How We Do Harm (32 page)

Also, in prostate cancer, patient groups have financial incentives to accept screening as the principal article of faith.
Screening sets off the demand for a cascade of services worth billions of dollars to various commercial interests.
Patient groups get money from the drug and device companies, and occasionally even hospitals and medical practices, because they push the envelope, making claims so outrageous that even special interests dare not make them.
Us TOO, which claims to be the world’s largest “grassroots, independent, patient-focused charitable organization” with more than 380 chapters in nine countries, is funded almost completely by the pharmaceutical industry.

Despite getting more than 90 percent of its funding from drug and device companies with an interest in prostate-cancer screening, Us TOO claims to be independent and not beholden to any company.
Moreover, it claims to provide unbiased information regarding screening and treatment.
If the drug maker Abbott Labs had worked up the audacity to say some of the things Us TOO and Zero say about the Abbott PSA test, the FDA would issue a warning letter and, likely, levy a fine.

I tell Ralph about the business model employed by the National Prostate Cancer Coalition, now called Zero (an organization that has attacked me personally, because I have publicly questioned whether screening and aggressive therapy saves lives).
Zero sends its employees to a particular locale, partners with a local cancer-treatment center, enlists some local celebrities, and offers free screening.
People found to have abnormalities are steered toward the local cancer-treatment center.
That center pays to advertise the screening push and helps Zero get donations.

Most of Zero’s budget comes via corporate donations from drug companies and surgical and radiation-treatment-device manufacturers.
The group’s funders include Amgen, AstraZeneca, Aventis, Cytogen, Merck, Pharmacia, and Pfizer.
My personal favorite Zero sponsor is Kimberly-Clark, the maker of Depend undergarments.

Jamie Bearse, a spokesman for Zero, says drug-company funding doesn’t create a conflict of interest since prostate-cancer screening saves lives, and that anyone who says otherwise is “misguided.”
Zero’s leader, Skip Lockwood, attacks me regularly because I was once quoted—accurately—as saying, “Prostate-cancer screening and aggressive treatment may save lives, but it definitely sells adult diapers.”

A review of Zero’s tax filings shows that Lockwood gets paid more to mislead and misinform men than I get paid to tell the truth.
I am especially amused by the folks at the American Foundation for Urologic Disease, an offshoot of the American Urological Association.
(These organizations seem to change names a lot.
They are now referred to as the American Urological Association Foundation.) One of my prized possessions is a letter from Ms.
Sandra Vassos, then the group’s executive director.
She didn’t even have the courtesy to write to me directly.
She wrote to my boss, explaining that my statements confused patients and kept them from getting screened.
She was in essence telling my boss to muzzle me.
Ironically, at the same time the AUA itself was saying “Prostate-cancer screening should only be done among well-informed men,” a guideline I still consider flawed, both conceptually and grammatically.

*

AFTER
understanding the problem overall, Ralph asks me to examine his case.
I agree, and he sends me the entire file—copies of lab reports and operative notes.

Originally, Ralph’s slightly elevated PSA of 4.3 ng/ml was most likely due to benign prostatic hyperplasia.
It’s a swelling of the prostate common in older men.
Most likely, it had nothing to do with his cancer.

His biopsies showed a small lesion with a Gleason score of 3 plus 3.
This is intermediate disease in terms of aggressiveness.
Only two of the twelve biopsies, 10 to 15 percent, had cancer.
This information, along with his age, seventy, at diagnosis, pointed to a cancer that many reasonable urologists would at that time have encouraged be watched.
Surveillance is an active, not passive, strategy.
Many of these patients will never progress.

Today, even more urologists would suggest that a patient like Ralph be watched, as it is more appreciated and accepted that patients in a similar situation don’t need aggressive therapy.
Indeed, recent data show that 1.3 million American men were needlessly treated for localized prostate cancer from 1986 to 2005.

Ralph got laparoscopic surgery early in the boom in this technology.
Today, it seems as if every hospital has bought one of the $3 million da Vinci robots, and everybody advertises having one.
Few people know how to use a da Vinci, and it takes more than a hundred operations to truly get comfortable with it.

In my practice, I have seen quite a few men who got a laparoscopic prostatectomy that left a small portion of the prostate behind.
The pathologist gets literally a bag of smashed prostate, so he cannot tell if the entire prostate has been removed.
The section of the prostate that is left behind can secrete PSA and lead to a low reading in blood tests.
If the retained prostate is all benign, the PSA should stay stable.
If it’s cancer, it will eventually rise in value.

I have refused to treat such patients with hormones or radiation and suggested they be watched.
They have left me for doctors who are willing to be more aggressive.
I had one patient say to me, “God damn it, I am an American.
You cannot tell me I have cancer and we are going to watch it!”

The majority of these men, who are treated with radiation or hormones or both, get no benefit from treatment.
They get only the side effects.
Radiation side effects include those that Ralph had: proctitis, inflammation and bleeding from the rectum, cystitis, burning on urination and a feeling of urgency, a rectal fistula in which bowels and bladder are connected.
The side effects of hormones can be diabetes, cardiac disease, osteoporosis, and muscle loss.

I would have tried to stop Ralph from getting his surgery.
I might have suggested repeating the biopsies and verifying the Gleason grade.
He had such a small amount of tumor in the biopsy specimen, and what was there was of such low grade, that if he had consulted me after he was operated on, given his stable PSA, I would have encouraged him to be watched rather than radiated.

At the time of his screening, diagnosis, and treatment, Ralph was actually confused by the information he received from the numerous sessions on the Net.
Us TOO and Zero increased Ralph’s confusion and worry.
They tend to make it seem so simple, cut-and-dry, without any questions about what to do.

