"Abiraterone and Enzalutamide Raise Metabolic, Cardiovascular Adverse Event Risks" [2]
I think an August 5, 2021 JAMA paper will give some perspective of historic alternative causes of death:
"Causes of Death Among Patients With Metastatic Prostate Cancer in the US From 2000 to 2016" [1]
It is based on U.S. SEER data from January 1, 2000, to December 31, 2016, so it includes the pre-Abi / pre-Enza period that I well remember, the transitional period - and is lacking the important most recent five years.
I expect the usual negative comments. "Ah, but things are so much better now!"
"A total of 26 168 patients with a diagnosis of metastatic PC were included in the analysis".
They note "a 1-year survival rate of 77.5%, and a 5-year survival rate of 26.4%."
"Of the total deaths, 13 011 (77.8%) were from PCa".
5.5% of deaths were due to other cancers.
Non-cancer cause of death (COD): "the most common noncancer CODs were cardiovascular diseases (SMR, 1.34 ...), chronic obstructive pulmonary disease (SMR, 1.19 ...), and cerebrovascular diseases (SMR, 1.31 ...)."
{SMR is Standardized mortality ratio.}
Deaths within 2 years of mPCa diagnosis:
"A total of 9869 deaths (59.0% of all deaths) occurred within 2 years after diagnosis of metastatic PCa".
"The most common noncancer COD was cardiovascular disease (653 deaths [42.1%]), followed by cerebrovascular disease (107 [6.9%]) and chronic obstructive pulmonary disease (COPD) (99 [6.4%])."
Deaths from 2 to 5 years of mPCa diagnosis:
"A total of 5290 men with metastatic PCa died from 2 to 5 years after their cancer diagnosis, of whom 4171 (78.8%) died of PCa".
"The most common noncancer COD was cardiovascular disease (335 patients [39.5%]), followed by COPD (72 [8.5%]) and cerebrovascular diseases (55 [6.5%])"
PCa aside. causes od death in this population were higher than in the general population - including: "septicemia, suicide, accidents, COPD, and cerebrovascular diseases".
Deaths more than 5 years after mPCa diagnosis:
"A total of 1573 men with metastatic PC died more than 5 years after their cancer diagnosis, of whom 1048 (66.6%) died of metastatic PCa".
"Among men with metastatic PC, the overall risk of death more than 5 years after diagnosis was significantly greater than that in the general US male population (SMR, 3.63 ...)".
Discussion.
"... we observed that the number of deaths from non–PC-related causes increased in association with increasing latency period after the diagnosis of metastatic PC, and cardiovascular and cerebrovascular diseases were the most common causes of non–PC-related deaths."
...
In the Abi/Enza analysis from Scout4answers:
"Abiraterone was significantly associated with an 84% and 37% increased risk for a major or minor diabetic event, respectively, and a 91% and 75% increased risk for a major or minor cardiovascular event, respectively."
I leave it to others to do the math.
...
Are there other, more recent, real-world US studies (not trials) that report causes of death in those who have used Abi and/or Enza?
Also, what about 5 year survival? How much better than 30% do we do?
...
This is how Jody Charnow reported the above data [3]:
"Approximately 1 in 6 deaths among men with metastatic prostate cancer are due to noncancer causes, according to a recent study.
"Cardiovascular and cerebrovascular diseases and chronic obstructive pulmonary disease (COPD) are among the most common noncancer causes of death."
Seems that we should be doing something about that - “These findings may provide insight into how men with metastatic [prostate cancer] should be counseled regarding future health risks and highlight the importance of multidisciplinary care for such patients” - as though we can easily overcome treatment-induced risks.
Of course, most are preoccupied with the 5 in 6 deaths.
...
