Faculty Bibliography

OBJECTIVES: To determine whether repeat biopsy is necessary when the diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN) is made with a 12-core biopsy. Repeated biopsy has been recommended for individuals with HGPIN noted on sextant prostate biopsy because of the high likelihood of cancer detection. Recently, we have recommended the routine use of 12 cores, rather than 6, to improve cancer detection. METHODS: The charts of all patients undergoing prostate biopsy during a 2-year period at the Manhattan Veterans Administration Medical Center were reviewed. Patients diagnosed with HGPIN on a 12-core biopsy were identified, and those undergoing a repeat 12-core biopsy within 1 year of the initial biopsy were evaluated to determine the rate of cancer detection. RESULTS: A total of 619 men underwent biopsy during the study period. Of 103 men diagnosed with HGPIN, 43 underwent a repeat biopsy within 1 year at the discretion of the managing urologist. The mean age and median prostate-specific antigen level of those undergoing a repeat biopsy was 65.5 years and 5.37 ng/mL, respectively. At the time of the repeat biopsy, 1 patient was found to have cancer (2.3%), 20 had HGPIN (46.5%), 20 had benign pathologic findings (46.5%), and 1 patient (2.3%) had atypical small acinar proliferation. CONCLUSIONS: A repeat biopsy after the diagnosis of HGPIN on 12-core prostate biopsy rarely results in cancer detection. In the absence of other factors increasing the suspicion of cancer, immediate repeat biopsy for HGPIN diagnosed on a 12-core biopsy is unnecessary

OBJECTIVES: To determine the effect of prostate volume on the specificity of prostate-specific antigen density (PSAD) and PSAD of the transition zone (PSA-TZ) in the detection of prostate cancer. METHODS: Between February 1994 and April 1998, transrectal ultrasound-guided prostate needle biopsies were performed in 235 men with serum prostate-specific antigen (PSA) levels between 4.0 and 10.0 ng/mL. The PSAD and PSA-TZ specificities were calculated at 95% sensitivity cutoff levels generated from the whole group, as well as from cohorts stratified by transition zone index or prostate volume. RESULTS: Statistical significance was noted between the benign (n = 176) and prostate cancer (n = 59) groups for all tested PSA parameters. At 95% sensitivity, PSA-TZ carried a specificity of 37.5% compared with 29.6% for PSAD. When applying a single 95% sensitivity cutoff derived from the entire group to individual volume-stratified cohorts, the specificity decreased to 0% in glands less than 30 g in size. A 95% sensitivity PSA-TZ cutoff generated individually for volume-stratified cohorts of glands less than 30, 30 to 40, and 40 to 60 g resulted in more consistent specificity of 28.2%, 35.2%, and 45.7% for each cohort, respectively. CONCLUSIONS: Unlike whole group-derived cutoffs, the use of volume-specific PSA-TZ cutoffs allows consistently high specificity in all volume-stratified cohorts. The discrepancies in the PSA-TZ and PSAD specificities in published reports are likely due to the application of published cutoffs to populations of differing prostate volumes. The use of volume-specific cutoffs results in reproducible specificity in populations with differing prostate volume distribution, and thereby definitively resolves the differences in PSA-TZ specificity reported in published reports

Replication-competent, attenuated herpes simplex virus-1 (HSV-1) derivatives that contain engineered mutations into the viral gamma34.5 virulence gene have been used as oncolytic agents. However, as attenuated mutants often grow poorly, they may not completely destroy some tumors and surviving cancer cells simply regrow. Thus, although HSV-1 gamma34.5 mutants can reduce the growth of human tumor xenografts in mice and have passed phase I safety studies, their efficacy is limited because they replicate poorly in many human tumor cells. Previously, we selected for a gamma34.5 deletion mutant variant that regained the ability to replicate efficiently in tumor cells. Although this virus contains an extragenic suppressor mutation that confers enhanced growth in tumor cells, it remains attenuated. Here, we demonstrate that the suppressor virus replicates to greater levels in prostate carcinoma cells and, importantly, is a more potent inhibitor of tumor growth in an animal model of human prostate cancer than the gamma34.5 parent virus. Thus, genetic selection in cancer cells can be used as a tool to enhance the antitumor activity of a replication-competent virus. The increased therapeutic potency of this oncolytic virus may be useful in the treatment of a wide variety of cancers