Is High-Grade Prostate Cancer Easier to Find in Smaller Prostates Because There Is More High-Grade Disease to Find? – Letter

Elliott et al. (1) report that prostate-specific antigen (PSA) performance was significantly better in identifying high-grade disease in men with smaller prostates. They use this observation to support the hypothesis that the increased detection of high-grade disease in the finasteride arm of the Prostate Cancer Prevention Trial was due to an artifact in which the reduction in prostate size made it possible for PSA testing to identify the cancer better in smaller prostates. In their analysis, however, they do not consider another explanation for their findings.

It is well established that patients with smaller prostates have more high-grade disease, more extraprostatic extension with positive surgical margins, and higher rates of biochemical progression following radical prostatectomy than men with larger prostates (2–4). Simply stated, did the authors find more high-grade cancer in smaller prostates because there was more high-grade disease to find and not because PSA was better at finding it? Although PSA may perform better in the absence of prostatic enlargement, when Freedland et al. (2) excluded men with T1c disease and examined only men who had abnormal digital rectal examinations, they found that the association between smaller prostate size, higher grade advanced disease, and biochemical progression remained statistically significant. In the authors' study, 39% of their patients were also diagnosed with palpable disease and those men with smaller prostates also had higher rates of Gleason 7 to 10 disease and higher PSA density (PSA divided by prostate volume). If so, how does this help explain the Prostate Cancer Prevention Trial findings as an artifact? If high-volume, high-grade disease was detected more often during the first 7 years in the finasteride arm, then one would assume eventually over time that there would be fewer patients with high-grade disease. Instead, at 7 years, there were almost twice as many high-grade cancers in the finasteride arm, and in the end of study biopsies, the number was the same, not fewer (5). The authors are at an institution that has emphasized the value of measuring tumor volume in radical prostatectomy specimens and may be able to determine if the volume of high-grade tumor in the smaller prostates was the same as in larger prostates. This would support their conclusion. If not, how is this an artifact?