In this case, both the surgeon and the radiation oncologist got paid.
They both likely thought they were doing the right thing.
However, these doctors benefited from Ralph’s treatment choices.
The surgeon made about $2,000 for the surgery, the hospital even more.
The radiation oncologist made in excess of $10,000 in professional fees, and the radiation facility got paid even more.

Ralph got the side effects, and his quality of life was destroyed.

*

DOES
treatment of localized prostate cancer save lives?

Ironically, throughout the epidemic of screening and radical prostatectomy in the 1990s, no study was done to show that any treatment of localized prostate cancer actually saved or prolonged lives.
Some men, of course, got treated and did well, but would they have done as well or even better with no treatment?

The first studies to show that treatment was beneficial were two radiation therapy studies published in 1997.
One study was done in Europe and the other in the United States.
Men, in these studies, whose disease was confined to the prostate or just outside the prostate were randomized to receive radiation or radiation with time-limited hormone therapy.
The men treated with radiation and hormone therapy as a group did better than those treated with radiation alone.

The only study to show radical prostatectomy to be beneficial was a Swedish study that randomized a nonscreened population of men with localized prostate cancer to radical prostatectomy or observation therapy and therapy upon progression of disease.
After an average of ten years of follow-up, radical prostatectomy showed some advantages.
It did save lives, but required eighteen men to be treated to save one life.
It is important that the men were not screened, as the follow-up for a screened population would have to be longer to see a difference, and the number needed to be treated to save one life would be greater than eighteen.

An American study, called the Prostate Cancer Intervention versus Observation Study, abbreviated as PIVOT, has randomized primarily older men with localized disease to surgery versus observation therapy.
It has had difficulty accruing patients as many doctors actively discourage it.
With great difficulty, it ultimately failed to show that immediate treatment was better than observation and treatment if needed.

Which treatment modality—radiation therapy or surgical radical prostatectomy—is most effective?

Three times in the last forty years efforts have been made to randomize men with localized disease to radiation versus radical prostatectomy and to follow them to see which treatment is better.
All three trials closed due to lack of accrual.
Urologists are the gatekeepers in prostate cancer.
They generally make the diagnosis, and urologists have not supported these trials.
I have actually heard several say they “know” that surgery is better, even though no data supports this view.
This is true prejudice.

From a more cynical point of view, urologists get to bill for prostatectomy or observation therapy.
A urologist referring to a radiation oncologist is a urologist forgoing income, and few patients know enough to ask for a referral to a radiation oncologist.
I am convinced that most urologists don’t consciously think this way, but a conflict of interest exists, and I cannot say what goes on in the subconscious.

*

DOES
screening for early-stage disease save lives?

We know screening
doesn’t
save lives for some cancers.
The right way to figure out whether a cancer can be treated with lives saved is through a prospective, randomized trial in which one group is screened and another is not.
Such studies need tens of thousands of patients and take a long time, a decade or two.

Two such trials were started in the early 1990s to assess prostate-cancer screening.
One of them is the Prostate, Lung, Colorectal and Ovarian Cancer Screening Study, or PLCO, sponsored by the U.S.
National Cancer Institute.
It began in 1992 and randomized seventy-two thousand men to screening or no screening.
Societal prejudice toward screening made it difficult to find men who would agree to take a 50 percent chance of being assigned to the group that got no screening.
Even after assignment, many men in the no-screening arm got screened, contaminating the results.
This has delayed getting an answer.
The study’s first analysis was published in the spring of 2009, seven years after Ralph was screened.
It showed no advantage to screening after a median of nine years of follow-up.

After the study’s first results were announced, pro-screening advocates argued that it failed to show that screening saved lives because of the contamination, or screening, in the group that was not to get screened.
In essence, the advocates were saying that the study was not reliable because they had successfully sabotaged it.

I believe that the PLCO prostate study is a legitimate first look.
Follow-up of the two groups needs to continue.
There were 2,820 prostate cancers on the screened arm and 2,322 on the control arm.
This indicates that the trial can be viewed as comparing a heavily screened group to a less heavily screened group.
Interestingly, overall risk of death was greater in the arm randomized to screening versus that in the control (fifty deaths versus forty-four).
That makes one wonder whether treatment brought on through diagnosis of prostate cancer actually kills.

Some of the findings concerning hormonal therapy and increased risk of diabetes, cardiovascular disease, and death are haunting.
Some experts have actually suggested that the twenty-year decline in prostate cancer mortality in the United States, which is often used by prostate-cancer advocates as proof screening saves lives, may partially be due to fatal disease from hormones.
Treatments resulting from prostate-cancer screening may be leading to a decrease in risk of prostate-cancer death by killing men with diabetes and cardiovascular disease before they can die of prostate cancer.

The second trial that took place in the 1990s, a European trial known under the acronym ERSPC, began as a conglomerate of nine studies in several European countries.
Some trials screened men every year, some every two years, one even every four years.
Some used the PSA blood test, some used the blood test and a digital rectal examination.
One stopped the digital rectal exam six years into the study.

Seven of the nine studies were pooled into an analysis that was advertised as showing that screening decreased risk of death by 20 percent.
It’s possible that the observation was a fluke.
The P value—estimate of statistical validity—in the trial was .04.
This is just barely less than .05, the level we consider statistically significant.
Anything below that level is classified as statistical noise.
Many of the study’s peculiarities and methodological flaws could have swung the result toward positivity.

The trial’s findings are fascinating.
Nonetheless, doctors needed to screen 1,410 men and diagnose and treat forty-eight men to prevent one prostate cancer death.
In other words, forty-nine men were likely put in diapers and worse for one of them to be saved.
This represents the
best-case
scenario.
Even if this ratio is real, I don’t find it compelling.

The European trials are supposed to continue, and the findings may grow in statistical significance.
Alternatively, the finding could lose its statistical significance.