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Abstract: Biopsy results from the Prostate Cancer Prevention Trial (PCPT) showed that prostate cancer exists at all PSA levels and that a significant number of men with “normal” PSA levels have high grade cancer. These findings and the low specificity of total PSA in discriminating cancer from benign disease have added to the debate about how best to use PSA in selecting men for prostate biopsy. Lower PSA thresholds for consideration of biopsy, particularly in younger men, are advocated by some. PSA velocity measurements may assist in the identification of men most likely to harbor cancer, and lower PSA velocity thresholds may be more appropriate in younger men. A more individualized approach using a predictive model developed from PCPT biopsy results is promoted by others. While able to incorporate risk variables other than PSA, including new markers, this risk calculator does not include PSA velocity since this variable was not found to have independent predictive value in this model. This article will present differing viewpoints on selecting men for prostate biopsy, one advocating the use of a PSA cut-off or PSA velocity measure (Dr. Catalona) and the other arguing for the routine use of established risk nomograms (Dr. Klein). [Copyright &y& Elsevier]

Abstract: For more than two decades, open radical prostatectomy has been considered the gold standard for the surgical management of prostate cancer. More recently, however, laparoscopic and now robotic approaches to radical prostatectomy have become increasingly popular. It is unclear whether these techniques are associated with any material advantage with regard to short-term convalescence. In addition, the high positive surgical margin rates reported with robotic prostatectomy are concerning, particularly early in the learning curve. Additional experience with these methods and long-term follow-up data are necessary to determine whether the cancer control and functional outcomes meet the standards of open radical prostatectomy. [Copyright &y& Elsevier]

Abstract: Currently, in the United States (US), most prostate cancers are diagnosed through screening with digital rectal examination (DRE) and measurement of serum prostate-specific antigen (PSA). The serum PSA level correlates directly with prostate cancer risk and aggressiveness, as well as the outcomes after treatment. PSA testing is also useful in monitoring patients for tumor recurrence after treatment. PSA testing has limited specificity for prostate cancer detection, and its appropriate clinical application has been the topic of debate. Accordingly, several variations on the PSA measurement have emerged as useful adjuncts for prostate cancer screening. These take into consideration additional factors, such as the proportion of different PSA isoforms (free PSA, complexed PSA, pro-PSA and B PSA), the prostate volume (PSA density), and the rate of change in PSA levels over time (PSA velocity or PSA doubling time). Widespread PSA screening is associated with a 75% reduction in the proportion of men who present with metastatic disease since 1985–89 in the US and a 32.5% reduction in the age-adjusted prostate cancer mortality rate through 2003. The history and evidence underlying each of these parameters are reviewed in the following article. [Copyright &y& Elsevier]

Abstract: Context: Prostate cancer screening is highly controversial, including the age to begin prostate-specific antigen (PSA) testing. Several studies have evaluated the usefulness of baseline PSA measurements at a young age. Objective: Review the literature on baseline PSA testing at a young age (≤60 yr) for the prediction of prostate cancer risk and prognosis. Evidence acquisition: PubMed was searched for English-language publications on baseline PSA and prostate cancer for the period ending April 2011. Evidence synthesis: In most published series, median PSA levels in the general male population range from approximately 0.4 to 0.7 ng/ml in men in their 40s and from approximately 0.7 to 1.0 ng/ml in men in their 50s. Evidence from both nonscreening and screening populations has demonstrated the predictive value of a single baseline PSA measurement for prostate cancer risk assessment. Specifically, men with baseline PSA levels above the age-group-specific median have a greater risk of prostate cancer diagnosis during the next 20–25 yr. Additional studies confirmed that higher baseline PSA levels at a young age are also associated with a greater risk of aggressive disease, metastasis, and disease-specific mortality many years later. Conclusions: Baseline PSA measurements at a young age are significant predictors of later prostate cancer diagnosis and disease-specific outcomes. Thus baseline PSA testing may be used for risk stratification and to guide screening protocols. [Copyright &y& Elsevier]

