Ozempic Bull**** (again)

[MidwestRadOnc]

Especially with the UA companies being chronically "understaffed" (sarcastic air quotes) and requiring 14 days for review and then 7 days to schedule a peer to peer.

This should be illegal. It's a delay tactic for cancer care. Obviously that sweet insurer lobby money will keep the grift going.

Our system can’t even do anything about the ozempic situation which threatens to make us insolvent. You think policymakers are going to fix prior auth for radiation? Our form of medicine, is not a drug (and especially not an experimental quick fix), so here we are. Nobody cares.

https://www.barrons.com/articles/wegovy-ozempic-obesity-drugs-healthcare-system-20307eea

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Members don't see this ad.

 

[medgator]

Our system can’t even do anything about the ozempic situation which threatens to make us insolvent. You think policymakers are going to fix prior auth for radiation? Our form of medicine, is not a drug (and especially not an experimental quick fix), so here we are. Nobody cares.

https://www.barrons.com/articles/wegovy-ozempic-obesity-drugs-healthcare-system-20307eea

Ozempic could reduce dialysis costs, cancer incidence, cabg rates etc in the future. Not sure that's a good long term way to look at it or example to use at all

 

[Mandelin Rain]

Ozempic could reduce dialysis costs, cancer incidence, cabg rates etc in the future. Not sure that's a good long term way to look at it or example to use at all

Yeah, I think GLP-1s will upheave medicine altogether. Less alcoholism. Less obesity related disease.

It has the potential to dramatically reduce the costs our current "sick-care" model.

 

[RickyScott]

Yeah, I think GLP-1s will upheave medicine altogether. Less alcoholism. Less obesity related disease.

It has the potential to dramatically reduce the costs our current "sick-care" model.

pill forms are in phase 3 trials.

 

[Mandelin Rain]

Not sure if anyone listens to Scott Galloway, but he sees GLP-1s as being a bigger economic disrupter than AI.

Seems crazy on it's face, but he lays out some of the secondary/tertiary downstream impacts of dramatic weight loss, and you think... maybe?

 

[MidwestRadOnc]

Sigh. That wasn't the point, but on that topic have we learned nothing from every other miracle weight loss drug in the past?

It is no question these are making the drug companies enormous fortunes.
What will be the effect of these drugs taken on a mass scale in 10 years? 20 years? There is already growing concern of dangers.
The American diet and lifestyle is the problem. The question is if a drug that treats the symptom and not the underlying cause will fall in an acceptable therapeutic window both medically and psychologically. Could, yes. It is an experiment and we will see. It is possible that, yes, it really is different this time.

My non-paralyzed gut is telling me that this is enabling bad behavior (i.e., the standard American lifestyle) for the majority of people, which carries other collateral consequences than just being fat. Don't eat processed foods and move 30 minutes a day and most people won't need this drug. And we are going to channel a huge part of the tax base (which we can clearly afford at the moment) to pharma to do it. I have, um, concerns, and would wager there will be a bigger price to pay as always.

 

[OTN]

Sigh. That wasn't the point, but on that topic have we learned nothing from every other miracle weight loss drug in the past?

It is no question these are making the drug companies enormous fortunes.
What will be the effect of these drugs taken on a mass scale in 10 years? 20 years? There is already growing concern of dangers.
The American diet and lifestyle is the problem. The question is if a drug that treats the symptom and not the underlying cause will fall in an acceptable therapeutic window both medically and psychologically. Could, yes. It is an experiment and we will see. It is possible that, yes, it really is different this time.

My non-paralyzed gut is telling me that this is enabling bad behavior (i.e., the standard American lifestyle) for the majority of people, which carries other collateral consequences than just being fat. Don't eat processed foods and move 30 minutes a day and most people won't need this drug. And we are going to channel a huge part of the tax base (which we can clearly afford at the moment) to pharma to do it. I have, um, concerns, and would wager there will be a bigger price to pay as always.

The cost of Ozempic is but a trifle compared with Social Security, Medicare, Medicaid (to a lesser extent), and interest on the national debt. A trifle. Meaningless.

 

[MidwestRadOnc]

The cost of Ozempic is but a trifle compared with Social Security, Medicare, Medicaid (to a lesser extent), and interest on the national debt. A trifle. Meaningless.

