they recommend biopsy for men 50 to 59 years old if eithercutoff is exceeded or only if both are exceeded. Additionally,in the original submitted article 50% of men who had aPSAV of 0 or less were excluded from analysis, and approx-imately 30% of those with cancer had no increasing PSA. Itis not clear to what extent these exclusions could have in-flated test performances.

I believe that given the limitations of absolute PSA levels toexclude the presence of cancer (reference 4 in article), PSAVwill be an important risk assessment tool that provides infor-mation regarding the presence of life threatening disease inmen with PSA less than the traditional cutoff of 4.0 ng/ml. Justas PSA is a better predictor of cancer in younger men with-out BPH, as the authors have shown so is PSAV. The mostimportant remaining question is whether our efforts to de-tect more cancer by lowering test thresholds will lead toimproved overall health outcomes for men.

H. Ballentine CarterDepartment of Urology

Johns Hopkins School of MedicineBaltimore, Maryland

REPLY BY AUTHORS

Carter, a respected authority and first to write about theclinical usefulness of PSAV, raises an excellent question ofwhether the exclusion of men with PSAV of 0 or less inflatedthe test performance of age adjusted PSAV. We discussedthis question several times when the analysis was per-formed, and we actually performed both analyses (includingand excluding men with PSAV of 0 or less). The changingpatterns of sensitivity and specificity among different agegroups from the 2 methods were similar. The decision toexclude men with PSAV of 0 or less was based on severalfactors. 1) In contrast to PSA, which almost always has avalue meaningful to a urologist, the clinical meaning ofPSAV is less clear-cut, especially when PSAV is 0 or less. 2)If PSAV is 0 or less, urologists will use PSA alone to evaluatethe risk of cancer. 3) Exclusion or inclusion of PSAV of 0 orless has the same meaning for the urologist. 4) Exclusion orinclusion of PSAV of 0 or less delivered the same messagethat PSAV should be age adjusted, a key finding of thisstudy.

AGE ADJUSTED PROSTATE SPECIFIC ANTIGEN CUT POINTS504