Purpose: To determine whether the number of unfavorable risk factors could be used to predict the risk of prostate cancer-specific mortality (PCSM) among men with intermediate- to high-risk prostate cancer. Methods and Materials: We studied 1,063 men who underwent radical prostatectomy (n = 559), external beam radiotherapy (n = 288), or radiotherapy plus androgen suppression therapy (n = 116) for prostate cancer between 1965 and 2002. Fine and Gray''s regression analysis was used to determine whether an increasing number of unfavorable risk factors (prostate-specific antigen level >10 ng/mL, Gleason score of ≥7, clinical Stage T2b or greater, or pretreatment prostate-specific antigen velocity >2.0 ng/mL/y) was associated with the interval to PCSM and all-cause mortality. Results: Median follow-up was 5.6 years. Compared with those with one risk factor, the adjusted hazard ratio for PCSM was 2.3 (95% confidence interval 1.1–4.8; p = 0.03) for two risk factors, 5.4 (95% confidence interval 2.7–10.7; p < 0.0001) for three risk factors, and 13.6 (95% confidence interval 6.3–29.2; p < 0.0001) for all four risk factors. The 5-year cumulative incidence of PCSM was 2.4% for one factor, 2.4% for two factors, 7.0% for three factors, and 14.7% for all four factors. Prostate cancer deaths as a proportion of all deaths was 19% for one factor, 33% for two factors, 53% for three factors, and 80% for four factors. Conclusion: The number of unfavorable risk factors was significantly associated with PCSM. Prostate cancer was the major cause of death in men with at least three risk factors. Therefore, these men should be considered for clinical trials designed to assess whether survival is prolonged with the addition of novel agents to current standards of practice. [Copyright &y& Elsevier]

Purpose: To determine whether phosphodiesterase-5 inhibitor documentation is associated with biochemical relapse-free and overall survival of patients with prostate cancer treated with radical prostatectomy.Materials and Methods: We undertook a retrospective cohort analysis of 3,100 patients with prostate cancer treated with radical prostatectomy between 2003 and 2015. The patients were categorized as a phosphodiesterase- 5- inhibitor user or non-user. The biochemical relapse-free and overall survival at 5-years and 10-years were determined.Results: Of the patients, 1,372 reported phosphodiesterase-5 inhibitor documentation, and 1,728 did not. The biochemical recurrence-free survival for non-users at 5- and 10-years follow-up was 87.6% and 85.3%, respectively, and the overall survival at these time intervals was 97.9% and 94.5%. The biochemical recurrence-free survival for phosphodiesterase-5 inhibitor users was 94.3% and 93.2% at 5- and 10-years follow-up, respectively, and overall survival was 99.2% and 95.8% at these intervals. The hazard ratio for biochemical recurrence-free survival was 0.44 (CI 0.34-0.56) and for overall survival was 0.65 (CI 0.45-0.94). On the multivariate analysis, phosphodiesterase-5 inhibitor documentation was associated with a lower risk of biochemical recurrence and death when corrected for the other variables. Age at surgery and Gleason scores >8 was associated with a higher risk of death. Higher pathological stage, higher Gleason score, presence of lymph node metastases, and nonwhite race were associated with a higher risk of recurrence.Conclusion: This retrospective analysis revealed a significant association of postoperative phosphodiesterase-5 inhibitor documentation with biochemical recurrence-free- and overall survival in patients with localized prostate cancer treated with radical prostatectomy. Larger scale studies are warranted to investigate the clinical significance of this association. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To compare the preoperative characteristics, postoperative prostate-specific antigen (PSA) doubling time (DT), and prostate cancer-specific mortality (PCSM) estimates after PSA failure in men diagnosed during a screening study versus a community referral population. A PSA-DT of less than 3 months is a surrogate endpoint for PCSM. Methods: From 1988 to 2002, 1492 of 9637 patients with clinically localized prostate cancer underwent radical prostatectomy and experienced PSA failure. They were either participating in a screening study (n = 841) or attended 1 of 44 community-based practices (n = 611). The distributions of PSA, Gleason score, tumor stage, and PSA-DT were compared using chi-square metric. The estimates of PCSM after PSA failure were compared using Gray’s P value. Results: Compared with the community population, the annually screened men experiencing PSA failure had a lower PSA level at diagnosis (5.1 versus 9.5 ng/mL, P <0.0001), were less likely to have Gleason score 7 to 10 cancer (25.1% versus 42.1%, P <0.0001), and were more likely to have low-risk disease (64.5% versus 23.8%, P <0.0001). Furthermore, the screened cohort had a reduction (P <0.0001) in the proportion with a PSA-DT of less than 3, 3 to 5.99, and 6 to 11.99 months and a significant increase in the proportion with a PSA-DT of 12 months or longer. After a median follow-up of 4.5 and 4.1 years after PSA failure in the screened and community cohorts, respectively, the PCSM estimates were lower (P = 0.0002) in the screened cohort (10-year estimate 3.6% [95% confidence interval 1.3 to 5.8] versus 11.3% [95% confidence interval 5.9 to 17.4]). Conclusions: Patients diagnosed by annual prostate cancer screening appeared more likely to experience an indolent PSA recurrence and less likely to die of prostate cancer after PSA recurrence compared with patients referred from the community. [Copyright &y& Elsevier]

