Faculty Bibliography

OBJECTIVE: To present an effective approach to the early detection of lethal prostate cancer using longitudinal data on prostate-specific antigen (PSA) and its rate of change, i.e. PSA velocity (PSAV). This longitudinal approach might also be extendible to other biomarkers. SUBJECTS AND METHODS: PSAV was calculated using five techniques for 634 subjects with at least three PSA measurements in a longitudinal ageing study, censoring PSA levels of > 10 ng/mL. The efficacy for predicting death from prostate cancer was assessed with concordance indices and by using net reclassification improvement (NRI), which indicated the net increase in sensitivity and specificity when adding a biomarker to a base Cox proportional hazards model. The PSAV techniques were compared for the 5-10 years before the clinical diagnosis of prostate cancer. The most effective technique was then applied at the transition point when each man's PSA history curve transformed from linear to exponentially increasing, and its predictive value was compared to that of concurrent PSA level. RESULTS: A PSA transition point was found in 522 (82%) of the 634 men, including all 11 who died from prostate cancer. At the transition point, the mean PSA level was 1.4 ng/mL, and PSAV but not PSA level was significantly higher among men who died from prostate cancer than among men who did not (P = 0.021 vs P = 0.112; Wilcoxon two-sample test). At the transition point, adding PSAV to a base model consisting of age and date of diagnosis improved the concordance index by 0.05, and significantly improved the overall sensitivity and specificity (NRI, P = 0.028), while adding PSA level to the same base model resulted in little improvement (concordance index increase < 0.01 and NRI P = 0.275). CONCLUSION: When the shape of a man's PSA history curve changes from linear to exponential, PSAV might help in the early identification of life-threatening prostate cancer at a time when PSA values are still low in most men.

OBJECTIVES: To further evaluate the relationship of prostate-specific antigen (PSA) with prostate size and tumor volume in a contemporary surgical series. Although early studies showed a strong correlation between PSA and tumor volume, it has been suggested that PSA is no longer a valid marker for prostate cancer and only correlates with prostate size. METHODS: From 2003 to 2009, 1234 men with data on prostate weight and total tumor volume underwent radical prostatectomy by a single surgeon. Prostate size was classified into tertiles: small (/= 54.6 g). Pearson correlation coefficients were used to examine the relationship of PSA with prostate size and tumor volume across different prostate sizes. RESULTS: Median preoperative PSA was 4.9 ng/mL (standard deviation +/- 4.6), mean prostate size was 51.7 g, and mean tumor volume was 5.6 cm(3). PSA had a significant correlation with prostate size only at a prostate weight >/= 54.6 g (P = .02). Regardless of prostate size, PSA had a more robust significant correlation with tumor volume than with prostate size (all P < .0001). CONCLUSIONS: PSA was significantly correlated with prostate size only in the largest prostate glands, but was significantly associated with tumor volume in small, medium, or large prostates. Thus, PSA continues to be a better marker for tumor volume than for prostate size.

The discovery of prostate-specific antigen (PSA) as a biomarker represented a major discovery in the early diagnosis and monitoring of prostate cancer. However, the use of PSA is limited by the lack of specificity and an inability to differentiate indolent from life-threatening disease reliably at the time of diagnosis. A multitude of studies have aimed to improve the performance of PSA as well as identify additional biomarkers. The purpose of this study is to review available data on prostate cancer biomarkers for prostate cancer screening and prognostication, including prostatic acid phosphatase, PSA, PSA derivatives (PSA density, free PSA, pro PSA, and PSA kinetics), PCA3, GSTP1, AMACR, and other newly emerging molecular and genetic markers.

OBJECTIVES: To examine the long-term survival following radical prostatectomy in the population with high-risk prostate cancer. Despite considerable stage migration associated with widespread prostate-specific antigen screening, as many as one-third of incident prostate cancers have high-risk features. These patients are often treated with combined radiation and androgen deprivation therapy, and less is known about the long-term survival in this population after radical prostatectomy (RP). METHODS: Between 1992 and 2008, 175 men underwent RP by a single surgeon with D'Amico high-risk prostate cancer (clinical stage >/=T2c, biopsy Gleason score 8-10, or prostate-specific antigen >20 ng/mL). In this population, we examined the rates and predictors of biochemical progression, metastatic disease, and cancer-specific mortality. RESULTS: Among 175 high-risk patients, 63 (36%) had organ-confined disease in the RP specimen. At 10 years, biochemical recurrence-free survival was 68%, metastasis-free survival was 84%, and prostate cancer-specific survival was 92%. The 10-year rate of freedom from any hormonal therapy was 71%. Of the high-risk criteria, a biopsy Gleason score of 8-10 (vs