He's baaaaack: Top pathologist Dr. Jonathan Epstein updates AS audience
First appearance since April 2023
By Howard Wolinsky
After a falling out nearly two years ago with Johns Hopkins, his professional home for nearly 40 years, Dr. Jonathan Epstein, top-gun pathologist, made a comeback at TheActiveSurveillor.com’s “Active Surveillance 2025.”
I broke the story in The Active Surveillor on Epstein’s mysterious disappearance; my colleagues at the Washington Post and I found more details. You can read more here. But the point is as an attendee to the webinar put it: “Dr. Epstein is back in the saddle.”
Epstein is in the process of launching his new 2nd opinion pathology practice in NYC. I’ll share more details when they’re available.
He has made a huge impact on his field, reforming the Gleason system and impacting the lives of tens of thousands of men like us with his pathology reports. When he was at Hopkins, he and his team signed off on 12,000 cases a year. I got a second opinion from him when I was newly diagnosed in 2010.
When I was organizing AS 2025, I put Epstein on my wish list of speakers. I was stunned when he accepted—without hesitation—my invitation.
(Dr. Jonathan Epstein)
Epstein and the other speakers got Five Star ratings from attendees.
This was a special event for paid subscribers to the newsletter. But I asked the attendees if they would support releasing the video to all-comers. Only one objected.
I am writing a series of articles on the program based on the talks.
And you now can watch the video on YouTube. The video from the TheActiveSurveillor.com’s Jan. 4 webinar, “Active Surveillance 2025: The Year In Review” is now available to all here:
After viewing the video, please respond to the survey: https://forms.gle/iww9y9gcj44Ei5PLA. Based on the survey, I have decided to hold AS 2026: Year In Review” next year. (Some asked for quarterly and even monthly programs. I’ll take that under advisement. I already run monthly programs for Active SUrveillance Patients International (ASPI.)
Epstein last spoke to AS patients in April 2023 at a webinar I organized for Active Surveillance Patients International where he answered questions and also was featured in the AS 101 series created by leading AS support groups in the U.S. and Canada.
In his Jan. 4 talk, Epstein stressed the importance of patients getting a second opinion. Sure, that’s the focus of his business model, but we owe it to ourselves to get the best eyes we can to look at our pathology slides. You want a uropathologist who has focused on reading prostate cancer slides.
He said: “Before talking about the pathological features of the cancer itself, it's critical to make sure that you actually have an accurate diagnosis of cancer in that one might assume once a pathologist diagnoses cancer, it should be straightforward. It should be objective and 100 percent accurate. Unfortunately, there are a lot of mimickers of prostate cancer and there are sometimes when prostate cancer's overdiagnosed when, in fact, a man does not have cancer.”
Epstein said: “The first step if I were diagnosed with cancer would be to get a confirmation that the diagnosis is accurate by sending it for a second opinion. … if your diagnosis is incorrect, everything going forward will be incorrect. Now, once you're diagnosed with cancer and in terms of, Are you a candidate for active surveillance?”
He noted that there's about a 20 percent chance of a different grade when viewed by an expert when your biopsy is reviewed. “So it's not insignificant in any respect,” he said.
That could either be an upgrade or downgrade, but 20% of the time patients get Gleason or Grade Group scores that have been downgraded or upgraded when an expert reviews them.
I have heard story after story of men whose Gleason/GG scores have been downgraded, sparing them from a walk on the path of aggressive treatment when they should be on Active Surveillance train. But again, it can go either way.
Epstein stressed a second opinion is in order even if you get a Gleason 6 on the firtst go: “There are some men diagnosed with a Gleason 6, No. 1, may not have cancer, or there could be Gleason 7 (3+4), Grade Group 2 in there, which was not graded correctly by the pathologist.
“So I would say the majority 80-90 percent, if you're diagnosed with a Grade Group 1 will be a Grade Group 1 on review. But 10 percent may be Grade Group 2, and that could change potentially how you go forward. And again, everything going forward is based on an accurate diagnosis of your cancer and the grade, and it's a small investment with a second opinion, and most insurances cover it to have the right diagnosis and feel comfortable going forward with that.”
Epstein noted that there been some changes in the past year in how doctors view prostate cancer and whether patients are candidfates for Active Surveillance, especially a “de-emphasis on cancer volume.”
“So, on the initial criteria that we propose for ideal candidates of Active Surveillance, cancer volume, number of cores involved by cancer, the percentage of the core involved by cancer, was something that was one of those factors. I think now with MRI, where volume of the cancer, the number of cores with cancer, I think that should be de-emphasized in terms of the extent of the cancer.
“More importantly is the grade of the cancer and certain other pathological parameters of the cancer. In terms of the grade of the cancer, again, numerous studies have shown there is subjectivity in grading of cancer, both undergrading and overgrading. So it is, again, critical to get an accurate reading on the pathology.
“One also can't assume just because you're at a good institution, top-notch international, nationally recognized institution that the pathologist reading those slides may not be an expert in prostate pathology. Likewise, you could be in a smaller hospital, and they may not be an expert in prostate pathology. So, unfortunately, you choose your urologist. You choose your clinicians. Most of time, you're not choosing your pathologist, and you don't know where your pathology is going to.”
Epstein urges caution about AI hype and prostate diagnosis and grading. He noted that AI is not used much yet clinically.
“There are a lot of AI platforms out there. Each AI algorithm is based on pathology grading, for example, the slides. And that basically tells the AI what to the grade is eventually. So the AI is only as good as whoever is grading the tissue for the AI platform. Second of all, unfortunately in pathology, there's just tremendous variability between laboratories in terms of how slides look even within the lab on a given day by day, how slides will appear such that if the AI is trained on a certain data set of slides from let's say one or two institutions, how that AI might work then from another lab where the slides look totally different may not necessarily be as accurate or the same.”
