Bladder cancer: new advances in management

Bladder cancer is the fifth most common cancer across Europe and in the UK, there are over 10,000 new cases each year.¹ It is mostly diagnosed in patients over the age of 55 years with the average age at diagnosis currently 73 years.² However, treatment options are limited, and survival rates are poor.

The five-year survival rate for bladder cancers diagnosed in Europe is around 68% and over 65,000 patients died from it in 2018 alone.^1,2

Urothelial carcinoma is the most common type of bladder cancer, accounting for 90% of all cases.³ Yet, between 15% and 18% of bladder cancer cases are diagnosed as advanced or metastatic and survival is extremely poor at this stage with only 5% of patients with metastatic disease living longer than five years.⁴

In recent years, however, there have been a number of new advances in bladder cancer research with the aim of providing pioneering targeted treatments to patients that could improve quality of life and disease outcomes.

Diagnosis of bladder cancer

The good news, according to Dr Joaquan Casariego, Therapeutic Area Lead for Oncology at Janssen EMEA, is that bladder cancer says hello in a clear way. Common symptoms include a burning sensation when passing urine, sudden urges to urinate, and unintentional weight loss.

He adds if any patient presents to primary care with these symptoms then they should be further investigated, especially in men as bladder cancer is five times more common in men than it is in women.³

In advanced metastatic bladder cancer symptoms are usually more severe and include pelvic pain, blood in the urine, bone pain and a need to urinate on a more frequent basis.

“It is important to catch the disease in the early stages when the prognosis of patients is so much better,” he says. “The prognosis varies significantly across the range of disease stages. Around 5% of patients are diagnosed when the cancer has spread to other parts of the body, such as other organs. Only around one in 10 people will survive their disease for five years or more when the disease is diagnosed at the latest stage.

“With approximately 151,000 new cases diagnosed each year in Europe, there is critical and urgent need for us to find new, innovative solutions that can address the poor clinical outcomes faced by these patients.”

Risk factors for bladder cancer

In addition to age, smoking is the single biggest risk factor associated with bladder cancer,¹ accounting for an estimated 40-70% of all cases, according to Dr Casariego. Other risk factors include exposure to certain industrial chemicals (accounting for around 25% of cases) as well as radiotherapy, previous treatment with certain chemotherapies, having diabetes, having an indwelling catheter, long-term urinary tract infections, bladder stones, early menopause and schistosomiasis.

Treatment of bladder cancer

Dr Casariego says treatment depends on the stage of cancer and a high unmet need still remains for most patients in the advanced stages.

In some cases, if it is caught early enough, bladder cancer can be treated with surgery alone. Transurethral resection of bladder tumor (TURBT) is the most common treatment for early-stage or superficial (non-muscle invasive) bladder cancers and the goal is to take out the cancer cells and nearby tissues down to the muscle layer of the bladder wall. For intermediate-risk patients, this may be followed by chemotherapy and/or immunotherapy.

Platinum-based chemotherapy is currently the first-line standard of care for eligible patients with advanced disease based on high initial response rates. However, most patients will ultimately experience disease progression within nine months of initiation of treatment.^5,6

For high-risk patients, intravesical adjuvant therapy is advised and/or, in select cases, removal of the bladder, which can have a major impact on quality of life.

New developments on the horizon

“As a company we are committed to advancing treatments for our patients that also push us towards early interception of bladder cancer”, says Dr Casariego. “Last year we acquired a clinical-stage product, which uses a silicone-based drug delivery device that allows for the continuous release of medication into the bladder.

“We are also directing our research and clinical trials towards targeted therapy. This is a new era of testing biomarkers and personalised medicine. The role of biomarkers is very well established in oncology and if we identify which pathway is leading the growth of a tumour, we can aim to stop or delay disease progression.”

He says that research have shown that there are genetic conditions underlying the cancer itself and in over half of bladder cancers specific alterations can be identified that serve as predictive biomarkers.

“The growth of big data helps because we have thousands of patients in very different sub populations with many different genome biomarkers,” he says. “If we can select out those patients that are likely to have a best clinical outcomes from targeted treatments then this opens up a new world for cancer treatment.”

One area of interest in bladder cancer is fibroblast growth factor receptor (FGFR) genes as they are linked to tumour growth and metastasis. Research has found that 20% of patients with bladder cancer have alterations to FGFR genes.⁷ Dr Casariego believes that treatments that specifically target FGFR alterations may serve a current unmet need in bladder cancer making this a potential area for oncologists and urologist to focus on for treatment options.

He added: “In the future, hopefully patients will have genome testing in primary care so we can provide the best treatments with the best outcomes at the right time. We are investing in research for innovative treatment options to improve patient quality of life and outcomes, particularly at the advanced stage of the disease when the cancer is most aggressive.”

References

European Cancer Patient Coalition White Paper on Bladder Cancer 2016. Available at: https://ecpc.org/wp-content/uploads/2019/08/. Accessed May 2020
Bellmunt J, Orsola A, Leow JJ, et al. Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25 Suppl 3:iii40-8.
net. Bladder cancer introduction. Available at: https://www.cancer.net/cancer-types/bladder-cancer/view-all. Accessed May 2020.
Queen’s University Belfast. Cancer incidence, prevalence and survival statistics for Northern Ireland: 1993-2017. Bladder cancer (C67), 2019.
Bukhari N, et al. Update on the treatment of metastatic urothelial carcinoma. Scientific World Journal. 2018;2018:5682078.
Von der Maase H, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. Journal of Clinical Oncology. 2005;23(21):4602-4608
Loriot, Y. et al. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2019; 381: 338-348