Case deliberations: To treat or not to treat with testosterone therapy?

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Case deliberations: To treat or not to treat with testosterone therapy?
18 March 2019

Testosterone therapy (TTH) as a plausible treatment for a patient was examined during “Plenary Session 06: The role of the urologist in sexual and fertility issues of cancer survivorship”, which was chaired by Dr. Maarten Albersen (BE) and Prof. Jens Sønksen (DK).

Moderator Assoc. Prof. Ege Can Şerefoğlu (TR) defined the patient case scenario and set the stage for the deliberations.

The case
The patient is a 58-year old male suffering from prostate cancer (PCa) with a PSA level of 7.6 ng/mL. He underwent transrectal ultrasound (TRUS) guided biopsy, which revealed that he had a Gleason score of 3 + 3 PCa. At that time, he reported no erectile dysfunction (ED).

The patient underwent robotic-assisted radical prostatectomy (RARP) with bilateral nerve-sparing (BNS). The pathology revealed that he has a Gleason score of 4 + 3 PCa. He was taking a daily dose of 5mg of Tadalafil.

During a follow-up three months after the operation, his PSA was undetectable (< 0.1 ng/mL) and the patient was suffering from ED despite the Tadalafil. On the sixth-month, his PSA was still undetectable and he still suffered from ED. He was still taking Tadalafil. This time, the patient reported depressive thoughts, fatigue and loss of libido.

When his testosterone (T) levels were checked, they were at 7.6 nmol/L (8-12 nmol/L) which is lower than the normal range. Two weeks later, his T levels were at 7.2 nmol/L (8-12 nmol/L).

Pro: Patient is a candidate for TTH
“If the patient is highly symptomatic, testosterone therapy (TTH) should be seriously considered. The comorbidities associated with low T level may be more likely to kill him rather than his prostate cancer,” said Prof. John Mulhall (US), who gave the caveat to use TTH term instead of testosterone replacement therapy (TRT).

Prof. Mulhall stated that the risk of poor nerve recovery is a concern and should be communicated to the patient prior to the decision of whether or not to forego TTH. He added, “I believe the Saturation Model is valid because I’ve shown vivo data on PSA’s response to testosterone. The only issue is at what T level is the patient’s androgen receptor fully saturated?”

While larger, longer analyses are required, there is a signal that testosterone therapy is safe in a man with this patient’s pathology (Gleason 7 or organ-confined).

“I encourage all of the oncologists in the room to not be so PSA-centric and to focus on quality of life and overall holistic help of the patient. In my opinion, until we have data demonstrating that TTH is unsafe in the prostate cancer population, which we do not have, I believe that choosing the scientific approach should lead us to prescribe TTH if the patient so wishes.”

Con: “I would be reluctant to give this man TRT”
Prof. Bertrand Tombal (BE) stated that he would be reluctant to give the patient TRT because evidence is “weak” and the risk of recurrence is not negligible. He asserted that the T levels of the patient should have been measured before the prostatectomy and that the patient should have given a questionnaire to check for preliminary signs of androgen-deficiency.

Prof. Tombal discussed the Coffey Paradox: If PCa cells retaining Androgen Receptor (AR) expression, TRT-induced AR signalling up-regulates c-Myc translation and protein stability to stimulate malignant growth. Thus in AR expressing PCa cells, AR signalling is converted from a growth suppressor to an oncogene.

He underlined that 5 alpha-reductase inhibitors reduce the risk of progression, and provided data that show testosterone made the PCa more aggressive.

Poll results
After the debate, Prof. Şerefoğlu asked the audience “Would you consider TRT for this hypogonadal PCa patient?” The audience keyed in their answers via the EAU Events App. About 83% voted “Yes” and the 17% voted “No”