Decipher risk: prostatectomy RP vs radiation.

@wwsmith I guess it's all about keeping on top of published clinical trials. Fortunately, seems like searches turn up all kinds of Prostate trial reports.

@jeffmarc Often, clinical trials compare standard of care against a new promising procedure or combination of promising procedures (rather than just against a placebo).

Where they may use a placebo is when they are doing an “add-on” study, like where a placebo is used in combination with a current standard of care (e.g., ADT) to evaluate the efficacy of a new drug (e.g., ARPI).

For example, there’s a study (MAGNITUDE trial) comparing Zytiga/prednisone + niraparib against Zytiga/prednisone + placebo. Zytiga/prednisone is standard of care in both cases; no one is getting a placebo alone.

I was offered the opportunity to be part of a clinical trial; I opted out of that opportunity. Though I understood the purpose and possible future value of a clinical trial, my attention was singularly focused on treating my disease. I did however choose to have my proton radiation treatment results submitted into a registry (https://clinicaltrials.gov/study/NCT02040467). Hopefully, that will help someone make a treatment decision one day.

@brianjarvis
The Arches trial was where they compared ADT to ADT plus Enzalutamide. One Group only got ADT and a placebo. Not a very good trial for somebody that has a serious case of prostate cancer and doesn’t get both drugs.

The stampede trial did the same thing with ADT and abiraterone.

Both of these trials would be a very bad idea for somebody with a serious prostate cancer case.

This was discussed a lot in ancan.org meetings. People came in that were interested in doing those trials and were advised not to when they had serious cases that called for both drugs.

@fritzo Even our current best prostate cancer scanning technology, the PSMA PET scan, is still very weak in that the smallest cancer cell cluster it can see is 2mm which requires 8 million cancer cells to create. Given this situation, it is very easy for some cancer escape to have already occurred and not be seen. Without definitive proof of escape, we are left with evaluating a lot of indirect clues towards the possibility that escape has already occurred.

The more you have of these high risk factors, the more likely that escape has already occurred. High Decipher score, intraductal, cribriform, seminal vesicle invasion, perineural invasion, extraprostatic extension (EPE), extracapsular extension (ECE), and even just lesions that abut the capsule wall. In my own case, I had a high Decipher score (0.81) and two lesions that abutted the capsule wall. The high Decipher score and the two capsule abutting lesions suggested that I needed more ADT than normal with radiation and that's why I had to use one year of ADT with just a contained 3+4 case.

@jeffmarc
I know in some medical trials, they then offer the placebo group the drug if results are promising. However, that clearly is not an option with this treatment protocol of combination therapy.

@brianjarvis
The Arches trial was where they compared ADT to ADT plus Enzalutamide. One Group only got ADT and a placebo. Not a very good trial for somebody that has a serious case of prostate cancer and doesn’t get both drugs.

The stampede trial did the same thing with ADT and abiraterone.

Both of these trials would be a very bad idea for somebody with a serious prostate cancer case.

This was discussed a lot in ancan.org meetings. People came in that were interested in doing those trials and were advised not to when they had serious cases that called for both drugs.

@wwsmith So glad you were able to get that appropriate length of ADT on top of the radiation. A bit terrifying about the lack of sensitivity on the PSMA PET.

Candidly, all along, I've been making all of my decisions based not so much on what the docs say and choose the side effects that are least disagreeable, but on which procedure offers the most recurrence treatment options.

That is why I am strongly favoring RP as first course of action. My PSMA PET show no evidence of metabolically active nodal or visceral metastatic disease and the MRI/biopsy indicates that it was contained within the prostate and not in the walls. So, since it is contained, surgery is a good first course of action. If it it wasn't contained, that Decipher score of .61 would push me toward radiation. And yes, from what you've shared, cells could have escaped detection.

For recurrence after surgery, course of action sounds like IMRT radiaiton/ADT. After that, not sure if its more ADT or Adaptive Therapies based on genetic testing.

I'm sure there are all kinds of variables I'm not comprehending yet, but this is where my head is right now. Thanks for all the great information!!

@jeffmarc We know that now. But at the time, Enzalutamide (Xtandi; an ARPI) + ADT had only been approved for metastatic and nonmetastatic HRPC. The purpose of the ARCHES trial was to determine the efficacy and safety of enzalutamide + ADT in mHSPC.

So yes, it made very good sense to have both groups use what was then standard of care (SOC) for mHSPC to both receive ADT; then to have one group “add-on” Enzalutamide to the ADT and the other group to “add-on” a placebo to the ADT (both groups at least getting SOC).

Actually, it was a very good “add-on” trial. What they found was that Enzalutamide with ADT significantly reduced the risk of metastatic progression over time versus placebo plus ADT in men with mHSPC, consistent with the results of enzalutamide plus ADT in previous clinical trials in HRPC.

The discussions that occurred in the AnCan group, were those of desperate men who would have tried and done anything in their circumstances. The purpose of a well-run “add-on” clinical trial is to first determine the efficacy and safety of a drug combination, and then to move forward from there.

Jeff, I was diagnosed with a 4+3 Gleason score cancer in January 2025, with very large tumor on right side and a smaller one on left. A PMSA pet scan in February showed no cancer outside of prostate. I was 72 years old in very good shape. I had RARP surgery in May and the biopsy review showed that I did not have clear margin on the right side and that the cancer had already spread to both of the vascular bundles. Due to the large tumor on the right side that nerve could not be saved but the nerve on the left side was. I had a very large prostate, almost 3 times the normal size that protruded into the neck of the bladder requiring a surgical reconstruction of the bladder neck before the urethra was reattached. This added about 40 minutes to the surgery time, so it was a long surgery which the surgeon said went very well. As a result of the spread of the cancer I was rated a TB3 high risk patient. Recovery was normal, no major issues outside of normal recovery. I did wear the catheter for 14 days due to the bladder reconstruction. The very good news is that the 4 PSA tests thru the 9 months post surgery show < .1 PSA, so no active cancer at this time. Incontinence was minimal and pretty much back to normal with some very minor leakage if I bend down in a weird position. No recovery of the nerve yet so waiting on it while doing penal rehab with vacuum pump and daily 5mg dose of cialis. Bimix injections do the trick for now (I had painful reactions to Trimix). So in my case I do feel that surgery was the right solution based on the end findings and results. I also have to give credit to an excellent surgeon. Wishing you the best of luck, it’s tough but something we have to do to get to the other side of this disease. Rick