Well, there is enough concern that Barron's, BI, Bloomberg, and every other financial news outlet recently published on it. If Medicare spending is a death by a thousand cuts, then what's a thousand and one I guess is the argument? Ozempic could be a big one, though.

 

[OTN]

Well, there is enough concern that Barron's, BI, Bloomberg, and every other financial news outlet recently published on it. If Medicare spending is a death by a thousand cuts, then what's a thousand and one I guess is the argument? Ozempic could be a big one, though.

Much easier to write an article about a single drug than expose the entire fiscal house of cards that is the federal government.

 

[Mandelin Rain]

Would I rather the US Government/taxpayers stop heavily subsidizing incredibly terrible food produced by multinational corporations, deal with food deserts, and require corporations to offer mandatory exercise breaks during the work day? Sure.

But it won't happen for the same reason US government/taxpayers won't stop subsidizing United Health Care record profits.

Too much money involved.

I see GLP-1s as a potential off-ramp for people who don't want to stay in their status quo offered up to them.

 

[MidwestRadOnc]

Would I rather the US Government/taxpayers stop heavily subsidizing incredibly terrible food produced by multinational corporations, deal with food deserts, and require corporations to offer mandatory exercise breaks during the work day? Sure.

But it won't happen for the same reason US government/taxpayers won't stop subsidizing United Health Care record profits.

Too much money involved.

I see GLP-1s as a potential off-ramp for people who don't want to stay in their status quo offered up to them.

It is sad that you may be right. We are venturing into "harm reduction" territory. If we can't get people to stop using drugs/overeating processed foods with added sugars, then how do we reduce personal and societal harm without enabling?

In my Midwestern area, I am already seeing entrepreneurial-minded NPs setting up cash-only ozempic virtual clinics. Mmmm, reminds me of pill mills and weed doctors. I would imagine this is exponentially worse in California.

 

[RickyScott]

It is sad that you may be right. We are venturing into "harm reduction" territory. If we can't get people to stop using drugs/overeating processed foods with added sugars, then how do we reduce personal and societal harm without enabling?

In my Midwestern area, I am already seeing entrepreneurial-minded NPs setting up cash-only ozempic virtual clinics. Mmmm, reminds me of pill mills and weed doctors. I would imagine this is exponentially worse in California.

its much easier to quit cocaine or heroin than keep weight off with diet and exercise. Diet and exercise fail over 90%+ of time in the management of obesity.

 

[MidwestRadOnc]

its much easier to quit cocaine or heroin than keep weight off with diet and exercise. Diet and exercise fail over 90%+ of time in the management of obesity.

When you quit Ozempic, the weight comes back for the exact reasons you say. So we're talking about lifetime drugs. What's the effect of Ozempic for weight loss over a lifetime? Statins are still controversial and GLP-1 drugs for weight loss are in their infancy.

These drugs probably need to be combined with careful follow-up, resistance exercise and specific macronutrient formulations. How many are doing that vs. continuing sedentary lifestyles eating Krispie Kreme? Especially if the NP-run online cash-clinics are managing it?

I think it's valid to have questions and concerns over this rather than just say, quitting sugar is too hard and imply that doing so is harmful because it could cause Ozempic-hesitancy or something. We've been through this before. These are never black-or-white/science-is-settled scenarios.

 

[communitydoc13]

Same conversation...different handle.

Not sure how GLP-1 drugs relate to normal patient volume, but am sure that the world we live in (while good IMO) presents challenges and experiences that we are variably selected for evolutionarily.

I have no problem with medications for ADHD, depression, anxiety, obesity, tobacco abuse, HTN or DM. Should these things be prescribed judiciously...sure. That's why there are doctors and a medical establishment. Also true that diet, exercise, social support are all important in managing all of these conditions. Also true that there will inevitably be surprises regarding long term toxicities/side effects of GLP-1 drugs. There are always surprises regarding all medical interventions.

It is neigh impossible presently to get insurance approval for GLP-1 drugs without a diagnosis beyond obesity. So, the patients you know who are on them are either likely to have other manifestations of metabolic syndrome or to be paying out of pocket.