He said another thing that has changed in recent years is that Active Surveillance is the recognition “that there are maybe some men with certain volume of Pattern 4, certain architectural patterns of 4 that still could be candidates for Active Surveillance. So it's critical once you have a Pattern 4 recognized, Grade Group 2, which is 3+4 equals 7, to see what is that Pattern 4? What percent Pattern 4? For example, somebody with five or 10 percent Pattern 4 within the 3+4 equals 7, could be a candidate for active surveillance. I would argue somebody with 40-50 percent Pattern 4 and 3+4 equals 7 would not be a candidate, because that's bordering on a 4+3 equals 7 or Grade Group 3.”
He added that “what's called a cribriform Pattern 4 is a more adverse morphological feature. Cribriform comes from the word sieve, think of it like swiss cheese. Basically, a sheet with little punched-out holes in it. But even within a cribriform pattern, there are kind of more adverse types of cribriform patterns and others that may not be as adverse. And so, there's, again, tremendous variability amongst pathology reporting. A lot of pathologists do not report percent Pattern 4. They don't report if there's cribriform Pattern 4. And if they report cribriform Pattern 4, they may not substratify cribriform Pattern 4 into those that are more aggressive.”
In his reports, he said he lists “the percent of Pattern 4, also state whether there is large cribriform glands of Pattern 4. And there are different definitions of large cribriform glands of Pattern 4. I use one that is objective that also correlates with in studies, the more aggressive behavior, such that if one did have these large cribriform Gleason Pattern 4s on a biopsy or with a Grade Group 2, in my opinion, that would argue against Active Surveillance.”
Epstein said the presence of intraductal carconoma of the prostate could rule out AS. “You don't see that often in Active Surveillance men, but nonetheless it can be present, that should be a contraindication in general for active surveillance is intraductal carcinoma of the prostate. Numerous studies have shown this as an aggressive marker when you find intraductal cancer, but again, there is subjectivity in terms of reproducibility issues with the diagnosis of intraductal cancer of the prostate. I'm currently on an international consensus panel working on trying to develop criteria where hopefully there will be greater reproducibility and consensus on the diagnosis of intraductal cancer. The diagnosis still uses our original criteria that I worked on many years ago that still currently the accepted criteria for intraductal cancer.”
He added: “You may also hear term called AIP, or atypical intraductal proliferation. And what AIP is is kind of a broader lesion that's worse than what is called high-grade prostatic intraepithelial neoplasia or high-grade PIN, kind of stratifying between high-grade PIN and intraductal cancer. Some of these AIP lesions border on intraductal cancer. Some AIP lesions are less worrisome. Consequently, if you're diagnosed with AIP on your biopsy, in addition to cancer, I think it's important to discuss with a pathologist just given the AIP that you have, is it closer to intraductal cancer where I should be concerned about staying on Active Surveillance? Or is it an AIP that's not as worse and closer to high-grade prostatic intraepithelial neoplasia, which should not be a factor in terms of staying on active surveillance.”
Epstein also mentioned research he did showing the importance of perineural invasion once you're on Active Surveillance. “Having perineural invasion along with a higher PSA and PSA density is a risk factor for having progression subsequently. And so, again, it's not if you have perineural invasion you should go off Active Surveillance. Having perineural invasion is more somewhat of a worrisome features. So I would argue that intraductal cancer truly is a contraindication. Large cribriform cancer is a contraindication for active surveillance. Perineural invasion is not a contraindication, but is something that is more worrisome and maybe, for example, one should have a rebiopsy in a closer interval than if, for example, perineural invasion was not present.”
Next up from “AS 2015: The Year In Review” will be a story about the presentation by Christian Pavlovich, MD, head of AS at Johns Hopkins.
Check out my new companion blog, Prostate Cores featuring nuggets of news about PCa, BPH, cancer, etc.
MRI-invisible lesions: A good sign—like a Gleason 6? Still time to sign up—don’t be invisible
By Howard Wolinsky
Did you know that it’s possible for prostate cancer can be confirmed by a pathologist but the lesion can be invisible in an MRI?
Is this a good thing? Many researchers think it is.
Dr. Mark Emberton, Professor of interventional oncology at University College London and Dean of its Faculty of Medical Sciences, will be speaking to the ASPI webinar about MRI-invisible lesions on Saturday, January 25, 2025, from noon – 1:30 p.m. Eastern (5:00pm-6:30pm UK time). Emberton is a pioneer on the use of MRIs in diagnosing, classifying and monitoring prostate cancer.
Don’t be invisible. Register here: https://zoom.us/meeting/register/tJYldu-qqzojGNEzCkgPQuTOWYGhcL80Dhec'
MRI-invisible lesions are considered a good thing comparable to Gleason 6.
Professor Emberton’s clinical research is aimed at improving the diagnostic and risk stratification tools and treatment strategies for prostate cancer (PCa). He specializes in the implementation of new imaging techniques, nanotechnologies, bio-engineering materials and non-invasive treatment approaches, such as high intensity focused ultrasound and photo-dynamic therapy.
His research has been published in over 300 peer-reviewed scientific papers in journals including BMJ, Lancet Oncology and European Urology. He has also contributed to the development of guidelines for the management of PCa and lower urinary tract symptoms, published by the International Society of Geriatric Oncology and the European Association of Urology.
If you have questions, please send them to: contactus@aspatients.org