This was also the theme in hemonc today: [4]
"Noncancer causes of death ‘increasingly pertinent’ among men with advanced prostate cancer"
"“As such, identifying the causes of deaths among these patients may help with multidisciplinary treatment planning,” Samuel W. D. Merriel, MSc, clinical senior research fellow in the College of Medicine and Health at University of Exeter in the U.K., and colleagues wrote. “[Alhalabi and colleagues] postulate that hormone therapy treatments may increase the risk [for] cardiovascular and cerebrovascular disease in patients treated for metastatic prostate cancer, a theory that is supported by some epidemiological and biomedical evidence.”"
...
ditto The ASCO Post:
'As stated by the investigators, “Owing to improved survival among U.S. patients with metastatic prostate cancer, patients tend to live long enough after a prostate cancer diagnosis for non–cancer-related comorbidities to be associated with their overall survival. Although studies have investigated causes of death among patients with localized prostate cancer, data are lacking regarding causes of death among patients with metastatic prostate cancer.”'
Not quite! The risk of non-cancer deaths appears to be increased by PCa therapy. The major causes are more likely than in the general population.
...
Scout was merely pointing out that Abi & Enza add to the problem. The price for improved overall survival.
Thanks for adding perspective to the discussion. I think a total lack of Testosterone has many effects on our body that are not beneficial in the long run. Measuring and reporting on the #s is clearly fraught with many difficulties.
Patrick, always a treat to see your posts. Love your focus on Research. I receive a Newsletter through Darryl, and HU that discussed the most recent data. Also not good for Cardio events. I saved it, and will try and dig it up. I keep seeing Men on this site have success with Estrodial patches with the claim of success at keeping Cardio Vascular events much lower, than ADT3, and keeping T below 10, with PSA stable at <0.1. If this is true, and Cardio events with ADT3 are real, why do we not see E2 patches as more of the SOC?
I think it's because some of the goes that tried the estrogen patches had very bad results. Some guys get good results and others get terrible results, just like with many drugs and treatments.
Thank you that is a lot to digest.Scary to think about the possibility of not living 5 more years. I had bio recurrence in 2019 so im on my 3rd year, just started lupron 2 months ago. I feel like I don’t have cancer! And never had felt like I had mHSPC. Im 64 have had cancer now for 7 years. I plan on living for a long time.
Im presently doing SARMS with my lupron
I will be switching to GTX-024 starting tomorrow instead of rad-140.
Im going to ask again for E2 0.5mg patches 2x/week to start and see how that goes.
SERDS are another option but need to do more studying on them.
Sure! So far it’s been 3 weeks now. I started 1 month after first lupron shot. First couple weeks on lupron i had no hot flashes, felt malaise, worked out but not intense. I started getting joint and tendon pains in wrists and forearms.
Then i started SARM RAD-140 10mg/day for 10 days straight with mild exercise weights stationary bike.
I also started with Carderine (technically not a SARM) for reducing possible SE of high triglycerides and low HDL. Athletes take Carderine for indurance. Lipid, T,?PSA, CBC, CMP on 20th) I will know more then.
I have not had anymore joint muscle and pain within a week of SARMS.
I will be getting my Osterine powder in Thursday and will convert it to liquid then encapsulate and I will be taking 10mg/day a dropping rad-140. Osterine is better at fighting cancer where rad 140 has very slight affinity to dht, aromatase and cyp17a1
Plenty of research on GTX-024 (Osterine or enobosarm.
Selective androgen receptor modulators activate the canonical prostate cancer androgen receptor program and repress cancer growth
Excerpt from this article;
We selected several SARMs that had progressed through various stages of preclinical or clinical evaluation and demonstrated physiological effects and a lack of toxicity. GTX-024, also known as enobosarm, has been extensively studied in humans, with clinical trials evaluating the effects on cancer cachexia and muscle wasting (33). GTX-024 and a related SARM, GTX-027, suppressed the growth of triple-negative breast cancer (TNBC) xenografts without adverse effects on animal health (34). GTX-024 has been evaluated in phase II clinical trials of AR-positive breast cancer (NCT02971761; NCT02368691), with no reported adverse safety signals (35).
