Novel AR-Targeted Therapies for mHSPC: Which One to Choose

[Benkaymel]

An interesting article comparing ARTTs for mHSPC -

onclive.com/view/novel-ar-t...

A comment stood out for me that many may already be aware of but worth highlighting anyway:

... an analysis of the ARCHES study found that many patients receiving enzalutamide had radiographic progression despite not showing PSA progression, a finding he noted that could be applied to any AR therapy. “We’re all used to lying back and not doing imaging very often when you see that PSA [level] go down. But we saw that approximately one-third of patients with imaging showing progression at soft tissue or new bone metastasis didn’t have any rise in PSA [level] at all, and that’s kind of a scary thought".

[Tall_Allen]

Agree that the gold standard is PET/CT and over-reliance on PSA is dangerous. Double negative and t-NEPC can take over if scans are not monitored.

[dhccpa in reply to Tall_Allen]

What's the best scan or combo of scans to monitor progress of ongoing distant metastatic PCa? I've never had a PSMA scan.

[Tall_Allen in reply to dhccpa]

The best scan for monitoring progression, in fact the only one you can use, is whichever one you used previously.

[dhccpa in reply to Tall_Allen]

Thanks, that'll be Axumin then.

[garyjp9 in reply to Tall_Allen]

I have N1 disease but no scans since my surgery 9/20. My PSA went to undetectable after starting ADT/Abi/Pred in 11/20. My MO just tracks PSA, not even testosterone. Should I be asking for a scan? (I expect he would answer "it won't show anything because you have an undetectable PSA.")

[Tall_Allen in reply to garyjp9]

You had high PSA to start with, so PSA is still your best early indicator.

[garyjp9 in reply to Tall_Allen]

Thank you

[Medline]

This is not surprising because PSA is actually a proteolytic enzyme that has anti-angiogenic [doi.org/10.1080/00365510903...] and anti-metastatic [doi.org/10.1016/j.tranon.20...] properties. In contrast, overexpression of PSMA enzyme is associated with high angiogenesis [doi.org/10.1186/1756-9966-2...] activity.

[dhccpa in reply to Medline]

So PSA should rise when taking Xtandi?

[RugbyVLS]

People should have a look at the 2022 PCRI Mid-Year update. There are two rather long and informative videos available, but the one that is significant to this discussion is Dr. Kwon’s presentation on Day 1 and his insistence that regular imaging should be done to assess disease progress regardless of PSA levels. This does not seem to be standard practice for most oncologists. This may be an area where patient self-advocacy is critical.

[RugbyVLS]

Also see: urotoday.com/conference-hig...

"Dr. Armstrong concluded his presentation discussing a post hoc analysis of ARCHES assessing radiographic progression in the absence of PSA progression in patients with mHSPC with the following take-home messages:

In this post hoc analysis of ARCHES, there was frequent discordance between radiographic progression and PSA progression by PCWG2 criteria or any PSA rise over nadir in patients with mHSPC treated with enzalutamide + ADT

Survival outcomes remain worse for patients with radiographic progression (with or without PSA progression) compared with outcomes of non-progressors

Regular imaging is recommended to detect radiographic progression among patients treated with potent androgen receptor pathway inhibitors, such as enzalutamide + ADT, as serial PSA monitoring alone may not be sufficient to detect radiographic progression in many patients"

[Benkaymel in reply to RugbyVLS]

Thanks Rugby, I'll be sure to point this out to my CO!