AS pioneers decode famed researcher's PCa scare, declare Active Surveillance safe option

Drs. Klotz, Carroll for the defense of AS

(Drs. Laurence Klotz (above) and Peter Carroll, AS pioneers, find NIH’s Collins an outlier.)

By Howard Wolinsky

Francis Collins, MD, PhD, is one of the most prominent physician-scientists in the world. He led the Human Genome Project to map human DNA and later served as director of the National Institutes of Health, one of the top research institutions in the world.

When Collins speaks, the scientific world at least listens.

With the best of intentions, Collins told the story about his surging cancer on April 12  in the Washington Post, how he went from low-risk PCa to a raging Gleason 9 seemingly overnight. It was the story from PCa hell, the worst nightmare for those of us on Active Surveillance for low-risk Gleason 6 prostate cancer.

He explained in The Post: “Why am I going public about this cancer that many men are uncomfortable talking about? Because I want to lift the veil and share lifesaving information, and I want all men to benefit from the medical research to which I’ve devoted my career and that is now guiding my care.”

Collins was diagnosed with low-risk prostate cancer five years ago and was provided with Active Surveillance (AS), close monitoring, by the experts at the preeminent National Cancer Institute. 

He would have been a great spokesman for AS. But he didn’t go public with this information until the Snarling Tiger with fangs bared was breathing down his neck.

We first heard about Collins when he faced an emergency situation as his prostate-specific antigen (PSA) blood test shot up to 22 and his Gleason score hit an alarming 9.  We don’t know how fast that happened or what his previous levels were.

These are among the many gaps in Collins’ account.

I approached him to see if we could fill in the blanks. He politely declined, leaving many of us wondering what had happened.

His story raised more questions than it answered, resulting in some men doubting the safety of Active Surveillance, close monitoring of prostate cancer, and others wondering why a 74-year-old man would opt for a radical prostatectomy when radiation has been held up as safer for oldsters.

This was the exact opposite of Collins’ goal as a would-be advocate, and I suspect and hope in the years ahead, he will become a leading figure in PCa advocacy, especially driving for more funding for PCa research.

I heard through the PCa grapevine that the National Cancer Institute (NCI), whee he was cared for and which he once oversaw as NIH director, tried to talk Collins out of going public with his story. NCI communications and top officials did not respond to my queries about this. If true, I wondered why they would prefer Collins’ silence.

Are they concerned about confusing the PCa patients all 3 million of us, and the health professionals who care for us? Those who are paying attention, including physician experts, are already confused.

Are they worried about their image as an institution? 

I suggested to top leadership at NCI that they issue some explanation about what is going on, how safe AS is. No response so far

This was the exact opposite of Collins’ intention as a would-be advocate.

What’s the National Cancer Institute have to say?

I heard through the grapevine that NCI tried to talk Collins out of going public with his story. NCI did not respond to my queries about why they would prefer Collins remain silent. 

Is NCI concerned about confusing the PCa public, all 3 million of us? No worries. We’re already confused if we’re paying attention, including physician experts and patients alike.

Was NCI worried that their image as an institution would be tarnished?  Hey, you guys are working for us, We the People. It’s time to fess up.

I suggested to the top leadership at NCI that they issue some explanation about what is going on and about the safety of AS. No response.

A webinar

The AnCan Foundation asked me to organize a webinar on these issues and invite Active Surveillance Patients International to be a co-host. 

I lined up two of the developers of AS, Drs. Laurence Klotz and Peter Carroll, to address the Collins affair. I also invited a leader at NCI, but again, no response, though I have spoken with him many times over the years, The cone of silence.

You can watch the Zoom here. Also, I covered this topic here in TheActiveSurveillor.com.

Bottom line: Chances are, surveillors, you’re OK

First off, you should know:

-- Cases like Collins do occur, where the Sleeping Lion becomes a Snarling Tiger.

--But they are exceedingly rare. Black swan events.

