Bladder cancer more commonly afflicts the elderly. Death from bladder cancer increases exponentially once it invades the muscle (MIBC). Treatments for MIBC are complex and multimodal. Approximately six million Americans per year are diagnosed with new-onset dementia and specifically Alzheimer’s disease. the risk of developing dementia following treatment in other cancers requiring multimodal treatment such as muscle-invasive bladder cancer has not been studied before. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database to identify patients diagnosed with clinical stage T2-T4a, N0, M0 transitional or urothelial bladder cancer from January 1, 2002, to December 31, 2011. We restricted our cohort to patients who underwent treatment without Alzheimer’s disease and related dementia diagnosis 12 months prior to bladder cancer treatment.
Of the 4,814 patients, 2,403 (49.9%) underwent radical cystectomy (RC), and 2,411 (50.1%) underwent resiniferatoxin (RTX) and/or cyclophosphamide (CTX). The median duration of follow-up was 712 days. A total of 320 (13.3%) RC patients received neoadjuvant CTX. Overall, 837 (17.4%) patients developed Alzheimer’s disease and related dementia following bladder cancer treatment. Crude incidences of post-treatment Alzheimer’s disease and related dementia in patients who underwent RC versus RTX and/or CTX were 288 and 305 cases per 10,000 person-years, respectively. There was no significant difference in the incidence of Alzheimer’s disease and related dementia following either treatment. Of the associated comorbidities, cerebrovascular stroke, depression, Parkinson’s disease, and psychotic comorbidity were associated with time to first dementia diagnosis with Parkinson’s disease (hazard ratio [HR] 2.20, 95%; 1.30-3.73) having the greatest risk. Patients diagnosed with Alzheimer’s disease and related dementia had worse overall (HR, 2.64; 95% Confidence Interval [CI], 2.41-2.89) and cancer-specific (HR, 2.45; 95% CI, 2.18-2.76) survival than those without a dementia diagnosis following treatment.
The present study is the first to describe the incidence and impact of Alzheimer’s disease and related dementia in MIBC. Moreover, we found no difference according to treatment type which important given concerns of anesthetic risks of surgery and chemotherapy in the elderly. We identified predictors (cerebrovascular stroke, depression, Parkinson’s disease, and psychotic comorbidity) for those especially at increased risk of Alzheimer’s disease and related dementia following treatment in which targeted interventions may be employed perioperatively to improve survival outcomes. Limitations include observational study design and the use of administrative claims data to derive diagnoses that lack causation and may underestimate our findings, respectively. Our findings reinforce the benefit of routine geriatric assessments, including their functional status, physical performance and fall risk, comorbid medical conditions, depression, social activity/support, nutritional status, and cognitive status. Such efforts would align with standard of care recommendations by the American Society of Clinical Oncology.
Written by: Usama Jazzar, BS, and Stephen B. Williams, MD, MS, FACS, Medical Director for High Value Care, UTMB Health System, Chief, Division of Urology, Associate Professor (Tenured), Urology and Radiology, The Robert Earl Cone Professorship, Director of Urologic Oncology, Director of Urologic Research, Co-Director, UTMB Surgical Outcomes Research Program, The University of Texas Medical Branch, Galveston, Texas