Prognostic Factors in Prostate Cancer: Gleason Scores, PSA Levels, and Genomic Testing

In the third segment of our prostate cancer roundtable, In this video, the panel explores how they assess the prognosis for prostate cancer patients across various stages of the disease, from localized to metastatic hormone-sensitive cases. The discussion covers key factors such as Gleason scores, imaging results, PSA levels, and the use of genomic assays to personalize treatment plans. The panelists also share their approaches to incorporating next-generation sequencing and germline testing into their decision-making process, particularly for patients with high-risk or metastatic disease. They delve into the prognostic value of certain mutations like BRCA1/2 and PALB2 and how these can impact treatment strategies.

Watch part 4 of this series: Triplet Therapy vs. ADT: Choosing the Right Approach for Metastatic Prostate Cancer

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Dr. Appleman:
So the next topic we were going to talk about was before we get into the treatment data, thinking about when we’re meeting a patient, what do we think is going to happen to them? Are they someone whether it’s with local disease, locally advanced disease, new hormone-sensitive metastatic disease, is that someone who we’re really worried about, or someone we think might get years of disease control with androgen deprivation therapy? And what are the factors that you all look at when you meet a patient, look at their pathologic data, their radiographic data, the laboratory data to help you prognosticate how they’re going to do?

Dr. Mehta:
So, usually in a community settings, I tend to, if patient has a prostate biopsy, definitely, I look at Gleason score, Gleason 8. If there is an MRI or an imaging as T-3, T-4 lesion seminal vesicle invasion. Then definitely I look at the PSA volume and the velocity. If PSA is by high-risk criteria by NCCN, about 20, then certainly the threshold goes higher that using apart from androgen deprivation to use AR agonist right away for sure, because we know this patient.

And then I think following the velocity. Now patient got surgery, then we definitely look at is it early recurrence. If post-prostatectomy, PSA never became undetectable and now velocity is higher than those patients, we know that we are going to be in challenge. That’s how I make the decision. What are the other factors you’ve been using?

Dr. Kelly:
Yeah. I agree with you, Dr. Mehta. We’re using the same things, grade group four, grade group five, taking a look at the biopsies, taking a look at the percentage of the cores that are involved, high percentage of the cores, how many cores are involved, taking a look at the pathology probiform pattern being present. But otherwise those same things with regards to looking at very high risk or high risk per our NCCN guidelines.

Dr. Appleman:
Do you all look at either next-generation sequencing of genomic or tumor DNA or any of the gene expression panels?

Dr. Mehta:
We’ve been participating the NRG-GU009 and 10 trial for decipher-based genomic assays. So all the patients, we’ve been trying to put them through intermediate-risk, especially if they choose the radiation arm. And at this point, I tell the patient, maybe this genomic assay will tell us are we a good risk or more a personalized way. The way I present the patient is more is it a bad cancer or an ugly cancer? And if it’s a bad cancer, we tend to do the standard of care, but ugly one, that’s where we want to reach out and use from our armor more and use the medicines.

Dr. Appleman:
In terms of what I do, I try always to get the genomic data for patients with new metastatic disease and for the localized or newly recurrent after prostatectomy if they have a detectable PSA after their surgery and Gleason 9 and they’re in their 50s, those are the people where I may send it even though it may not change their management right now, I find it prognostically valuable to see do they have loss of two out of three of the bad tumor suppressors P to the RBP-10, do they have an S-pop mutation, which may project excellent response to androgen deprivation? Do they have micro-satellite instability where down the road they’re going to be the people who respond really well to immune checkpoint inhibitor, BRCA mutation, etc.? So I don’t need it immediately for the highest localized or the biochemical recurrence patients, but I sort of like to have that data in my pocket.

Dr. Mehta:
And are you using tissue-based or liquid-based or whichever is the easiest?

Dr. Appleman:
I always do whatever’s the easiest in life. I think if it’s pretty recent, I’ll use the tumor, especially if they’ve had a prostatectomy recently or prostate biopsies. If it’s been years, I’ll either try to get a fresh biopsy, which I haven’t been that aggressive about, or use the liquid I think more and more.

Dr. Wong:
Yeah, I agree. Sometimes just practically speaking, you don’t have the NGS test results back by the time that you feel you need to make a treatment decision. But in the rare cases where I did have that information and they had RB-1 or P-10 or something like that, it probably did push me towards more aggressive therapy, maybe doing triplet therapy instead of just ARSI and ADT.

And then again, this doesn’t help with your initial choice of therapy, but I also use PSA response at 28 weeks because there were a couple of SWOG trials that showed at 28 weeks after starting treatment, if you had a PSA of I believe greater than 4, 0.2 to 4, or less than 0.2, that was very prognostic of overall survival. And there’s been a couple patients who’ve had a simultaneous malignancy maybe what looks like a localized renal cell carcinoma. And we’re wondering do we need to do anything about that? And I’ve used the PSA response at 28 weeks to give me an overall sense of how that patient might do. And if they have a longer projected overall survival, then we might consider taking that out with surgery.

Dr. Chablani:
Yeah. And I’ll just add that in addition to whatever has already been said, agree with tissue NGS, I’ve also been trying as much as possible to send germline testing for all my high-risk patients as well as metastatic castrate sensitive, castrate-resistant if it hasn’t been done yet. Sometimes it’s not easy to get the tissue, it was the initial prostate biopsy or prostatectomy was done years ago or the tissue is not good enough for NGS tests testing anymore. So you don’t want to not be able to identify that patient with the BRCA1, BRCA2, PAL-B-II is important mutation. So sending the germline testing is just another way to kind of cover your bases and pick up all the genetics that we can potentially target with our treatments.