TRT in Patients with Known Prostate Cancer
A growing body of evidence suggests a margin safety for TRT in hypogonadal men with treated PCa. Several studies have demonstrated symptomatic improvement in hypogonadism without the development of biochemical recurrence in PCa patients after RP. In 2004, Kauffman and Graydon presented the first published report of seven symptomatic hypogonadal men who had undergone RP and were treated with TRT.
All men were eugonadal preoperatively and had Gleason 6 or 7 localized disease. In follow-up that ranged from 1-12 years, PSA levels remained undetectable and there was no evidence of clinical recurrence. Notably, one patient had positive surgical margins at the apex and his PSA remained undetectable after 12 years of TRT.30
Agarwal et al also demonstrated a similar safety profile in their reports of 10 men who underwent RP and received TRT. After a median follow-up of 19 months, all had symptomatic benefit from TRT without any evidence of biochemical recurrence.31 Khera et al evaluated 57 men who received TRT after RP. After treatment periods that ranged from 1-136 months, none of the men had an increase in their PSA values.32
Sathyamoorthi et al presented data from 133 patients, including some patients from the Khera study, followed for a mean of 12 months. There were no PSA recurrences and no statistically significant increases in PSA. Sixteen of these patients had high-grade disease (Gleason 8) or positive margins.33
The results of studies in hypogonadal men with PCa treated with brachytherapy and/or external beam radiation are equally heartening, and also reveal a margin of safety for TRT in men who have close follow-up. Sarosdy followed 31 men with regular PSA and testosterone levels for a median of five years after brachytherapy with or without external beam radiation treatment for Gleason 5-9 PCa who were receiving TRT for symptomatic hypogonadism. Only one man had an increase in his PSA values after starting TRT.
Although he continued his TRT, his PSA value ultimately declined. The most recent serum PSA levels were below 0.1 in 23 patients (74%), 0.1-0.5 in seven (23%), and 0.5-1.0 in one (3%). No patients, however, underwent prostate biopsy to exclude cancer recurrence.34 Morales et al followed five men with PCa who underwent EBRT and received TRT for a median of 14.5 months. One man had a transient increase of his PSA above 1.0, but no patient had a PSA above 1.5 while receiving TRT.35
Recently, Morgentaler et al presented their data with testosterone replacement in patients on an active surveillance protocol for PCa. Fourteen patients were followed for a mean of 23 months. Thirteen patients had prostate biopsies showing a maximum Gleason score of 6 and one patient had evidence of Gleason score of 7.
The mean PSA in the group increased from 3.7 to 5.5 over 23 months of follow-up. These short term data suggest that the rate of disease progression is not higher than the natural history of the disease. One patient without evidence of PSA increase desired a repeat biopsy, which revealed one core of Gleason 7. The final pathology after RP was Gleason 6 cancer involving 5% of the gland. 36
The limitations of these studies are clear, and include small sample size, non-randomized design, and relatively short follow-up. The aim of these studies is to begin the process of exploring the possibility of establishing the safety of TRT in men who have been diagnosed with PCa.
Current Guidelines Regarding TRT
The guidelines for treatment published in 2008 by the writing group for four international andrology societies concluded that:
“Men successfully treated for prostate cancer and suffering from confirmed symptomatic hypogonadism are potential candidates for testosterone substitution after a prudent interval if there is no clinical or laboratory evidence of residual cancer. The risks and benefits must be clearly discussed with and understood by the patient and follow up must be particularly careful.”9
The 2010 Endocrine Society Guidelines remain clear that “testosterone is contraindicated in prostate cancer.” However, in the body of they report, they mention the following:
“Although some clinicians have suggested that patients with organ-confined prostate cancer who have undergone radical prostatectomy and have been disease-free 2 or more years after radial prostatectomy and who have undetectable PSA levels may be considered for testosterone replacement on an individualized basis, the lack of data from randomized trials precludes a general recommendation.”37
This shift in discussion stands in stark contrast to the historical perception that any history of prostate cancer is an absolute contraindication to TRT.