AS, an overnight success story? Hardly: early advocate

Visionary Mike Scott sees more growth ahead for AS

By Howard Wolinsky

Active Surveillance (AS) is the kind of overnight success that takes three, almost four decades to succeed.

About 35 years ago, Gerald Chodak, MD, of the University of Chicago, began warning that low-risk prostate cancer was being overtreated and overdiagnosed.

Chodak, who died in 2019, said screening with PSA (prostate-specific antigen) blood testing should be proven to have a benefit before it was rolled out. It didn’t happen that way. An epidemic of side effects, such as impotence and incontinence, occurred in men who underwent unnecessary radical prostatectomy and radiation therapy.

In the New England Journal of Medicine in 1994, Chodak and colleagues called for conservative management of these patients, an idea that evolved into Active Surveillance. Chodak became the godfather of AS.

Peter Albertsen, MD, of the University of Connecticut, in the 1990s began producing the research that proved the benefit and feasibility of the yet-to-be-named strategy now known as Active Surveillance. Laurence Klotz, MD, of the University of Toronto, one of the pioneers in the field, who considered Chodak his mentor, dubbed the strategy of close monitoring of low-risk to favorable intermediate-risk prostate cancer “Active Surveillance.”

You need great marketing backed with solid research to get a idea to catch on amongst doctors and their patients.

E. Michael “Mike” Scott, a pharmaceutical communications expert by profession., said Albertsen “was pretty much publicly scorned when he presented his findings at the American Urological Association.”

(Michael Scott)

Some of you may know Scott, founder of Prostate Cancer International (PCai), from his old support group for patients on AS. He recently launched with the University of Maryland the Prostate Cancer Active Surveillance Research Initiative program to tease out research questions to plan the future of AS.

Back in 1989, Scott was running a medical communications company and working with what was then Schering Plough to help launch flutamide (Eulexin). He said that when he first met Chodak and many other leading urologic oncologists.

In 1995, Scott developed the first iteration of The Prostate Cancer InfoLink, and in 1997 he organized a meeting in Fort Worth, Texas, that led to the formation of what was then the National Prostate Cancer Coalition (now ZERO).

I've been friends with Mike since 2016 when I started my column, “A Patient’s Journey” on MedPageToday.com. He frequently cited my articles--often with humor and a critical eye. In 2017, he submitted my name as a speaker at the meeting of the ASCO Genitourinary Cancers Symposium. ASCO picked me to be the first patient ever to speak at its meeting. It was a bit of a disaster but it turned me into an advocate.

Like low-risk prostate cancer for which it was developed, AS was slow-growing.

I wrote in EMBO (European Molecular Biology Organization) reports about the paths of acceptance of new ideas in science: “The advancement of scientific knowledge is an uphill struggle against ‘accepted wisdom.’”

So it went for Active Surveillance. The road to AS was strewn with patients afflicted with impotence, incontinence, shortened penises, hot flashes, brain fog, and a torture chamber other horrors that came as side effects from a radical prostatectomy, or radiation therapy. Patients who had undergone unnecessary treatment could have lived with their lame prostate cancer and died from something else.

The first studies came out in the mid-1990s. When I was diagnosed in 2010 with very low-risk prostate cancer, only 6-10% of candidates opted for AS. This rate held steady for many years. Then there was a breakthough of AS.

Matthew Cooperberg, MD, MPH, of UCSF, told Chuck Ryan, MD, CEO of the Prostate Cancer Foundation, in UroToday that he has new research showing that the solid majority of eligible low-risk patients now go on AS.

We finally broke out of the 6-10% acceptance rate for AS in the 2010s Cooperberg said, “We had been stuck for many years. That's 10% of low-risk patients getting Active Surveillance. We had made it up to about 40% by 2013 or '14.”

By 2020, the AS rate has reached 60%.

The American Urological Association finally designated AS as the preferred treatment in 2017. The National Comprehensive Care Network, the major source of guidelines, finally did the same in 2019--though it faltered and reversed itself last fall--after Cooperberg set off a twitterstorm.

As a patient on AS, I used to feel like the Maytag repairman. I was Mr. Lonely like in Bobby Vinton’s ballads. Until 2017, other than a cousin of mine, I didn’t know anyone else on AS. But I knew plenty of patients who were struggling with the after-effects of “definitive” treatment.

Not anymore . I see in patients gathering, sometimes by the hundreds, at webinars from Active Surveillance Patients International, the first international advocacy and education group for AS), and the weekly meeting and webinars from AnCan Virtual Support Group for AS, the first group of its kind.

I asked Mike Scott to comment on this latest news on AS reaching the 60% rate. He responded thoughtfully, skeptically, and somewhat optimistically in this e-mail interview:

The Active Surveillor (TAS): Is this a remarkable public health achievement?

Mike Scott: Yes and no. It is remarkable because of the rate of adoption over the past decade. On the other hand, it is less than remarkable given that the over-treatment of low-risk forms of prostate cancer was being suggested nearly 35 years ago … As you are aware, Klotz was one of the first to ‘hear’ Gerry Chodak and to initiate his AS research at the University of Toronto. Even in 2012, there was a horrified silence at the AUA when the VA's PIVOT data were first presented by Tim Wilt. Arguably, 30 years from concept to widespread acceptance.

