Two sequential diagnoses of atypical foci suspicious for carcinoma on prostate biopsy: a follow-up study of 179 cases.

OBJECTIVE: To follow-up the outcomes with patients who have had 2 consecutive "atypical foci suspicious for carcinoma (ATYP)" diagnoses from prostate biopsies. MATERIALS AND METHODS: A total of 516 men who had prostate core biopsy specimens with 2 sequential diagnoses of ATYP from 2003 to 2012 from 1 institution were studied. RESULTS: Of the 516 men, 179 underwent additional repeat biopsy (34.8%) after 2 ATYP diagnoses. No difference was found between the patients with and without a repeat biopsy after 2 ATYPs in terms of patient age, serum prostate-specific antigen levels, and digital rectal examination and transrectal ultrasound findings. On repeat biopsy after 2 ATYP findings, 95 of the 179 men (53.1%) had benign prostatic tissue or high-grade prostatic intraepithelial neoplasia, 65 (36.3%) had cancer, and 19 (10.6%) had a third finding of ATYP. The Gleason score in the cancer group was 3+3=6 (50 patients, 77%), 3+4=7 (12 patients, 18.5%), 4+3=7 (1 patient, 1.5%), and 4+4=8 (2 patients, 3%). No difference was seen between those without (benign, high-grade prostatic intraepithelial neoplasia, or ATYP) and with cancer in terms of patient age, serum prostate-specific antigen level, digital rectal examination and transrectal ultrasound findings, and interval between the 2 ATYP biopsies and the interval between the first ATYP and last biopsy. CONCLUSION: The results of our study have shown that 36.3% men will be diagnosed with cancer on biopsy after 2 ATYP diagnoses, with 23% having a Gleason score of ≥7. Because no clinical features were predictive of which patients would have cancer on the follow-up biopsy, close follow-up and repeat biopsy are warranted.

Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA.

More than 1,000,000 men undergo prostate biopsy each year in the United States, most for "elevated" serum prostate-specific antigen (PSA). Given the lack of specificity and unclear mortality benefit of PSA testing, methods to individualize management of elevated PSA are needed. Greater than 50% of PSA-screened prostate cancers harbor fusions between the transmembrane protease, serine 2 (TMPRSS2) and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) genes. Here, we report a clinical-grade, transcription-mediated amplification assay to risk stratify and detect prostate cancer noninvasively in urine. The TMPRSS2:ERG fusion transcript was quantitatively measured in prospectively collected whole urine from 1312 men at multiple centers. Urine TMPRSS2:ERG was associated with indicators of clinically significant cancer at biopsy and prostatectomy, including tumor size, high Gleason score at prostatectomy, and upgrading of Gleason grade at prostatectomy. TMPRSS2:ERG, in combination with urine prostate cancer antigen 3 (PCA3), improved the performance of the multivariate Prostate Cancer Prevention Trial risk calculator in predicting cancer on biopsy. In the biopsy cohorts, men in the highest and lowest of three TMPRSS2:ERG+PCA3 score groups had markedly different rates of cancer, clinically significant cancer by Epstein criteria, and high-grade cancer on biopsy. Our results demonstrate that urine TMPRSS2:ERG, in combination with urine PCA3, enhances the utility of serum PSA for predicting prostate cancer risk and clinically relevant cancer on biopsy.