Hopkins researchers: Confirmatory biopsies can be deferred in men diagnosed with low-risk PCa considering AS but who have negative MRI scans

Making Active Surveillance a bit less active? Welcome to 2025.

(Editor’s note: It’s a New Year, and the digital ink is still wet on a study that may be important for many of you who are newly diagnosed with low-risk prostate cancer. HW)

By Howard Wolinsky

If you are newly diagnosed and awaiting a confirmatory biopsy, researchers from Johns Hopkins Active Surveillance program have some news that might impact you: You might be able to defer confirmatory biopsies for up to three years.

They found that men found in a first biopsy to have low-risk prostate cancer despite having had with negative multi-parametric MRI scans ( known as MRI-invisible lesions) can delay confirmatory biopsies for more than 18 months, perhaps for two to three years, Christian Pavlovich, MD, professor in urologic oncology at the Johns Hopkins University School of Medicine and director of the Brady Urological Institute’s prostate cancer active surveillance program, told me an interview.

Pavolovich and his Hopkins colleagues reported the study in the January 1, 2025 edition of the Journal of Urology. Yasin Bhanji, MD, was the lead author.

Researchers concluded that their data support systematic and targeted confirmatory biopsy for men with positive MRI findings who are considering Active Surveillance, while men with Grade Group 1 cancer and negative MRI findings should be able to defer a confirmatory biopsy.

Those with positive MRI scans should undergo confirmatory biopsies 6-18 months after diagnosis to see if their Gleason score was accurately reflected on the first biopsy.

As many as 150,000 American men each year are diagnosed with low-risk prostate cancer (Grade Group 1/Gleason 6) and consider Active Surveillance, surgery, or radiation. 90,000 (60%) opt for AS.

Pavlovich explained that the “confirmatory biopsy” is the second biopsy after diagnosis, or the first surveillance biopsy. “(They’re the) same thing really. Only difference I see is that for some programs like ours we formally enroll men only after the confirmatory biopsy concurs that the cancer is not too aggressive for surveillance,” he said.

(Dr. Christian Pavlovich, Hopkins)

Hopkins does surveillance biopsies every 2-5 years depending mainly based on PSA and other biomarker information and on MRI data. It’s a far cry from 14 years ago, when I was diagnosed at University of Chicago, which was following the then-Hopkins protocol of annual biopsies. Routine (and still underused in the U.S.) prebiopsy MRIs were not available in ancient times. These MRIs spare about 50% from a biopsy, which are linked to infection, and unnecessary diagnosis and unnecessary AS.

(Pavlovich will be discussing this study during his presentation at the Active Surveillance 2025” webinar at noon Saturday, Jan. 4. Free passes are still available to paid subscribers to The Active Surveillor.)

Pavlovich and his colleagues report: “"Our data support confirmatory biopsy (systematic + targeted) for men with positive MRI considering AS, whereas men with GG1 cancer and negative MRI [MRI-invisible lesions] may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2 to 3 years.”

The researchers concluded: “The risks of grade reclassification to ≥ GG2 (and especially to ≥GG3 or of reclassification to [unfavorable intermediate-risk] PCa) were we believe sufficiently low in men with a negative MRI (performed at an experienced imaging center) that such men could be advised against [confirmatory biopsy] as a recommended criterion for starting AS. Such a programmatic change would result in deferring biopsies, with a margin of safety, for approximately 40% of men until a first surveillance biopsy in 2 to 3 years.”

He said increasing intervals reduces morbidity for patients “but we still believe that biopsy is the most accurate way to gauge progression.”

Increasing intervals means fewer biopsies, which means reduced morbidity and cost as well as a lower risk of potentially disabling and deadly sepsis if done transrectally.

Laurence Klotz, MD, one of the pioneers in AS, uses three- to five-year intervals in surveillance.

OK. Wait a minute. What are MRI-invisible lesions? This is where a pathologist is able to diagnose a cancer and give it a Grade Group or Gleason score, but the lesion is not observed on an MRI.

