Abstract and Introduction
Treatment recommendations for all stages of bladder cancer have been proposed in the form of clinical guidelines from the European Association of Urology and the American Urological Association. However, the therapeutic considerations, especially when dealing with elderly patients with limited functional status and associated comorbidities, may be much more complex. This retrospective study reviewed the records of 206 patients aged over 75 years with bladder cancer and compared their subsequent treatment with established European Association of Urology and American Urological Association guidelines to see if their actual treatment was concordant or discordant with the published recommendations. Overall guideline concordance was relatively high (88.8%) at this tertiary referral institution. While treatment of muscle-invasive bladder cancer in the elderly can be performed in accordance with accepted guidelines, the margin of error is greatly reduced and proper patient selection and attention to detail is critical to ensure a favorable outcome. Further research is needed to more objectively distinguish patients who may benefit from aggressive cancer therapy from those with serious competing risks who would probably die from other causes.
This article reviews the recent report from Bolenz and colleagues regarding the management of bladder urothelial carcinoma in the elderly. With advances in medical care, life expectancy continues to increase, with the percentage of persons aged 85 years or older estimated to more than double by the year 2050. Bladder cancer is primarily a disease of the elderly with the peak incidence occurring at 85 years. With current estimates of approximately 70,530 new cases of bladder cancer being diagnosed in the US per year and 14,680 deaths attributed to the disease, bladder cancer will probably be a major public health problem as the population continues to age.
Treatment recommendations for all stages of bladder cancer have been proposed in the form of clinical guidelines from the European Association of Urology[4,5] and the American Urological Association. Although these guideline recommendations provide a relatively straightforward evidence-based rationale for treatments, the actual practice and therapeutic considerations are much more complex. Nowhere is this more clearly demonstrated than in the treatment of the elderly patient with muscle-invasive bladder cancer (MIBC), where the clinician must account for various patient factors (e.g., comorbidities, quality-of-life concerns/expectations and functional limitations), as well as treatment-related factors (e.g., surgeon experience and availability of medical support staff and services).
Although the term 'elderly' refers to advanced chronological age, perhaps the more important factors in determining treatment decisions are the functional status and associated comorbidities of the individual patient. Clearly, there is an association between age and accumulation of various comorbidities and resulting frailty (either perceived or real). Chronic pulmonary disease represents a common coexisting condition since the majority of bladder cancer patients are previous or current smokers. Chronic diseases, such as coronary artery disease, diabetes and hypertension, increase with age. The exact percentage of bladder cancer patients presenting with comorbidities varies widely in the literature. Among patients presenting with MIBC, 43% were reported to have comorbidities in a recent Danish population-based cohort study. Over an 11-year period, there was a notable increase in the number of patients with a Charlson Comorbidity Index (CCI) score of more than 3. Miller et al. also reviewed their experience with radical cystectomy patients and using the CCI found that 47% of their patients had some degree of comorbidity (CCI score ≥1), and 24% had a score of 2 or above. CCI score was a strong independent predictor of disease-specific survival in their study. Although these results were not stratified by age, it does highlight the fact that patients undergoing treatment for bladder cancer often have other significant complicating health issues. Utilizing the Surveillance, Epidemiology, and End Results database, Prout et al. found that more than 20% of the patients carried significant comorbidity in the form of hypertension and heart disease, and the American Society of Anesthesiologists physical status score also increased with age, indicating worse overall status.
Radical cystectomy with pelvic lymphadenectomy and urinary diversion remains the standard treatment for clinically-localized MIBC, as well as high-risk nonmuscle-invasive disease and select patients with locally advanced bladder cancer. The procedure has evolved to include wider resection margins and extended lymph node dissections as a result of an appreciation for the aggressive nature of the disease. The associated short-term and long-term morbidity of the surgery can be formidable even in otherwise healthy patients. A comprehensive multi-institutional collaborative review noted complication rates in the elderly of up to 50% or greater. A retrospective review of 283 cystectomy patients by Svatek et al. found that the incidence of any adverse event was approximately 50%; however, on further analysis, age was not associated with the rate of complications. Nontheless, these relatively high morbidity rates are likely to temper the enthusiasm for radical cystectomy in elderly patients despite clear clinical indications.[12–14]
Conservative bladder-sparing approaches are often considered in patients felt to to have high surgical risk, regardless of their age. A review of octogenarians undergoing organ-sparing treatment for bladder cancer demonstrated a significantly worse overall and cancer-specific survival in patients with pT2 disease. Two reports utilizing SEER registry data demonstrated that elderly patients were more likely to undergo bladder-preserving therapies for MIBC. The decision to undertake a less aggressive and effective therapy must be one based on a thorough discussion with the patient and should be individualized based on operative risk assessment and treatment goals.
Several retrospective series have demonstrated acceptable clinical outcomes for radical cystectomy in the elderly. Chang et al. reviewed their experience with 44 patients with MIBC who underwent cystectomy, all of whom were at least 75 years of age, and had an American Society of Anesthesiologists score of 3 or greater. Two patients had major complications, ten had minor complications, and there were no postoperative deaths, suggesting an acceptable risk of morbidity/mortality in this population. Additional reviews have not demonstrated any consistently increased perioperative risk of mortality and morbidity solely on the basis of age. A review of 106 cystectomy patients did not find an independent association between age and perioperative morbidity or mortality; however, preoperative comorbidity was a predictor of postoperative complications. Other studies have also suggested that preoperative comorbidity, rather than age, is the most important predictor for perioperative morbidity.[8,19–21]
Even with recent advances in minimally invasive and robotic-assisted techniques, radical cystectomy with urinary diversion remains a major surgical undertaking with associated risks of metabolic, physiologic and psychologic alterations in both the short- and long-term. While previous reports have suggested acceptable outcomes in the elderly, it must be kept in mind that these represent highly select patients (felt to be acceptable surgical candidates) being treated at high volume tertiary referral centers. This is highlighted by the fact that population-based reports show a much lower utilization of radical cystectomy in this patient population.[9,13,16,22] In the report from Bolenz et al., this exact issue of concordance with established treatment guidelines in elderly patients was investigated. They retrospectively reviewed the records of 206 consecutive patients aged over 75 years with biopsy-proven bladder cancer and compared their subsequent treatment with the established European Association of Urology (EAU) and American Urological Association (AUA) guideline recommendations. The actual treatment patterns for these patients (focusing on utilization of perioperative intravesical chemotherapy, restaging transurethral resections, and timely use of cystectomy and/or systemic chemotherapy when indicated) were then scored as concordant or discordant with the published guidelines. Median follow-up was 14.7 months and overall survival was the main study end point. The prognostic significance of clinicopathologic variables, including various comorbidity risk scores, and treatment pattern concordance on overall survival were then determined by multivariable regression analysis. They reported that of the 99 patients aged over 75 years who met the criteria for cystectomy, 87 patients were treated with curative intent with either cystectomy or definitive chemoradiation. This simply demonstrates that properly selected elderly patients with MIBC are often referred to high-volume academic centers for surgical management.
Radical cystectomy can be associated with a formidable recovery process even for young and otherwise healthy individuals. For elderly patients who often have preexisting comorbid conditions there is little room for error. Attention to detail is absolutely critical to ensure acceptable perioperative outcomes. Even minor complications can lead to a 'slippery slope' of further related morbidity in patients with preexisting limited functional reserve.
Aging Health. 2010;6(5):607-610. © 2010 Future Medicine Ltd.
Cite this: Management of Bladder Cancer in the Elderly - Medscape - Oct 01, 2010.