--AS is a safe option. You can be like a pig in shit.

Dr. Klotz says it may be the biology

University of Toronto’s Klotz, who coined the term, “Active Surveillance” in the late 1990s, said:

“Bottom line in my view on this whole situation is that we know there's nothing novel about this. We know it happens. It's rare. It perhaps is unfortunate that it happened to -- of course, it shouldn't happen to anybody. But if it happened to someone who has such a high profile in the biomedical field, but it really does not in any way, in my view, change the approach, the concept, the safety.”

Let’s assume Collins is a compliant patient who stuck with routine surveillance, exams, PSAs, MRIs and biopsies at NCI.

We don’t know whether Collins is a Gleason 3+3 (Grade Group 1) or 3+4 (Grade Group 2), something he omitted from his commentary. Maybe he thought that would lose the general reader. It’s not for us prostate cancer nerds.

Why advanced cancers can be missed

So why does a high-risk Gleason 9 show up like a ninja in the night?

Klotz said there are two major reasons:

—The first is MRIs and biopsies—radiologists and pathologists—simply missing aggressive cancers. It happens.

—Second, more aggressive cancers can develop alongside the original lesions.

Dynamic biology

Klotz explained that “all biology is dynamic.”

He added: “Things change. New cancers develop. You can have a patient with no cancer who down the road is diagnosed with a Gleason 9 cancer. So the dynamic nature of biology means that it changes over time. And one of the key questions in this field s what's the rate of progression from … to higher-grade cancer?”

He said most cases occur in men who have high-volume cancer. We don’t know the volume of Collins’ cancer,

Klotz said: “It's extremely rare to get a low-volume Grade Group 1 cancer that progresses to significant high-grade cancer. And the rate has been modeled by a few groups, including ours, and the consensus is it's somewhere around 1.5 percent per year. So that means in the short term, like, say, the five-year time frame, it's pretty uncommon.

“Once you get up to 10-15 years, it's about 20 percent of men … upgraded. Most of them are upgraded to Grade Group 2, about 80-85 percent. So the proportion who have true upgrading over time as Francis Collins did from [maybe Gleason 6 to Gleason 9] is really very, very small, in the range of one percent or less.

“We know these people occur. You can have patients who are never diagnosed that have negative biopsies who progress that way. It's also very rare, but it happens.”

Klotz says MRIs have been a game-changer. Yet MRIs are not widely used in the U.S. for surveillance. I read a recent study involving major medical stations where fewer than 16% of patients--mainly minority men--had undergone MRIs befoe biopsies.

He concluded: “ One of the tangential messages to this, it's not so much our subject for discussion tonight, but it's my view that these systematic biopsies, because of what we've learned from the genomics and the natural history, the Memoria[-Sloan-Ketteringl series, our series and others, that you don't have to worry about these invisible cancers. They don't do anything. They are genetically very favorable and indolent, and it also I think is a message a lot of men on surveillance worry about -- what about the cancer I don't know about just like Francis Collins? Well, guys like Francis Collins, fortunately, are absolutely the exception, not the rule, and they really don't change the fundamental appeal of Active Surveillance at all.”

Carroll, of the University of California, San Francisco, said he informs his AS patients that about 30 percent will be upgraded by five years after diagnosis and about 50 percent by 10 years after diagnosis.

“The important thing to realize there is most of these upgrades or changes in volume are rather subtle. The major upgrade-free survival rate is much better. So if you see Grade Group 1 [at] about 10 years, we'll see about 18 percent of patients have more of a higher-grade. But about one-third of these upgrades that occur are Grade Group 4 or 5. T3b, that's actually one percent.”

[FYI: T3b: The tumor has spread to the seminal vesicles. T4: The tumor has spread to tissues next to the prostate other than the seminal vesicles. For example, cancer may be growing in the rectum, bladder, urethral sphincter (the muscle that controls urination), and/or pelvic wall.]

