Remain calm: Prominent doctor's PCa became a Snarling Tiger overnight. But that's not likely to happen to you.

(Editor’s note: I wrote about the case of Dr. Francis Collins and his rapidly advancing prostate cancer in my blog in MedPageToday: https://www.medpagetoday.com/special-reports/apatientsjourney/109711?trw=no But I have more to say here.)

By Howard Wolinsky

Five years ago, Francis Collins, MD, PhD, one of the most prominent medical scientists in the world, was diagnosed with low-risk prostate cancer.

Then, at age 69, he went on Active Surveillance (AS), monitoring his disease closely, the standard of care for men diagnosed with prostate cancer.

(Dr. Francis Collins)

Collins, who led the Human Genome Project and is the former director of the National Institutes of Health, like many men on AS, didn’t broadcast his condition. Men with,low-risk prostate cancer can go about their business without disclosing their cancer because they just require doctor visits maybe a couple of times a year.

Surveys show about 30% of these patients keep their counsel because of the stigma of cancer that could somehow interfere with their job situation.

Too bad Collins opted not to become the poster child for AS back five years ago. The AS movement might have made some gains earlier. It remains to be seen whether the Collins impact will be negative now.

He could have lent credibility and spread the word about AS. Currently, AS is followed in the U.S. by 60% of men with low-risk (Gleason 6) and 20% of men with intermediate-risk (Gleason 3+4) prostate cancer. We have a long way to go to reach the 90%+ uptake of AS in Sweden, U.K. and the state of Michigan.

To his credit, on April 12, Collins went public with his story about his cancer in a commentary in the Washington Post.

He wrote: “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.”

I’m sure is story will help many of the 300,000 American men who will be diagnosed with PCa this year per the American Cancer Society.

But I am concerned that the seemingly overnight increase in the aggressiveness Collins’ cancer will be upsetting to some patients considering AS or already following the protocol and are experiencing “anxious surveillance.” Research showed that over half of the men on AS are anxious and 10% are severely anxious and might be considering undergoing otherwise unnecessary treatment.

Collins is clearly a supporter of AS. He followed it himself. He followed it until he couldn’t. His wimpy Sleeping Lion cancer converted into a dangerous Snarling Tiger,

His story now less about AS. Rather it was about how “the horse got out of the barn,” as Collins told National Public Radio: “…if the horse is the cancer and the barn is the prostate, we're not just going to get rid of the horse, we're going to get rid of the barn, too…”

Collins considers his five years on AS a success—despite the latest development. He found his cancer “early,” before the cancer “horse” had left the prostate barn and become incurable.

But I think he was not considering the impact his story might have on thousands of men less educated about the ways of prostate cancer who are now in real-time considering the option of active surveillance and of the many who already are on surveillance.

I know a bit about the mindset of men with low-risk prostate cancer. I helped start support and education groups for these men (Active Surveillance Patients International and AnCan’s Virtual Support Group for Men on AS) because I observed the fear and anxiety low-risk patients experienced in general PCa support groups that seem to not focus on AS but on the side effects of treated and aggressive cancers—urinary incontinence and impotence with men who had undergone prostatectomy, fecal incontinence in men who underwent radiation, and the weight gain, fatigue, heart disease, erectile dysfunction, memory loss and more in men who undergo hormone deprivation therapy.

The point of Active Surveillance was to avoid these side effects. However, I saw many men drop out of support groups because they feared that these side effects were in their future.

That’s why I suspect Collins’ commentary has the potential of inadvertently frightening men with low-grade cancer as they read about Collins’ horse rapidly leaving the barn.

If this happened to one of the best doctors in the world cared for at one of the best institutions in the world (NIH), what about me?

The black swan

I urge calm.

Collins’ story is Collins’ story. The odds are against this happening to you.

Collins experienced a “black swan event,” a rarity.

In what appeared to be a short period, Collins's PSA shot up to 22 ng/mL, where a “normal” PSA at his age would be about 5. His Gleason score to measure the aggressiveness of his cancer alarmingly shot up to a 9, from possibly a Gleason 3+4=7 or 3+3=6.

His piece doesn’t say his previous PSA or Gleason were or when they were measured.

He declined to be interviewed.

It’s a shame that he didn’t share more of the meaningful details of his cancer to help his fellow patients and expert physicians provide more explanation about of what happened.

What about the AS community?

Paul Schellhammer, MD, an advanced prostate cancer patient and urologist himself and professor emeritus at East Virginia Medical School, offered words of caution.

(Dr. Paul Schellhammer)

“The AS community will need to be ready for the concern re the top doc in the top hospital progressing from Gleason Grade Group 1 to 5.” (Grade Groups are newer designations for the aggressiveness of prostate cancer.)

(Schellhammer is a past president of the American Urological Association, but is not speaking for them here.)

There are tens of thousands of men on AS, harboring cancers they can live with and will never kill them. That’s no longer Collins’ situation.

