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Association Between Metabolic Syndrome and Recurrence of Nonmuscle-Invasive Bladder Cancer in Older Adults - Beyond the Abstract

Two-thirds of new cancers are diagnosed in older adults, who also often have two or more chronic conditions, also known as multiple chronic conditions (MCC).1 Cancer patients and survivors are increasingly older and medically complex, and this impacts the management of both the cancer and other chronic conditions. The interplay between aging, MCC, and cancer is particularly relevant to the burgeoning population of older adults with nonmuscle-invasive bladder cancer (NMIBC). Bladder cancer has the highest median age at diagnosis of all cancer sites (73 years), and the incidence is projected to increase by 54% over the next 10 years.2,3 Prior work from our group has shown that bladder cancer patients have a median of eight co-existing chronic conditions.4 The combination of advanced age and smoking history are risk factors for bladder cancer and also for metabolic syndrome (MetS) and related chronic conditions such as hypertension, hyperlipidemia, diabetes, and obesity.


Over 40 million Americans have MetS which includes the following traits: abdominal obesity, elevated blood pressure, impaired blood sugar, elevated triglycerides, and low high-density lipoprotein.5,6 In addition to the MetS link to cardiovascular disease, abdominal obesity is a pro-inflammatory state that has been identified as a risk factor for cancer.7 Prior studies have suggested an association between MetS and bladder cancer; however, few studies have examined the association between MetS and long-term NMIBC outcomes such as recurrence.8 The objective of our study was to evaluate the association between MetS and recurrence in older adults with NMIBC.9

We examined recurrence outcomes in a large cohort of 1485 older adults (age ≤ 60 years) diagnosed with NMIBC (AJCC stage ≤ 1) from two community-based health systems (Geisinger and Kaiser Permanente Northwest). Patients were diagnosed between 2003-2015 and had a median follow-up time of 5.9 years. We used cancer registry data to identify NMIBC patients and conducted an extensive chart review of pathology reports to confirm stage and grade for initial diagnosis and all subsequent recurrences. 

We defined MetS as the presence of three of the following: hypertension, hyperlipidemia, or body mass index (BMI) ≥ 30kg/m2. MetS traits were defined using a combination of structured electronic health record data and diagnosis codes attached to any clinical encounters. The primary outcome was time to recurrence. We developed Cox proportional hazards models adjusting for age at diagnosis, health system, smoking status, initial tumor size, number of specimens with cancer, and stage/grade. We conducted a competing risks analysis because in this older, medically complex population, some patients may have died before having a recurrence outcome.

Of our 1485 patients, 23% met the criteria for MetS. MetS patients were more often male (84.2%) and current or former smokers (82.6%). Median follow-up for all patients was 5.9 years, 39.2% of patients died during the follow-up time, and greater than one-third of the cohort had a recurrence. In the fully adjusted Cox proportional hazards model accounting for competing risks, we found no association between MetS status and time to recurrence (adjusted hazard ratio 0.87, 95% confidence interval 0.70-1.08). As expected, initial tumor size and the number of specimens with NMIBC at initial diagnosis was highly associated with time to recurrence.

To our knowledge, this is the largest study evaluating the association between MetS and recurrence in NMIBC. We had a large sample size from two, geographically diverse integrated health systems with long follow up. In future work, we will consider adding lab values and medication histories to delineate how treatment and management of MetS impact outcomes for older adults with NMIBC. Though ours was a negative study, we believe that conducting this type of research to define the relationships between co-existing chronic conditions and cancer outcomes is critically important to the growing population of older adults with cancer, their caregivers, and healthcare providers.

Written by: Tullika Garg, MD, MPH; Carmit K. McMullen, PhD; Matthew E. Nielsen, MD, MS; Terrence E. Murphy, PhD; H. Lester Kirchner, PhD

  1. Department of Urology, Geisinger, Danville, PA
  2. Department of Population Health Sciences, Geisinger, Danville, PA
  3. Center for Health Research, Kaiser Permanente Northwest, Portland, OR
  4. Department of Urology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC
  5. Section of Geriatrics, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT
References:

  1. DeSantis, Carol E., Chun Chieh Lin, Angela B. Mariotto, Rebecca L. Siegel, Kevin D. Stein, Joan L. Kramer, Rick Alteri, Anthony S. Robbins, and Ahmedin Jemal. "Cancer treatment and survivorship statistics, 2014." CA: a cancer journal for clinicians 64, no. 4 (2014): 252-271.
  2. Smith, Benjamin D., Grace L. Smith, Arti Hurria, Gabriel N. Hortobagyi, and Thomas A. Buchholz. "Future of cancer incidence in the United States: burdens upon an aging, changing nation." Journal of clinical oncology 27, no. 17 (2009): 2758-2765.
  3. “Cancer Facts & Figures 2017.” Accessed October 5, 2020. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2017.html.
  4. Garg, Tullika, Amanda J. Young, Korey A. Kost, John F. Danella, Sharon Larson, Matthew E. Nielsen, and H. Lester Kirchner. "Burden of multiple chronic conditions among patients with urological cancer." The Journal of urology 199, no. 2 (2018): 543-550.
  5. Ford, Earl S., Wayne H. Giles, and Ali H. Mokdad. "Increasing prevalence of the metabolic syndrome among US adults." Diabetes care 27, no. 10 (2004): 2444-2449.
  6. Alberti, K. G. M. M., Robert H. Eckel, Scott M. Grundy, Paul Z. Zimmet, James I. Cleeman, Karen A. Donato, Jean-Charles Fruchart, W. Philip T. James, Catherine M. Loria, and Sidney C. Smith Jr. "Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity." Circulation 120, no. 16 (2009): 1640-1645.
  7. Renehan, Andrew G., Marcel Zwahlen, and Matthias Egger. "Adiposity and cancer risk: new mechanistic insights from epidemiology." Nature Reviews Cancer 15, no. 8 (2015): 484-498.
  8. Lenis, Andrew T., Kian Asanad, Maher Blaibel, Nicholas M. Donin, and Karim Chamie. "Association between metabolic syndrome and recurrence of nonmuscle invasive bladder cancer following bacillus calmette-guérin treatment." Urology practice 5, no. 2 (2018): 132-138.
  9. Garg, Tullika, Amanda J. Young, Maureen O'Keeffe-Rosetti, Carmit K. McMullen, Matthew E. Nielsen, Terrence E. Murphy, and H. Lester Kirchner. "Association between metabolic syndrome and recurrence of nonmuscle-invasive bladder cancer in older adults." In Urologic Oncology: Seminars and Original Investigations. Elsevier, 2020.
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