Your middle aged friends who over the past couple of years have somehow managed to lose 30-50 pounds or sometimes much more and keep it off (and yes, they may look older) have a good chance of being on one of these drugs. I wouldn't judge any of them. I do however wish that culturally we were more comfortable disclosing our use of these medications and our medical conditions (particularly mental health).

In the short term, it is the pricing that is the problem.

 

[MidwestRadOnc]

I wouldn't judge any of them. I do however wish that culturally we were more comfortable disclosing our use of these medications and our medical conditions (particularly mental health).

You don't have any argument from me there. It is interesting that the stigma has been lifted from T-supplementation in men. People talk about that openly now. Regarding mental health, as physicians if we seek to acquire treatment for something like substance abuse it can literally be a threat to our career.

SSRIs (psychotropics) and ADHD drugs (amphetamine) are routinely overprescribed, alarmingly so in adolescents and children. It's easy to offer a pill for a multifactorial problem that varies person-to-person. Oxycontin was an easy solution to chronic pain. I am suspicious.

 

[evilbooyaa]

We really doing ANOTHER thread on Ozempic?

I guess we are. Posts moved to its own thread. Didn't we already have some strongly opinionated Rad Onc talking about the evils of Ozempic use/abuse running rampant and eating at the moral fabric of our society (more so than the other things that do that on a daily basis)

 

[MidwestRadOnc]

It was a random comment that triggered a side discussion. It is bizarre the reactions that even gentle criticism of or even a quip about this drug in particular generates. Agree it has nothing to do with rad onc. I don't care if you delete the convo.

 

[VA Hopeful Dr]

pill forms are in phase 3 trials.

Or they're already out: see Rybelsus

When you quit Ozempic, the weight comes back for the exact reasons you say. So we're talking about lifetime drugs. What's the effect of Ozempic for weight loss over a lifetime? Statins are still controversial and GLP-1 drugs for weight loss are in their infancy.

These drugs probably need to be combined with careful follow-up, resistance exercise and specific macronutrient formulations. How many are doing that vs. continuing sedentary lifestyles eating Krispie Kreme? Especially if the NP-run online cash-clinics are managing it?

I think it's valid to have questions and concerns over this rather than just say, quitting sugar is too hard and imply that doing so is harmful because it could cause Ozempic-hesitancy or something. We've been through this before. These are never black-or-white/science-is-settled scenarios.

Not among those of us who actually treat CV disease or try to prevent it.

 

[seper]

Testosterone supplementation is OK now?

 

[TheWallnerus]

The UCSF group is doing some mathematical simulations now that, given cancer patients on the whole potentially weighing millions of pounds less per year, the reduced mass will require less electricity for treatment couches to move (IGRT shifts) and less fossil fuel use for cars to drive patients back and forth for treatments.

(But I think ozempic has some flatus issues too, so that could offset the above.)

We will just have to wait on the modeling outcomes.

 

[Palex80]

Testosterone supplementation is OK now?

Yes!
Although some departments chairs may benefit from testosterone withdrawal.

 

[VA Hopeful Dr]

Testosterone supplementation is OK now?

If done by someone who doesn't run a "men's health clinic" or a "wellness center", yes. Otherwise, no.

 

[MidwestRadOnc]

Testosterone supplementation is OK now?

Joe Rogan and Jeff Bezos approved. That’s where we are now.

I’d rather supplement exploitative academic satellite rad onc income by running an online test clinic (ie, being a drug dealer), than running interference for Evicore to withhold needed cancer care. There is at least a shred of honor in the former.

 

[TheWallnerus]

Joe Rogan and Jeff Bezos approved. That’s where we are now.

I’d rather supplement exploitative academic satellite rad onc income by running an online test clinic (ie, being a drug dealer), than running interference for Evicore to withhold needed cancer care. There is at least a shred of honor in the former.

You know I think there’s some favorable high level evidence for test suppl in older dudes tho right? Someone get out their Google.

 

[medgator]

If done by someone who doesn't run a "men's health clinic" or a "wellness center", yes. Otherwise, no.

Urologist in town who does it hardcore, even in prior PCa patients

 

[MidwestRadOnc]

You know I think there’s some favorable high level evidence for test suppl in older dudes tho right? Someone get out their Google.

Just had the opposite conversation with a patient struggling with weight gain on ADT.

