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:





Thursday, June 4, 2020

Importance of Adding ADT to Brachy Boost Therapy for Men with Unfavorable-Risk Prostate Cancer

Last month, we looked at Level 1 evidence (highest level, superseding all previous studies) that for unfavorable risk patients, brachy boost therapy (BBT) [external beam therapy (EBRT) with a brachytherapy boost to the prostate] has better results when accompanied by 18 months of androgen deprivation therapy (ADT). (see this link)

Now a meta-analysis has reaffirmed that finding. The two studies were probably submitted for publication at about the same time, which explains why the meta-analysis doesn't include data from RTOG 01.03 RADAR. In the Jackson et al. meta-analysis (and Medpage summary), there were:
  • 6 randomized trials of EBRT with or without ADT comprising 4,663 patients.
  • 3 randomized trials of EBRT with or without a BBT comprising  718 patients.
    • One of those trials included ADT, the other two did not
Their analysis found that ten-year overall survival was:
  • improved by 30% by the addition of ADT to EBRT
  • not improved by the addition of BBT to EBRT (at least when ADT was not included)
  • The addition of ADT had a bigger impact than the addition of BBT
  • The trial that included both ADT and BBT had the best results
Because this meta-analysis included trials with men from different risk levels, it gives no direction about which therapy is best for favorable- vs unfavorable-risk men. DART 01/03 GICOR proved that adjuvant ADT only provides an added benefit to EBRT in high-risk men (vs intermediate risk men). Furthermore, BBT did not benefit and did add toxicity to favorable-risk patients (see this link).

Some of the trials did not include radiation doses now considered curative. It also did not look at ADT duration.