Will AS 2.0 with non-steroidals be a hit? Or the next 'New Coke' disaster?

Also, The Active Surveillor annual report

By Howard Wolinsky

The 17th-century philosopher and Anglican bishop, George Berkeley, posed a famous question: “If a tree falls in a forest and no one is around to hear it, does it make a sound?"

I ask another question as an AS patient: If patients on Active Surveillance (AS) are given powerful drugs to treat their wimpy cancers, will they still be on active surveillance?

Berkeley said yes to the falling tree—that God was listening.

The preliminary answer to the second question is yes, sort of. It will be a new type of AS on non-steroidals to keep patients away from radiation therapy and radical prostatectomies.

Let’s call it AS 2.0.

Classic AS has never involved anything more than managing low-grade, slow-growing cancer with a distant, early warning system of digital rectal exams, regular prostate-specific antigen (PSA) blood levels, magnetic resonance imaging (MRI) scans, and biopsies.

But what if prostate doctors souped treatment up by adding to the AS cocktail powerful hormonal meds used to treat advanced cancers?

Could it be a game-changer? Could it give anxious patients more confidence to stay on monitoring for the long haul? Will AS 2.0 be worth enduring the expense and side effects?

Or will this be a situation like that faced by Coca-Cola in 1985 when it flopped in introducing New Coke to replace Coke Classic?

Could AS 2.0 be deja vu all over again, a situation of if it ain’t broke, don’t fix it?

This may be a semantic question, but the idea of giving powerful hormonal therapy at a high cost--in dollars as well as with potentially serious toxic adverse effects—has been getting growing attention as evidenced by the publication of new studies.

I’ve written about this idea in this blog as well as Medscape Medical News. In 2021, Dr. Michael Schweizer, a medical oncologist at the University of Washington and the Fred Hutchinson Cancer Center in Seattle, made a presentation on AS 2.0 to the AnCan Virtual Support Group I moderated.

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Prostate Cancer Research Institute leads the way in informing patients about prostate cancer. They regularly run videos on relevant topics. Alex Scholz, their CEO, interviewed me a year ago. She finally posted the interview. Please read the comments.

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Now a new preliminary Phase II  clinical trial from Schweizer and his team has shown the hormonal agent apalutamide may lower the rate of positive biopsies during follow-up.  The study will be published in the Feb. 1 edition of The Journal of Urology.

Patients underwent 90 days of treatment with apalutamide, an oral med in the ARI (androgen receptor inhibitors) category.

The study was small. Twenty-three patients were enrolled and 22 completed 90 days of apalutamide with a post-treatment biopsy.

Fifteen (65%) had Grade Group 1 (Gleason 6) disease, and all others had Grade Group 2 (Gleason 3+4 favorable intermediate-risk cancer. Seven (30%) had favorable intermediate-risk disease.

Of 22 evaluable patients, 13 (59%) had no residual cancer on post-treatment biopsy. The median time to a first positive biopsy was 364 days.

Not surprisingly, PSAs blood levels dropped while these men were being treated. PSAs increased after therapy ended.

In 65% of patients, PSA levels decreased by 90% or more with the addition of apalutamide. Five patients underwent radiation or surgery for prostate cancer at a median of about two years.

The addition of drugs clearly changes the nature of AS. There are no side effects to AS—unless you count emotional distress.

Schweizer & Co. note that 20-50% of men on AS 2.0 “convert” to treatment. Actually, what I’ve reported on is far worse—a whopping two-thirds of men on AS drop out by 10 years after diagnosis.

Schweizer and colleagues argue that the addition of ARI drugs could help men stay on  AS.

It would be a game-changer.

ARI meds—there are several—might help these patients stay on AS longer and avoid or delay radical prostatectomies or radiation treatment.

I think another potential advantage is ARIs potentially could lower emotional distress levels for some men with the promise of a drug that could help suppress cancer growth.

But at what cost? 

Researchers described apalutamide as “safe, well tolerated, and [having] minimal impact on quality of life.”

Well, 70% experienced fatigue and gynecomastia, breast enlargement.

Add in hormone imbalance, joint and muscle pain, taste changes, rash, cognitive impairments, hot flashes, anorexia, dry skin, libido decrease, itchy skin, nausea, and weight loss.

