Surveillance rising in patients with intermediate-risk prostate cancer, especially among patients having a PSA of 10 or less

Happy Thanksgiving

By Howard Wolinsky

Since the earliest days of Active Surveillance (AS) in the late 1990s, some patients with favorable intermediate-risk prostate cancer (Gleason 3+4 or Grade Group 2) and fewer yet with higher-grade intermediate-risk cancer (Gleason 4+3 or Grade Group 3) have hopped on the AS train.

Mostly, patients with low-risk Gleason 6/GG 1 have ridden the train, though some change going on there, too. (See below.)

But a new study in JAMA Network covering 2010-2020 has found AS has been increasingly accepted by patients with intermediate-risk prostate cancer, especially among those with a PSA of 10 or below. Patients and their urologists have been gaining more confidence that they safely follow intermediate-risk cancer with AS.

Senior author Michael Leapman, MD, clinical program leader of the prostate and urologic cancers program at Yale Cancer Center and an associate professor of urology at Yale School of Medicine, told me: “Most patients in this [intermediate-risk] category will not experience progression of disease (metastasis or regional spread) but the risks are not trivial either. It is important that we determine more rigorously which Gleason grade group 2 (and 3) cancers are less likely to progress. If this can be done in a very reliable way, a substantial number of men could avoid treatment.”

The researchers reported that between 2010 and 2020, AS and its less-intense brother Watchful Waiting (WW) more than doubled in patients with intermediate-risk prostate cancer, including favorable-risk and higher-grade intermediate varieties.

Leapman, who writes an occasional blog in this newsletter, said, “We know that many prostate cancers will not spread or cause symptoms if untreated. There have been major changes over the past decade with much more use of initial monitoring for cancers determined to be ‘low risk.’ We wanted to determine whether conservative management, including Active Surveillance or Watchful Waiting, has also increased for cancers with ‘intermediate risk’ features as well.”

Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER) program, which collects cancer information from various parts of the U.S. They looked for people diagnosed with intermediate-risk prostate cancer based on criteria, including Gleason score, PSA level, and stage of the disease.

In the study, 147,205 individuals were identified with intermediate–risk prostate cancer from 2010 through 2020. The proportion of patients diagnosed with intermediate–risk prostate cancer increased overall from 41.7% in 2010 to 47.3% in 2020.

Researchers reported that AS/WW use increased from 5.0% in 2010 to 12.3% in 2020--a more than 50% increase among intermediate-risk patients.

AS/WW use increased from 13.2% in 2010 to 53.8% in 2020 among intermediate-risk patients with GG1, from 4.0 to 11.6% among those with GG2, and 2.5% to 2.8% among those with GG3.

Leapman told me: “By almost all systems, ‘intermediate risk’ is defined by having some adverse features. This can include a high PSA level (usually 10 ng/mL or above), or high stage (a physically palpable tumor on examination). In this study we used any intermediate-risk definition. This shows that although active surveillance is increasing in the “intermediate risk” group, it is increasing most among patients who meet the definition based on having a PSA of ≥10. AS is increasing in Gleason grade group 2 as well but most of the increase is driven by those meeting intermediate risk for other reasons.”

AS/WW use increased from 3.4% in 2010 to 9.2% in 2020 among intermediate-risk cases with PSA values of 10 ng/mL or below; and from 9.3% in 2010 to 20.7% in 2020 among those with PSA values ranging from 10 to 20 ng/mL.

Of those with PSA values ranging from 10 to 20 ng/mL, 37% had GG1 vs 17.5% of those with PSA values lower than 10 ng/mL.

(Dr. Michael Leapman-Yale.)

As usual the U.S. lags other countries such as Sweden, where sources say about 20% of intermediate-risk patients go on AS.

AS/WW clearly has room to grow among intermediate-risk patients. Consider the innovative MUSIC program in Michigan, which has reported that 45% of patients with intermediate-risk disease chose active surveillance in 2021 compared with 13% in 2013.

Leapman told me AS/WW uptake is now the largest category among patients with localized disease.

I was on a panel in 2017 Freddie Hamdy, MD, co-principal investigator of the famed ProtecT trial, which demonstrated the safety of Active Surveillance.

After the session, Hamdy told me that in the years ahead he expected the majority of AS patients would be those with intermediate-risk cancers. Hamdy’s forecast was on the money.

Leapman said he agreed and that intermediate-risk patients are “the new frontier” for AS/WW.

In summary, he said: “Most patients in this category [Grade Group 2 and 3] will not experience progression of disease (metastasis or regional spread) but the risks are not trivial either. It is important that we determine more rigorously which Gleason grade group 2 and 3 cancers are less likely to progress. If this can be done in a very reliable way, a substantial number of men could avoid treatment.”

While increasing in intermediate-risk, AS declining in low-risk patients

By Howard Wolinsky

In December, I will have been on Active Surveillance for very low-risk prostate cancer for 14 years. I am one of the Methuselahs of AS.

Sounds like a good thing. But is it? Could it have been oversurveillance for low-risk disease after a period of overdiagnosis and overtreatment?

Is the pendulum swinging the other way as researchers seek the right balance?

In fact, fewer of us are being diagnosed with lower-risk prostate cancers and are going on Active Surveillance. In fact, experts, especially from U.K. and also U.S., pointed out to me, if I came in with a rising PSA today, I likely would not have been diagnosed with cancer at all. I would have undergone a pre-biopsy MRI, an AI test like Artera, or a biomarker test to rule out the need for a biopsy. This testing reduces biopsies by about 50%

If you avoid unnecessary biopsies, you avoid risks of sepsis and other infections.