For what it’s worth my MO (Dr Mark Scholz) who treats about 3000 PC patients at any one time, has his own theory on cardiovascular events for men on ADT. His practice has shown him that the men on ADT that stay fit and exercise and don’t gain weight, rarely have cardiovascular events. While those that don’t…..do. His hypothesis is that it isn’t the ADT meds themselves that cause heart problems but rather the associated weight gain and muscle loss that lead to cardio events. Bottom line he believes is that we have some control. Eat right, work out hard, lift weights and don't gain weight. If you do, perhaps the cardiovascular issues from adt won’t be an issue for you.
However we must bear in mind that many or almost all AdvPca men have pre medical problems such as cardiovascular, diabetes, hypertension and what not. With all the meds we take to get rid of the disease burden it inadvertently adds more pressure to our fragile body.
And our sedentary lifestyle due to work, exhaustion and raising families, we tend to be sporadic with our exercise, diet and self care. So, I’m not surprised that we succumbed to other morbidities while battling PCa.
Good report as it makes us think. I have a close buddy whose PSA was rising very fast while he tried every protocol. He got tired and took a break from all the meds to rest actually. And when he did return to restart his battle again he and his doctors were baffled by the decrease in PSA, good blood panels and he was rested and felt fine. But then again everyone of us is different. He found a new vigor to confront his demons and a great attitude to boot.
I thought of trying to add info about heart effects, but, good that you did. My husband is currently losing strength in his arms, 1st upper arms cannot reach up and it is continuingIs this the muscle wasting you speak of ? SARMS with my lupron?
He had a 7-8 month time without lupron, and the PSA was rising. from 6.8 Nov to 33.2 in april 2022. Has had Pca since 2012 , RP, not contain gleason 4+4. casodex, then lupron and radiation for 3 mo. then intermittent till 2019 , then continuous.
A break with his insurance left him without MO, and Lupron.
Search quick find young new MO fellow.
Wanted him on Xtandi, he took it about 5 days, and felt pain across chest radiating to back, other pain too .
Just stopped., now has extensive pain and mets, bone, possible liver.
But the fact that he is losing arm strength and seems frail is more than I have seen on this board so far.
Thank you for the caring you show for others and the generous amount of your time it took to compile this research. When I see the words, "was also" and "ditto" as the lead in to a new paragraph one realizes that these are the synopsizes of other, supporting studies and observations--not a one trick pony.
These drugs, effective as they are at controlling cancer for a time, are aging accelerators. Anyone who’s taken them knows this. It’s in the side effects you can feel and in the ones you don’t.
The physical condition most guys are in at Pca diagnosis is poor, almost always worse than we think. We tend not to know our numbers and overestimate our heath. There are exceptions of course. But even for those fit and strong, the effect of these meds makes delaying decrepitude decidedly more difficult.
It is therefore often a rude awakening when we discover what is inadvertently meant by the rosy cliche that having Pca means ‘dying of something else first’.
It ostensibly refers to the typically slow growth of the disease. Probably it means more that co morbidities (especially cardiovascular disease) are accelerated by the drugs, killing us first.
Since death from metastatic Pca is best avoided, until there are more effective treatments for it, maybe it’s a blessing.
In the meantime, sadly, the amount of exercise and caloric restriction it takes to thrive on these drugs is hard work, much harder if health is not good going in. It can work wonders, but is not for everyone, unfortunately.
if you wish to think about it in this manner, all of our MOs' primary jobs are to keep us from dying of PCa long enough to die from something else. if the study lasted long enough, you would have 100% mortality, obviously - something is going to get every one of us eventually.
that 'five year' spectre has been around awhile, and is still a scary haunt. I'm a couple months away from my 2nd 'anniversary' since DX, certainly working at being around in excess of three more years, but you never know when your number is up. I believe that with new drugs and treatments that five year milestone should be moved farther out at some point. Do i think I will live long enough to see a cure? Skeptical.
It would be interesting to know more about PROSTATE CÁNCER RELATED causes of death, ie, when we die from prostate cáncer (not from other causes mentioned in the study) , what, specifically, are we most likely to die from according to statistics.
