Baseline testosterone/BMI ratio predicts which patients gain from androgen deprivation therapy

What's more, say the investigators, the ratio between baseline testosterone levels and body mass index (BMI) appears to have prognostic significance in determining which men with advanced disease are best suited to receive ADT and when they should get it.

Those conclusions were drawn from a trial of 77 men randomly assigned to undergo either immediate ADT or expectant management.

"Because of obesity's effects on testosterone levels, we believe it may influence which patients progress or fail to respond to deferred ADT, and which men who were immediately treated respond or fail."

The 77 men in the study were the ones from an initial group of 98 for whom baseline testosterone and BMI data were available. To better describe the association between disease outcome and circulating androgens, the authors divided baseline testosterone levels into low (≤240 ng/dL) and high (>240 ng/dL) groups.

They found that BMI had no effect on overall survival, progression-free survival, or prostate cancer-specific mortality between the immediate and delayed ADT cohorts. They also discovered that BMI was significantly negatively associated with baseline testosterone levels (p=.04) and that baseline testosterone levels decreased by 11.4 ng/dL for every one unit of BMI increase (p=.04).

Testosterone levels did not affect overall survival or prostate cancer-specific mortality in either treatment arm. However, while baseline testosterone also did not appear to influence progression-free survival among men who received immediate ADT, progression-free survival was significantly shorter in the delayed-treatment group (1.4 vs. 3.3 years, p=.01).

Patients in the deferred ADT group with early progression had a significantly lower testosterone:BMI ratio than those who progressed later did (p=.04).

"By looking at testosterone in the context of obesity, we found a more subtle mechanism of identifying men who may be at higher risk for disease progression based on their testosterone:BMI ratio and who would benefit from earlier hormonal treatment," Dr. Messing said.

Contradictory data

Indeed, the trial would appear to contradict at least some previously reported data. For instance, a number of previous studies concluded that obesity negatively affects survival, but that was not the case in the investigation conducted by Dr. Messing and colleagues.

In addition, men with low testosterone who develop the disease have been thought to do worse and to be less likely to respond to ADT because their tumors managed to grow in spite of relatively low levels of circulating androgens. But again, this was not the case with the Rochester team's findings, which were presented at the 2009 AUA annual meeting in Chicago.

"We still believe that men who are at considerable risk of death from their prostate cancer benefit from early ADT after definitive surgical resection," said Dr. Messing. "The prognostic significance of the testosterone:BMI ratio must be explored further in prospective trials before additional conclusions can be drawn. ADT is of tremendous benefit for the man with advanced prostate cancer, but refining who gets this treatment and when are of considerable importance."

Dr. Messing added that the significance of the testosterone:BMI ratio in intermediate and high-risk patients without lymph node involvement is still an open question.