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Commentary: how serious is getting a diagnosis of prostate cancer?

In this issue of The Oncologist, Drs. Loeb and Catalona propose a more aggressive strategy of screening for prostate cancer with the prostate-specific antigen (PSA) test than has generally been used in the U.S. [1]. The most controversial of these recommendations include beginning screening at the age of 40 (the “stopping age” is not addressed), routinely performing prostate biopsy on men with a total PSA level 2.5 ng/ml (regardless of age), and performing biopsies on men with lower total PSA levels who have a PSA velocity 0.4 ng/ml per year. Implicit in such recommendations is the growing concern about the sensitivity of the PSA test raised, for example, by data from the Prostate Cancer Prevention Trial (PCPT). The PCPT demonstrated that about 15% of men with a PSA level less than the traditional biopsy threshold of 4.0 ng/ml have prostate cancer at biopsy, with about 15% of those cancers being Gleason grade 7 or higher [2]. In truth, thanks to the PCPT, we now know that the PSA test is quite limited in terms of its ability to separate men with prostate cancer at biopsy from men without prostate cancer, with an area under the receiver operating characteristic (ROC) curve of 0.67, which means that just 67% of the time, a man with prostate cancer can be expected to have a higher PSA level than a man without prostate cancer (for a worthless test, the ROC curve area would be 0.5). Compare that discriminating ability with, for example, the ability of an atrial natriuretic peptide measurement to discriminate patients with heart failure from “all comers” with shortness of breath; 94% of the time, a patient with heart failure will have a higher level than a patient with another cause of dyspnea [3]. To compensate for the poor discriminating ability of total PSA, it is indeed tempting to lower biopsy thresholds and add new PSA derivative biopsy criteria to find as many prostate cancers that may be destined to cause future morbidity and mortality as early as possible. However, maximizing sensitivity comes at a price, and in this case, a double price. The first price is obvious, and is attributable to the deterioration in specificity that results from any attempt to increase sensitivity. This price will be paid by the additional men without prostate cancer who will undergo biopsy as a result of the more aggressive recommendations. In doing so, they will face the small but finite risks of complications a set of 10 –12 biopsies entails, and more importantly, subsequently live with the uncertainty and anxiety about whether their biopsy was a false negative, and the increased surveillance and subsequent testing that inevitably follows [4]. Welch and colleagues have estimated that the number of men in the U.S. aged 40 years and older requiring biopsy would increase from about 3 million with a biopsy threshold of 4.0 ng/ml to about 6 million with a biopsy threshold of 2.5 ng/ml [5]. And adding a relatively low PSA velocity threshold for biopsy would increase that number far further.