Testosterone replacement therapy displays long-term safety, efficacy in post-radical prostatectomy men

Chicago-Results of a single-institution study support the long-term safety and efficacy of testosterone replacement therapy for treating hypogonadism in men who have undergone radical prostatectomy, concluded investigators from Memorial Sloan-Kettering Cancer Center, New York.

The study, which was presented at the 2012 World Meeting on Sexual Medicine in Chicago, included data from 71 men enrolled in a prospectively constructed database. All men had undetectable PSA after radical prostatectomy, and the majority had organ-confined prostate cancer with a favorable progression-free probability based on nomograms. However, the series also included 13 men (18%) who had pT3 disease, positive surgical margins, or Gleason sum ≥8 on radical prostatectomy specimen.

All men had symptoms of hypogonadism and/or low bone mineral density and had two early-morning serum total testosterone levels <300 ng/dL. Median time to testosterone replacement therapy (TRT) initiation after prostatectomy was 18 months (range, 6 to 34 months). All patients had a minimum follow-up of 6 months after starting TRT, and 17 men (24%) were followed for more than 3 years (median, 49 months; maximum, 75).

TRT resulted in a statistically significant increase in serum total testosterone from 235 ng/mL at baseline to 615 ng/mL. Biochemical recurrence of prostate cancer was detected in a single patient at 33 months after surgery (15 months after starting TRT). The patient had pT3b prostate cancer and positive surgical margins. His PSA at biochemical recurrence was 0.12 ng/mL. TRT was stopped, and at last measurement 6 years later, his PSA was 0.86 ng/mL without salvage treatment for prostate cancer.

“There has been a long-standing concern that TRT increases the risk of prostate cancer. However, recent evidence suggests that prostate risks from TRT may not be as great as once assumed, and preliminary results from several small case series show no biochemical recurrences in men started on TRT after RP,” said first author Kazuhito Matsushita, MD, a former Memorial Sloan-Kettering research fellow.

“The recurrence rate in our study is likely no higher than that expected for this cohort of RP patients, and our favorable experience suggests that with careful monitoring, TRT may even be used in high-risk patients after RP,” added Dr. Matsushita, currently of St. Luke’s International Hospital, Tokyo.

Senior author John P. Mulhall, MD, noted that published data on TRT post-prostatectomy are limited, and that to his knowledge, the Memorial Sloan-Kettering cohort is one of the largest with long-term follow-up.

“We believe the idea that testosterone should not be given to men who have undergone RP for prostate cancer because it will ‘fuel the fire’ is incorrect. In fact, there is increasing interest in the concept that testosterone supplementation may even protect against PSA recurrence,” he told Urology Times.

“The latter information aside, our study provides an overwhelming signal that TRT after RP can be done safely, including in men with unfavorable pathology, assuming careful patient selection and careful monitoring,” added Dr. Mulhall, director of the male sexual and reproductive medicine program at Memorial Sloan-Kettering.

“The question remains to be answered whether urologists practicing in the community will initiate TRT on their own or if they will feel more comfortable having the patient managed by specialists at a referral center.”

At Sloan-Kettering, post-prostatectomy patients started on TRT are followed with serum PSA every 3 months for the first year, then every 6 months over the next 2 years and yearly thereafter. Based on patient preference and serum LH, treatment is initiated with transdermal testosterone or clomiphene citrate (Clomid).

The men in the series had a median age of 62 years at the time of starting TRT. Their median PSA level prior to prostatectomy was 4.5 ng/dL, and the median Gleason sum on prostatectomy specimen was 7. No patient had lymph node-positive disease. Eighteen men (25%) had been on TRT prior to prostatectomy.