Abstract: Objectives: To assess the current incidence of prostate carcinoma detection in serial biopsies in a prostate-specific antigen-based screening population after a diagnosis of isolated high-grade prostatic intraepithelial neoplasia (HG-PIN) in needle biopsy tissue. Methods: We retrospectively identified 190 men with a diagnosis of isolated HG-PIN in needle biopsy tissue. Most men (86%) were diagnosed from 1996 to 2000. Logistic regression analysis was used to predict the presence of carcinoma in these 190 men and in a control group of 1677 men with only benign prostatic tissue in needle biopsy tissue. Results: The cumulative risk of detection of carcinoma on serial sextant follow-up biopsies was 30.5% for those with isolated HG-PIN compared with 26.2% for the control group (P = 0.2). Patient age (P = 0.03) and serum prostate-specific antigen level (P = 0.02) were significantly linked to the risk of cancer detection, but suspicious digital rectal examination findings (P = 0.1), the presence of HG-PIN (P = 0.2), and the histologic attributes of PIN were not (all with nonsignificant P values). HG-PIN found on the first repeat biopsy was associated with a 41% risk of subsequent detection of carcinoma compared with an 18% risk if benign prostatic tissue was found on the first repeat biopsy (P = 0.01). Conclusions: The results of our study have shown that the current level of risk for the detection of prostate carcinoma in a screened population is 30.5% after a diagnosis of isolated HG-PIN in a needle biopsy. This risk level is lower than the previously reported risk of 33% to 50%. HG-PIN is a risk factor for carcinoma detection only when found on consecutive sextant biopsies. The data presented here should prompt reconsideration of repeat biopsy strategies for HG-PIN, and re-evaluation of the absolute necessity of repeat biopsy for all patients with HG-PIN. [Copyright &y& Elsevier]

Abstract: Prostate inflammation can lead to an elevation in the serum PSA concentration and confound the use of PSA kinetics. This can have considerable clinical consequences, since these measurements form the basis for important clinical decisions. Thus, there has been investigation into ways to decrease the confounding from inflammation, including repeat PSA measurements after a period of observation or a course of empiric antibiotics. This article reviews the evidence about elevations in PSA due to prostatitis and describes the controversy over the optimal approach to reduce its confounding impact on prostate cancer screening. [Copyright &y& Elsevier]

Objective: To evaluate prognostic markers, prostate-specific antigen, prostate health index (PHI), and prostate volume indexed measures (prostate-specific antigen density and prostate health index density) for predicting positive prostate cancer biopsies in magnetic resonance (MR) transrectal ultrasound fused versus nonfused transrectal ultrasonography biopsy.Methods: A retrospective cohort of 211 patients that had at least 1 suspected MR lesion, Prostate Imaging-Reporting and Data System ≥3, and subsequent biopsy (2015-2017). Clinical characteristics and prognostic biomarkers were evaluated as predictors of prostate cancer detection by type of biopsy guidance (fused vs nonfused).Results: One-hundred twenty-one patients had nonfused and 90 had fused biopsies. PHI and PHID had greater area under the receiver operating characteristics curve (AUC) in predicting positive biopsies than prostate-specific antigen or PSAD for both nonfused and fused biopsy. PHI 0.78 (95% CI 0.67-0.88) and PHID 0.82 (95% CI 0.73-0.91) had the greatest AUC for predicting biopsy results for nonfused and fused biopsies, respectively. Multiple-variable models did not improve model fit compared to single variables. Based on Youden's index, a cut-off value of 45.9 for PHI in nonfused and 0.64 for PHID in fused biopsies would reduce the number of negative biopsies by 77.3% and 63.4%, respectively, but the percentage of missed clinically significant cancer biopsies would be 19% and 12%, respectively.Conclusion: Our findings demonstrate that the choice of prognostic biomarkers for predicting positive biopsies is a function of the biopsy guidance method. Volume indexed derivatives appear to have greater value when a MRI-US fused method is used. [ABSTRACT FROM AUTHOR]