Let’s assume Collins was a “compliant” patient and followed the recommended protocols with PSAs every three months or so. Maybe his PSA was trending up and so his urologist might have stepped up surveillance as he went from say a 10-15 to a 22 PSA. That is shocking.

But the experts I talked to said this extremely rare.

Snarling Tiger overnight

The experts say Collins likely started with a Gleason 6 or 3+4 and suddenly developed an aggressive cancer. Virtually overnight, he went from a Sleeping Lion to a Snarling Tiger Gleason 9.

It happens. Rarely.

Brian Helfand, MD, PhD, urology chief at NorthShore University HealthSystem outside Chicago, said, “PSA can increase very quickly with an aggressive tumor [that is] rapidly dividing, or [has] a high tumor volume/burden.”

(Dr. Brian Helfand)

He added: “It is very possible for new prostate tumors to form. Sometimes a man may originally only have grade group 1 tumors and can form de novo a higher grade tumor. That is why regular monitoring is important. We recommend at least every 6-month blood test and a biopsy, usually every 2 years. This can be intensified for some men with rising values or decreased for men with low blood values and negative imaging studies.”

The experts stress the safety of AS and how it is uncommon for patients who follow the protocols to fall between the cracks.

What the ‘fathers’ of AS say

Laurence Klotz, MD, of the University of Toronto, and Peter Carroll, MD, MPH, the developers of AS in the 1990s, reassured the AS population that Collins was an outlier, not the usual story.

(Dr. Laurence Klotz)

Klotz observed: “There is a saying in law, ‘Bad cases make bad law/’ A case like this doesn’t change anything at all. [Collins] developed a new cancer, which was likely diagnosed early because he was on surveillance. Cases like this are well documented but are rare. Perhaps 0.1 to 0.5% of men on surveillance. Biology is dynamic and perfection in anything is not attainable.”
Carroll backed Klotz: “We do not know the details of (Collins’) case (PI-RADS at diagnosis, PSAD [PSA Density], tumor volume, genomic testing, frequency of testing, etc.). Such knowledge refines risk.

(Dr. Peter Carroll)

“I agree completely with Laurie [Klotz]. This is a rare event, I have seen them, but they are exceedingly uncommon. The data on AS is clear and refined and supports its widespread use in well-evaluated patients. It would be unfortunate to say … that a very rare event leads us back to the era when too many men underwent treatment with its attendant costs (psychological, physical, and monetary) with no benefit.”

Some good news

Collins wrote that a PET scan showed that his cancer had not spread beyond the prostate capsule so it would be treatable. He opted for surgery. Active surveillance detected the cancer sooner than if he hadn’t been monitoring.

His father had been diagnosed with prostate cancer it would not be suprising if he was on the alert.

He wrote: “My situation is far better than my father’s when he was diagnosed with prostate cancer four decades ago. He was about the same age that I am now, but it wasn’t possible back then to assess how advanced the cancer might be. He was treated with a hormonal therapy that might not have been necessary and had a significant negative impact on his quality of life.”

Collins’ intentions obviously are good. And his words are powerful. I just hope AS patients won’t use them as an excuse to unncessarily exit surveillance.

He wrote: “Early detection really matters, and when combined with Active Surveillance can identify the risky cancers like mine, and leave the rest alone.”

We all need to emphasize this point.

Don’t internalize Collins’ story

(Dr. Todd Morgan)

Todd Morgan, MD, chief of urology at the University of Michigan in Ann Arbor, said “Yes, providers could use this example to argue against AS. But we don’t base treatment recommendations on individual anecdotes, rather on large-scale data.”

As Morgan told me, most physicians won’t use anecdotes to make their points. But some patients may prefer anecdotes to help them understand and cope with the shock of being diagnosed with the “Big C” in general, or even the “Little C” of low-risk prostate cancer.

My advice to patients is to go with the science. The science backs AS for those of us with low-grade cancers, but be aware there can be outliers.

Morgan added, “When we look at the most robust active surveillance studies, there is no getting around the fact that there is a small (1-2%) risk of metastasis for men on surveillance over the long term. A slightly higher number will develop high-grade disease while on surveillance. Is this progression of the existing Gleason 6 cancer or the development of an entirely new high-grade cancer? It can be either, and undoubtedly treatment guards against this to some extent. But the reason why surveillance is the standard of care for low-risk patients is due to the significant potential impact of treatment on quality of life and the rarity of scenarios like Dr. Collins (who still may well have curable disease!).”

Is surgery the right choice?

Several readers of this blog questioned whether Collins should be treated with surgery rather than radiation and hormone therapy.

Helfand said that radical prostatectomy can be an effective approach. “A lot of microscopic perforations of the capsule can be fully treated. If [there is] gross extracapsular extension, then we can still offer surgery but radiation and hormones may be more effective in that setting.
Collins already has become a powerful spokesperson for prostate cancer. Let’s wish him a speedy, uneventful recovery.