This phenomenon has been known since prostate MRIs became available about 15 years ago. But many experts recognize an increasing importance to patient care MRI-invisible lesions as a marker for safety, with some comparing invisible lesions, even higher grade ones, as being comparable in safety to Gleason 6 lesions.

Pavlovich told me that 40-50% of GG 1 men in Hopkins AS program have negative MRIs—MRI-invisible lesions.

Applied nationally, this could mean that up to 45,000 U.S. men a year who have been diagnosed with a first biopsy but whose MRIs were negative (MRI-blind lesions).

Pavlovich added: “It’s a moving target. As we move forward the percent of men on AS with MRI lesions is increasing (as it should) – as men without lesions are being biopsied less frequently.”

He added: Some might say they never should have been biopsied… but some have very high PSA, PHI, GG2 disease, large volume disease, etc so I stand by diagnosis when suspicion of higher grade disease exists. MRI is not the only diagnostic test and can still be subjective in that it varies in quality by reader, center, expertise, etc.”

Pavlovich explained the current protocol at Hopkins: “If initial MRI is negative I now defer confirmatory biopsy for 18-24 months typically (this is new). If initial MRI is positive (PIRADS 3,4,5) then confirmatory biopsy is recommended in 12 months typically, per guidelines.”

Observation: It might help to defer these biopsies, but I expect this will impact emotional stress/anxiety issues in these men.

In the study, 522 men with GG1 PCa on diagnostic biopsy had a confirmatory biopsy during the study interval; notable among their characteristics is that 59% had a positive MRI. The overall rate of group grade reclassification to Grade Group 2 or higher at confirmatory biopsy was 20%, while the rate of grade reclassification to GG 2 or higher in men with positive MRI was approximately 3-fold higher than in men with negative MRI (27% vs 9.2%).

So we gotta’ accentuate the MRI positives in recommending confirmatory biopsies.

Systematic sampling of men with positive MRI at confirmatory biopsy resulted in similar grade reclassification rates as targeted sampling, researchers said.

In an editorial, “Can We Be Less Active in Prostate Cancer Surveillance?”, Drs. Miko Filon and Brock O’Neill, of the University of Utah, Huntsman Cancer Institute, in Salt Lake City, said the Hopkins and another at the University of California, San Francisco (I’ll be covering that study soon on the need for systematic biopsies) “add to the growing literature that mpMRI is helpful in distinguishing between a more aggressive prostate cancer biology and disease that is likely to be more indolent. For example, molecular and genetic studies suggest that MRI-invisible lesions may be characterized by unique molecular pathways or tumor microenvironments that escape current imaging techniques and represent a less aggressive biology.^”

They added that further research is needed to ensure “deimplementing” current practices does not expose patients to unnecessary harm, but the new studies “are important additions that raise questions about currently recommended AS practices.”

Dr. Mark Emberton, professor of interventional oncology at University College London and Dean of its Faculty of Medical Sciences, a strong advocate for the importance MRI-invisible lesions, emphasizes the concept for men with GG2 and above.

I asked him about the value to GG1 patients. He said he does biopsy men with MRI-invisible lesions.

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MRI-invisible lesions: A good sign—like a Gleason 6?

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?

You do if you read the previous article.

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

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Good news for Israeli Prime Minister

By Howard Wolinsky

Israeli Prime Minister Bejamin Netanyahu has plenty of issues to occupy his mind.

But his doctors said Sunday, prostate cancer is not one of them.mNetanyahu had his prostate removed Sunday after he was discovered to have a prostate infection. Removal of the prostate is not uncommon in such patients.

Netanyahu faced a risk of 3-17% that cancer would be found in a biopsy of his tissue. But he got lucky.

Dr. Ofer Gofrit, head of the urology department at Jerusalem’s Hadassah Medical Center, said in a video statement late Sunday that the procedure had gone well and “there was no fear” of cancer or malignancy. “We only hope for the best,” he said.

In a statement, Netanyahu thanked his doctors. His office said he was “fully alert” and was taken to an underground recovery unit fortified against potential missile attacks. Netanyahu was expected to remain in the hospital for several days of observation.

The surgery delayed by a few days his need to report to a court for a corruption trial,

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