Based on current studies and anecdotal evidence, several urologists feel it’s relatively safe to administer Testosterone Replacement Therapy (TRT) for men with prostate cancer who are on active surveillance or those who have been treated with prostatectomy or cryosurgery.
However, they emphasize that it is critical that these men should be closely monitored.
In the past, TRT was not considered for men suffering from prostate cancer. But, based on new research, times have changed, and TRT is often prescribed for prostate cancer patients, according to Wayne J.G. Hellstrom, MD, professor of urology and chief of andrology at Tulane University School of Medicine in New Orleans, Louisiana.
“About 20 years ago, when I gave a course at the American Urological Association [AUA] and would ask if anybody in the audience would give testosterone to a man who had prostate cancer, 3 of maybe 300 to 400 urologists would put up their hands. Now, probably 75% to 80% of urologists will give testosterone to men in these circumstances,” he stated. Until recently, he added, urologists were reluctant to give testosterone to men with prostate cancer for fear of “fueling the fire.”
This fear was due to a study in the 1940s by Dr. Charles Huggins that found a link between androgenetic hormones and prostate cancer, according to Dr. Arthur L. Burnett II, MD, professor of urology at Johns Hopkins University in Baltimore, Maryland. Recent guidelines, however, are varied and do not always confirm the findings of Dr. Huggins.
The latest guidelines
The authors of an editorial comment published earlier this year in the International Brazilian Journal of Urology found: “Last guidelines’ revisions show some changes on CaP [prostate cancer] as a definitive contraindication for TRT [testosterone replacement therapy]. The Endocrine Society has the strictest guidelines, advising against T in patients with an unevaluated prostate nodule, PSA >4ng/mL, or PSA >3ng/mL in high-risk patients (i.e., African Americans or a first-degree relative with CaP). Only the AUA and ISSM [International Society for Sexual Medicine] recommend offering T on a case-by-case basis for all patients with CaP. Patients treated for localized CaP with no evidence of active disease (measurable PSA, abnormal digital rectal examination findings, evidence of bone or visceral metastases) are candidates for replacement under the Canadian Medical Association Journal, European Association of Urology (EUA), and British Society for Sexual Medicine guidelines (BSSM).”
"There are no randomized placebo-controlled trials giving men testosterone therapy after prostate cancer treatments. However, initial studies have not demonstrated any increased risk of biochemical recurrence,” according to Mohit Khera, MD, professor of urology at Baylor College of Medicine in Houston, Texas. He added that the AUA released its guidelines in 2018, recommending clinicians should inform patients of the absence of evidence linking testosterone therapy to the development of prostate cancer,
“However, the guidelines go on to state that patients with testosterone deficiency and a history of prostate cancer should be informed that there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy,” he said.
“This was based on expert opinion. There are no randomized placebo-controlled trials giving men testosterone therapy after prostate cancer treatments. However, initial studies have not demonstrated any increased risk of biochemical recurrence.”
Every patient is unique.
Men with symptoms of low testosterone (aka “Low-T”) can experience relief, including increased muscle mass, a boost in mood, less brain fog, and an awakened libido from TRT. “A significant number of men as they age are more likely to have prostate cancer, but they’re also more likely to have symptomatic hypogonadism, and treatment may be warranted for these guys,” noted Hellstrom.
According to Khera, testosterone might play a vital role in prostate cancer patients' health and quality of life. “Specifically for men with a history of prostate cancer, testosterone therapy can improve recovery of erectile function following…treatment. Testosterone plays a key role in overall erectile function.”
Although every case is unique, Hellstrom said he does not worry about starting or continuing TRT in certain patients. “As far as patients who have localized prostate cancer on surveillance and those men who have had local therapy, which may be radical prostatectomy, radiation, or cryotherapy, there is really no good evidence that men are worse off if they are hypogonadal and treated appropriately,” he pointed out.
“It’s important that those men who are treated recognize that they need to be followed closely, which involves testosterone [level monitoring], PSA [prostate-specific antigen], and digital rectal exams every 3 to 6 months during treatment.”
Dr. Burnett II said, “In a man who gets the diagnosis and has high-grade disease, the PSA [level] is rapidly going up, and on top of that, he says he gets a so-so benefit from the testosterone, you’d say then let’s withdraw the testosterone.”
For Burnett, things get disquieting as prostate cancer progresses or there is metastatic disease: “If the PSA [level] is rapidly increasing, you know that prostate cancer is increasing in the body, and that would increase my hesitancy about testosterone replacement.”
Not everyone agrees. Treating men with metastatic prostate cancer is still highly controversial due to the fear that TRT will increase the chance the cancer will grow, Hellstrom said.
However, he added that this is being tested by investigators studying intermittent high-dose androgen therapy in men with metastatic prostate cancer and seeing that “in a significant number of these men, the actual prostate cancer and the PSA levels regress.”
Should urologists stop TRT when men are first diagnosed with prostate cancer? Not necessarily, but for Khera, there is an exception, and that is “the patient who is going on to receive radiation therapy and will require androgen deprivation therapy [ADT]. In these patients, we stop testosterone in preparation to start ADT.”
In most cases of early disease, these physicians think it’s safe to keep men with no evidence of metastases on testosterone. “I would keep him on it with the understanding that he has close follow-up,” Hellstrom said.
According to Khera, urologists should decide to continue therapy on a case-by-case basis, depending on the Gleason score, tumor grade and stage, and anxiety and tolerance levels.
“If it’s pretty low-threat prostate cancer and a man says I’d rather jump off a cliff than stop my testosterone, then I might say, ‘I want you to hear all the risks, but I can’t oppose you using it,’” Burnett added, noting that in every case, including new diagnoses, it’s crucial to consider the benefit a man gets from taking testosterone.
“In a man who gets the diagnosis and has high-grade disease, the PSA [level] is rapidly going up, and on top of that, he says he gets a so-so benefit from the testosterone, you’d say then let’s withdraw the testosterone.”
“We are recognizing that testosterone therapy can be beneficial when correctly administered in prostate cancer patients,” Burnett said. “However, a lot of this is anecdotal, and some is a bit of the Wild West regarding the safety of who can and cannot be treated with it, considering where the literature is right now,”
The good news is that investigators are starting to conduct randomized controlled trials, including researchers from Johns Hopkins and Brigham and Women’s Hospital, in Boston, Massachusetts, to determine the potential benefits and risks of TRT in men treated for prostate cancer.
“We’re trying to make a statement that may afford the urologists out there the necessary literature support, so if they put somebody on therapy, they can really counsel them,” Burnett said.
Javaroni V. Editorial comment: testosterone replacement therapy (TRT) and prostate cancer: an updated systematic review with a focus on previous or active localized prostate cancer. Int Braz J Urol. 2022;48(1):188-195. doi:10.1590/S1677-5538.IBJU.2022.01.08
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