Objective: To better assess the increased utilization of multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy of the prostate, we compared prostate cancer detection rates among (a) men undergoing MR-ultrasound (US) fusion biopsy, (b) mpMRI cognitive-registration biopsy, and (c) conventional transrectal US-guided biopsy for the detection of prostate cancer.Materials and Methods: We present a retrospective review of consecutive patients undergoing mpMRI of the prostate with subsequent prostate biopsy from October 2013 to September 2015. Lesions concerning for prostate cancer visualized on mpMRI were targeted with cognitive-registration or MR-US fusion biopsies. A cohort of men undergoing conventional prostate biopsy was utilized for comparison. Rates of cancer detection were compared among the 3 cohorts.Results: A total of 231 patients underwent mpMRI-targeted biopsy (81 fusion, 150 cognitive). There was no difference in prostate specific antigen, mpMRI-defined Prostate Imaging Reporting and Data System score or number of lesions, or history of prostate cancer among the cohorts. The overall detection rate of cancer was significantly higher in the fusion cohort (48.1%) compared with both the cognitive (34.6% P = .04) and conventional (32.0%, P = .03) cohorts. Cancer detection rates were comparable in the MRI-cognitive and transrectal prostate US biopsy groups (34.6% vs 32%). MR fusion detected significantly more Gleason ≥7 cancer (61.5 vs 37.5%, P = .04) and significantly less Gleason 6 cancer (38.5 vs 62.5%, P = .04) compared with conventional biopsy.Conclusion: Targeted biopsy of the prostate using MR-US fusion increased the cancer detection rate compared with both cognitive registration and conventional biopsy and was associated with detection of higher-grade cancer compared with conventional biopsy. [ABSTRACT FROM AUTHOR]

Background Associations have been documented recently between some of the 23 single nucleotide polymorphisms newly discovered with the Collaborative Oncological Gene-environment Study iCOGS array that indicate prostate cancer (PCa) risk and aspects of disease aggressiveness. The utility of these iCOGS SNPs remains to be determined in active surveillance (AS). Objective To determine associations between iCOGS SNPs and upgrading among men who underwent surgical treatment and AS for low-risk PCa. Design, setting, and participants The genotypes of the 23 iCOGS SNPs were determined for all white subjects with biopsy Gleason score (GS) 6 including 950 men who underwent definitive treatment with surgery and 209 men who elected AS. The clinical and pathologic characteristics were documented for all subjects. Outcome measures and statistical analysis Men who underwent surgery were grouped according to their pathologic GS (upgraded was defined as GS ≥7; nonupgraded remained GS 6). Men who were enrolled in AS were also grouped according to their GS on subsequent surveillance biopsies. Statistical analyses were performed comparing the genotypes between the upgraded and nonupgraded groups. Results and limitations Overall, 31% and 34% of men were upgraded in the surgery and AS cohorts, respectively. Three iCOGS SNPs were significantly associated with the risk of upgrading in the surgical cohort. After correction for multiple testing, only rs11568818 on chromosome 11q22 remained significantly associated with upgrading. Assessment of this allele in the AS cohort reveals that it was present at noteworthy higher frequencies in men with high-grade disease on surveillance biopsies compared with nonupgraded men ( p = 0.003). This study was primarily limited by the homogeneous patient population. Conclusions This is the first report of a SNP on chromosome 11q22 associated with higher grade disease in a surgical cohort that is also validated for eventual upgrading in a prospective AS cohort. Patient summary We examined the relationship between a group of genetic markers and prostate cancer (PCa) aggressiveness in a group of patients who underwent surgery for PCa and a group of patients who were enrolled in active surveillance. We found that these genetic markers helped predict which patients had more aggressive disease in both groups. [ABSTRACT FROM AUTHOR]