But is this really minimal? Each patient needs to decide what’s acceptable. There are no free rides.

Several other recent studies have explored the use of hormonal therapy for men with low- to intermediate-risk prostate tumors. In June 2022, JAMA Oncology published findings from the ENACT trial, which compared the ARI enzalutamide, another ARI,  to AS in 227 men with low- to intermediate-risk prostate cancer.

The trial launched in 2016, before AS flourished as an approach to managing the disease in the United States. (Other countries have had far greater AS success than we have in the U.S.: 60% recruitment of candidates vs. 94% in Sweden and 91% in Michigan.)

On the surface, the study was a success. Compared with AS alone, the drug reduced the risk of pathologic or therapeutic progression of prostate cancer by 46%.

However, “enza”―which crosses the blood-brain barrier―was associated with significant side effects, including decreases in energy and libido, a gain in visceral abdominal weight, and the possibility of worsening cardiovascular risks or complications, depression, bone demineralization, and hot flashes. 

Christopher Booth, MD, of the Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, Ontario, Canada, said, “I cannot see how this represents an important advance for patients. I worry we are taking a step backward if clinicians begin to adopt this approach over true active surveillance."

He suspects drug companies may try to cash in on the growing market of patients with early, localized prostate cancer that they previously ignored.

Pharmaceutical companies have told me they had no interest in pursuing meds for AS. But there is a potential bonanza in AS 2.0 with meds. About one-third of the 268,000 men a year diagnosed with prostate cancer, fall into the low-risk category.

ARIs don’t come cheap. Wholesale prices can run into low six figures a year.

Schweizer told me last summer: “I think drug companies would love to tap into the 'active surveillance market.' The challenge is that there's no clear pathway to getting FDA approval in this setting, as clinical trial endpoints have not been validate.”

Still, he thinks, “Medications could become part of routine management of men on AS, but we need better ways to identify patients who need treatment." 

So what do you think? Would you want to be an AS 2.0 with meds?

And what do you think about the tree falling in the forest?

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The Active Surveillor Annual Report

By Howard Wolinsky

This newsletter, The Active Surveillor (TAS), has reached the one-year mark. It just passed its 600th subscription. In fact up to 607 now.

Thanks to all for subscribing.

Each TAS issue on average has 800-1,000 readers. Sometimes, there are as many as 2,000.

The open rate of posts is 60 -70%. I’m told 40% is considered good. This means The Active Surveillor: Saving Prostates Daily is reaching its target readership.

I try to publish at least one story every 7-10 days. Sometimes it’s more. If I see something newsy, I go to press more frequently.

I know it’s more than some of you want to or can stand to read.

One reader explained that he quit his subscription because he didn’t want to think about his cancer once a month. I get it.

One solution is only to read the newsletter once a month or only when a headline grabs your attention.

Some readers don’t mind and may like more frequent stories.

I don’t know who’s who so I go with my gut.

I have been a newsman for more than 50 years. I like to share what’s up. So I could do a daily newsletter. As we old newspaper journos used to say: “Reporters Do It Daily.” With the internet cycle, it’s more like every two minutes or fewer. So I am restraining myself.

I hope you can hang in there with me. I am committed to the newsletter for at least another year. TAS started on a whim when I tried out Substack newsletter software.

When I launched this newsletter, I promised I would not require paid subscriptions. I never will. But you can pay for subscribers and support the cause and help me defer my expenses. I am operating in the red.

About 10% of subscriptions are paid, bringing in just over $3,000 in 2022. I am grateful for the support.

I had about $5,000 in expenses in 2022, mainly for transcription of interviews, upgraded internet services and purchase of computer gear (a new microphone and internet camera), subscriptions to Zoom, Skype, etc., and for Substack software and banking fees, which take 15%. Also, as the Coen Bros. said in “Raising Arizona”: ”Government, do take a bite, don’t she?” So 35% goes to someone other than me.

In the end, I lost about $2,000 on the year. I can absorb the red ink—my goal is to at least break even.

I would encourage you, but I won’t require you to go for a paid subscription to help me meet that goal.

Recently, one of the top urologists in the world told me, “You know you don’t have to do this anymore.” By this he meant, AS and this newsletter. “You dodged the bullet. You can just live your life.” But he said he “got” the drive to help fellow patients.

