Paper of interest to MHSPc

[Proflac]

I have not read the full paper yet but this looks interesting from the abstract

Comparison of Systemic Treatments for Metastatic Castration-Sensitive Prostate Cancer

JAMA Oncol; 2021 Jan 14; EPub Ahead of Print; L Wang, CJ Paller, H Hong, et al

[Garbonzeaux]

Can you provide a link?

[Proflac in reply to Garbonzeaux]

jamanetwork.com/journals/ja... Abstract only unless you have access to full text from this link. Oncology Daily Digest gives the following THM: "TAKE-HOME MESSAGE

The authors analyzed seven trials with 7287 patients to evaluate the addition of docetaxel, abiraterone acetate, apalutamide, or enzalutamide to androgen-deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer. When added to ADT, abiraterone acetate (HR, 0.61), apalutamide (HR, 0.67), and docetaxel (HR, 0.79) best improved overall survival. When added to ADT, enzalutamide (HR, 0.39), apalutamide (HR, 0.48), abiraterone acetate (HR, 0.51), and docetaxel (HR, 0.67) best improved radiographic progression–free survival. Docetaxel, however, was associated with substantially increased serious adverse events.

According to these data, abiraterone acetate and apalutamide appear to provide the greatest overall survival benefits with relatively low risk for serious adverse events."

Its a meta analysis - which has the benefit of large numbers but lots of methodological limitations so should be taken with caution. Interesting nonetheless.

[Tall_Allen in reply to Proflac]

It's the kind of analysis I always warn against, One can only compare roughly when there are different sets of patients for each drug. The HRs for all those drugs are way too close to say one is better than the other. The only way to do that is a comparative study where patients are randomized to one drug or the other. When STAMPEDE compared docetaxel to abiraterone randomly, they found them to be equivalent. Moreover, side effects were similar in degree, but not in kind:

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

Also, the sequence abiraterone -> enzalutamide lasts longer than the reverse sequence.

[Mascouche in reply to Tall_Allen]

Hi TA,

Not asking you because I am lazy but because you are more well versed in this than most people...

Do you know if there is a site or an article somewhere that would provide information on things like the percentage of people with various profiles (Gleason score, mets or not, etc.. who never become castration resistant? Or who were able to just have some radiation and ADT for X months/years only vs those who had to stay on ADT forever or had to change ADT along the way because they stop working?

I am asking because when you read many of the posts here, it does look like a bleak and nearly hopeless future ahead of us. But then again, I believe that is likely because most people with a good outcome don't feel the need to visit a site like this one here so that likely introduces a strong bias towards treatments that do not work versus what it might be like for real out there.

[Tall_Allen in reply to Mascouche]

Yes, I agree that on an advanced prostate cancer forum, you will never hear about curative therapies for localized PC. In fact, I never post such articles on this forum. I do post them regularly on the Malecare Prostate Cancer Network Forum. There are many such stats in my blogs. Use the search feature.

[Mascouche in reply to Tall_Allen]

ok thanks

[dhccpa in reply to Mascouche]

Or were you asking about metastatic patients only, not non-metastatic patients.

[Mascouche in reply to dhccpa]

It was in general

[Mascouche in reply to Tall_Allen]

Hi again Tall_Allen,

I've checked your blogs and while I did find things of interest, I haven't found what I had in mind. Let me try to phrase things a little differently.

Is there somewhere a kind of roadmap that would indicate how likely people progress from being hormone sensitive to being castration resistant to having neuroendocrine prostate cancer (and other variations if there are more)?

[Tall_Allen in reply to Mascouche]

Everyone progresses from hormone-sensitive to castration-resistant eventually (if something else doesn't kill them first). While castration-resistance (progression without testosterone present) is a first step, there is also resistance to second-line hormonal therapies that will always occur (if one lives long enough). Neuroendocrine PC has been found in 17% of heavily treated patients:

ascopubs.org/doi/full/10.12...

There are many other resistant subtypes that will be detected if one lives long enough with metastatic PC. We haven't yet come up with a drug that the cancer won't eventually become resistant to. Cancer reproduces and mutates rapidly, so it always gets around whatever we throw at it.

What we have found is that reducing the cancer load by heavy, early systemic treatment (and debulking if used early enough) does delay the emergence of resistant subtypes. The delays are large compared to when the same drugs are used later. You can read about that here:

prostatecancer.news/2017/06...

[Mascouche in reply to Tall_Allen]

I knew you were a good one to ask about this type of info. Many thanks.