H. Ballentine Carter prostate cancer was when PSA levels were below 4.0 ng/mL [Fig. 1 in (4)]. Also, men who have life-threatening prostate cancers have a higher PSA velocity than men who do not have prostate cancer (7), and PSA velocity is associated with death from pro state cancer both before and after treatment (8, 9). Yet Thompson et al.(4) found that PSA velocity was not associated with the development of prostate cancer or the development of high-grade cancer. One explanation for the findings reported by Thompson et al. is that the cancers detected (or a substantial proportion of them) were not life threatening. Almost half of the cancers detected were in men who had PSA values of 2.0 ng/mL or less [table 3 in Thompson et al.(4)]. The probability of finding a small-volume, potentially harmless prostate cancer increases as PSA level decreases (10). Thus, the risk assessment tool described in the current study may not be relevant for the detection of life-threatening prostate cancers. However, other factors not found to be important in the current study may turn out to be important predictors of life-threatening cancer. What are the implications of this study? According to the risk assessment tool described by Thompson et al., to avoid a 20% risk of harboring prostate cancer would require the biopsy of all men (regardless of family history and DRE findings) at or before they reached a PSA level of 2.0 ng/mL [fig. 3 in (4)], a level well below the “standard” dichotomous value of 4.0 ng/mL. Although the authors do not endorse a specific threshold probability of prostate cancer risk at which a biopsy should be performed, most physicians (and, probably, patients) would not be comfortable with a 20% likelihood of cancer. The authors previously reported (5) a positive biopsy rate of 15% for men with PSA levels below 4.0 ng/mL who underwent a six-core biopsy (most urologists today perform 12 or more cores). Approximately 80% of men in the US population have PSA levels below 4.0 ng/mL (11). Thus, among all men with PSA levels below 4.0 ng/mL, the proportion of prostate cancers that could be detected with a biopsy would be 12%. By contrast, approximately 10% of the male population has a PSA level of 4.0–10.0 ng/mL (11) and the positive biopsy rate in these men is approximately 30%. Thus, among all men with PSA levels between 4.0 ng/mL and 10.0 ng/mL, the proportion of cancers that could be detected with a biopsy would be 3%. The current estimated prevalence of prostate cancer in the United States is 1.8 million (12). If we were to diagnose only a fraction of those cancers in men who have a PSA level below 4.0 ng/mL, we would easily double the current prevalence of prostate cancer, at which point the prevalence of prostate cancer would be greater than that of all other cancers combined among men (12). In light of current estimated prostate cancer overdiagnosis rates of 30%–50%(13, 14), further increases in overdiagnosis would have a huge impact on the unnecessary treatment of prostate cancer.