TAS: What other development in medicine would you consider to be comparable?

Scott: In 1982, two Australians (Barry Marshall, MD, and Robin Warren, PhD) at the then-obscure University of Western Australia in Perth first presented data suggesting that peptic ulcers were caused by a bacterial infection now identified as Helicobacter pylori.

(Barry Marshall, MD. No one believed him either.)

At a meeting in Brussels where he presented these data, I told Barry Marshall that I believed he would get a Nobel for this finding. In 1984, they reported their findings in the Lancet, including the results of an experiment in which Marshall infected himself with the bacteria, got an ulcer, and then cured himself using an antibiotic. For most of the next decade, the gastroenterology community rejected Marshall and Warren's findings. In 2005 they were awarded a Nobel Prize for their findings. In this case, 27 years from concept to real acceptance.

TAS: Why did AS finally happen? And so fast? Are you surprised?

Scott: It happened because strong data supported the findings -- very strongly in the case of very low-risk disease and strongly in the case of low-risk disease. (See the additional comments below.)

TAS: Did patients and support groups help this along?

Scott: Yes and no. There were certainly believers who told others about their experiences, but all too often the patients and the support groups failed to support personal experiences with the data coming out of Scandinavia and Toronto and Johns Hopkins, and UCSF.

It was the data from the ProtecT trial in the UK that really turned the key because the study was so large and was at least partially randomized AND it addressed THREE types of initial management.

I actually don't think this all happened particularly fast. There was a predictable progression from early adoption (by some doctors and some patients) to compelling data (in 2012 and later) and strong recommendations in standard guidelines to acceptance by the urology community.

As a different comparison, driven by commercial interests of hospitals and some physicians, laparoscopic radical prostatectomies in the US started to be done ‘routinely’ by about 1998, and by 2010 (or perhaps earlier) patients were routinely demanding that their surgeries be done ‘using the robot.’ THAT was arguably ‘fast.’

(NOTE: Dr. Chodak opposed the spread of PSA testing until proven. He was a stickler for research. He also took the same stand on robotic surgery.)

TAS: Is a 60% acceptance rate enough?

Scott: I haven't had a chance to read the relevant papers to be clear about the data. Arguably I believe that good goals for the percentage of men who were initially managed on AS by 2030 in the US would be: (a) 95% of well-characterized patients who have very low-risk disease; (b) 80-85% of well-characterized patients who have low-risk disease; and (c) perhaps as many as 50-60% of well-characterized patients who have favorable intermediate-risk disease.

One of the major current problems is whether we are appropriately characterizing a high-enough percentage of the patients before they are actually placed on an appropriate AS protocol. The other factor that we have yet to deal with is the percentages of patients who drop off AS long before there is any good reason why they should do this (other than fear and anxiety because of ‘cancer’).

Additional remarks from Scott:

1: IF we were to rename (say) very low-risk prostate cancer as something else, then how should it be diagnosed and managed? Arguably it will still need to be diagnosed. (So if that is the case, how? By biopsy? I would hope we can find a less invasive method.) There WILL be patients who are inaccurately diagnosed as having very low-risk disease when it turns out to be low-risk or even favorable, intermediate risk. Probably not that many, but there will always be some.

2: The fact that we have seen a major change in the initial acceptance of AS over the past 10 years should not be seen as a ‘Eureka’ moment. I would argue that the Eureka moments came with Peter Albertsen's analysis of the Connecticut cancer registry data and Klotz's decision to start managing a definable set of patients on AS.

3: It will probably take us another 20+ years to really be able to find the best ways to characterize patients as being appropriate or not appropriate for initial management on AS. It is my personal belief that there is a small subset of men who have a small amount of unfavorable, intermediate-risk prostate cancer (as currently defined) who may actually be good candidates for initial management on AS (perhaps 10%?).

A major priority for the patients and patient advocacy community MUST BE the funding of high-quality research to refine the characterization of men who meet acceptable standards for management on AS and who can be advised that they have a high probability of being able to defer any invasive therapy for a minimum of (say) 5 years and thus maintain their quality of life for at least that length of time. I am not even sure (at present) what the percentage of all newly diagnosed prostate cancer patients is in the U.S. is that has either very low- or low-risk disease, but I am pretty sure it is > 50% of all the newly diagnosed patients each year and it might be as high as 70%.

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Please sign up for the program on the future of AS: "Your Voice in the Future of Active Surveillance," on April 22 at 11 a.m.Eastern/4 p.m. GMT. Register here: https://zoom.us/meeting/register/tJEtfuuqrzwtHNPuqzkigx65YBk8vV-teUdy

AnCan’s Virtual Support Group for AS is holding a webinar on “decisional regret” with low-risk prostate cancer at 8 p.m. Eastern April 6. No registration. Just go to the URL below. The program features researcher Chris Wallace, MD, PhD, who also will answer other questions on prostate cancer.

Go to the Barniskis Room: https://www.gotomeet.me/AnswerCancer Or call +1 646 749 3129 Access Code: 222-583-973 (Barniskis Room)