Bladder Cancer

What are the unmet needs in bladder cancer treatment?

The treatment of bladder cancer has transformed in recent years, however there remains a need for more novel, effective treatment options with safer toxicity profiles, tailored therapies, and strategies to combat treatment resistance^1,2.

Variations in treatment response across clinical trial and real-world data highlights the need to tailor the therapeutic approach to each individual patient¹. Advances in genomic and precision medicine are showing promise to identify molecular subtypes and novel biomarkers associated with better treatment response, with an aim to optimise patient selection for specific treatments¹. Potential indicators of bladder cancer treatment response have been identified for immune checkpoint inhibitors and targeted kinase inhibitors, and efforts continue to evolve in this space^1,3.

As many patients with bladder cancer develop treatment resistance over time, there remains a need for innovative treatment approaches for bladder cancer which can target evolving vulnerabilities^1,4. Ongoing efforts to develop a wider range of innovative treatment options as well as combination therapies targeting distinct mechanisms of action may be promising strategies to improve outcomes in bladder cancer and minimise treatment resistance^1,4.

How common is bladder cancer?

Bladder cancer was the 10th most often-detected cancer worldwide in 2020, and while worldwide statistics differ, it is more prevalent in highly developed societies such as Western and Southern Europe and North America^4,5. Approximately 90% of bladder cancer cases are urothelial carcinoma, with squamous cell carcinoma, sarcomas and metastasis of other neoplasms accounting for the remainder⁴. Over 90% of bladder cancer diagnoses are established in people aged over 55 years⁶, and the mean age of onset is 73 years in the US⁴. The 5-year survival rate for bladder cancer is about 96%, however this decreases to less than 5% for those with metastatic disease⁶.

What are the risk factors for bladder cancer?

The main risk factors for bladder cancer include tobacco smoking, exposure to chemicals such as arsenic and aromatic amines, family history and male sex^4,6. Tobacco smoking is considered a particularly important risk factor due to its prevalence worldwide, and has been associated with bladder cancer at an earlier age⁴. Bladder cancer is around 4 times more common in males than females⁶.

What are the treatment options for bladder cancer?

The overall treatment approach is informed by whether bladder cancer is non-muscle invasive or muscle invasive and the clinical stage⁴. Treatment options for bladder cancer include transurethral resection of the bladder tumour, surgery (radical cystectomy), chemotherapy, radiation and bacillus Calmette-Guérin therapy^4,7-9. In recent years, the treatment landscape in urothelial carcinoma has evolved to include more specific treatments such as immune checkpoint inhibitors, as well as targeted treatments and antibody-drug conjugates⁹.

What are the targeted treatments for bladder cancer?

Targeted treatments for bladder cancer include tyrosine kinase inhibitors such as fibroblast growth factor receptor (FGFR) inhibitors, and angiogenesis inhibitors which target the epidermal growth factors receptor families, as well as antibody-drug conjugates^2,9. The pan-FGFR inhibitor erdafitinib was the first FDA-approved targeted therapy for locally advanced or metastatic urothelial carcinoma, indicated for use in patients with susceptible FGFR2/3 alterations following platinum-containing chemotherapy⁹, and other FGFR inhibitors are in clinical development^4,9,10. The antibody-drug conjugate enfortumab vedotin has also been FDA-approved for patients with locally advanced or metastatic urothelial carcinoma who have progressed despite treatment with platinum chemotherapy and immunotherapy, or those who are platinum-ineligible after ≥1 prior lines of therapy^9,11. However, both of these targeted treatments are not currently approved in Europe⁹.

Targeted treatments have changed the treatment paradigm in bladder cancer¹, with a renewed interest in using relevant targets to guide individualised treatment selection in patients with urothelial carcinoma¹²; however, treatment resistance remains a challenge1. Research continues into development of further targeted treatments for bladder cancer, combination treatments, and identification of actionable targets to guide further developments in precision medicine to optimise and improve treatment response in patients with urothelial carcinoma^1,3,4.

References

1. Zhou Z, Li M. Targeted therapies for cancer. BMC Medicine. 2022;20(1):90.
2. Scholtes M, Akbarzadeh M, Zwarthoff E, Boormans J, Mahmoudi T, Zuiverloon T. Targeted Therapy in Metastatic Bladder Cancer: Present Status and Future Directions. Applied Sciences. 2020;10(20):7102.
3. Guercio BJ, Iyer G, Rosenberg JE. Developing Precision Medicine for Bladder Cancer. Hematol Oncol Clin North Am. 2021;35(3):633-653.
4. Szklener K, Chmiel P, Michalski A, Mańdziuk S. New Directions and Challenges in Targeted Therapies of Advanced Bladder Cancer: The Role of FGFR Inhibitors. Cancers (Basel). 2022;14(6).
5. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021;71(3):209-249.
6. Maiorano BA, De Giorgi U, Ciardiello D, Schinzari G, Cisternino A, Tortora G, et al. Immune-Checkpoint Inhibitors in Advanced Bladder Cancer: Seize the Day. Biomedicines. 2022;10(2).
7. Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, Dominguez Escrig JL, et al. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). Eur Urol. 2022;81(1):75-94.
8. Amaro F, Carvalho M, Bastos MdL, Guedes de Pinho P, Pinto J. Pharmacometabolomics Applied to Personalized Medicine in Urological Cancers. Pharmaceuticals. 2022;15(3):295.
9. Cathomas R, Lorch A, Bruins HM, Compérat EM, Cowan NC, Efstathiou JA, et al. The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma. European Urology. 2022;81(1):95-103.
10. US Food and Drug Administration. Balversa® (erdafitinib) tablets - Full Prescribing Information. Janssen-Cilag SpA; Revised April 2020 2020. Available at: https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/BALVERSA-pi.pdf. Accessed 22 April 2022.
11. US Food and Drug Administration. Padcev®(enfortumab vedotin-eifg) - Full Prescribing Information Astellas Pharma US Inc; Revised July 2021 2021. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761137s006s008lbl.pdf. Accessed 22 April 2022.
12.  Katsila T, Liontos M, Patrinos GP, Bamias A, Kardamakis D. The new age of -omics in urothelial cancer - re-wording its diagnosis and treatment. eBioMedicine. 2018;28:43-50.