Screening Smarter, Not Harder for Prostate Cancer

The current battle around using the PSA test to screen for prostate cancer boils down to weighing the harms and benefits of two probabilities:

The probability of saving more lives by detecting prostate cancer earlier with PSA screening;


The probability of overdiagnosis leading to unnecessary (and expensive) treatment for a prostate cancer that is not life-threatening.

The United States Preventive Services Task Force (USPSTF), the New England Journal of Medicine, and most recently, Consumer Reports have claimed that the probability of overdiagnosis so greatly outweighs the probability of saving more lives that the PSA test should be avoided altogether.  Better for a man not to know his PSA than to be subject to the harmful effects of being treated unnecessarily for a slow-growing cancer.

Prostate cancer advocacy organizations such as Zero, Us TOO, and the National Comprehensive Cancer Network (NCCN)—a consortium of major US cancer research and treatment centers—assert that it’s better to screen and save men from a painful death.  Virtually every man whose elevated PSA reading led to a malignant biopsy believes in screening, too, passionately claiming that the PSA test saved his life.

Dan Zenka, VP of Communications at the Prostate Cancer Foundation (PCF), who himself has advanced prostate cancer, writes in his blog, My New York Minute, that with “advances in new biomarkers, we will see more clarity–for patients and physicians alike–in making better informed decisions.” Zenka observes that new technologies that distinguish between aggressive cancers requiring treatment and less aggressive cancers needing only to be monitored “will also take the heat off of the often misunderstood and maligned PSA test.”

But until these improved tests become widely available, using the PSA test to screen for cancer will continue to be a polarizing topic.

In the midst of this fray, a team of researchers at the Fred Hutchinson Cancer Research Center in Seattle is seeking to find a middle ground in the PSA test controversy by advocating “Screening Smarter, Not Harder, for Prostate Cancer.”*

These researchers have developed what they call a “microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies.”  They are asking, are there new screening strategies that would mitigate the tradeoff between saving more lives and the potential harms of overdiagnosis?

ProbSavedVsOverdiagnosis_simpleThe team ran 35 variations of prostate cancer screening protocols through its computer model, evaluating the impact of changing variables such as the age bracket in which to screen, frequency of testing, and the PSA levels that should trigger a biopsy.

They then compared the model’s 35 outputs that predicted (among other things) the probability of saving a life versus the probability of overdiagnosis to the current “reference strategy”—the most commonly followed screening protocol—that recommends annual screening from age 50 to 74 and calling for a biopsy if PSA exceeds 4.0 nG/dL.

The model clearly revealed the tradeoffs.  The NCCN’s recommended strategy (shown in the diagram at left as strategy #1) of screening annually and conducting a biopsy if PSA exceeds just 2.5 “saved the most lives . . . but the lifetime risks for a false-positive result and overdiagnosis are nearly twice that of the reference strategy.”  On the other hand, a strategy identical to the “reference”–with exception of stopping the PSA test five years earlier at age 69–increases the probability of saving lives without increasing the probability of overdiagnosis.

Another significant finding was that increasing the PSA “biopsy trigger” level by age group “reduces overdiagnoses by one third while only slightly altering the [number of] lives saved.”

The unsurprising conclusion of the research team is that there is no single protocol applicable to everyone that stands out as superior to all others.  Instead, screening protocols need to take additional variables into account, including as a man’s age and risk for cancer.  As the researchers observe, “these adaptive, personalized strategies represent prototypes for a smarter approach to screening.”

Will the standoff at the PSA Screening Corral continue unabated?  Probably. But these voices from Seattle offer a “bipartisan” approach to the much-maligned PSA test by predicting the tradeoffs between saving lives and overdiagnosis.  By altering the PSA screening protocol to a more age-appropriate, personalized model, perhaps we can communicate a clearer and less contentious message about screening for both men and their doctors, as we await new technology that will hopefully render PSA screening superfluous.

* Roman Gulati, MS; John L. Gore, MD; and Ruth Etzioni, PhD; “Comparative Effectiveness of Alternative Prostate-Specific Antigen–Based Prostate Cancer Screening Strategies;” Annals of Internal Medicine Vol 158 Num 3, pp 145-153

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