At this point, from my everything I've learned on this topic, If I were a moderately overweight middle aged man who struggled to shed it with dietary changes, I absolutely would supplement T and hit the gym if the alternative was ozempic. Increased lean muscle mass does wonders and ozempic is going to do the opposite.

Now excuse me while I eat the cinnamon rolls my staff brought for my concerningly high birthday while I still can.

 

[communitydoc13]

Urologist in town who does it hardcore, even in prior PCa patients

I don't think there is actually strong data against it in PCa?

I believe the percentage of middle and older men who would qualify based on present standards for normal T is pretty low (2-4%)?

There are risks no doubt and I suspect abuse (prescribing T in men with normal T) is rampant. (to @MidwestRadOnc 's point: I'm sure there is significant GLP-1 abuse among the healthy, low visceral fat, low lipids, very low cardiac risk and normal (fat by certain cultural standards) body habitus, predominantly female crowd as well).

A very short trial (2 year f/u) demonstrated no increase in cardiovascular events but did show an increase in blood clots, arrhythmias and kidney problems for T.

I personally suspect that T is antithetical to very high longevity (although it is a robust measure of health in young men).

T is a remarkable performance enhancer and the direct to patient marketing is absurd. I once saw a chart of T levels for Olympic level athletes....clustered at the top of the legal levels (for both male and female athletes).

T also impacts behavior pretty remarkably.

Wonder what a study of T levels of age matched male attendings by specialty would look like?

I absolutely would supplement T and hit the gym

I do think there is data that weight training can promote T. Extreme endurance athletes often struggle with low T levels (perhaps a stress response).

 

[MidwestRadOnc]

I personally suspect that T is antithetical to very high longevity (although it is a robust measure of health in young men).

I have this concern as well from what we know from animal models when it comes to protein and overall caloric intake and the metabolism to support that. Greenland sharks live for something like 500 years and just kind of float there in a semi-frozen state. How long do hummingbirds live?

T is a remarkable performance enhancer and the direct to patient marketing is absurd. I once saw a chart of T levels for Olympic level athletes....clustered at the top of the legal levels (for both male and female athletes).

The tales of what happens in the Olympic village every 4 years when you put this specific population of young people together are well known.

 

[Ray D. Ayshun]

I had a patient use T for cluster headaches through salvage RT. Talk about a fun first PSA recheck...

 

[MidwestRadOnc]

I had a patient use T for cluster headaches through salvage RT. Talk about a fun first PSA recheck...

Umm.... if supplemental T is causing what should be an undetectable PSA to become detectable, i would be concerned.

(PDF) TESTOSTERONE (T) CHALLENGE IN MEN POST-RADICAL PROSTATECTOMY (RP) WITH PROFOUNDLY LOW TESTOSTERONE

PDF | Testosterone (T) Challenge in Men Post-Radical Prostatectomy (RP) with Profoundly Low Testosterone John P. Mulhall*, New York, NY, Serkan Deveci,... | Find, read and cite all the research you need on ResearchGate

www.researchgate.net

https://www.sciencedirect.com/science/article/abs/pii/S1743609522000704

 

[TheWallnerus]

Umm.... if supplemental T is causing what should be an undetectable PSA to become detectable, i would be concerned.

(PDF) TESTOSTERONE (T) CHALLENGE IN MEN POST-RADICAL PROSTATECTOMY (RP) WITH PROFOUNDLY LOW TESTOSTERONE

PDF | Testosterone (T) Challenge in Men Post-Radical Prostatectomy (RP) with Profoundly Low Testosterone John P. Mulhall*, New York, NY, Serkan Deveci,... | Find, read and cite all the research you need on ResearchGate

www.researchgate.net

https://www.sciencedirect.com/science/article/abs/pii/S1743609522000704

Ha. Maybe we ought to “challenge” all undetectable PSAs with test. You got me thinking.

 

[Ray D. Ayshun]

Ha. Maybe we ought to “challenge” all undetectable PSAs with test. You got me thinking.

I guess in essence that's what I was able to do. Nothing like a post-salvage PSA of "undetectable" in a patient on supplemental T, though maintaining it wnl. In any case, I have immediate proof that I hit at least most of the prostate cancer, which may come as a shock to MRO, though he may already believe I always hit some of it.

 

[OTN]

I had a patient use T for cluster headaches through salvage RT. Talk about a fun first PSA recheck...

