Metabolic syndrome and some of its components (specifically obesity, insulin resistance and dyslipidemia) have been identified as risk factors for the development of aggressive prostate cancer (PC). Conversely, there’s evidence that pharmacologic treatments for metabolic syndrome, including statins, metformin and aspirin, reduce the risk of lethal PC.
Adam S. Kibel, MD, chief of the Division of Urology at Brigham and Women’s Hospital, Jiun-Hung Geng, also of the division, and colleagues recently conducted the first study of how the combination of metabolic syndrome and its treatment affect response to androgen deprivation therapy (ADT) in castration-sensitive PC. They determined metabolic syndrome was associated with earlier progression to castration-resistant PC (CRPC).
In Prostate Cancer and Prostatic Diseases, they also say statin use by men with metabolic syndrome significantly slowed that progression.
The retrospective study included 409 men with metastatic castration-sensitive PC who were evaluated between 1996 and 2014 and received first-line ADT. The researchers searched their records for information on metabolic syndrome, statin use, aspirin use and metformin use during the six-month period before initiation of ADT.
All patients were followed until they developed CRPC, died, were lost to follow-up, or follow-up ended on July 31, 2019, whichever came first.
Prevalence of Metabolic Syndrome
Metabolic syndrome was diagnosed according to a modified version of the American Heart Association definition. Body mass index ≥30 kg/m2 was used as a surrogate for waist circumference, which was not available.
Metabolic syndrome was present in 176 of the 316 patients for whom data were available (56%). At baseline 123 of the patients in that subgroup were using a statin, 86 were using aspirin, and 25 were using metformin.
CRPC and Metabolic Syndrome
Over the median follow-up time of 59 months, 356 patients developed CRPC. In multivariable analysis adjusted for demographic and PC-specific factors, metabolic syndrome was significantly associated with shorter time to CRPC (HR, 1.41; 95% CI, 1.09–1.81).
Within five years after ADT initiation, 82% of patients with metabolic syndrome had CRPC compared with 66% of those without metabolic syndrome.
CRPC and Components of the Metabolic Syndrome
Elevated fasting glucose was significantly associated with time to CRPC (HR, 1.44; 95% CI, 1.02–2.02). There were no associations between ADT response and increased blood pressure, obesity, abnormal cholesterol levels or abnormal triglyceride levels.
CRPC and Treatment of Metabolic Syndrome
In the adjusted model, patients who had metabolic syndrome and used a statin were less likely to develop CRPC than those who had metabolic syndrome but did not receive statin therapy (HR, 0.70; 95% CI, 0.49–0.98). Aspirin and metformin use were not associated with CRPC risk.
Five years after starting ADT, 91% of patients with metabolic syndrome who did not use a statin had CRPC. The corresponding percentages were 79% of patients with metabolic syndrome and statin use and 71% of patients with neither.
Applying the Findings to the Clinic
Patients presenting with metastatic castration-sensitive PC should be screened for metabolic syndrome and, if appropriate, educated that metabolic syndrome is a risk factor for earlier progression. Such patients may benefit from statins to delay CRPC development.
The study was not powered to explore the influence of metformin on ADT response in the cohort because so few patients with metabolic syndrome used it. Randomized trials, including the STAMPEDE platform trial, are investigating whether metformin protects against disease progression in men with metastatic prostate cancer.