The Ugly Tradeoff: Over-Treatment vs. Preventable Death

Those of us in the prostate cancer community are all too aware of the 2011 USPSTF guidelines that call for discontinuing PSA screening for all men because a high PSA leads too often to unnecessary “over- treatment” with its expense and attendant quality of life (QoL) issues such as impotence and incontinence. Better to remain ignorant, the USPSTF argues, since men hearing “you have cancer” will inevitably over-react, rushing too quickly to be treated for a cancer that probably will do no harm. But “too bad” about the men dying of the cancer’s more aggressive form when they could have been cured earlier because they never had a PSA test showing an elevated PSA that may have led to a a biopsy that may have led to treatment.

scalesIn 2012, the American Urological Association issued its own less draconian screening guidelines, saying there is little point in screening men younger than 40 or older than 70. Prostate cancer is rare in men under 40 and actuarially, most men over 70 will die of something else first.

Recently, researchers at the Fred Hutchinson Cancer Research Center in Seattle constructed a mathematical model to test the USPSTF and AUA recommendations in order to project the likely effects of the two screening guidelines between 2013 and 2025. (1) The models were based on “reconstructed screening patterns and prostate cancer incidence in the United States.” 

The model’s two outputs were incidence (rate of prostate cancer diagnoses) and mortality (deaths from prostate cancer). They compared the model’s projections of following the USPSTF or the AUA guidelines.

To serve as the baseline, the model predicted that continuing to follow the existing “screen everyone” guideline would result in total over-treatment of between 710,000 to 1,200,000 men over the next 12 years (2013 to 2025). To provide some perspective to those numbers, at the current annual rate of about 230,000 diagnoses per year, about 2.8 million men are likely to be diagnosed with prostate cancer in the same period. In other words, the model is projecting that of almost 3 million men that would be diagnosed, somewhere between 25% and 42% of them would not need to have been treated for cancer. That’s a lot of unnecessary surgeries and radiation (and a lot revenue for urologists and radiation oncologists).

Although there would be substantial over-treatment by continuing the “test everyone” method, the model also predicted that between 36,000 and 57,000 deaths prostate cancer would be prevented by continuing mass screening.  This projection answers the USPSTF “no screening” guideline question in reverse. Yes, discontinuing PSA-based screening altogether would certainly prevent that large number of men being treated unnecessarily. But it would also mean the between 36,000 and 57,000 men would die of prostate cancer whose deaths could have been prevented. In other words, no screening at all basically means a return to the pre-PSA days when men with prostate cancer were diagnosed only after they had symptoms such as unexplained weight loss or bone pain, which almost always meant Stage IV prostate cancer—too late to cure.

The researchers then ran their model using the 2012 AUA guidelines. It predicted that between 2013 and 2025, that 64% to 65% of over- diagnoses would be eliminated, but that 36% to 39% of preventable deaths would still occur.

These results suggest that by continuing to screen men between the ages of 40 and 70 almost two-thirds of over-treatment—and all its attendant QoL issues— would be eliminated. But it also meant there were still more than 35% of preventable cancers that would be missed before they became too advanced to cure. Following the AUA guidelines certainly suggests a much better —although certainly far from perfect—outcome than abandoning PSA screening altogether, as our benevolent federal government would prefer.

Of course, all these numbers are just the projections by a computer model based on current technology: the PSA test with all its inherent ambiguity. There are other biomarkers in development that will be superior to PSA for screening, especially at determining whether the cancer is aggressive and requires treatment or is slow-growing and unlikely to do any harm if left untreated. We can hope that these new tools become available sooner rather than later and render this model’s projections obsolete. The goal is always fewer men treated unnecessarily—and fewer men dying needlessly.

As an engineer, I know all too well that every project involves trade-offs. That’s why as a group we’re wont to say, “there is no free lunch.” (Which may also explain why so few engineers become politicians…) The question becomes, even if the less drastic AUA guidelines are followed, is it worth it over the next 12 years to spare more than 620,000 men the QoL after-effects of receiving surgery or radiation they did not need, but still at the cost of upwards of 17,500 men dying of a cancer diagnosed too late? (2)

The question remains: Is the tradeoff between over-treatment and preventable cancer deaths worth it? It probably depends on where you’re standing. What do you think?

(1) Source: Gulati Tsodikov, et al; Expected population impacts of discontinued prostate-specific antigen screening; Cancer; 2014 July 25.

(2) The math: Average total number (incidence) of men over-treated for prostate cancer occurring between 2013 and 2025 if no screening a la the USPSTF: 955,000 [average of 780,000 and 1,200,000]. If AUA guidelines are followed incidence is reduced to ~621,000 [955,000 x 0.65 = 620,750]

Average number of preventable deaths from prostate cancer (mortality) occurring between 2013 and 2025 if no screening: 46,500 (average of 36,000 low estimate and 57,000 high estimate). If AUA guidelines are followed, mortality is reduced to ~17,500 [46,500 x (.375) = 17,440]

Comments

  1. Greg Hoffman says

    Well thought out and written article, Craig. As you pointed out. the AUA approach certainly bodes better for earlier detection and treatment and thus, better outcomes. While not perfect, it begs the question, “Why in the name of better health and earlier treatment would the government, a la the USPSTF approach, allow men to play Russian Roulette with their health and longevity?” As a PCa survivor and constant battler visa-vie ADT, Casodex, Trelstar, Xgeva, Xtandi, et al, I cannot stress enough the value in early detection (and, to a degree, some collateral damage of over-treatment) in treating this insideous and slow-life-sucking condition. Let’s hope cooler, calmer, smarter heads prevail and we see increased awareness, better diagnostics, better treatment, better outcomes and, ultimately, a cure for Prostate Cancer. Be well, Craig, and please keep these informative and thought provoking posts coming.

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