Testosterone replacement therapy reduces BCR after RP

I'm waiting for my first (ever) T results. My sex drive has dropped way down the past 6-8 months (achieving erections and orgasms are not the problem). A couple of uro visits ago I discussed possible T replacement (if needed) given my RP pathology and post-RP PSA levels. We may continue that discussion depending on test results. In the meantime I sent this paper to my uro, who said he wasn't familiar with these specific results regarding BCR when I mentioned I had glanced at a paper on this topic.

Testosterone replacement therapy reduces biochemical recurrence after radical prostatectomy (2020, Full Text, Thomas E. Ahlering et al.)
(Direct link doesn't work -- just click on the title on the search results that come up. I've pasted the abstract here.)

"Objective
To evaluate risk of prostate cancer biochemical recurrence (BCR) after radical prostatectomy (RP) in men receiving vs not receiving testosterone replacement therapy (TRT).

Patients and Methods
A total of 850 patients underwent RP by a single surgeon. All patients had preoperative testosterone and sex hormone-binding globulin levels determined; free testosterone was calculated prospectively. In all, 152 (18%) patients with low preoperative calculated free testosterone (cFT) levels and delayed postoperative sexual function recovery were placed on TRT and proportionately matched to 419 control patients by pathological Gleason Grade Group (GGG) and stage. Rates and time to BCR [two consecutive prostate-specific antigen (PSA) levels of ≥0.2 ng/mL] were compared in univariate and multivariate regression; Cox regression was used to generate a survival function at the mean of covariates.

Results
The median follow-up was 3.5 years. There were no statistically significant differences in demographics or general health complications between groups. BCR occurred in 11/152 (7.2%) and 53/419 (12.6%) patients in the TRT and control groups, respectively. In adjusted time-to-event analysis, TRT was an independent predictor of recurrence-free survival. After accounting for GGG, pathological stage, preoperative PSA level, and cFT, patients on TRT were ~54% less likely to recur (hazard ratio 0.54, 95% confidence interval 0.292–0.997). In men destined to recur, TRT delayed time to recurrence by an average of 1.5 years.

Conclusion
In our experience, TRT after RP significantly reduced BCR and delayed time to BCR. There was no identifiable general health complications associated with TRT. These findings are hypothesis-generating and require confirmation with multi-centred, prospective randomised controlled trials."

[Emphasis mine]

Your thoughts in my case (4 years post RP)?

Djin

It seems a bit obvious to me. I am assuming most surgery patients have a similar testosterone level after surgery to pre-surgery and that the T supplement is to get those patients with low T to normal levels after surgery. Thus I might expect the results to be similar for the two groups. However, the study seems to implies that a low T level is not good before/after surgery which seems odd since PCa thrives on testosterone. I think I am more confused after reading these results, must have missed something….

Djin - Are you thinking your T must be good since you made it 4 years?

Post Edited (Mumbo) : 7/23/2021 6:36:13 PM (GMT-6)

Well, if a guy is comfortable with the belief that he's "cured," I guess he could be comfortable with TRT. I'm not so sure, especially for a G9.

mattam said...
Well, if a guy is comfortable with the belief that he's "cured," I guess he could be comfortable with TRT. I'm not so sure, especially for a G9.

I don't know if i'm cured--no guy does. And I'm just reading up in case I am low-T. The study wasn't huge and G9 men are always a small cohort of all-Gleason studies. Another enticing finding was that for men destined for BCR, T therapy resulted in a 1.5 yr delay -- it did not hasten it.

My point was that I think it's more likely that I haven't experienced BCR because the PCa was removed than that low or high T has kept it at bay. At, say, 8 yrs post op, I would have reason to be more confident, of course.

Djin

Author Dr. Ahlering is one of the best in the business. He's probably done 3000 DaVinci Ralps by this time. Highly regarded in the profession. Anybody who is fortunate enough to get him as a surgeon is in good, good hands. Nice to see he's sharing his experience through medical studies with the world.

