CHICAGO—Studies presented at the 2019 American Urological Association annual meeting add to a growing body of evidence showing that testosterone replacement therapy (TRT) is safe for selected men with a history of prostate cancer (PCa).
The studies found no increase in the risk of adverse oncologic outcomes following treatment—even among men with high-risk PCa—or while on active surveillance. Two of these studies were co-led by J. Kellogg Parsons, MD, MHS, Professor of Urology at the University of California, San Diego, who told Renal & Urology News he believes the research to date, despite being mainly observational cohort studies, is sufficient to support the use of TRT in selected men with low-risk PCa, particularly those who have undergone definitive treatment with surgery or radiation and have no evidence of residual disease.
“It is highly unlikely that we will ever have a randomized clinical trial of hypogonadal men with prostate cancer who are randomized to testosterone replacement or no testosterone replacement,” Dr Parsons said. Such a trial would pose substantial ethical problems, and the extremely large number of patients needed would be a major challenge, he said.
Although testosterone promotes prostate tumor growth, no solid scientific evidence exists to prove that use of TRT to achieve normal testosterone levels in hypogonadal men with a history of localized PCa worsens outcomes, he said, adding that he is comfortable prescribing TRT to “appropriately selected patients.”
At the conference, Dr Parsons and his colleagues presented findings from 2 population-based national cohorts identified using a Veterans Affairs health system database. The cohorts included 28,651 men who underwent RP and 41,544 who underwent RT. Both studies demonstrated that the risks of biochemical recurrence (BCR), death from PCa, death from causes other than cancer, and death from any cause did not differ significantly between patients who received TRT after treatment and those who did not, after adjusting for potential confounders.
In the RP cohort, 1.6% of patients received TRT following surgery. The median time from surgery to TRT was 3 years. Patients had a median follow-up of 7.4 years. The investigators defined BCR as a post-RP PSA level of 0.2 ng/mL or higher.
In the RT cohort, the median time from RT to TRT was 3.5 years. For patients who received androgen deprivation therapy (ADT), the median duration of the treatment was similar between the TRT and no-TRT groups (185 vs 186 days, respectively). The investigators defined BCR as a post-RT PSA level of 0.2 ng/mL or higher.
Dr Parsons and his collaborators stated that, to their knowledge, the RP and RT population-based cohorts combined made possible the largest comparative analyses to date of TRT following definitive treatment in an equal access health system.
In another study, Helen Levey Bernie, MD, and colleagues at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York found that TRT was not associated with worse outcomes in men who underwent RP for high-risk PCa, defined as a Gleason score of 6 or 7 accompanied by positive surgical margins, lymph node involvement, seminal vesical involvement, or as Gleason score 8 or higher disease regardless of pathologic findings. The study included 1407 patients, of whom 614 (44%) had low testosterone (low T), defined as an early morning total testosterone [TT] level below 300 ng/dL). The low T group included 24 patients who received TRT and 590 who did not.
A total of 906 men (64%) experienced BCR: 57% of men with normal TT, 75% of those not on TRT, and 46% of those on TRT. In adjusted analyses, low T and TRT were not associated with BCR, Dr Bernie’s group reported. The investigators defined BCR as a postoperative PSA level of 0.1 ng/mL or higher.
In a fourth study, John P. Mulhall, MD, of MSKCC, and collaborators examined the effect of TRT prescribed to men following RP for organ-confined Gleason 6 or 7 PCa. The study included 360 patients who had low T (less than 300 ng/dL) and post-RP undetectable PSA levels prior to the start of TRT. The men had a mean age of 59 years and a mean preoperative PSA level of 4 ng/dL. The median time post-RP before TRT was started was 9 months. The median post-RP duration of TRT was 66 months. One patient experienced BCR 2.5 years post-RP. Dr Mulhall’s team concluded that TRT in this carefully selected group of patients appears to be safe 3 years post-TRT administration.
Dr Mulhall also presented findings from a study of 86 testosterone-deficient men who received TRT while on AS for PCa. Data suggested that TRT did not result in significant PSA changes. The mean duration on AS prior to initiation of TRT was 13 months. Mean duration on TRT at last follow-up was 19 months. The mean PSA level change per patient was 0.6 ng/mL, with 26% of men experiencing a PSA level increase of 1 ng/mL or higher. Sixteen percent of men opted for definitive therapy for their cancer, a rate of progression to definitive therapy similar to previously reported data, according to the investigators.
At the 34th Annual European Association of Urology Congress in Barcelona, Spain, in March, a team from the University of California, Irvine, led by Thomas Ahlering, MD, reported on a study demonstrating that TRT in men with low-risk PCa was associated with a significant decreased risk of BCR following robot-assisted RP. The study found that 9.9% of men who received TRT experienced BCR compared with 23.5% of men who did not.
Sarkar R, Parsons JK, Einck J, et al. Safety of testosterone replacement therapy after radical prostatectomy (RP) for localized prostate cancer: A population-based analysis. Presented at the 2019 American Urological Association annual meeting held May 3-6 in Chicago. Abstract PD28-12
Sarkar R, Parsons J, Einck J, et al. Safety of testosterone replacement after radiation therapy for localized prostate cancer: A population-based analysis. Presented at the 2019 American Urological Association annual meeting held May 3-6 in Chicago. Abstract MP58-12
Bernie HL, Salter CA, Schofield EA, et al. Biochemical recurrence rates in men with high grade prostate cancer on testosterone therapy. Presented at the 2019 American Urological Association annual meeting held May 3-6 in Chicago. Abstract MP58-10.
Mulhall J, Benfante N, Teloken, et al. Testosterone therapy in men with Gleason 6-7 prostate cancer. Presented at the 2019 American Urological Association annual meeting held May 3-6 in Chicago. Abstract MP58-13
Mulhall J, Benfante N, Teloken P, et al. Testosterone therapy in men on active surveillance for prostate cancer. Presented at the 2019 American Urological Association annual meeting held May 3-6 in Chicago. Abstract MP58-14.
Towe M , Huynh LM, El-Khatib FM, et al. Testosterone replacement therapy prevents disease progression in men undergoing radical prostatectomy. Presented at the 34th Annual European Association of Urology Congress, held in Barcelona, Spain, March 15-19. Abstract 646.
This article originally appeared on Renal and Urology News