Obesity may increase the long-term risk of disease progression in men on active surveillance for low-risk prostate cancer (PCa), according to study findings presented at the Canadian Urological Association annual meeting in St. John’s, Newfoundland.

Bimal Bhindi, MD, and colleagues at the University of Toronto studied 565 PCa patients on active surveillance for low-risk disease. Patients underwent digital rectal examinations (DRE) and PSA testing every 3 months (6 months in stable patients). The men had confirmatory biopsies at a median of 1 year. Of the 565 patients, 124 (22%) were obese (body mass index [BMI] of 30 kg/m2 or greater). The cohort had a median follow-up of 48 months.

The researchers observed pathologic progression (defined as no longer meeting criteria for low-risk criteria on follow-up biopsy) in 168 men (30%) and therapeutic progression (defined as intent to start active treatment) in 172 men (30%). Obesity was not associated with reclassification risk after confirmatory biopsy. It was associated with an increased risk of progression beyond confirmatory biopsies. Each 5-unit increment in BMI was associated with a significant 49% increased risk of pathologic progression and a significant 37% increased risk of therapeutic progression.

In a poster presentation, Dr. Bhindi’s group concluded that their findings have implications for risk assessment and counseling for men currently on active surveillance.

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Other studies have suggested that obesity might impede PCa detection because of increased prostate size, more difficult DRE, and PSA hemodilution. Studies have also suggested that obesity also might cause biologic abnormalities that promote carcinogenesis, cancer proliferation, and progression, they explained. The new study suggests that in patients on active surveillance, there may be a true biological progression risk rather than merely an issue of misclassification.

In an interview with Renal & Urology News, Dr. Bhindi explained that when patients are diagnosed with low-risk PCa and go on active surveillance, there are always two questions: was a higher-risk cancer misdiagnosed as low risk and will this cancer progress?

“We typically perform a confirmatory biopsy at an average of 6-12 months following the initial diagnosis to make sure we did not miss a higher risk cancer,” Dr. Bhindi said. “Our study found no association between obesity and risk of re-classification at the time of confirmatory biopsy. The next phase [of the study] was the longer-term monitoring. During this phase, we detected that obesity is associated with an increased risk of progression.”

The apparent link between obesity and an increased risk of cancer progression while on active surveillance presents a clinical dilemma, Dr. Bhindi said. “Obese men are at an increase of dying of other causes such as cardiovascular disease, making them great candidates for active surveillance: They will die of something else before prostate cancer. On the other hand, they are also at an increased risk of cancer progression. This makes decision-making challenging for obese patients with low risk prostate cancer. We feel active surveillance should still be used in obese men, but increased vigilance is required.”

Dr. Bhindi added that obesity is, theoretically, a modifiable risk factor. “Thus the next logical question is, can this risk of progression be modified by diet, exercise, and/or certain medications? This will be the topic of future studies.”

From the August 01, 2014 Issue of Renal and Urology News