Managing bladder cancer in the elderly
‘At the present point, only about half of all MIBC patients are in a position to be fully cured of their cancer 5 years after diagnosis.’ Dr Anne E Kiltie, Associate Professor, Department of Oncology, University of Oxford, details the management of bladder cancer in the elderly and explains why there is an urgent need to improve current treatment strategies
Bladder cancer is the 4th most common cancer in UK males (14th in females), with 10,341 new cases diagnosed in 2013 and 5,242 deaths in 2012. (1) Three-quarters of patients are men and more than half are over 75 years of age. Around a quarter of patients with the disease suffer from bladder cancer that has invaded the muscle wall. Other patients present initially with the superficial disease confined to the lining of the bladder, but this can progress to muscle-invasive bladder cancer (MIBC) in a proportion of patients. Logically speaking, up to one third of all patients may have muscle-invasive disease at some point.
At the present point, only about half of all MIBC patients are in a position to be fully cured of their cancer 5 years after diagnosis, so there is an urgent need to improve on current treatment strategies. In Europe, the ‘gold standard’ treatment for MIBC is removal of the bladder and adjacent organs (prostate in men, uterus, ovaries and anterior vaginal wall in women) and lymph nodes. However, there has been a long history of use of radiotherapy for treatment of bladder cancer in the United Kingdom. Results appear similar from both approaches; although there has been no successful randomised controlled comparison between the two, as patients often die of metastases, when the disease spreads to other parts of the body (including lungs, bones, brain). Patients who are fit enough and with adequate kidney function are also offered a short course of cisplatin-based chemotherapy before their definitive treatment, which improves the survival rates by 5%.
More recently the use of ‘chemoradiation’ has become a standard of care, where radiotherapy is accompanied by the use of drugs which make the radiation more effective. Chemoradiation is more effective at killing tumour cells than radiation alone, but this may be at the expense of causing increased side effects to the local normal tissues, including the bladder and the adjacent bowel and rectum which inevitably receive some radiation dosage from the treatment fields.
The median age of patients treated with radical radiotherapy, where the treatment intention is to cure the patient rather than just provide symptom relief, in our joint uro-oncology clinic over the past five years was 81 years, which seems quite elderly. However, an 81 year old man in the UK is currently expected to live an additional 7.7 years and an 81 year old woman 9.0 years, so these patients would have been expected to live to nearly 90 years old had they not developed muscle-invasive bladder cancer. (2) A rather shocking statistic is that competing mortality only accounts for one-third of deaths in patients with MIBC over the age of 80 years. (3) This means that two-thirds of these patients are dying of their bladder cancer rather than another cause, reflecting the low numbers receiving radical treatment (12% vs 52% of under 60 year olds).
Patients in their 80s can be treated by cystectomy but in this age group the mortality rate from the operation rises sharply from the 3% expected in younger patients. The median age at cystectomy is 68 years and only a small number of procedures are carried out in the UK over the age of 80 years. (4) This means that such patients are often offered radiotherapy treatment if they are considered radically treatable, and such treatment is well tolerated in patients of this age group.
However, the 2015 National Institute for Health and Clinical Excellence bladder cancer guidelines (5) recommend that patients are offered radiotherapy with a radiosensitiser rather than radiotherapy alone when radical therapy is suitable. Unfortunately, patients over the age of 75 years generally do not have adequate renal function to receive cisplatin-based chemotherapy and the median age of patients in the two recent randomised trials of non-cisplatin radiosensitisers, namely BCON (6) and BC2001 (7), were 74 years (oldest 90 years) and 71.9 years (oldest 76.2 years) respectively. Therefore, clinical trials do not address the issue of treatment of the elderly directly.
There is an urgent clinical need to find radiosensitising treatments that are suitable for elderly patients, so that they can also receive the current standard of care. These should be easy to administer with minimal toxicity to the normal tissues, whilst improving tumour control. It is unlikely that we will be able to find an effective agent that confers no additional toxicity, so it is also important to identify biomarkers, either in the patient’s blood or within their tumour that could identify individuals most likely to benefit from adding a radiosensitiser. Biomarkers should also identify those patients who are unlikely to benefit, so that they can avoid the additional potentially harmful treatment and receive radiotherapy alone.
In an era where the population is aging but people in their 80s have a good quality of life and life expectancy, it is important to find suitable radiosensitising agents to add to their bladder cancer radical radiotherapy treatment, so that this cohort of patients can receive standard of care and treatment similar to their younger counterparts
Anne is also Honorary Consultant Clinical Oncologist, Oxford University Hospitals NHS Foundation Trust.
1. Bladder Cancer Statistics, Cancer Research UK
3. Br J Cancer (2003) 108:1534-40.
4. Luke Hounsome, Predictors of use of orthotopic bladder reconstruction after radical cystectomy for bladder cancer, National Cancer Intelligence Network, 2011
5. Bladder cancer: diagnosis and management, National Institute for Health and Care Excellence, 2015
6. J Clin Oncol (2010) 28:4912-8
7. New Engl J Med (2012) 366:1477-88