non–muscle-invasive bladder cancer (NMIBC). Non–muscle-invasive bladder cancer is a heterogeneous disease that leads to significant variability in the intensity of surveillance and treatments to decrease the risk of local recurrences and progression to more invasive disease. National guidelines advocate for risk-adapted surveillance and treatment in this patient population.2 High-risk NMIBC carries the highest risk of recurrence and progression. The financial costs associated with the treatment of high-risk NMIBC arise from frequent cystoscopic surveillance, adjunct testing (eg, urine cytology), periodic cross-sectional imaging, intravesical treatments (eg, bacillus Calmette-Guérin [BCG] therapy), transurethral resections of bladder tumor (TURBT) under general anesthesia, and definitive treatments for progression to muscle-invasive disease (eg, radical cystectomy). Recent publications quantifying the costs of care for this group with high-risk NMIBC have demonstrated that the most significant costs incurred are owing to disease progression and subsequent definitive treatments.3 Furthermore, the costs incurred by this patient population have been shown to lead to financial toxicity and adverse effects on quality of life.4 Adherence to guideline-directed care and the costs of treating high-risk NMIBC in the US Veterans Health Administration (VHA) are less understood.

In JAMA Network Open, Williams et al5 evaluated the oncologic outcomes and health care costs among 412 patients with high-risk NMIBC managed across the national integrated VHA system from 2000 to 2015. Although this is a small cohort of patients, the authors included a population consisting of a male-to-female ratio of 4:1, 50 Black patients (12%), and 15 Hispanic/Latino patients (4%) from Department of Veterans Affairs centers across the US. The authors report several key findings worth examining: (1) there was adequate use of and adherence to induction BCG therapy (95%) but less so for maintenance BCG therapy (37%); (2) cancer progression was associated with significantly increased financial costs at 5 years ($232 729 vs $94 879; P < .001); and (3) the presence of carcinoma in situ (Cis) was independently associated with cancer progression (hazard ratio,1.99; 95% CI, 1.44-2.75) and worse 10-year bladder cancer–specific survival (87% vs 94%). The higher costs came specifically from outpatient care, pharmacy, and surgery-related costs during progression. In an integrated health care system, these findings highlight the importance of adherence to guideline-directed risk stratification and treatment along with a focus on progression as an important cancer-specific end point to curtail.

In a recent VHA study, Caputo et al6 evaluated the treatment of 121 patients with newly diagnosed NMIBC from January 2016 through January 2017 and found that repeated TURBT was performed in only 56% of patients with high-risk NMIBC (n = 68), 66% received induction intravesical therapy, and 56% of responders received maintenance BCG therapy. The use of induction BCG is lower but use of maintenance therapy among responders is higher compared with the findings by Williams et al.5 The American Urology Association guidelines recommend repeated TURBT within 6 weeks of the initial resection for all high-risk tumors followed by induction BCG therapy to lower the risk of recurrence and progression.2 In a non-VHA population, approximately 50% of patients with high-risk NMIBC are estimated to receive induction BCG therapy.7 Using Markov models, Mossannen et al3 simulated the 5-year costs of surveillance for NMIBC among all risk categories. In agreement with the findings of Williams et al,5 they noted that the primary driver of costs was progression to muscle-invasive disease requiring definitive therapy, which accounted for 92% of the overall cost for high-risk disease. The financial tradeoff of novel treatments for BCG-refractory disease, such as pembrolizumab8 and nadofaragene firadenovec,9 will need to be studied, because these treatments decrease the risk of progression in only a subset of patients.

In summary, the findings from Williams et al5 and others emphasize the importance of initiatives to improve guideline-directed quality of care across different health care delivery settings. Important initiatives for high-risk NMIBC include assessments of quality and use of initial and second TURBT, quantification of barriers to use of and adherence to induction and maintenance BCG therapy, and improvement of use of radical cystectomy for appropriately selected patients. These initiatives will help decrease disease progression among this patient population and ultimately help curtail costs. Furthermore, initiatives to improve smoking cessation rates and use of prehabilitation around the time of radical cystectomy may help decrease the costs associated with disease recurrences and perioperative complications, respectively.

