Testosterone Therapy After Prostate Cancer Treatment: A Review

Testosterone Therapy After Prostate Cancer Treatment: A Review of Literature (2021, Review, Full Text)

"Abstract
Introduction
Although testosterone therapy (TTh) is the standard practice in otherwise healthy hypogonadal men, this therapy has historically been contraindicated in men with a history of prostate cancer. Recent evidence suggests that there is minimal or no prostate cancer growth in the setting of TTh administration in men definitively treated for non-metastatic prostate cancer.

Objective
To review the evidence supporting the safety and efficacy of TTh in patients previously treated for localized prostate cancer.

Methods
A literature review of the PubMed database was performed to identify studies evaluating the safety and efficacy of TTh in patients with a history of prostate cancer. Search terms included Testosterone Therapy, Testosterone Replacement Therapy and Radical Prostatectomy, Radiotherapy, External Beam Radiation Therapy, EBRT, Brachytherapy; Prostate Cancer and Hypogonadism, Low Testosterone; Bipolar Androgen Therapy.

Results
Available literature provides evidence for the safe application of TTh in patients previously treated for prostate cancer with either radical prostatectomy or radiotherapy. Furthermore, there exists evidence that severely hypogonadal levels of testosterone may lead to worse oncological outcomes. More recent research has begun to elucidate the effectiveness of bipolar androgen deprivation therapy in the treatment of prostate cancer. This mechanism of action increases the level of evidence indicating that the traditional management of maintaining testosterone levels at low levels may no longer be standard of care. TTh likely has a role in improved erectile function and other quality-of-life concerns in patients developing testosterone deficiency after being treated for prostate cancer.

Conclusions
TTh should be offered to select hypogonadal patients who have a history of definitively treated prostate cancer. Adequately designed randomized controlled trials are necessary to confirm the safety and efficacy of TTh in this population."

(Emphasis mine. See Full Text. See also Ref. 67:

Diagnosis and Treatment of Testosterone Deficiency: Updated Recommendations From the Lisbon 2018 International Consultation for Sexual Medicine (2019, Morgentaler et al.)

"Conclusions
Treatment of TD offers multiple benefits for sexual symptoms as well as for general health, without compelling evidence for increased risk of prostate cancer or cardiovascular events."

Djin

That is interesting.
And even though there’s been evidence in the past of no harm being done with t replacement, it still feels so counterintuitive

When I was first diagnosed I thought Standard Medical Practice of dosing until failure was contrary to principles of Evolution. I reasoned that the cancer always adapts to it's current environment. The environment created by any treatment is a harsh one to live in for a cancer cell, but what troubled me was that it was stable. So, it's really tough in there for PC but a few cells are getting by and they will ultimately adapt. At that point I told my Dr. I did not want to take any treatment until failure.

I read a 2017 Article by Gatenby and Zhang "Integrating Evolutionary Dynamics into the Treatment of mCRPC" and, in the view of the authors, I was on the right track. I read other articles by Gatenby and Zhang and was impressed by their logic, which I have discussed in other posts. Unfortunately they are not considered mainstream, largely I think because they don't do large Clinical Trials. AND they used [insert eerie music] mathematics.

I visited Gatenby and Zhang. They have seven Applied Mathematicians on their staff. They have promoted "Adaptive Therapy" -- take a med until your PSA drops 50% [an arbitrary number, which they now believe should be higher] then stop med. When PSA returns to previous high restart and repeat. In one trial with 16 people with Abiraterone the group had a longer time to resistance and, in the aggregate, used less than 1/2 the amount of Abi.

Concerning persistently low T producing persistently low PSA their reasoning is as follows. CSPC does not "become" resistant; there are already resistant cells there. By maintaining prolonged low T you're killing all the non-resistant cells, i.e. you're breeding resistant ones. Cancer cells are competing for space and resources. In a low T environment resistant cells are more fit than sensitive cells. However, in the presence of T the sensitive cells are more fit for survival. Why? Because the resistant cells incur significant metabolic costs to maintain resistance. By backing off treatment your treatment the sensitive cells outcompete the resistant cells, putting evolutionary pressure on them. Once PSA has risen (they're working on the math to see how much) to a certain point reapply the med. By modulating the therapy and periodically changing the environment it will take the cancer cells longer to attain full resistance.

Maintaining persistently low T gives an advantage to cells that can survive that environment.

I requested bipolar androgen therapy ("BAT") which I've spoken about at length in other posts and won't repeat here. My PSA went up (I was still Hormone sensitive). When BAT was discontinued it went down. I had done Abi for around 7 months prior to BAT, had four months of undetectable PSA but I did not go resistant to ABI. When BAT was over [Oct. 2019] I did not restart Abi. I rocked along on Lupron for a while and then went hormone resistant. I then went on ENZO. Enzo is cross resistant with Abi. But, having not gone Abi resistant the Enzo was powerful. I took it for 24 days July/Aug. 2020. My PSA went from 2.0 to 0.2 I will resume once PSA returns to 2.0. It is now almost six months I've been off Enzo and it's not back to 2.0 yet.

Yesterday was the fourth anniversary of my first treatment. A scan I had in Aug 2020 was better than a scan I had had over a year and a half before.

I'm very interested in the information you posted because I've been concerned about being on Lupron for four years. I'm always a bit tired, I have cognitive issues [slow thinking; starting a sentence and halfway through forgetting where I was going . . .]. I have been thinking that when my most recent Lupron shot expires (March) I should consider either going off Lupron for a while and, possibly, more BAT (assuming I could get someone to administer it). Also, I am keenly aware that I am not an ONC. I have a relationship with my ONC, who is highly respected in the medical community, that I consult other ONCs but no treatment is undertaken without his prior knowledge and consent. He has always consented. There are around 4 or 5 ONCs who I just talk to periodically and, based on those conversations decide what happens next. So, in one sense I am controlling my own treatment but always under supervision and recommendation of at least one of the ONCs.

Standard Medical Practice/Phase III trials, always lags new developments. When I was hormone sensitive I lobbied for access to second gen hormone treatment and met with resistance. Why? Because all the Trials had been on Hormone resistant patients; trial results were not yet available for Hormone sensitive. Subsequently the results of those trials came out and confirmed that these treatments did work (probably better) administered sooner.

Every treatment decision is a guess. If there's a Phase III result the guess is more solid but it's still a guess. I want to push the envelope with things based on sound reasoning, knowing that it's a crap shoot. As I said, I want to be in control of my treatment, but under supervision of willing medical personnel.

I do not want to be in a Clinical Trial. I would consider it if it meant getting some treatment otherwise unavailable but otherwise my view is I AM a Clinical Trial, n=1. So far, I'm doing pretty well.

Thank you for calling this to our attention.

Thanks for the information, I didn't know about this Article.

As for gasoline on fire that was the comment of one ONC that was part of a reply to one of my posts on Androgen Deprivation therapy.

Very interesting about the PSA info. I was not hypogonadal until I started hormone therapy. Except for bipolar androgen therapy ("BAT"). I've had T<10 for four years. I felt great on BAT -- felt like I used to. I even thought "wow, I didn't realize how bad the side effects of that hormone therapy were". Then they took me off it and I said "oh, I remember now - it stinks".

Administering BAT puts the ONC in an uncomfortable position. It's not an approved treatment and it has the opposite effect of accepted hormone therapy. Once my PSA started rising they were out.

One has recommended intermittent hormone therapy. I don't think I'll be able to get BAT so that might be an option. It takes a good while for your testes to start rolling again after being shut down for four years. The one benefit of intermittent hormone therapy is that it's not a treatment they can take me off of.