Many doctors, especially in U.K., have bragged about their declining AS uptakes.

Several experts have told me if I started on this “journey” with a rising PSA today as opposed to 2010, I most likely would not have been diagnosed with prostate cancer and would have avoided risks for emotional distress or financial toxicity, such as insurance discrimination.

Jim C. Hu, MD, MPH, a urology professor at Well Cornell Medicine, and colleagues reported in the Journal of the National Cancer Institute that between 2010 and 2018, the incidence of low-grade PC (GG1 or Gleason 6) decreased from 52 to 26 cases per 100,000 population in the U.S.

They said that the incidence of GG1 as a proportion of all PCa decreased from 47% to 32%, and the proportion of GG1 at radical prostatectomy pathology decreased from 32% to 10% . However, metastases at diagnosis increased from 3.0% to 5.2%.

My urologist, who is cautious, has not ordered an MRI or biopsy for me since 2016. I’ve even considered dropping surveillance.

We follow my so-called cancer—only seen once in five previous biopsies back when we underwent biopsies annually—with PHI (Prostate Health Index) blood test, which include a regular PSA.

Some doctors would say I am on watchful waiting. My doctor calls it active surveillance, which is the intent. I call it passive-aggressive surveillance.

If my PHI rises. it would trigger an MRI. If the PIRADS score is high, I’d have a biopsy. (Make mine transperineal, please.)

But your situation is likely different from mine. Hence, the need to personalize our protocols.

Clock is ticking: The Active Surveillor’s ‘AS 25’ webinar coming up Jan. 4, 2025

By Howard Wolinsky

Paid subscribers and founding members get a free pass to “AS25,” a special program this newsletter is hosting at noon-1:30 p.m. Saturday Jan. 4, 2025.

If you want to join us, get a paid subscription here:

This is the first such program TheActiveSurveillor.com has hosted. The point is to provide a premium to paid subscribers.

If you can’t afford it, or have specail circumstances, such as living in a country facing a banking boycott with the U.S., let me know and we’ll work it out.

The main point of linking subscriptions to free entry to the program is in effect making a donation to keep this newsletter afloat. Sorry. It may seem free, but I devote considerable time to producing the newsletter two or three times a week, turning down lucrative work. I will report on any news coming out of the webinar.

One bit of the news. Famed uropathologist Jonathan Epstein, MD, is making his first appearance at a patient meeting in almost two years. He had kept a low-profile since resigning from Johns Hopkins in February 2024 following a dispute with Hopkins, his professional home for almost 40 years.

Dr. Epstein will be speaking on a panel on what happened in prostate cancer in 2024 and what’s on tap for 2025.

Previously announced panelists are:

—Brian Helfand, MD, PhD, chief of urology at NorthShore University HealthSystem outside Chicago, an expert not only in prostate cancer but also in molecular biology.

—Christian Pavlovich, MD, who runs the Active Surveillance program at Johns Hopkins and recently co-authored a major study on diet.

—Timothy Showalter, MD, MPH, medical director of Artera AI, which has made news with its prostate test to help patients decide whether to go on AS.

Unsolicited testimonial

Bill Peck: I love the Active Surveillor ... I was diagnosed with PCa in Sept (3+4 in 2 cores, < 5%). Radiation oncologist said, "When do you want to start?" ... and I was like "Hold on a sec, ok?"

I also found this article which is great and I am sharing with my children:

https://howardwolinsky.substack.com/p/prostate-cancer-treatment-is-not

Thanks, Bill. Love you back. Howard

ASPI presents: How you can help advance research on Active Surveillance

By Howard Wolinsky

Without clinical trials, such as ProtecT, patients with lower-risk prostate cancer would have had no choice other than aggressive treatment with risks of side effects impacting their quality of life. I have participated in about a dozen trials as a patient and a patient researcher.

I highly recommend participation in trials. I have been in studies on diet and low-risk prostate cancer, genetics and medications and low-dose aspirin and preventing heart attacks. You’re paying it forward when you join in.

Look for trials on Active Surveillance that you potentially can join at ClinicalTrials.gov

Active Surveillance Patients International (ASPI) is holding a webinar at 12:00PM ET Saturday, November 30, entitled “How you can help in clinical research on Active Surveillance.”

REGISTER HERE: https://zoom.us/meeting/register/tJIocOCupz4jGtX8fHJ036bYGHYIjLfwfRzk

Speakers will include Kevin Shee, MD, PhD, a researcher at the University of California, San Francisco, and Mike Scott, founder of Prostate Cancer International and an early advocate for Active Surveillance.

Dr. Shee has been involved in multiple studies, the most recently one on whether men 75 and above should stop active surveillance.

Though not a prostate cancer patient himself, Mike Scott was the founder of one of the first support groups for men on AS. ASPI this year presented him with its 2024 Thráinn Thorvaldsson Award for Patient Advocacy.

A question-and-answer session will follow the presentations.

If you have questions, please send them to: contactus@aspatients.org

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Climbing Dr. Geo’s ‘Prostate Cancer Summit,’ addressing AS, herbs, diet, prostate massage, and more

By Howard Wolinsky

Dr. Geo Espinosa (you may know him as the author and podcaster “Dr. Geo,”), the naturopath specializing in prostate care on faculty at New York University, is hosting a free week-long “Prostate Cancer Summit” you shouldn’t miss.

The free event runs an “encore weekend” November 29 - December 1, 2024. Register here: https://drtalks.com/summit/prostate-cancer-summit/?uid=814&oid=83&ref=4266 Dr. Geo is interviewing more than 40 experts on prostate cancer plus me.