It may not have the same level of public awareness as other cancers but there’s no doubting that bladder cancer, of which urothelial carcinoma is the most common form, carries a high burden of disease for patients.[1],[2],[3],[4] In Europe alone, we saw more than 203,000 new diagnoses during 2020 and over 67,000 deaths, contributing to it being the 5th most common cancer. [5],[6] As a continent, this is the second highest incidence in the world.[5]
If identified early enough, the prognosis for patients can be quite good.[6] People diagnosed with localised bladder cancer have a five-year relative survival rate of around 70%.[7] However, once the disease becomes metastatic, spreading beyond the bladder to nearby organs or lymph nodes, the chances of a positive outcome reduce considerably.[6] To the point that only 8% of people will survive for five years or more when it’s diagnosed at a late, metastatic stage.[6]
Hurdles in the early and more advanced stages of the disease
The problem is exacerbated by the fact that common, early-stage symptoms, such as blood in the urine, frequent urination and the persistent urge to urinate are sometimes mistaken for signs of other conditions like urinary tract infections, resulting in delayed diagnosis and delays in referral, especially for women.[6],[8] This gives the cancer more time to develop to an advanced stage, negatively impacting the patient’s likelihood of survival and causing significant declines in mental and physical quality of life due to factors like depression, bodily pain and reduced ability to work standard hours or perform their job.[9],[10]
These factors all contribute to a significant unmet need for advanced stage bladder cancer patients and their families – and a pressing, at times frustrating, challenge for all of us who work in the cancer community.[10] Advanced bladder cancer is a complex disease that affects many people.[11] But early attempts to identify bladder cancer susceptibility genes have proved unsuccessful.[12],[13] Despite a high number of genomic alterations, it’s been extremely challenging to find actionable biomarkers to use in the creation of new treatments.[14],[15]
Yet progress is being made.[3],[14],[16] As I was delighted to attend this month’s American Society of Clinical Oncology (ASCO) annual meeting, I had the opportunity to hear more firsthand about the latest advances in bladder cancer care. Advances that are testament to a combination of hard work in the lab and the potential of precision medicine.
A challenging path in the development of targeted therapies for bladder cancer
Thanks to the Cancer Genome Atlas, researchers were able to look at 33 cancer types and investigate 30 potentially predictive genomic biomarkers for muscle-invasive bladder cancer (MIBC).[14],[17] From these 30, they arrived at five targets showing particular promise for the development of targeted therapies.[14] These are:
- Deregulated fibroblast growth factor (FGF) signaling through alterations of FGF receptor 3 (FGFR3) which contributes to tumorigenesis in multiple cancers, and up to 20% of MIBC[14],[18]
- The tumor suppressor p53 as a marker of poor prognosis in bladder cancer[14]
- Human epidermal growth factor receptor 2 (HER 2)[14]
- Epidermal growth factor receptor (EGFR)[14]
- PIK3CA, which is altered in approximately 20% of cases of MIBC[14]
Continued research into these biomarkers is an important step as the use of precision medicine in bladder cancer continues to evolve.[14] Similar to the way in which the BReast CAncer gene 1/2 (BRCA1/2) genes have been used to identify people at risk of developing breast and ovarian cancers, being able to pinpoint the biomarkers associated with bladder cancer, and its most advanced stages, such as metastatic urothelial carcinoma (mUC), means we can test for them in patients.[14],[19]
Crucially, this opens the door to developing targeted treatments based on the individual biomarkers someone displays.[14] So, if we know from either clinical trial data or real-world evidence that a certain medicine or therapy works best with patients exhibiting a specific biomarker, clinicians can then screen for those with this marker and select treatments accordingly.[14],[15] This reduces time spent on drugs and therapies that don’t work and improves the possibility of success.[16],[20]
In conclusion: the right treatment, to the right patient, at the right time!
