Faculty Bibliography

PURPOSE: Prostate specific antigen and free prostate specific antigen have limited specificity to detect clinically significant, curable prostate cancer, leading to unnecessary biopsy, and detection and treatment of some indolent tumors. Specificity to detect clinically significant prostate cancer may be improved by [-2]pro-prostate specific antigen. We evaluated [-2]pro-prostate specific antigen, free prostate specific antigen and prostate specific antigen using the formula, ([-2]pro-prostate specific antigen/free prostate specific antigen x prostate specific antigen(1/2)) to enhance specificity to detect overall and high grade prostate cancer. MATERIALS AND METHODS: We enrolled 892 men with no history of prostate cancer, normal rectal examination, prostate specific antigen 2 to 10 ng/ml and 6-core or greater prostate biopsy in a prospective multi-institutional trial. We examined the relationship of serum prostate specific antigen, free-to-total prostate specific antigen and the prostate health index with biopsy results. Primary end points were specificity and AUC using the prostate health index to detect overall and Gleason 7 or greater prostate cancer on biopsy compared with those of free-to-total prostate specific antigen. RESULTS: In the 2 to 10 ng/ml prostate specific antigen range at 80% to 95% sensitivity the specificity and AUC (0.703) of the prostate health index exceeded those of prostate specific antigen and free-to-total prostate specific antigen. An increasing prostate health index was associated with a 4.7-fold increased risk of prostate cancer and a 1.61-fold increased risk of Gleason score greater than or equal to 4 + 3 = 7 disease on biopsy. The AUC of the index exceeded that of free-to-total prostate specific antigen (0.724 vs 0.670) to discriminate prostate cancer with Gleason 4 or greater + 3 from lower grade disease or negative biopsy. Prostate health index results were not associated with age and prostate volume. CONCLUSIONS: The prostate health index may be useful in prostate cancer screening to decrease unnecessary biopsy in men 50 years old or older with prostate specific antigen 2 to 10 ng/ml and negative digital rectal examination with minimal loss in sensitivity.

PURPOSE: The European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 20% mortality reduction with prostate-specific antigen (PSA) screening. However, they estimated a number needed to screen (NNS) of 1,410 and a number needed to treat (NNT) of 48 to prevent one prostate cancer death at 9 years. Although NNS and NNT are useful statistics to assess the benefits and harms of an intervention, in a survival study setting such as the ERSPC, NNS and NNT are time specific, and reporting values at one time point may lead to misinterpretation of results. Our objective was to re-examine the effect of varying follow-up times on NNS and NNT using data extrapolated from the ERSPC report. MATERIALS AND METHODS: On the basis of published ERSPC data, we modeled the cumulative hazard function using a piecewise exponential model, assuming a constant hazard of 0.0002 for the screening and control groups for years 1 to 7 of the trial and different constant rates of 0.00062 and 0.00102 for the screening and control groups, respectively, for years 8 to 12. Annualized cancer detection and drop-out rates were also approximated based on the observed number of individuals at risk in published ERSPC data. RESULTS: According to our model, the NNS and NNT at 9 years were 1,254 and 43, respectively. Subsequently, NNS decreased from 837 at year 10 to 503 at year 12, and NNT decreased from 29 to 18. CONCLUSION: Despite the seemingly simplistic nature of estimating NNT, there is widespread misunderstanding of its pitfalls. With additional follow-up in the ERSPC, if the mortality difference continues to grow, the NNT to save a life with PSA screening will decrease.

OBJECTIVES: A PSA velocity (PSAV) >0.35 ng/ml/year approximately 10-15 years prior to diagnosis is associated with a greater risk of lethal prostate cancer. Some have recommended that a PSAV >0.35 ng/ml/year should prompt a prostate biopsy in men with a low serum PSA (<4 ng/ml) and benign DRE. However, less is known about the utility of this PSAV cutpoint for the prediction of treatment outcomes among men undergoing radical prostatectomy (RP). METHODS: Between 1992 and 2007, 339 men underwent RP at our institution with a preoperative PSA <4 ng/ml, benign DRE, and multiple preoperative PSA measurements. PSAV was calculated by linear regression analysis using all PSA values within 18 months prior to diagnosis. Kaplan-Meier survival analysis was performed, and biochemical progression rates were compared between PSAV strata using the log-rank test. RESULTS: The preoperative PSAV was >0.35 ng/ml/year in 124 (36.6%) of 339 men. Although there were no significant differences in clinico-pathological characteristics based upon PSAV, men with a PSAV >0.35 ng/ml/year were significantly more likely to experience biochemical progression after RP at a median follow-up of 4 years (P = 0.022). CONCLUSIONS: In this low-risk population with a preoperative PSA <4 ng/ml and benign DRE, approximately 1/3 had a preoperative PSAV >0.35 ng/ml/year. Physicians should carefully monitor men with a preoperative PSA >0.35 ng/ml/year as they are at increased risk of biochemical progression following RP

OBJECTIVES: To describe the distribution and implications of prostate-specific antigen velocity (PSAV) by prostate-specific antigen (PSA) in an unselected population. A PSAV >0.35 and >2.0 ng/mL/y have been associated with an increased risk of prostate cancer (CaP) death more than 10 years and 1 year before diagnosis, respectively. It is unknown how frequently PSAVs of this magnitude occur in community men. METHODS: From the Baltimore Longitudinal Study of Aging, we examined the PSAV distribution in 786 men with serial PSA measurements (3474 PSAV observations) at total PSA levels <10 ng/mL. We also determined whether PSAV altered the probability of overall and life-threatening CaP at PSA levels <3 and 3-10 ng/mL. RESULTS: Overall, the mean PSA and PSAV were 1.3 ng/mL and 0.05 ng/mL/y, respectively. PSAV rose continuously with increasing PSA (P <.0001), and was significantly higher in cancers than controls for observations at PSA levels <3 ng/mL (P = .02) and 3-10 ng/mL (P = .0008). The probability of life-threatening CaP was 3% at a PSA <3 ng/mL, but increased to 13.6% with PSAV >0.4 ng/mL/y. At PSA levels of 3-10 ng/mL, the probability of life-threatening CaP was 9.8% based on PSA alone vs 12% with PSAV >0.4 ng/mL/y. CONCLUSIONS: PSAV was significantly higher in CaP observations than controls in all PSA ranges studied and altered the risk of overall and life-threatening CaP at a given PSA level. Because the value of PSAV is PSA-dependent, the PSA level should be taken into account when interpreting PSAV.