Benefit of Annual Prostate Cancer Screening in Low and Average Risk Men Is Still Uncertain — Due to Flaws, the Latest American Study Adds Nothing Especially Helpful to Our Thinking — Regarding the 13-Year Follow-Up to the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

© 2012 Peter Free

 

07 January 2012

 

 

The benefit of annual digital rectal exams and tracking levels of prostate-specific antigen (PSA) in low and normal risk men is still debatable — but notice a flaw in this most recent study

 

The actual benefit of annual prostate cancer screening in low and average risk men is still unclear.

 

Note

 

I have addressed this subject before: here, here, and here.

 

The most recent study on prostate screening was published yesterday.  It summarizes the prostate-related results of a 13-year analysis of the American Prostate, Lung, Cancer, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

 

The analysis was aimed at detecting whether yearly prostate cancer screening, using digital rectal examinations and prostate-specific antigen blood testing, is effective in reducing cancer deaths in men.

 

The paper’s abstract indicates that such screenings are not effective in reducing mortality:

 

Results

 

Approximately 92% of the study participants were followed to 10 years and 57% to 13 years.

 

At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm.

 

Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% [detection] in the intervention arm . . . .

 

After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms . . . .

 

No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age . . . pretrial PSA testing . . . and comorbidity . . . .

 

Conclusions

 

After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.

 

© 2012 Gerald L. Andriole, E. David Crawford, Robert L. Grubb III, Saundra S. Buys, David Chia, Timothy R. Church, Mona N. Fouad, Claudine Isaacs, Paul A. Kvale, Douglas J. Reding, Joel L. Weissfeld, Lance A. Yokochi, Barbara O’Brien, Lawrence R. Ragard, Jonathan D. Clapp, Joshua M. Rathmell, Thomas L. Riley, Ann W. Hsing, Grant Izmirlian, Paul F. Pinsky, Barnett S. Kramer, Anthony B. Miller, John K. Gohagan, and Philip C. Prorok, Prostate Cancer Screening in the Randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality Results after 13 Years of Follow-up, Journal of the National Cancer Institute, doi: 10.1093/jnci/djr500 (early online publication, 06 January 2012) (paragraph split)

 

 

Did you detect the flaw in this study?

 

It’s hidden in the abstract’s conclusion.

 

 

Explaining the glitch in the American study — and why its analysis adds nothing to what we already (don’t) know

 

A lack of rigor in applying the scientific method usually means that results are ambiguous or meaningless.

 

Here, the control arm for the prostate screening study permitted men to get occasional digital rectal exams and PSA checks.  A scientifically proper control arm would have prohibited both.

 

Oops.

 

 

“Oops” is facetiously meant, of course — medical ethics get in the way of insisting on scientifically rigorous controls

 

We cannot ethically commit people to such long studies and simultaneously tell them that they can’t take advantage of screening methods that might just help them avoid dying.

 

In effect, this extended Trial is (practicably-speaking) aimed at detecting whether frequent (yearly) scheduled screening is better than less frequent (somewhat random) screening in detecting prostate cancer using the digital rectal exam and PSA level checking techniques.

 

But, as such, the study is not especially helpful.

 

Why ambiguity is a necessary corollary to investigations of this kind is not clear, until one thinks about the statistical complexity involved in detecting biological causation.  Living systems have too many interacting variables to rigorously separate.  These multiplex interactions confound our ability to detect much of anything with obviously accurate certainty.  (I’ve written more about that, here)

 

 

The study’s lead author attempted to interpret the results for medical practice

 

The study’s lead author drew tentative conclusions regarding what the study’s essentially negative findings mean for medical practice:

 

“Now, based on our updated results with nearly all men followed for 10 years and more than half for 13 years, we are learning that only the youngest men — those with the longest life expectancy — are apt to benefit from screening.

 

“We need to modify our current practices and stop screening elderly men and those with a limited life expectancy,” says [Gerald L.] Andriole . . . .

 

“Instead, we need to take a more targeted approach and selectively screen men who are young and healthy and particularly those at high risk for prostate cancer, including African-Americans and those with a family history of the disease.”

 

© 2012 Carolyn Arbanas, Mass prostate cancer screenings don’t reduce death, Washington University-St. Louis (06 January 2012) (paragraph split)

 

Dr. Andriole went to recommend that men obtain a baseline PSA test in their early forties.  High levels at that time may predict more aggressive forms of prostate cancer.

 

On the other hand, men with love PSA levels at in their early forties are not likely to develop “lethal prostate cancer and could potentially avoid additional testing.”

 

Notice, however, the weasel words “could potentially avoid.”

 

That is not a criticism of Dr. Andriole.  It is an indication of the unpredictability of disease in a biological environment we know so little about.

 

 

I’m not alone in doubting the hands-on utility of this study’s negative findings

 

ABC News commented:

 

Experts told ABCNews.com that the latest findings from the PLCO don't lend much to either side of the argument because the study contained numerous flaws.

 

One of them, they explained, is because although one group was screened annually, more than half of the men in the other group did get occasional screening as part of their usual medical care, making it difficult to figure out the true effect of screening.

 

"There was also a large study in Europe that had significant flaws as well, and that study showed a mortality benefit, so the two largest studies had these similar flaws and came to different conclusions," said Dr. Durado Brooks, director of prostate and colorectal cancers for the American Cancer Society.

 

"There are no clear answers to take away from this."

 

© 2012 Kim Carollo, Routine Prostate Cancer Screening Doesn't Reduce Risk of Death, ABC News (06 January 2012)

 

Kim Carollo’s article is one of the better ones on this subject.  I recommend it to men wanting a background framework with which to address the issue with their physicians.

 

 

The moral? — the cost-benefit value of prostate cancer screening remains a difficult question for men at average to low risk

 

For men at elevated risk, screening is a no-brainer.