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Outcomes of Radiosensitisation in Elderly Patients with Advanced Bladder Cancer – Beyond the Abstract

Bladder cancer is a disease of the elderly with 55% of new cases in the United Kingdom diagnosed in patients that are ≥75 years old.1 The disease burden of bladder cancer is likely to increase given our aging population. There is a lack of evidence to guide treatment decisions in older patients with bladder cancer. Elderly patients are under-represented in clinical trials and are therefore potentially undertreated in routine clinical practice compared to their younger counterparts.2-4 Insufficient evidence for treatment efficacy and fears for worse toxicity in a population with a higher co-morbidity burden are common reasons for a more conservative treatment approach in older patients. Traditionally, muscle-invasive bladder cancer, which represents a third of bladder cancer diagnoses and is associated with poor prognosis, has been treated with radical cystectomy and pelvic node dissection.5-7 More recent guidance recommends bladder preservation strategies as an equally effective option to surgical treatment, especially for less fit patients.8-9 Bladder preservation describes the combination of transurethral resection of the bladder tumour and radiotherapy with concurrent radiosensitisation.

In this article, we show similar survival and toxicity outcomes in patients with muscle-invasive bladder cancer older than 75 years who received bladder-sparing treatment with gemcitabine radiosensitisation (GemX protocol) compared to their younger counterparts.10 In a separate, age-specific analysis of the Bladder Carbogen and Nicotinamide (BCON) trial, we demonstrate comparable toxicity and local progression-free survival in older patients who received CON radiosensitisation compared to younger patients. Outcomes between GemX and CON in older patients were also found to be comparable. We conclude that radiosensitisation with either GemX or BCON is effective and well tolerated in older patients with a low co-morbidity burden.

In our study, age had some prognostic power in overall survival, but not in progression-free survival, disease specific-survival or local progression-free survival.10 Indeed, the prognostic significance of age has been debated in more recent years and the definition of an “elderly” person remains controversial.11 There is a paradigm shift to factor functional or biological rather than chronological age in treatment decision-making as it is thought to more accurately reflect physiological and pathological processes.11-13 Tools such as the Comprehensive Geriatric Assessment involve a multi-disciplinary, holistic evaluation of frailty in older patients and have been shown to predict morbidity and mortality in cancer.14,15 However, challenges associated with the practical application of these tools such as the time required for completion and the need for dedicated, specifically-trained teams in clinics have limited their routine use.14-15

Currently, decision making relies on clinical acumen based on limited high-level evidence and clinician experience. Older patients are expected to have more co-morbidities, including worse renal function, and have demonstrated worse compliance to chemotherapy as part of radiosensitisation and neo-adjuvant chemotherapy compared to younger patients in this study.10 It is therefore paramount that older patients who are given radiosensitisation with or without neo-adjuvant chemotherapy are very carefully selected. We hope that the results of our study will contribute to evidence supporting the use of radiosensitisation in fit, older patients and encourage its use by more clinicians. Future work should focus on assessing the feasibility and effectiveness of introducing tools such as the Comprehensive Geriatric Assessment in clinical practice and clinician education on the evaluation of frailty and patient selection. 

References:

  1. Bladder cancer incidence statistics. Cancer Research UK. Available from:  [Accessed 24.07.18].
  2. Noon AP, Albertsen PC, Thomas F, et al. Competing for mortality in patients diagnosed with bladder cancer: evidence of undertreatment in the elderly and female patients. Br J Cancer 2013;108:1534-1540.
  3. Shenoy P, Harugeri A. Elderly patients’ participation in clinical trials. Perspect Clin Res 2015;6(4):184-189.
  4. Talarico L, Chen G, Pazdur R. Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol 2004;22(22):4626-4631.
  5. Witjes AJ, Compérat E, Cowan NC, et al. EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer 2013.  [Accessed 24.07.18].
  6. Rodel C, Grabenbauer GG, Kuhn R, et al. Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol 2002;20(14):3061-3071.
  7. Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 2001;19:666-675. 
  8. Witjes AJ, Compérat E, Cowan NC, et al. EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer 2015. [Accessed 04.10.16].
  9. National Institute for Health and Clinical Excellence. Bladder cancer: diagnosis and management (February 2015). [Accessed 24.07.18].
  10. Christodoulou M, Reeves KJ, Hodgson C, et al. Outcomes of radiosensitization in elderly patients with advanced bladder cancer. Radiother Oncol 2018. doi: 10.1016/j.radonc.2018.05.022. [Epub ahead of print].
  11. Weizer AZ, Palella GV, Montgomery JS. Managing muscle-invasive bladder cancer in the elderly. Expert Rev Anticancer Ther 2010;10(6):903-915.
  12. Crews DE, Zavotka S. Aging, disability, and frailty: implications for universal design. J Physiol Anthropol 2006;25(1):113–118.
  13. Shariat SF, Karakiewicz PI, Palapattu GS, et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J Urol 2006;176:2414-2422.
  14. Extermann M, Hurria A: Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol 2007;25:1824-1831.
  15. Puts MTE, Santos B, Hardt J, et al. An update on a systematic review of the use of geriatric assessment for older adults in oncology. Ann Oncol 2014;25:307-315.
Written by: Marianna Christodoulou1 and Ananya Choudhury1,2*
1. Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester Academic Health Science Centre
2. Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre

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