I've had some family members with cluster headaches so bad they would not hesitate to take any and all interventions, prostate cancer be damned.

 

[communitydoc13]

Ha. Maybe we ought to “challenge” all undetectable PSAs with test. You got me thinking.

Interesting concept. T challenge to elicit radiographically (by PSMA PET) evident disease and therefore tailor salvage treatment volumes and dosing. Gotta be a young, potentially high-T, early career attending willing to try this trial.

T will bump up PSA pretty quickly and XRT will drive it down somewhat slowly, so a salvage case with a PSA of 0.5 and a negative PET may get a bump from T if started during XRT regarding an early PSA measurement.

Of course, the benefits of ADT regarding pCa are often substantial.

 

[Lamount]

Just had the opposite conversation with a patient struggling with weight gain on ADT.

At this point, from my everything I've learned on this topic, If I were a moderately overweight middle aged man who struggled to shed it with dietary changes, I absolutely would supplement T and hit the gym if the alternative was ozempic. Increased lean muscle mass does wonders and ozempic is going to do the opposite.

Now excuse me while I eat the cinnamon rolls my staff brought for my concerningly high birthday while I still can.

Semaglutide + hitting the gym is my preference. Semaglutide has been shown to decrease cardiovascular whereas testosterone has only been shown to be non-inferior to placebo.

I am sure both have their role for the right population.

 

[MidwestRadOnc]

Ha. Maybe we ought to “challenge” all undetectable PSAs with test. You got me thinking.

Lead your patients down the hormonal primrose path.

How's that testosterone making you feel?
Awesome! I feel like I'm 20 again! (wife smiles)
Well, your PSA came back up.
So I have to stop the testosterone?
Yes, but also we need to give you this other shot instead to lower your testosterone.
How low?
Zero
How long?
Forever.

 

[Ray D. Ayshun]

Interesting concept. T challenge to elicit radiographically (by PSMA PET) evident disease and therefore tailor salvage treatment volumes and dosing. Gotta be a young, potentially high-T, early career attending willing to try this trial.

T will bump up PSA pretty quickly and XRT will drive it down somewhat slowly, so a salvage case with a PSA of 0.5 and a negative PET may get a bump from T if started during XRT regarding an early PSA measurement.

Of course, the benefits of ADT regarding pCa are often substantial.

I've wondered about trying to time the PSMA PET to around 2-3 weeks after Lupron to coincide with T flare.

 

[communitydoc13]

I believe that the concept of T being used as a radiosensitizer has been floated in the past.

I would not advocate for T challenge in all post-prostatectomy patients. (No way). We don't need to look for more patients to treat earlier in this particular disease.

In the salvage setting it is an interesting concept IMO.

 

[evilbooyaa]

I've wondered about trying to time the PSMA PET to around 2-3 weeks after Lupron to coincide with T flare.

Lupron will down regulate PSMA-receptor expression in the prostate cells. PSMA PET in a newly diagnosed recurrent patient should be done prior to administration of ADT...

https://www.nejm.org/doi/full/10.1056/NEJMoa2215025

Testosterone supplementation, at 33 months median f/u from initiation, in a group of patients WITHOUT prostate cancer or prostate nodules and without elevated PSA, recent cardiovascular or CV-equivalent event did not show any increase in cardiovascular end points but did show increased rates of A-fib, acute kidney injury, and PE

Also, testosterone increases risk of bone fracture (probably because you feel younger and do more stupid **** to injure yourself)

https://www.nejm.org/doi/full/10.1056/NEJMoa2308836?query=featured_home

Can't make any statements about safety of T in patients with any history of prostate cancer

 

[MidwestRadOnc]

Lupron will down regulate PSMA-receptor expression in the prostate cells. PSMA PET in a newly diagnosed recurrent patient should be done prior to administration of ADT...

Is there any data on the timeframe over which sensitivity decreases?
I frequently run into scenarios and questions from referrings about the utility of PSMA pet after starting ADT after x, y, or z months. My answer is chance of false negative increases, but I can't really say how much and it's a case-by-case gut feeling based on initial risk factors and how long they've been androgen-deprived.

