Wednesday, June 10, 2020

Testosterone Therapy Does Not Increase the Risks of Prostate Cancer Recurrence or Death After Definitive Treatment for Localized Disease

In the largest observational study so far, Sarkar et al. reported that men in the US Veterans Administration (VA) database who received surgery or radiation for localized prostate cancer and then received testosterone replacement therapy (TRT) for low testosterone were at no greater risk for recurrence than a matched sample of such men who received no TRT.

The VA database included 28,651 men treated with prostatectomy (RP) and 41,333 men treated with primary radiation (RT) between 2001-2015. Of those men:
  • 469 of the RP group received TRT
  • 543 of the RT group received TRT
  • Median follow-up was 7 years
Comparing the men who received TRT to a matched group of men who didn't, they found:
  • There was no difference in biochemical recurrence
  • There was no difference in prostate cancer mortality
  • There was no difference in overall mortality
The database did not include data on serum testosterone levels or duration of TRT.

This confirms a couple of smaller (sample size about 100) retrospective studies at Baylor College of Medicine on men who had received RP and RT.

Before treated men rush out to supplement testosterone, we should acknowledge that all of these studies are retrospective. Although the authors of the VA study made an effort to match the patient and disease characteristics of men who received TRT and those who did not, it is entirely possible that there were characteristics that were not included in the database. In other words, doctors may have been biased by other factors to select patients for treatment.

We should also acknowledge that in the Baylor studies and others, PSA did increase after TRT in both groups, although usually not to the extent that a biochemical recurrence was declared. This is expected in men who received RT because they still have intact prostates that may still secrete PSA from benign sources. However, it is more concerning in men who have had RP because benign prostate tissue should have been eliminated, and even Gleason score 6 prostate cancer may progress, albeit slowly (see this link).

Until we have a prospective randomized trial (like this one with results expected in 2024), patients and their doctors must make this decision based on available data and judgment. While it is undoubtedly true that castration levels of testosterone (below 50 ng/dl) discourage prostate cancer progression, Morgentaler's testosterone saturation theory says that above some minimal testosterone level (around 120 ng/dl), adding more testosterone does not further encourage prostate cancer progression. Many urologists now believe this. However, testosterone sold in the US is required to have a black box warning against its use in men who have had prostate cancer. Getting one's doctor to prescribe it may be challenging.

Also, see the following articles about the experimental use of high-dose testosterone for metastatic prostate cancer:





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