Predicting progression

Caroll said some of the progressions are predictable, such as with higher-volume GradeGroup 1.

He added:

—Younger patients have a lower rate of upgrading compared to older patients.

—PSA density (PSAD) is a good predictor. [PSAD=PSA divided by the gland volume.] Carroll said a higher PSAD predicts progression. —Genomic tests, Decipher, Prolaris, Oncotype DX, predict progression.

More on PSAD:

—PI-RADS scores for MRIs of 4 or 5 can predict progression at first diagnosis or over time. [Biopsies typically are recommended for PI-RADS 4-5.]

Again, he said cases like Collins are extremely rare.

Collins’ case also was confusing to some AS patients because as an older patient at age 74 he opted for a radical prostatectomy. We often hear radiation recommended over surgery for older patients.

Caroll made a case for surgery: “I happen to think that surgery is a very good and perhaps a preferable treatment option for men with high-risk disease. We've looked at this over the years in a large cohort. There may be survival advantage with surgery compared to radiation. I have about 700 patients who have been on surveillance [who] have come to me for surgery. If you look overall, about eight percent of the men who upgraded and gone on to surgery have Grade Group 4 or five. T4 disease less than one percent.

“And recurrence-free survival after delayed prostatectomy is actually quite good. Again, metastasis-free survival is excellent over time. Eighty-seven percent for Grade Group 4 disease.”

Carroll joked, “The definition for older patients changes each year on my birthday. So, what I think you need to do is you need to look at the age of the patient, overall health, and how bad the cancer is. I think there's clearly a role for prostatectomy in men over the age of 70, clearly a role.

“But you make treatment decisions based on three criteria: cancer grade extent, genomics, MRI, the biologic characteristics. You look at the age and health of the patient, how you treat someone who's got a three-year life expectancy because they have a bad heart or lung. Totally different than someone who is going to live 10, 15, 20 years.

“And lastly, patient preferences. Patients may have a strong [preference]- once patients are given good information, and that's one of my concerns. I'm very comfortable with decisions men make, but they need to make them on the best available evidence, and frequently they don't get it. But I think the two patients I'm operating on tomorrow are in their 70s. I'll see -- the average age of my patients tends to be younger because I have a lot of young patients coming to me. But a high-risk tumor in an older patient can be lethal.”

Watch the Zoom here.

Join the patient’s ‘Journal Club‘ at UCSF May 14

Matthew Cooperberg, MD, MPH, an Active Surveillance champion, is holding a pioneering free “journal club: where patients can hear leading researches dfiscuss their work and ask questions. The next session is at 5 pm Eastern May 14. Register here: https://tinyurl.com/4tamfuuk

“A traditional journal club involves a group of docs ± trainees reading cutting-edge papers and discussing their strengths and limitations and implications for research/practice,” Cooperberg told The ACtive Surveillor.

He added: “The Prostate Cancer Journal Club for Patients presents recent, game-changing medical papers while avoiding medical jargon and focusing on direct impact on patients’ treatments. The purpose is to educate patients to help them make better-informed decisions about their prostate cancer care in collaboration with their doctors.”

The next session is entitled “PSA rising after prostatectomy and/or radiation therapy for prostate cancer?” and covers the practice-changing finding, from the EMBARK clinical trial.

Lead investigators Stephen J. Freedland, MD, and Neal D. Shore, MD, will be featured with commentary by Rana McKay, MD.

PCa—not just for old men: Join ASPI webinar on May 25

Prostate cancer typically is diagnosed in men in their late 60s. It’s considered a disease of aging, an old man’s disease.

But Gabe Canales tells a different story.

He was diagnosed when he was 35. At an upcoming webinar for Active Surveillance Patients International (ASPI), Canales will share his prostate cancer experience and how it can help you and your sons and grandsons.

The webinar will be at noon Eastern Saturday, May 25. Register Here: https://tinyurl.com/3sexhrrp

(Gabe Canales, of Blue Cure, https://bluecure.org/)