 

[Ray D. Ayshun]

Is there any data on the timeframe over which sensitivity decreases?
I frequently run into scenarios and questions from referrings about the utility of PSMA pet after starting ADT after x, y, or z months. My answer is chance of false negative increases, but I can't really say how much and it's a case-by-case gut feeling based on initial risk factors and how long they've been androgen-deprived.

I just did a google investigation and it seems that PSMA Suvmax is increased between weeks 1-4, decreased at 3 months.

 

[RickyScott]

I just did a google investigation and it seems that PSMA Suvmax is increased between weeks 1-4, decreased at 3 months.

i was told that initially after admin of lupron psma suv increases

 

[DoctwoB]

Lupron will down regulate PSMA-receptor expression in the prostate cells. PSMA PET in a newly diagnosed recurrent patient should be done prior to administration of ADT...

https://www.nejm.org/doi/full/10.1056/NEJMoa2215025

Testosterone supplementation, at 33 months median f/u from initiation, in a group of patients WITHOUT prostate cancer or prostate nodules and without elevated PSA, recent cardiovascular or CV-equivalent event did not show any increase in cardiovascular end points but did show increased rates of A-fib, acute kidney injury, and PE

I'd say that's a bold interpretation of the trial. Showed no statistically significant difference in any of the mentioned end points between T and placebo. While VTEs were 1.7% in T arm vs. 1.2% in placebo arm, you could just as easily point to death from CV causes at 3.4% in T arm and 4.0% in placebo arm. Neither are significant.

Also, testosterone increases risk of bone fracture (probably because you feel younger and do more stupid **** to injure yourself)

https://www.nejm.org/doi/full/10.1056/NEJMoa2308836?query=featured_home

Can't make any statements about safety of T in patients with any history of prostate cancer

We can make plenty of statements about safety of T and prostate cancer

"There is no clinical evidence that testosterone therapy increases risk of recurrence or progression of prostate cancer"

In men with prostate cancer, there is no risk that higher endogenous testosterone levels increases risk of recurrence or progression (except when on ADT)

https://www.sciencedirect.com/science/article/abs/pii/S1558767318300326

"There is retrospective evidence that testosterone therapy does not increase risk of recurrence or progression of prostate cancer"

Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease - Prostate Cancer and Prostatic Diseases

The safety of testosterone therapy (TT) after definitive treatment for localized prostate cancer remains undefined. We analyzed the risks of biochemical recurrence and mortality in men receiving TT after treatment for localized prostate cancer. Cohort analysis using the national US Veterans...

www.nature.com

"patients without prostate cancer on testosterone therapy do not have a higher risk of developing prostate cancer"

Prostate Safety Events During Testosterone Replacement Therapy

This randomized clinical trial examines the effects of testosterone replacement therapy on major adverse cardiovascular events in men with hypogonadism.

jamanetwork.com

The whole T and prostate cancer story to me is an interesting one. We create these stories in our heads that have no basis in scientific fact, such as "we lower T to treat prostate cancer, thus higher T must be bad for prostate cancer", and then it becomes incumbent on us to create mountains of evidence to overcome the supposition that is based on an idea with no evidence. All the while ignoring the fact that men naturally produce testosterone, and except when trying to reach castrate levels we do nothing to modulate it (for good reason) in the management of prostate cancer.

We also have no data about the effects of ozempic on prostate cancer recurrence, and yet we are happy to give it.

 

[communitydoc13]

I'd say that's a bold interpretation of the trial. Showed no statistically significant difference in any of the mentioned end points between T and placebo. While VTEs were 1.7% in T arm vs. 1.2% in placebo arm, you could just as easily point to death from CV causes at 3.4% in T arm and 4.0% in placebo arm. Neither are significant.

The investigator reported events are right in the text...seems like a mixed bag to me and the absolute numbers of any given event are low enough that confidence shouldn't be high, however the pattern of events makes some "sense".

T was associated with increased risk of non-fatal arrhythmias, acute renal injury and urinary retention at levels that I suspect reflect a real effect. T does increase BP.

T is likely somewhat protective regarding DM (presumable better muscle mass and activity), syncope (increased BP), heart failure and acute respiratory failure (see DM rationale). Presumably T improves activity in this population.

The very short term f/u of the trial should be noted. As should the fact that these are men with symptomatic hypogonadism, not regular blokes with age normal T.