Perhaps the best way to sum it up is to use a phrase that we hear quite a lot in relation to an emerging generation of precision medicines across the medical community: right treatment, right patient, right time. After years of painstaking research and development, sometimes with little reward, precision medicine is at last unlocking the possibility of more targeted and, consequently, more effective treatments for advanced bladder cancer patients.[14] It’s, of course, just the beginning. As a community, we should continue to track the latest developments and advances and come together to make them a reality for patients living with bladder cancer.
[1] Cancer.net. Bladder cancer: introduction. Available at: https://www.cancer.net/cancer-types/bladder-cancer/introduction Last accessed: May 2023.
[2] Perlis, N., Krahn, M., Alibhai, S. et al. Conceptualising global health-related quality of life in bladder cancer. Quality of Life Research. 2014;23:2153–2167.
[3] Fradet Y, et al. Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up. Ann Oncol. 2019;30(6):970-976.
[4] European Federation of Pharmaceutical Industries and Associations (2023). Time for more ambition on bladder cancer policy (Guest blog). Available at: https://www.efpia.eu/news-events/the-efpia-view/blog-articles/time-for-more-ambition-on-bladder-cancer-policy/ Accessed June 2023.
[5] Globocan 2020. Europe Cancer Factsheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf Last accessed: May 2023.
[6] World Bladder Cancer Patient Coalition. Understanding bladder cancer impact. Available at: https://worldbladdercancer.org/wp-content/uploads/2022/08/WBCPC-A4-Infographic-v5.pdf. Accessed May 2023.
[7] www.cancer.gov. (2023). Bladder Cancer Prognosis and Survival Rates - NCI. Available at: https://www.cancer.gov/types/bladder/survival. Last accessed: May 2023.
[8] Edmondson AJ, et al. The patients’ experience of a bladder cancer diagnosis: a systematic review of the qualitative evidence. J Cancer Surviv. 2017;11(4):453-461.
[9] Smith AB, et al. Impact of bladder cancer on health-related quality of life. BJUI International. 2018;121(4):549-557
[10] Mohamed NE, et al. Muscle invasive bladder cancer: from diagnosis to survivorship. Adv Urol. 2012;2012: 142135.
[11] Wong VK, et al. Imaging and Management of Bladder Cancer. Cancers (Basel). 2021; 13(6): 1396.
[12] Knowles MA. What we could do now: molecular pathology of bladder cancer. Mol Pathol. 2001 Aug;54(4):215-21.
[13] Gu J, Wu X. Genetic susceptibility to bladder cancer risk and outcome. Per Med. 2011 May;8(3):365-374.
[14] Guercio BJ, et al. Developing Precision Medicine for Bladder Cancer. Hematol Oncol Clin North Am. 2021;35(3):633-653.
[15] Castaneda PR, et al. Identifying novel biomarkers associated with bladder cancer treatment outcomes. Front Oncol. 2023 Mar 29;13:1114203.
[16] European Federation of Pharmaceutical Industries and Associations. Unlocking the potential of precision medicine in Europe – Improving cancer care through broader access to quality biomarker testing: Policy Recommendations. Available at: https://www.efpia.eu/media/589727/unlocking-the-potential-of-precision-medicine-in-europe.pdf. Last accessed May 2023.
[17] CellPress. Welcome to the Pan-Cancer Atlas. Available at: Welcome to the Pan-Cancer Atlas (cell.com). Last accessed: May 2023.
[18] Weickhardt AJ, et al. Dual targeting of FGFR3 and ERBB3 enhances the efficacy of FGFR inhibitors in FGFR fusion-driven bladder cancer. BMC Cancer. 2022;22(478).
[19] Olopade OI, Grushko TA, Nanda R, Huo D. Advances in breast cancer: pathways to personalized medicine. Clin Cancer Res. 2008 Dec 15;14(24):7988-99.
[20] European Federation of Pharmaceutical Industries and Associations. About Medicines: Precision Medicine. Available at: https://www.efpia.eu/about-medicines/development-of-medicines/precision-medicine/#/. Last accessed May 2023.
