ADT - What Historical Precedent?

[6357axbz]

How was it determined that ADT for mPCa, which inevitably results in mCRPca, was preferable to allowing mPCa to progress without ADT? Thanks.

[Magnus1964]

ADT drugs are palliative not cures. They provide extended quality life for Pca.

[6357axbz in reply to Magnus1964]

That is correct

[tango65]

ncbi.nlm.nih.gov/pmc/articl...

[6357axbz in reply to tango65]

Thanks tango. Good stuff.

[tango65 in reply to 6357axbz]

I believe monotherapy with castration or LHRH offers a survival advantage. This study indicates that treatment with castration alone offers a survival advantage over patients treated with bicalutamide alone.

sci-hub.tw/https://www.gold...

[Tall_Allen]

It started with estrogen, which was both palliative and extended life, but there were serious blood clots from oral estrogens. The first anti-androgens (flutamide) did not cause blood clots, so they quickly replaced estrogen. And when the first GnRH agonists were developed, they became the standard of care. The first actual proof of survival benefit came in 1990 with a double-blind RCT that proved that a combination of leuprolide and flutamide extended life more than leuprolide alone. The combination of castration with second line hormonal agents (abiraterone and enzalutamide) were later proven to increase survival over castration alone. So there is no proof of monotherapy survival benefit, but there is a lot of proof of combination survival benefit.

[6357axbz in reply to Tall_Allen]

Thanks TA. That’s what I was wondering, i.e., “So there is no proof of monotherapy survival benefit, but there is a lot of proof of combination survival benefit.”

[Tall_Allen in reply to 6357axbz]

I should add that no proof of survival benefit is not the same as proof of no benefit. In fact, there almost certainly is a benefit, IMO.

[Fuzzman77 in reply to Tall_Allen]

Allen, you are a walking encyclopedia of prostate cancer. Really appreciate you sharing your knowledge.

[GP24]

cancerres.aacrjournals.org/...

[billyboy3]

THE BEST AND ONLY OPTION TO CONSIDER IS COMBINATION ADT, starting with IHT, Intermittment Hormone Therapy for as long as it effectively reduces one's pas. This is the gold standard. You can also advodart to this mix.

You got on a cycle of say 3 to 4 months, until your psa reaches its lowest point for two months, then you off all drugs, and take your psa monthly until it rises to a maximum of 4-subjective number. Then you go back on your combination again.

The off cycles give your body a chance to recover and get ready for the next round.

Once this fails, the it is onto the last of the latest drugs.

Good luck.

[6357axbz in reply to billyboy3]

Thanks bb3

[Patrick-Turner]

A very long time ago, doctors in late 19th century discovered eunuchs in Chinese and Persian empire state Palaces never got Pca, because their testosterone was interrupted by completely removing testicles and male Rodgers, so the "men" looking after harems could not cause any pregnancies in the multiple wives of men in power.

Then it became normal practice for western men to have testicles removed if they had any trouble peeing which could be BPH or early Pca, a common ailment of wealthy old men able to afford the luxury of early surgical intervention. Poor men who got old enough to get Pca or a whole pile of other ailments just died fast, hence low life expectancy in bygone times.

The Lancet magazine has the gory history of what western doctors did for men with prostate troubles from 1880s onward. Often, what was done had little lasting effect on relieving the peeing problem, and the man got worse, his Pca went to his bones, and he died in agonising pain. So the surgical castration was a temporary remedy.

I think it was in about 1941 that testosterone was deemed to be the agent that speeded a man's death if he got Pca, so drugs to avoid the cutting away of testicles were invented. The Psa chemical was found many years later, and it was found to be an indicator of prostate condition and cancer status.

It was found through trial and error that good way to treat Pca was to give ADT aka chemical castration until that became ineffective, which it always did, between a month or 10 years after it began. Then chemo was used, and very often that failed, so a man went to palliative care and said goodbye. The invention of chemo often did little to extend a man's life with Pca.

Radiation was tried, and early applications often had horrific side effect outcomes, and didn't halt the Pca growth.

I was diagnosed 4 years too late in 2009, Gleason 9, 9/9 positive biopsy samples, inoperable PG tumor, many mets probably already established, and without ADT, I would have died in about 2011 or 2012. So ADT gives longer life to Xtandi give a bit more, and now we have Lu177, so I am not in palliative care right now because all 4 types of chemo possible all failed to work, something not uncommon.

The Lancet gives medical history better than I can, and I found 1880's copies available online after a Google search.

Tall Allen has a good explanation below....

Patrick Turner.

[6357axbz in reply to Patrick-Turner]

You say, “many mets probably already established”. So am I correct that you don’t know for sure whether or not you have distant metastases? I would think that knowledge would be huge for you, the difference between a curable and a non-curable disease and a guide to proper treatment.

[j-o-h-n in reply to Patrick-Turner]

When it comes to removing our gonads:

Should they Lancet-alot or Lancet-alittle?

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 02/11/2020 8:17 PM EST

[MateoBeach]

Thanks for your historic review. Glad you are still with us and contributing your knowledge. If you have the Lancet link(s) would love to read theier expended perspectives.

[Patrick-Turner in reply to MateoBeach]

Its over ten years since I explored Lancet, links all gone now, but Google should lead you.....

Patrick Turner.

[klaas40]

According to Medscape, Sept 22, 2019: “Considered to be the primary approach in the treatment of symptomatic metastatic prostate cancer, androgen deprivation therapy (ADT) has been found to be palliative, not curative.”

[Horse12888]

To answer the original question, there have been hundreds of studies conducted since 1941 when the discovery was first made that validate the effectiveness of short-term ADT as adjuvant therapy for high-risk (G8+) patients, and for recurrences where PSA is doubling quickly. My MO at USC runs many of these, and they're huge (tens of thousands of men).

It's true ADT universally results in castrate resistance, but leaving aggressive PCa untreated is a terrible idea, and there are are numerous drugs and other treatments for mCRPC--more every couple of years.

A more interesting question, IMO, is this: Given the extremely unpleasant SEs, is it worth it? That depends on one's age/life expectancy and one's clinical situation, but also on the value one puts on one's sex life, other QoL issues, sense of duty to loved ones, and general outlook on risk.

There are people who roll the dice. Those who wind up dying in agony wish they hadn't; those whose cancer doesn't progress are thrilled with their choice.

Nowadays, it looks like one can have one's cake and eat it too. In the UK, the standard of care includes high-dose transdermal estradiol, which results in castration but with a far more tolerable profile of SEs.