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How I handle testosterone therapy in men with prostate cancer
Dr. Pastuszak gives an overview of his approach to treating hypogonadal men with prostate cancer. The diagnosis of hypogonadism in men with prostate cancer is the same as in men without prostate cancer; i.e. presence of both low testosterone levels and symptoms indicative of hypogonadism. Prostate cancer variables to consider are PSA levels, type/grade of prostate cancer, prostate cancer treatment type (surgery, radiation, active surveillance) and post- treatment PSA.
PSA levels are often used for monitoring and treatment decisions in prostate cancer patients. In men on active surveillance, testosterone therapy is more likely to be prescribed to a man with stably elevated PSA levels than a rapidly rising PSA level. In patients who have undergone surgery or radiation, undetectable PSA or PSA of 0.5 ng/mL, respectively, qualifies men for testosterone therapy.
Dr. Pastuszak presents data on testosterone therapy in men with surgically and radiation treated prostate cancer. In one study, 103 hypogonadal men with prostate cancer who had undergone prostatectomy were treated with testosterone for up to 36 months (treatment group), while 49 non-hypogonadal men with prostate cancer who had undergone prostatectomy were used as a reference group.1 There were 77 men with low/intermediate risk prostate cancer and 26 with high risk prostate cancer included in the analysis. There was a statistically, but not clinically, significant increase in PSA levels in low/intermediate risk (from 0.004 to 0.007 ng/mL) and high risk (from 0.004 to 0.009 ng/mL). Interestingly, biochemical recurrence was higher in the reference group (8 patients or 16%) than in the testosterone treated group (4 patients or 4%). It was concluded that testosterone therapy is effective and, despite followed by a minor increase in PSA, does not appear to increase prostate cancer progression or recurrence rates, even in men with high risk prostate cancer.
In another study, 98 hypogonadal were men treated with testosterone therapy after radiation for prostate cancer.2 Tumor Gleason score was 5 in 3 men (3.1%), 6 in 44 (44.9%), 7 in 28 (28.6%), 8 in 7 (7.1%) and 9 in 4 (4.1%). Median follow-up was 40.8 months. A non-significant increase in mean PSA was observed from 0.08 ng/mL at baseline to 0.09 ng/mL. Among patients at high risk, PSA significantly increased from 0.10 to 0.36 ng/mL. Six men (6.1%) met criteria for biochemical recurrence. It was concluded that testosterone therapy in men following radiation therapy for prostate cancer was associated with a minor increase in serum PSA and a low rate of biochemical recurrence.
Data on testosterone therapy in men on active surveillance for prostate cancer likewise looks promising. A retrospective chart review identified 28 men with hypogonadism who underwent testosterone therapy for at least 6 months while on active surveillance for Gleason 3 + 3 and Gleason 3 + 4 prostate cancer.3 A comparison group of 96 men on active surveillance for prostate cancer with untreated hypogonadism was identified at the same institution. The active surveillance protocol followed modified Epstein criteria and allowed inclusion of men with a single core of low-volume Gleason 3 + 4 prostate cancer. Mean age was 59.5 and 61.3 years, and mean follow-up was 38.9 and 42.4 months for the testosterone treated and non-testosterone group, respectively. Of all 28 men in the testosterone treated group, 3 (10.7%) men developed an increase in Gleason score while on active surveillance. Of 22 men in the testosterone treated group with Gleason 3 + 3 disease, 7 (31.8%) men developed biopsy progression including 3 men (13.6%) who developed Gleason 3 + 4 prostate cancer. Of 6 men with Gleason 3 + 4 disease at baseline, 2 (33.3%) men developed an increase in tumor volume, and none developed upgrading beyond Gleason 3 + 4. All 96 men in the non-testosterone group had Gleason 3 + 3 disease at baseline and, 43 (44.7%) developed biopsy progression, including 9 men (9.38%) with upgrading to Gleason 7 (3 + 4). Biopsy progression rates were similar for both groups and historical controls. It was concluded that biopsy progression in men on active surveillance appears unaffected by testosterone therapy over 3 years.3 Prospective placebo-controlled trials of testosterone therapy in hypogonadal men on active surveillance should be considered given the symptomatic benefits experienced by treated men.
Needless to say, a vigorous surveillance protocol is critical when giving testosterone therapy to men with prostate cancer. Monitoring of PSA and DRE should be done every 3-6 months and 6-12 months, respectively.
Alexander Pastuszak, MD, PhD Assistant Professor Center of Reproductive Medicine Division of Male Reproductive Medicine and Surgery Scott Department of Urology Baylor College of Medicine
Pastuszak AW, Pearlman AM, Lai WS, Godoy G, Sathyamoorthy K, Liu JS, Miles BJ, Lipshultz LI, Khera M. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol. 2013 Aug;190(2):639-44.Return to content
Pastuszak AW, Khanna A, Badhiwala N, Morgentaler A, Hult M, Conners WP, Sarosdy MF, Yang C, Carrion R, Lipshultz LI, Khera M. Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer. J Urol. 2015 Nov;194(5):1271-6
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Kacker R, Hult M, San Francisco IF, Conners WP, Rojas PA, Dewolf WC, Morgentaler A. Can testosterone therapy be offered to men on active surveillance for prostate cancer? Preliminary results. Asian J Androl. 2016 Jan-Feb;18(1):16-20.Return to content