Prato,

I think that no one would suggest a single study is enough to bring about a change in SOC. At the visit previous to my last one, my uro and I both thought it was pointless to test my T only if I would want replacement therapy if it were indeed low. I too, am thinking about waiting another year (which will make 5 -- if I do it at all). Perhaps by then there will be confirmation/refutation of this study's result. This last visit, however, I decided I did want to at least know if my sex-drive decline is related to low T.

I must say that the idea that T could actually delay the start of BCR is an enticing one (as you know, I have not had ART or SRT).

Djin

Djin - FWIW, I had my T tested by my GP about a year after surgery as I was wondering about T and ED. It was 718 so no problem there. Back in 2014, I was tired all the time one winter so I had my T tested and it was 314 which was on the low side so we retested 2 weeks later and it was 546. As I recall, my doctor said T is quite variable over the course of a day and over longer periods so testing has to be done over longer periods at the same time of day to come to any conclusions.

Just to gratuitously chime in. . . as a TRT patient before, during and after RT, there are a trainload of variables that will ultimately need to be considered before a patient can make a fully informed decision about starting TRT after treatment for PCa.

I am not a medical professional, and am of limited knowledge in this important area, so I will just enumerate the few things I can think of.

First, the patient's diagnostic pathology will make a major impact on TRT decisions. For example, my pre-treatment diagnosis was favorable intermediate risk PCa, with 3 cores having low % involvement G3+3 and one core having very low involvement G3+4. Very close to AS territory, but I chose treatment due to the presence of G4 in that one core. With lower risk PCa, the risk of introducing (or maintaining) TRT has been shown to be very low (see Dr. Abraham Morgentaler's research). This is probably true of any PCa case where the standard of care does NOT include ADT. The human body cannot discern between the T that your body produces and that which you purchased at the pharmacy. . . AS LONG AS THE PATIENT'S T IS KEPT WITHIN A NORMAL RANGE. (caps are my own idea.) In other words, if SOC does not call for removing/reducing T in this patient, there is no harm then in maintaining that normal level for him if his own body cannot do so.

Where this study becomes so critically important is for all of those patients for whom ADT WAS part of their original Standard of Care. These men may find themselves in that segment of the population who, for reasons not clearly known, remain hypogonadal (low T) after cessation of their ADT regimen.

I sincerely applaud Dr. Ahlering for pursuing such a study and Djin for posting it for our group follow-up, as I honestly know the impact low T has on my life and would like to see as many men as possible having a chance to avoid it in the future.

I am severely hypogonadal and my numbers run 25 or less
Year's of opiate use has destroyed my ability to make testosterone. I've been on TRT for years and when my family doctor found out about my Pca he stopped it.
In a few months I was miserable. Horrible anxiety,timidity and depression coupled with irritability.
I found a clinic and started TRT once again.
I Have told my RO that I do not plan on stopping.
I'm taking a risk but my quality of life suffers greatly without it.
Last PSA was 2.3

Glen

Djin,


Thought 1:
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Can't imagine why Labcorp would not provide free T units. Maybe suppressed in their portal - I don't access my results that way, so not sure. Suggest you go into the Labcorp test menu, easily found online, try to find the specific Labcorp test code number (if your doc provided them) and look at the units in the sample report, or test details if no sample report is given.

For reference, I put one of my recent T reports here (Labcorp codes in ink):

https://i.imgur.com/caumewk.png



Thought 2:
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You seem about where I was when starting TRT. T was bumping in 300's and free at or below bottom of standard range. I went on androgel for a couple years, then switched to T-cyp injections. Stayed on that a year or two until seeing what I thought was some rising uPSA that might be related. All along, I was not feeling what I thought were acceptable results for all the trouble. I was also seeing my (self-tested) E2 running way high, sometimes twice the Labcorp high point of normal range. Could not get help from PCP, Uro or endocrinologist to get me on some Arimidex (anastrazole) or other AI inhibitor. The risk of being on TRT with a pos margin was just not worth it to me, though I generally do believe what Morgentaler theorizes. Anyway, to be safe, I just voluntarily stopped it all in 12/2018 and went on pretty intensive aerobics/weights to try to handle things myself. The results I posted above seem pretty positive. That's all without TRT and seems pretty good for a 72 yr old.