My goal has been to help overcome the overtreatment and overdiagnosis of prostate cancer.

In my time on AS, the approach has blossomed.

I have seen the proportion of candidates for AS opting for it increase from 6% in 2010 to 60% in 2021. Great improvement, but far from the 90%+ that has been demonstrated in Sweden and in the great state of Michigan.

As a patient who was urged to undergo unnecessary surgery STAT and take on the risks of impotence, incontinence, and worse, I committed myself to promote AS as a journalist and in my new unfamiliar roles as an advocate and an activist.

When I was diagnosed with a single core of Gleason 6, less than one millimeter, I only knew only one other guy on AS, my cousin Maxim in Berkeley, California. I wouldn’t meet another AS patient for seven years.

This isolation of AS patients in 2017 motivated Icelander Thrainn Thorvaldsson and Americans Mark Lichty, Gene Slattery, and to found Active Surveillance Patients International. We have reached thousands of patients and caregivers in more than 20 countries, from Canada and the U.S. to Lebanon and Bulgaria to Hong Kong, India, and Australia.

We’ve had webinars with top European docs such as Sweden’s Ola Bratt, UK’s Rick Popert, Norway’s Truls Bjerklund Johansen, Australia’s Jeremy Grummet, and Holland’s Chris Bangma (“father” of AS in Europe).

Mark Lichty and I co-founded an AS virtual support group on Rick Davis’ AnCan platform in 2019.

It quickly thrived as a monthly and then a weekly meeting with blockbuster webinars featuring top docs, such as Drs. Laurence Klotz and Peter Carroll, founders of AS; top-gun pathologist and second opinion maven Jonathan Epstein; urologist Scott Eggener, who is promoting the idea of renaming Gleason 6 as a noncancer; Ming Zhou, a pathologist who debated Eggener and switched sides; and genetics guru Brian Helfand.

There have been so many more.

These days, The Active Surveillor has often co-hosted major webinars with other A-list organizations, such ASPI, AnCan, Malecare, Prostate Cancer Support Canada, Prostate Forum of Orange County, Prostate Health Education Network, Europa Uomo, the Walnut Foundation, etc.

Our speakers have included Dr. Kevin Ginsburg, of the MUSIC (Michigan Urological Surgery Improvement Collaborative), which has achieved a 91% uptake of AS in the Mitten State, Dr. Peter Albertsen, the AS pioneer from UConn, and Dr. Vincent Gnanapragasam, developer of the Predict Prostate communications tool.

The Active Surveillor last year was co-founder of the video series AS 101 featuring leading doctors explaining the basics of AS to a patient-partner couple, Larry and Nancy White. View AS 101 videos: https://aspatients.org/a-s-101/. See below for information about the premiere of another program.

TAS has campaigned here for a switch to safer transperineal biopsies to avoid sepsis. Sign the petition here: https://chng.it/7bQsWSfK

TAS has promoted the idea of renaming Gleason 6 as a noncancer to try to reduce emotional distress and financial toxicity from the diagnosis of a non-lethal, so-called cancer.

TAS has fought insurance discrimination against patients on AS and for the inclusion of more Black patients and other minority patients in programs to follow AS.

Happy 2023! Live long and prosper with a Gleason 6 or 3+4 and above.

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AS pioneers featured in two free webinars

Time to register for two free webinars on active surveillance with two prophets in the land of prostate cancer.

Active Surveillance Patients International (ASPI) and AnCan Virtual Support Group for Patients on Active Surveillance are both holding seminars within two days of each other, Jan. 28 and Jan. 30, respectively.

ASPI first presents the latest episode in the cliff-hanging AS 101 video series, featuring Dr. Laurence Klotz, “father of AS.” Active Surveillance Patients International (ASPI) will premier AS 101 Episode 3 video on Saturday, Jan. 28, 2023, at 12-1:30 p.m. Eastern. To register, click here.

AnCan is featuring Dr. Mark Scholz, co-author of the groundbreaking “Invasion of the Prostate Snatchers.”

Scholz’s program is entitled, "Invasion of the Prostate Snatchers: The return 13 years later. An evening with Dr. Mark Scholz." To register, click here.

In both cases, if you can’t make it, register and you’ll get a link to the recording.

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