RARP vs RT plus ADT for Gleason 8 with cribiform and high Decipher

I'm 71, I was diagnosed with Gleason 4+3 with Cribriform in June of 2025. I survived a bad heart attack in 2016 and have heart failure as a result, but I take my heart conditions very seriously and with the diet and lifestyle changes I made after my heart attack, and with my outstanding cardiology team's treatment, I am largely asymptomatic and have very few limitations. I had clearance from my cardiology team to be as aggressive as possible, including surgery. Nonetheless, I chose radiation and will begin 20 fractions of VMAT on 02/23/26.

I am at Duke. I have a urologic oncologist, radiation oncologist, and medical oncologist. All were in agreement that radiation was the best choice for me, and that was the conclusion I had come to after much research and review of clinical trials. My PSMA-PET scan was negative and I have no extracapsular extension, no perineural invasion, no seminal vesicle involvement. I had one PI-RADS 3 lesion shown on my mpMRI. My 13-core biopsy came back with one precancerous core, and two 4+3 with Cribriform, one at 90% grade 4 and the other at 80% grade 4. I am in good shape and exercise regularly. I did not want to deal with the real possibility of long-term or permanent incontinence. I was also concerned with the likelihood of micrometastasis because of the amplification of aggressiveness caused by the Cribriform pattern. The odds of spread were not insignificant and I did not want to deal with the side effects of surgery....some of which would be long term or permanent....and the side effects of ADT + radiation. And a big part of this calculus was what my realistic life expectancy is with my heart conditions. In consulting with my heart failure team, I have a probable life expectancy of 15 years or so from a cardiology standpoint, and with the current state of drug and radiation therapy, my oncology team is very confident that were I to have a recurrence, they could keep it under control. I want to die of the heart issues, not cancer.

So I am on 6 months of hormone therapy. My ADT med is Orgovyx, the latest and greatest ADT med + secondary agent....Nubeqa, the latest androgen receptor inhibitor (ARI). I am being treated as if my cancer were Gleason 4+4 because of the Cribriform pattern and the rate at which my PSA was rising. It rose from 3.8 to 9.6 in 6 months and from 9.6 to 17.0 in 8 months. Orgovyx is a pill (as is Nubeqa) and is easier on the heart and quicker to impact testosterone when starting or stopping. If you have an injected GnRH agonist like Lupron or Eligard, you are stuck with the side effects until the drug wears off, which, depending on the length of effectiveness of the dose, is a month or months. There is also testosterone flair with GnRH agonists that must be counteracted with an older ARI, Bicalutamide (Casodex). Orgovyx is a GnRH antagonist and does not have those issues. On Orgovyx you reach castration level in a matter of several days. And when you come of Orgovyx, your testosterone recovers much quicker than with the older ADT meds. 1 month after initiating the drug therapy, my testosterone was at 15, down from 290, and my PSA had dropped from 17.1 to 0.26. I had blood work a few days ago and my testosterone was at 21 and my PSA was at 0.01. This was an excellent response and my MO said it was prognosticated a very good response to the combined ADT+ARI+ radiation therapy. The latest research shows significant benefit to the dual drug (ADT+ARI) therapy over ADT alone in unfavorable intermediate (4+3) and favorable high grade (4+4) cancer . My MO said the objective with my treatment plan is curative.

When I begin VMAT in one week, I will have been on the ADT + ARI for just over 3 months with 3 months to go. My side effects have been minimal....a little bit of fatigue and a little more brain fog. I have had no joint pain, no hot flashes, no weight gain, and no adverse impact on my blood work numbers. I have blood tests often because of my heart conditions and the numbers have not changed....at all. I know there are plenty of men who have significant side effects, but that has not been my experience. The latest generation of ADT and ARI drugs, which I am on, are better in that regard.

The drugs you are taking are the best. I’ve had prostate cancer for 16 years, Four reoccurrences, And I’m on Orgovyx And Nubeqa the last 3 years, Just like you. It has kept me undetectable for the last 27 months since I had a metastasis zapped on my spine. Nubeqa doesn’t pass the blood brain barrier so it doesn’t cause brain fog and doesn’t cause fatigue for almost everybody. A great drug and no side effects.

The thing is while you can stop Orgovyx As long as your testosterone is down, it will usually take at least three months before your testosterone can hit around 250. A lot faster than leuprolide. Orgovyx has a 25 hour half-life.

The real question is do you have large cribriform? It is much more aggressive than Small cribriform. A lot of doctors will put exactly what type it is in your biopsy, but not all do it. Large cribriform is larger than .25 mm. According to UCSF doctors, in one of their meetings, large cribriform Is equivalent to having a five in your Gleason score.

Your radiation plans sound ideal and it’s good to hear you’re not having much of the way of side effects from ADT.

@jeffmarc, thank you. Unfortunately, mine is large cribriform and the second opinion read on my biopsy slides was performed by Jonathan Epstein, so I’m sure it’s right. I did not know about that level of elevation of the grade that you mentioned……great.

@klw23
Hope all goes well, I am waiting to get PSMA scan and Decipher test results. I am leaning toward removal. But will wait for test results and the consultation scheduled, one with RO and other with surgeon.