Back to top
Article Information

Published: March 31, 2021. doi:10.1001/jamanetworkopen.2021.3816

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Sanchez A et al. JAMA Network Open.

Corresponding Author: Neeraj Agarwal, MD, Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah (NCI-CCC), 2000 Circle of Hope Dr, Ste 5726, Salt Lake City, UT 84112 (neeraj.agarwal@hci.utah.edu).

Conflict of Interest Disclosures: Dr Agarwal reported consulting for Astellas Pharma Inc, AstraZeneca, AVEO Pharmaceuticals, Inc, Bayer AG, Bristol-Myers Squibb Company, Calithera Biosciences, Inc, Clovis Oncology, Eisai Co, Ltd, Lilly, EMD Serono, Exelixis, Inc, Foundation Medicine, Inc, Genentech, Inc, Janssen Pharmaceuticals, Inc, Merck & Co, Inc, MEI Pharma Inc, Nektar, Novartis AG, Pfizer Inc, Pharmacyclics LLC, and Seagen Inc. No other disclosures were reported.

Svatek  RS, Hollenbeck  BK, Holmäng  S,  et al.  The economics of bladder cancer: costs and considerations of caring for this disease.   Eur Urol. 2014;66(2):253-262. doi:10.1016/j.eururo.2014.01.006 PubMedGoogle ScholarCrossref
Chang  SS, Boorjian  SA, Chou  R,  et al.  Diagnosis and treatment of non–muscle invasive bladder cancer: AUA/SUO guideline.   J Urol. 2016;196(4):1021-1029. doi:10.1016/j.juro.2016.06.049 PubMedGoogle ScholarCrossref
Mossanen  M, Wang  Y, Szymaniak  J,  et al.  Evaluating the cost of surveillance for non–muscle-invasive bladder cancer: an analysis based on risk categories.   World J Urol. 2019;37(10):2059-2065. doi:10.1007/s00345-018-2550-x PubMedGoogle ScholarCrossref
Ehlers  M, Bjurlin  M, Gore  J,  et al.  A national cross-sectional survey of financial toxicity among bladder cancer patients.   Urol Oncol. 2021;39(1):76.e1-76.e7. doi:10.1016/j.urolonc.2020.09.030 PubMedGoogle ScholarCrossref
Williams  SB, Howard  LE, Foster  ML,  et al.  Estimated costs and long-term outcomes of patients with high-risk non–muscle-invasive bladder cancer treated with bacillus Calmette-Guérin in the Veterans Affairs Health System.   JAMA Netw Open. 2021;4(3):e213800. doi:10.1001/jamanetworkopen.2021.3800Google Scholar
Caputo  JM, Moran  G, Muller  B, Keller  AT, Li  G, Anderson  CB.  The management of newly-diagnosed non–muscle invasive bladder cancer in Veterans Integrated Services Network 02 of the Veterans Health Administration.   Mil Med. 2020;185(1-2):276-281. doi:10.1093/milmed/usz166PubMedGoogle Scholar
Witjes  JA, Palou  J, Soloway  M,  et al.  Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guérin (BCG): results of an international individual patient data survey (IPDS).   BJU Int. 2013;112(6):742-750. doi:10.1111/bju.12012PubMedGoogle ScholarCrossref
Gill  J, Prasad  V.  Pembrolizumab for non–muscle-invasive bladder cancer—a costly therapy in search of evidence.  Published online December 30, 2020.  JAMA Oncol. doi:10.1001/jamaoncol.2020.6142PubMedGoogle Scholar
Boorjian  SA, Alemozaffar  M, Konety  BR,  et al.  Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non–muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.   Lancet Oncol. 2021;22(1):107-117. doi:10.1016/S1470-2045(20)30540-4 PubMedGoogle ScholarCrossref