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Patterns of Treatment of High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC) Patients Among Arab Urologists - Beyond the Abstract

Bladder cancer ranks as the tenth most frequent type of cancer and has a substantial impact on global healthcare systems.1 It is highly prevalent in Arab countries, with an estimated age-standardized incidence rate of 9.9/100,000.2 The management of non-muscle invasive bladder cancer (NMIBC) has been especially challenging recently due to BCG shortages, with little guidance provided to practicing urologists on alternative treatments.

The situation has been further compounded by the recognition of BCG unresponsive cases who are unfit for radical cystectomy (RC) or who refuse to undergo such a morbid procedure.3-5 One of the most promising emerging therapies in this setting is intravesical sequential doublet chemotherapy (SDC): gemcitabine/docetaxel (Gem/Doce) or gemcitabine/mitomycin C (Gem/MMC).6,7 For high-risk BCG-naïve patients, Gem/Doce provides a recurrence-free survival (RFS) rate at 24 months of nearly 80%, making it an excellent alternative to BCG. For BCG failures, both Gem/Doce and Gem/MMC rescue about 40% of high-risk cases with minimal toxicity at 2 years. Furthermore, the low cost of these widely available generic drugs makes SDC an affordable and tolerable alternative to other costly novel treatments under development.

As the incidence of bladder cancer increases worldwide, clinical surveys become a necessary tool to understand the practice patterns of urologists in order to optimize cost-effective therapy. Our group has previously administered a survey in the US to depict the current management of BCG unresponsive disease.9 Using a similar design, we worked with the Arab Association of Urology (AAU) to administer a similar survey in order to gather information regarding the treatments and choices available to NMIBC patients failing BCG therapy.10 This survey was sent by email to urologists who were listed in the AAU database. Between October 17, 2023, and November 17, 2023, responses were collected from 22 Arab countries from a total of 106 participating urologists.10

Certain significant findings from the survey are worthy of special attention. Firstly, 68% of Arab urologists reported experiencing BCG shortages, suggesting these are a persistent issue in Arab countries, which replicates the situation in many regions of the world. This should serve as a warning that BCG alternatives are needed to ensure optimal patient care.

Regarding the BCG failure situation, half of the Arab urologists selected RC as the most favored initial therapy for high-risk BCG-unresponsive cases. This was in contrast with surveys assessing urologist practice in other countries. Merely 24% of US urologists who participated in a recent similar survey (a total of 259 urologists) regularly recommend RC for these patients.9 Moreover, only 30% of Arab urologists used intravesical chemotherapy as the primary treatment for BCG-unresponsive disease while in regions like the US, Europe, and eastern Asia, intravesical chemotherapy has been used to manage up to 50% of BCG-unresponsive cases.9,11 The preferred choice of intravesical chemotherapy drugs also differed by region. Arab urologists most commonly employed single-agent Gem or MMC therapy, accounting for 60% and 19% of the respondents, respectively. In Europe, MMC was favored, whereas Gem, MMC, and Gem/Doce were the most widely used drugs for the same indication in the US (49%, 23%, and 15% of respondents, respectively). By contrast, epirubicin, doxorubicin, and Gem were the most often prescribed intravesical medications in China accounting for 37%, 34%, and 26% of respondents, respectively.9,11

Interestingly, our survey offers evidence that the nation's economic standing may influence the choice of treatment and outcomes for NMIBC. Urologists in high-income Arab countries were more likely to select intravesical chemotherapy or RC as their preferred course of treatment, whereas urologists from low-middle-income Arab countries were more likely to opt for less successful options such as resection and surveillance or even repeat BCG therapy. However, there is recent evidence that this may be changing as 20% of Arab urologists in low-income countries are starting to use intravesical chemotherapy, and only 2% of these urologists cite drug prices as the main obstacle to use.10 Using a large Scandinavian cancer database, NMIBC patients with higher socioeconomic status were offered additional treatment options and were found to have a higher overall and bladder cancer-specific survival.12 Affordable cost-effective alternative therapies for NMIBC may help improve overall access to equitable care by unburdening the health care system.

Both patients and their urologists should be made aware of alternative therapies such as SDC that provide long-term effective treatment for NMIBC rather than just delaying RC. The ability to choose among multiple options for bladder preservation may go far toward improving patient quality of life.

Written by: Mohamad Abou Chakra, MD,1 Neal D. Shore, MD, FACS,2 & Michael A O'Donnell, MD1


  1. Department of Urology, The University of Iowa Hospitals and Clinics, Iowa City, IA
  2. Carolina Urologic Research Center, Myrtle Beach, SC
References:

  1. Gill E, Perks CM. Mini-Review: Current Bladder Cancer Treatment-The Need for Improvement. Int J Mol Sci. 2024 Jan 26;25(3):1557.
  2. Al Saidi I, Mohamedabugroon A, Sawalha A, Sultan I. Epidemiology of Bladder Cancer in the Arab World: 2019 Global Burden of Disease Data. Asian Pac J Cancer Prev. 2022 Sep 1;23(9):2907-2919.
  3. Jeong SH, Ku JH. Treatment strategies for the Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer. Investig Clin Urol. 2023 Mar;64(2):103-106.
  4. Babjuk M, Burger M, Capoun O, et al. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). Eur Urol. 2022 Jan;81(1):75-94.
  5. 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.
  6. Hannouneh ZA, Hijazi A, Alsaleem AA, et al. Novel immunotherapeutic options for BCG-unresponsive high-risk non-muscle-invasive bladder cancer. Cancer Med. 2023;12(24):21944-21968.
  7. Nazmifar M, Williams C, Naser-Tavakolian A, et al. Clinical and Preclinical Therapies for Bladder Cancer Following Bacillus Calmette-Guérin Failure. J Urol. 2023;209(1):32-48.
  8. Abou Chakra M, Packiam VT, Duquesne I, Peyromaure M, McElree IM, O'Donnell MA. Combination intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) as first-line or rescue therapy: where do we stand now? Expert Opin Pharmacother. 2024:1-12.
  9. Abou Chakra M, Shore ND, Dillon R, O'Donnell MA. US Clinical Practice Patterns of Intravesical Chemotherapy for Bacillus Calmette-Guérin-Unresponsive and Bacillus Calmette-Guérin-Exposed Nonmuscle-Invasive Bladder Cancer. Urol Pract. 2024;11(1):97-107
  10. Moussa M, Abou Chakra M, Shore ND, Papatsoris A, Farahat Y, O'Donnell MA. Patterns of treatment of high-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) patients among Arab urologists. Arch Ital Urol Androl. 2024:12244.
  11. Broughton EI, Gooden KM, Mycock KL, et al. Multi-country clinical practice patterns, including use of biomarkers, among physicians' treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). BMC Urol. 2022;22(1):27.
  12. Russell B, Hemelrijck MV, Gårdmark T, et al. A mediation analysis to explain socio-economic differences in bladder cancer survival. Cancer Med. 2020;9(20):7477-7487.
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