Molecular Pathology

[Vp7174]

Good Morning All,

If anyone on here has knowledge they could share on the attached pathology which calls out some mutations, that would help me to understand where I sit, and maybe more so, what I can do about it. When asking my Medical Oncologist to review it, he basically tells me there is no action we can take towards it. If there is a person who understands these, and can maybe share some of your experience on what I could bring up during my next visit, that would be great. I understand that no one on this site can give me medical advice, I am merely looking for a better explanation on what I have on the report, and what what I can potentially do to address them, if anything. I have had an RARP on 8/11/22, (all scans were clear prior to the surgery) Post Surgery Pathology showed, all Margins Clear, 15 lymph nodes clear, but Focal EPE was present. Gleason 4+3, with some Tertiary pattern 5. PSA 7 weeks out was a detectable .20, then .27, then .28. To complicate things, I have Crohn's, so a complete salvage radiation attempt has it's risks. We did a PSMA 11/18 to see if we see anything. There was very very slight uptake in 1 obturator lymph node, of which my doctors don't feel is compelling enough to target it with focal radiation. They are suggesting to sit tight a bit, and monitor the PSA, and when I get to .5, rescan. If I am going to wait, I want to know if I can do anything with the mutations I've attached. Thanks for taking the time to review my post.

[Tall_Allen]

Your MO is right. Your MSI and TMB are average, so there are no immunotherapies that would work for you. TP53 and PTEN loss are common mutations seen in PCa patients, and there are no SOC therapies. Same for the rest.

Ipatasertib is an investigational medicine that inhibits AKT and works well in patients that have PTEN loss. It recently proved to be useful combined with abiraterone in men with castration-resistant PCa. It isn't yet approved, but if someday you should progress to castration-resistance, it may be approved by then. Hopefully, you will receive curative salvage radiation long before.

thelancet.com/journals/lanc...

There is a similar experimental medicine. capavasertib, which is in a clinical trial for men with metastases who are still hormone-sensitive:

clinicaltrials.gov/ct2/show...

[Vp7174 in reply to Tall_Allen]

Thank you for providing an explanation Allen. In terms of being Hormone Sensitive, that will hopefully show a positive response to Hormone Therapy. What about any cancer cells that are not hormone dependent, and also may not express PSA/PSMA. Is there a way to target those cells for detection and/or treatment? In your opinion, is the RGCC testing worth anything? They claim to be able to see CTC's, and then create an SOT therapy based off their results. In other words, if the best option (and I am not suggesting you are saying it's best or not) for me specifically is to wait a bit, I would want to know that I am doing what I can in the interim to keep this in check. Or,, on the other side of things, perhaps I may potentially cause more harm. As you can tell, I am struggling with the "wait for progression" approach, and questioning whether it is the best option and wondering if there is another possible approach that hasn't been brought to the table.

[Tall_Allen in reply to Vp7174]

I'm confused - according to what you wrote you are not even metastatic, let alone castration resistant, right? You seem to be at a point where SRT may be curative.

[Vp7174 in reply to Tall_Allen]

Yes, you are correct.. I am not confirmed as metastatic at this point, and I’m being asked to wait it out until PSA rises to .5 at which time I’ll have another set of scans. In the interim, while I am waiting, I’d like to be able to do whatever I can to slow things down. That’s really the long and short of it.

[Tall_Allen in reply to Vp7174]

There is nothing you can take to slow things down other than ADT. I think it is a bad idea to wait for PSA to reach 0.5 just so you can do scans - that is just inviting your cancer to spread.

[Vp7174 in reply to Tall_Allen]

Yes. I agree. This is where I am struggling. I just had scans last month when I was at .27, but they did not reveal much except for the “possibility” of a lymph node. I have just 2 options that were presented to me, and for the record I’m under the care of a top rated center in NYC (and in the country). I’m in the process of setting up another opinion from MD Anderson

Options:

A. Radiate the whole bed and risk potential rectum damage. Given the association with my Crohn’s being mostly in the rectum. (currently it’s under control).

B. Hold tight a moment, let things progress a bit and rescan in hopes of seeing that one lymph node become more visible on the scans. Then target that one area with Proton or SBRT (they are stating that Proton is a better fit for me, due to me having Crohn’s)

I will see what they have to say at MD Anderson.

[Tall_Allen in reply to Vp7174]

I think that

1) it is a bad idea to wait for metastases to become detectable--it's a self fulfilling prophecy and

(2) it is a really bad idea to target individual lymph nodes - either via salvage pelvic lymph node dissection or via radiation to oligometastases in Pelvic Lymph Node. We know both are useless as cures. It's important that patients understand the detection limits of even the best PSMA PET scan: metastases smaller than 4 mm, and those that put out only small amounts of PSA remain invisible. If there are metastases in one lymph node that you can see, there are undoubtedly many more that you can't see. You have to treat what you can't see.

OTOH, the recent SPPORT trial has shown that salvage whole pelvic radiation and 4-6 months of ADT is likely to be curative:

prostatecancer.news/2022/05...

As for the Crohn's, there is some evidence that suggests that radiation may not trigger a new episode, although it should be avoided if there is an active outbreak:

practicalradonc.org/article...

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

It is also a good idea to use a lower dose per fraction, and no margins on the bowel side. I don't know if protons are better than X-rays for this, but the new MRI-guided X-ray linacs (Viewray MRIdian or Elekta Unity) with careful contouring of the bowels would seem to be ideal for this purpose.

[Vp7174 in reply to Tall_Allen]

Allen. I really appreciate your detailed feedback. I’m going to take this information and run with it. Thank you again!