Low free testosterone predicts prostate cancer reclassification

By Joanna Lyford, Senior medwireNews Reporter

Lower levels of free testosterone predict an increased likelihood of disease reclassification in men with prostate cancer, researchers report.

The findings are relevant because approximately one-third of men with disease reclassification will progress and require active treatment, say the researchers writing in BJU International.

A team led by Ignacio San Francisco (Pontificia Universidad Católica de Chile, Santiago) measured total and free testosterone levels in 154 men beginning an active surveillance protocol. The men’s median age was 62 years and they were followed up for a median of 38 months.

At the end of the study period, 35% had disease reclassification and began active treatment. The researchers remark that this most likely reflected incorrect disease misclassification at diagnosis rather than true disease progression.

A comparison of men who did and did not undergo reclassification revealed no differences in clinical characteristics, with the exception of free testosterone. At baseline, free testosterone levels were significantly lower in men who underwent reclassification than in those who did not, at 0.75 versus 1.02 ng/dL.

Using receiver operating characteristic curves, the team identified a free testosterone level of 0.45 ng/dL as the optimal cutoff. Men with levels below 0.45 ng/dL were 4.3 times more likely to undergo reclassification than those with higher levels.

While the 0.45 ng/dL threshold showed the best discriminative ability, all of the thresholds tested – ranging from 0.45 to 1.5 ng/dL – supported the finding of an inverse correlation between free testosterone levels and reclassification risk.

Finally, multivariate analysis showed that free testosterone levels below 0.45 ng/dL and a family history of prostate cancer were each significant independent predictors of disease reclassification in these patients, with hazard ratios of 2.41 and 2.32, respectively.

The researchers say that there are various explanations for their findings; low free testosterone has previously been found to be a risk factor for incident prostate cancer, prostate cancer progression and more aggressive disease. Also, the metabolic syndrome is associated with more aggressive prostate cancer and is also associated with lower androgen levels.

“It should be noted that, in the present study, we have only investigated free testosterone as a predictor of disease reclassification without any claims regarding causality, which, if present, could theoretically operate in either direction, i.e. [prostate cancer] may reduce free testosterone concentrations or low free testosterone may contribute to more aggressive [prostate cancer],” they write.

“To address this question, it would be necessary to design a study correlating values with low tissue testosterone levels and modulation of androgen-dependent genes that may be implicated in [prostate cancer] progression.”

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