Obesity Raises Metastasis Risk in Prostate Cancer Patients on ADT

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Obesity is associated with an increased risk for prostate cancer (PCa) progression among PCa patients treated with androgen deprivation therapy (ADT) after radical prostatectomy, according to a study.

The retrospective study, which included 287 patients treated with ADT with rising PSA after surgery without metastases, found that men with a body mass index (BMI) of 25-29.9 and 30 kg/m2 or higher (obesity) had a significant 3.6 times and 5.0 times increased risk of metastases compared with patients who had a BMI below 25, after adjusting for multiple variables. In addition, the higher BMI categories were associated with a nearly 3.4 and 3.9 times increased risk of progression to castration-resistant PCa, respectively, and an 8.2 and 6.6 times increased risk of PCa-specific mortality, but these increased risks did not reach statistical significance in adjusted analyses, investigators reported in BJU International (online ahead of print).

The researchers, led by Christopher Keto, MD, a fellow in Urological Oncology at Duke University Medical Center in Durham, N.C., and Stephen J. Freedland, MD, Associate Professor of Surgery (Urology) and Pathology in the Duke Prostate Center, observed that their findings, if confirmed, can help guide clinicians in risk stratification of patients undergoing ADT based on BMI. Counseling of obese men considering ADT should include discussion about lifestyle changes such as weight loss, exercise, and dietary modification, according to the researchers. Although it is unknown if such measures modify the risk of PCa-specific outcomes in obese men, they are known to reduce the risk of heart disease and are unlikely to be harmful, they noted.

Previous research

The new findings build on previous work by Dr. Freedland and colleagues as well as other research teams showing that obese men undergoing primary therapy with radical prostatectomy or external beam radiation are at higher risk for biochemical recurrence after treatment compared with normal-weight men. Previous research also has demonstrated that high BMI, while associated with a lower risk of a PCa diagnosis overall, is associated with an increased risk of high-grade PCa.

At the American Urological Association annual meeting in 2011, Dr. Freedland and his team reported on a study of 6,524 men demonstrating that obesity was associated with a 28% increased risk of high-grade PCa, defined as a Gleason score of 7 or higher, after adjusting for age and prostate volume. The men were enrolled in the four-year REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study funded by GlaxoSmithKline, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with a PSA level of 2.5-10 ng/mL and negative prostate biopsy.

Study rationale

For the latest study, Dr. Freedland's group hypothesized that obese men on ADT may be at increased risk for PCa progression because prior studies have shown that obese men have lower levels of testosterone compared with normal-weight men, and thus the tumors already may be primed to grow in a low testosterone environment. Additionally, despite lower testosterone levels prior to ADT, obese men have higher levels of testosterone while receiving ADT, suggesting the amount of ADT given (i.e., the doses of the drugs used to achieve androgen deprivation) may not be enough.

“These two factors plus the general link between obesity and aggressive PCa led us to this hypothesis, and indeed, the data support our hypothesis,” Dr. Keto told Renal & Urology News. “As such, we have yet another clinical scenario—this time men treated with ADT for rising PSA after radical prostatectomy—wherein obesity is linked with poor PCa-specific outcomes.”

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