We create these stories in our heads that have no basis in scientific fact, such as "we lower T to treat prostate cancer, thus higher T must be bad for prostate cancer", and then it becomes incumbent on us to create mountains of evidence to overcome the supposition that is based on an idea with no evidence.

Agree that no evidence....except that ADT therapy so effective in treating the disease.

I agree that post definitive therapy PCa patients should be candidates for T when appropriate.

Good research projects? How about trending PSA post definitive treatment in this population (T supplemented) and correlating with clinical evidence of disease recurrence. Might be able to come up with a "Modified Phoenix Criteria"... I'm sure someone is/has done this.

 

[DoctwoB]

The investigator reported events are right in the text...seems like a mixed bag to me and the absolute numbers of any given event are low enough that confidence shouldn't be high, however the pattern of events makes some "sense".

T was associated with increased risk of non-fatal arrhythmias, acute renal injury and urinary retention at levels that I suspect reflect a real effect. T does increase BP.

T is likely somewhat protective regarding DM (presumable better muscle mass and activity), syncope (increased BP), heart failure and acute respiratory failure (see DM rationale). Presumably T improves activity in this population.

The very short term f/u of the trial should be noted. As should the fact that these are men with symptomatic hypogonadism, not regular blokes with age normal T.

Agreed, we have no evidence that TRT improves, well, anything really in eugonadal men. It probably does increase athletic performance given widespread use in sports, but it wouldn't be the first time sports "science" turns out to be placebo.

Agree that no evidence....except that ADT therapy so effective in treating the disease.

I agree that post definitive therapy PCa patients should be candidates for T when appropriate.

Good research projects? How about trending PSA post definitive treatment in this population (T supplemented) and correlating with clinical evidence of disease recurrence. Might be able to come up with a "Modified Phoenix Criteria"... I'm sure someone is/has done this.

you'd be surprised, T therapy in prostate cancer has been taboo for so long it wasn't long ago that people were publishing case reports on it.

 

[Palex80]

Ha. Maybe we ought to “challenge” all undetectable PSAs with test. You got me thinking.

The ethics committee would like to have a word with you.

Lead your patients down the hormonal primrose path.

How's that testosterone making you feel?
Awesome! I feel like I'm 20 again! (wife smiles)

20 you say? What a coincidence... [Checks last PSA result.]

 

[evilbooyaa]

I'd say that's a bold interpretation of the trial. Showed no statistically significant difference in any of the mentioned end points between T and placebo. While VTEs were 1.7% in T arm vs. 1.2% in placebo arm, you could just as easily point to death from CV causes at 3.4% in T arm and 4.0% in placebo arm. Neither are significant.

That's literally what the authors state in their results, mang. Here is the exact quote from the abstract of the paper. "A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group". If you have an issue with it, take it up with NEJM, lol.

We can make plenty of statements about safety of T and prostate cancer

What I meant is that the main NEJM paper cannot make any statements about safety as it specifically excluded not only those with a history of pCA, but even those iwth nodules or high PSA (so even those at risk of pCA in the next 3 years, which was their median f/u)

"There is no clinical evidence that testosterone therapy increases risk of recurrence or progression of prostate cancer"

In men with prostate cancer, there is no risk that higher endogenous testosterone levels increases risk of recurrence or progression (except when on ADT)

https://www.sciencedirect.com/science/article/abs/pii/S1558767318300326

"There is retrospective evidence that testosterone therapy does not increase risk of recurrence or progression of prostate cancer"

Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease - Prostate Cancer and Prostatic Diseases

The safety of testosterone therapy (TT) after definitive treatment for localized prostate cancer remains undefined. We analyzed the risks of biochemical recurrence and mortality in men receiving TT after treatment for localized prostate cancer. Cohort analysis using the national US Veterans...

www.nature.com

"patients without prostate cancer on testosterone therapy do not have a higher risk of developing prostate cancer"

Prostate Safety Events During Testosterone Replacement Therapy

This randomized clinical trial examines the effects of testosterone replacement therapy on major adverse cardiovascular events in men with hypogonadism.

jamanetwork.com

it's 33 months of median f/u. Do we expect that to really be enough to see a spike in pCA diagnoses with testosterone in patients without prostate cancer? Again, it's the same TRAVERSE trial patients. Where they specifically excluded men with prostate cancer, prostate nodules, or elevated PSA.

