Testosterone therapy may be safe for use in men with advanced prostate cancer
Testosterone therapy was not associated with unexpected or rapid disease progression in a cohort of men with biochemical recurrence or metastatic prostate cancer, according to study findings.
Abraham Morgentaler, MD, FACS, associate professor of surgery in the department of urology at Beth Israel Deaconess Medical Center, Harvard Medical School, said the findings provide the first solid evidence that testosterone therapy may not be harmful for men with advanced prostate cancer.
“Although the number of men studied here is relatively small, it is clear that the conventional wisdom is wrong that raising testosterone in men with prostate cancer will necessarily precipitate rapid progression and/or death,” Morgentaler told Healio. “Bit by bit over the last 20 years, the urological community has recognized that testosterone therapy can provide important benefits to men and does not appear to worsen outcomes in men with localized prostate cancer or those men being carefully observed with active surveillance for low-risk prostate cancer. However, standard therapy for men with biochemical recurrence or metastatic disease has been androgen deprivation, which causes weakness, fatigue, muscle loss, fat gain, depression, loss of bone mass, erectile dysfunction, anorgasmia and loss of libido. Based on these results and my clinical experience with these men, I believe that testosterone therapy is a reasonable option for testosterone-deficient men with biochemical recurrence and symptoms related to their testosterone deficiency.”
Morgentaler and colleagues analyzed data from men who were treated with testosterone therapy at Men’s Health Boston from 2005 to June 2020 and had biochemical recurrence, metastatic prostate cancer or were treated with androgen deprivation therapy for high risk of recurrence after definitive local treatment. Relevant data were collected on prostate cancer status and prior treatment. Prostate-specific antigen (PSA) testing was done at 3-month intervals in the biochemical recurrence group for the first year and every 6 months thereafter. The metastatic prostate cancer group had PSA testing conducted every 3 months. Follow-up imaging was obtained every 6 months for men with metastatic prostate cancer and annually in the biochemical recurrence group.
The findings were published in Androgens: Clinical Research and Therapeutics.
No disease progression for most participants
There were 22 men included in the study, including 13 with metastatic prostate cancer, seven with biochemical recurrence and two with adjuvant androgen deprivation therapy. Testosterone therapy increased median PSA from 3.1 ng/mL to 13.3 ng/mL in the biochemical recurrence group, from 6.3 ng/mL to 17.8 ng/mL in the metastatic prostate cancer group, and from less than 0.1 ng/mL to 0.3 ng/mL for those treated with androgen deprivation therapy. The overall mortality rate was 13.6% and the prostate cancer-specific mortality rate was 4.5%.
The biochemical recurrence group had no deaths and one participant developed metastases after 16 months of testosterone therapy. No other complications were observed in the group, and four men continued testosterone therapy for up to 5 years.
The metastatic prostate cancer group had a 21.4% overall mortality rate and a prostate cancer-specific mortality rate of 7.1%. Follow-up imaging 3 to 12 months after starting testosterone therapy was available for 10 men, with seven showing no disease progression and three having new foci of bone metastases. Complications of testosterone included myocardial infarction at 6 months in a participant with three prior strokes, bone marrow replacement more than 3 years after the first development of bone metastases, urinary retention with urosepsis 3 months after testosterone therapy began and a case of recurrent deep vein thrombosis 8 months after testosterone initiation. Of the 11 men who did not die, five continued testosterone therapy.
No adverse events were reported for the androgen deprivation therapy group. One participant discontinued testosterone therapy after 1 year, and the second participant continued testosterone therapy combined with enzalutamide (Xtandi, Astellas/Pfizer).
“These results show that it is possible for men with advanced prostate cancer to do well for extended periods of time with testosterone therapy,” Morgentaler said. “In the past it would have been considered unethical to do a randomized controlled trial with testosterone therapy as one arm of the study. Further research should now be performed comparing testosterone therapy to no treatment for men with biochemical recurrence, and also a study comparing testosterone therapy vs. androgen deprivation for men with metastatic disease.”
Questions remain on disease progression
Some researchers said the findings are encouraging but identified several study limitations. In an accompanying editorial, Wayne J.G. Hellstrom, MD, FACS, professor and chief of the section of andrology, and Ayman Soubra, MD, a fellow, both in the department of urology at Tulane University School of Medicine, noted the study had a high risk for bias, and lacked a control group and a protocol to detail disease progression.
“Many hypogonadal men do obtain symptomatic relief from testosterone replacement therapy,” Hellstrom told Healio. “Hence, this is definitely a quality-of-life issue. However, the possibility of disease progression remains a concern.”
In a separate accompanying editorial, Jesse Ory, MD, a urologist, and Ranjith Ramasamy, MD, director of reproductive urology, both at the University of Miami, similarly said the study was a good first step, but the lack of complete data with disease progression was a concern.
“Since prostate cancer is a relatively slow process, it is possible that many of these men were progressing while on testosterone, but we don't know because of incomplete data,” Ory and Ramasamy told Healio.
Hellstrom, Ory and Ramasamy all agreed with Morgentaler on the need for a randomized controlled trial, but noted conducting such a study would be difficult. Hellstrom wrote that it will be a challenge to recruit enough men with hypogonadism and advanced prostate cancer for the study to be powered enough to detect significant findings. Ory and Ramasamy suggested the next study randomly assign men with advanced prostate cancer who reduced androgen deprivation to either testosterone or placebo with close follow-up, but acknowledged such a study would be difficult to perform.
“One would need to make sure men understand that by forgoing standard of care, they may be accelerating their death from prostate cancer,” Ory and Ramasamy said.
For more information:
Wayne Hellstrom, MD, FACS, can be reached at firstname.lastname@example.org.
Abraham Morgentaler, MD, FACS, can be reached at email@example.com.
Jesse Ory, MD, can be reached at firstname.lastname@example.org.
Ranjith Ramasamy, MD, can be reached at email@example.com