The question that springs to my mind is: if you die of something induced by prostate cancer or an associated treatment, how many of those are classed as survivors from prostate cancer in the survival statistics. So if someone dies from heart failure from a treatment is that person classified as a prostate cancer survivor.
Thanks for posting the research. At my diagnosis in 01/2015, my MO at the time, told me of the impact of ADT on cardio health. He mentioned that a heart healthy diet is also prostate healthy esp being on ADT. Had already been a marathoner, so had pretty good cardio health. But now 7 1/2 years on Lupron has zapped my endurance due to anemia (4.4) and low hemoglobin (13.1) . Still doing hikes and weight bearing exercises to offset the ADT side effects e.g. depression, osteoporosis ( DEXA showed osteopenia), fat gain, and muscle loss. Made dietary changes also to mostly plant based, lean protein, and whole grains. Cholesterol -170
A bit confusing and counterintuitive. All I know is that I am very fortunate to be among the 26.7 % surviving after 5 years, in fact in November 2022, surviving metastatic PC for 10 years , on Zytiga for 8 years, with a PSA undetectable!Wings
They started me on casodex, for a few months, also on Lupron from 2012 to 2017, then Lupron vacation , not taking it anymore sine 2017, ongoing Zytiga/Abiriatone Acetate(generic)from 2014 to present.
Yes, it was directed by him and I just confered with new Oncologist at City of Hope, L.A. , Tanya Dorff, who also concurred, and added that Lupron did the job of initially lowering my PSA, and now Zytiga is doing a far more superior job. (undetectable again on 7-22-22, that makes 7 years 10 months)
Jespersen CG, Norgaard M, & Borre M. (2014). Androgen-deprivation Therapy in Treatment of Prostate Cancer and Risk of Myocardial Infarction and Stroke: A Nationwide Danish Population-based Cohort Study. European Urology 65 (4): 704-709. doi.org/10.1016/j.eururo.20...
Background
Androgen-deprivation therapy (ADT) has been suggested to increase the risk for cardiovascular diseases, including myocardial infarction (MI) and stroke, but data are inconsistent.
Conclusions
In this nationwide cohort study of >30 000 prostate cancer patients, we found that endocrine hormonal therapy was associated with increased risk for MI and stroke. In contrast, we did not find this association after orchiectomy.
I'm wondering how "age" factors in with regard to general population suffering the same demise/timing. Average age of PCa is 65 if I recall, so is there an average age associated with StageIV progression? Overlay the general population statistics on the PCa ages and identify anomalies... Otherwise how do we associate causation or effect with regard to the PCa.
Thank for posting! Information and answers always cause more questions! Lol
A 5-year survival rate of 26 % for mPCa, a sobering thought. I think most of us automatically compare to time since dx and believe, as Patrick foresaw, "things are so much better now", this won't happen to me absolutely not.
Great post Patrick. Something we all think about. Of course, a little laughter goes a long way. Let's see if j-o-h-n has any heart attack jokes ....errrr, comments.
A sobering thought for newcomers must be the realization that this group is full of anomalies. Outliers that have survived 20 years on some form of ADT, etc. It give a false impression.
The survivors curse is to remember those who came & went within the usual timeframe.
The compensation is the rare post that brings a smile to one's face. You can't leave before training a successor.
Patrick, this was the article in Darryl’s MaleCare newsletter discussing increased cardio risks from ADT in recent Sweedish study of 40,000+ Men. malecare.org/increased-risk...
Conclusion: Since antiandrogens block the absorption of testosterone, but do not reduce circulating testosterone men seem to maintain the protective effect of testosterone.
How do anti androgens effect sexual ability / desire, by them selves?
Conclusion: Since antiandrogens block the absorption of testosterone, but do not reduce circulating testosterone men seem to maintain the protective effect of testosterone.
How do anti androgens effect sexual ability / desire, by them selves?
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