The whole T and prostate cancer story to me is an interesting one. We create these stories in our heads that have no basis in scientific fact, such as "we lower T to treat prostate cancer, thus higher T must be bad for prostate cancer", and then it becomes incumbent on us to create mountains of evidence to overcome the supposition that is based on an idea with no evidence. All the while ignoring the fact that men naturally produce testosterone, and except when trying to reach castrate levels we do nothing to modulate it (for good reason) in the management of prostate cancer.

We also have no data about the effects of ozempic on prostate cancer recurrence, and yet we are happy to give it.

I am not here to defend the statement that 'Testosterone harms men with pCA who are inappropriately hypoganadial'. Just stating that if you believe that dogma, this new trial (in NEJM!) does nothing to influence that opinion. The camps are split.

We need a study that says, we took 2000 hypogonadal pCA men who underwent treatment (let's say either RP or RT), half of them got testosterone, half didn't, chances of pCA returning was equal across the groups at 5+ year follow-up.

 

[ramsesthenice]

I'd say that's a bold interpretation of the trial. Showed no statistically significant difference in any of the mentioned end points between T and placebo. While VTEs were 1.7% in T arm vs. 1.2% in placebo arm, you could just as easily point to death from CV causes at 3.4% in T arm and 4.0% in placebo arm. Neither are significant.



We can make plenty of statements about safety of T and prostate cancer

"There is no clinical evidence that testosterone therapy increases risk of recurrence or progression of prostate cancer"

In men with prostate cancer, there is no risk that higher endogenous testosterone levels increases risk of recurrence or progression (except when on ADT)

https://www.sciencedirect.com/science/article/abs/pii/S1558767318300326

"There is retrospective evidence that testosterone therapy does not increase risk of recurrence or progression of prostate cancer"

Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease - Prostate Cancer and Prostatic Diseases

The safety of testosterone therapy (TT) after definitive treatment for localized prostate cancer remains undefined. We analyzed the risks of biochemical recurrence and mortality in men receiving TT after treatment for localized prostate cancer. Cohort analysis using the national US Veterans...

www.nature.com

"patients without prostate cancer on testosterone therapy do not have a higher risk of developing prostate cancer"

Prostate Safety Events During Testosterone Replacement Therapy

This randomized clinical trial examines the effects of testosterone replacement therapy on major adverse cardiovascular events in men with hypogonadism.

jamanetwork.com

The whole T and prostate cancer story to me is an interesting one. We create these stories in our heads that have no basis in scientific fact, such as "we lower T to treat prostate cancer, thus higher T must be bad for prostate cancer", and then it becomes incumbent on us to create mountains of evidence to overcome the supposition that is based on an idea with no evidence. All the while ignoring the fact that men naturally produce testosterone, and except when trying to reach castrate levels we do nothing to modulate it (for good reason) in the management of prostate cancer.

We also have no data about the effects of ozempic on prostate cancer recurrence, and yet we are happy to give it.

I’m largely with you on this one. I get that the concept of giving testosterone to someone with a history of a hormone sensitive tumor seems counter intuitive but let’s think this out a bit. If someone has their prostate removed or radiated, it is very unlikely to cause a de novo cancer they would not otherwise have had. The much more plausible concern is that you might speed up recurrence in someone with sub clinical disease who was probably going to fail eventually. Depending on the risk group, that may be a small subset to start with. Then the question becomes, how much faster will men recur if you boost their testosterone from 300 to 500? The next layer is, will that change the overall disease course and increase mortality? I bet if you carefully looked at a very large data set, there would be a very small effect and we would debate its clinical significance.

Personally, I think the much more relevant question that we don’t know is how long after treatment is it ok to start. In other words, at what point after treatment have enough cells died that someone is cured? It is feasible if you started too soon after therapy that you could potentially rescue a subset of cells that might otherwise die and compromise a cure. My best guess is that it’s probably on the order of how long it takes natural T recovery after a given duration of ADT (depending on risk group).

I don’t personally give it. But I love our men’s health group. They are ED wizards. They typically wait a year after all therapy and I don’t lose any sleep if they start someone on T. So far, I haven’t seen anything bad happen.