Thought 3:
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Suggest you monitor your estradiol yourself, even if your docs won't. The T from TRT won't help much if you are converting a lot of it to estrogen. This researcher Friedman has a theory that the estradiol is the problem with TRT and PCa, not the T itself:

https://www.researchgate.net/publication/305122202_the_relationship_between_testosterone_estradiol_and_prostate_cancer

There is a lot of stuff on one of the other boards, mostly for advanced PCa patients, that goes on about it. Sample:

https://healthunlocked.com/advanced-prostate-cancer/posts/135199608/dr.-edward-friedman-the-man-who-claims-pca-is-caused-by-estradiol

If your PCa advances, and I'm hoping it does not, you may find an additional home on that board.



Thought 4:
---------------

You seem like a thoughtful researcher and capable of absorbing complex publications and data. But if you are going to pursue TRT and want research or medical help deciding whether or how much of it to do, and for how long, just be generally aware that definitive answers may not be forthcoming.

A fellow PCa survivor and I have been going round and round with this stuff the last two years. He (a doc himself) has even been up to Mayo for one of those multi-day visits, many tests/labs of all sorts, multidisciplinary team of experts to go over everything. Even so, between us, we have recently realized and admitted to ourselves that we are not going to get help with all of this (TRT, PCa, possible recurrences, etc.). We think there is just no one doc that can tie it all together, and the separate specialists are just out there in their own worlds. Maybe you will fare better, hope so, but you may need to make future decisions based on "gut feel" rather than assured medical advice.


Thought 5:
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The possibility that TRT could help with PCa is pretty exciting. I had this one bookmarked away:

https://pubmed.ncbi.nlm.nih.gov/31498469/


Robert

DjinTonic said...
, but way over to the right after the value in a separate column, pg/mL. This is on the actual report you download. (However the summary page you first see in the portal has no units, which is rather odd.)

Well, that explains it, then. You know, for a well-regarded major lab, they sure do some funny things: like the occasional "way out of line" lab result (I've had one and others here have, too); switching back and forth on lower uPSA test range over the years, with never any advance warning or explanation; slowness in getting notices out to public about biotin use affecting certain of their tests--I noticed during my last blood draw, they now have a poster about biotin in their waiting room (finally!, but it's been reported on in medical pubs for several years now, I think).

DjinTonic said...

I haven't done much research -- I'm holding off until my uro chimes in. And these are probably essay questions.

Essay questions, indeed...I have years of links to pubs about this stuff that I can offer in the future. Seems you are in a holding pattern for now. And I am trying to wrap up executor duties on a relative's estate over next couple months. But, over time, I may be able to jump-start your research some, if you want to keep this thread going or start a new one when you are ready. It's going to be a tough road to a decision for you, I'm guessing. But, good luck, in advance.

Robert

I just got my 1-month repeat results back (early morning blood draw) in the Labcorp portal:

Free T (dialysis) is still low: 46 (last month 43), adult males = 52-280 pg/mL
% Free = 1.1 (last month 1.2) , adult males = 1.5 - 3.2%

Total T = 420 (last month 362), adult males = 264 - 916 ng/dL

New results:

LH = 3.7 mIU/mL, reference interval 1.7-8.6
FSH = 5.1 mIU/mL, reference interval 1.5-12.4
Prolactin = 8.6 ng/mL, reference interval 4.0-15.2

I'll see the comments my uro makes when he posts my results in his portal next week, but I'm leaning towards not doing anything and re-evaluating in a year, at my 5-year post-RP mark. It's not that I have no sex drive, and total T is WNL, so I'd rather not risk anything, at least yet.

Djin

Thanks, Robert!