Abstract: Objective: There are increasing reports of infectious complications following prostate biopsy due to fluoroquinolone resistance. To determine infectious complications at catheter removal following radical prostatectomy (RP), another setting in daily urological practice where fluoroquinolone prophylaxis is frequently used. Materials and methods: We prospectively examined urine culture results collected from 334 RP patients immediately prior to catheter removal. Patients received prophylactic antibiotics 1 day before, the day of, and for 5 days after catheter removal. Culture results were reviewed for bacterial species and antimicrobial susceptibilities. Patients with positive urine cultures resistant to the prophylactic antibiotic were switched to culture-specific antibiotic therapy and underwent follow-up culture. The frequency of urinary tract infection (UTI), complications, additional antibiotic therapy, and repeat urine cultures was determined within 60 days. Results: Of the 334 patients identified, 203 (61%) had cultures with no bacterial growth, and 48 (14%) had colony counts of <1,000 bacteria or Candida albicans and received no further antibiotics. The remaining 83 (25%) had positive culture results, of which 7% were resistant to ciprofloxacin. Twenty-four bacterial species were identified, with Pseudomonas aeruginosa (5%) Escherichia coli (4%), and Staphylococcus epidermidis (3%) being the most frequent. Only two (0.6%) men developed clinical symptoms consistent with UTI (i.e., suprapubic pain, fever) prior to catheter removal, and no serious complications occurred. Conclusions: A substantial proportion of RP patients have positive urine cultures at the time of catheter removal, despite the administration of prophylactic fluoroquinolone antibiotics. Potentially virulent organisms are commonly cultured, and ciprofloxacin resistance is frequent. However, outcomes are favorable when culture-specific oral antibiotic therapy is initiated. [Copyright &y& Elsevier]

Abstract: Objectives: Prostate cancer clinical staging has significant limitations in the ability to accurately risk-stratify patients for prompt treatment or expectant management. The University of California San Francisco Cancer of the Prostate Risk Assessment (UCSF CAPRA) was recently described as a straightforward staging system that uses clinical variables to generate a score ranging from 0 to 10. Our objective was to perform an external validation of the CAPRA score as a predictor of 5-year progression-free survival (PFS) in a single-surgeon radical retropubic prostatectomy (RRP) series. Materials and methods: We examined the performance characteristics of the preoperative CAPRA score (0–10) to predict biochemical progression-free survival (PFS) in 990 men who underwent RRP by a single surgeon from 2003 to 2009. Results: CAPRA scores were significantly associated with the risk of early biochemical progression in our series. For example, 5-year PFS was markedly different for scores at the extremes of 0 to 1 vs. ≥7 (95% vs. 40%, respectively). The concordance index was 0.764 for the prediction of biochemical progression using CAPRA scores in this cohort, which compares favorably with the concordance index of 0.66 in the original CaPSURE dataset. Conclusions: Our results validate the UCSF-CAPRA score as a significant predictor of 5-year PFS in a single surgeon series. The CAPRA score is a simple preoperative tool that can be readily applied in clinical practice to help risk-stratify prostate cancer patients. [Copyright &y& Elsevier]

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 (≤41.2 g), medium (41.3-54.5 g), and large (≥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 cm3. 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. [Copyright &y& Elsevier]

Objectives: To examine the treatment outcomes of men who would have been eligible for active surveillance (AS) but underwent immediate radical retropubic prostatectomy (RRP). AS protocols are designed to spare the potential morbidity of treatment to patients with low-risk prostate cancer (PCa). Methods: From a prospective RRP database, we evaluated the tumor features and treatment outcomes for men who would have met 1 of 3 published AS criteria: (1) clinically localized disease, Gleason ≤7, and no significant comorbidities (Patel et al, J Urol. 2004;171:1520-1524) (2) T1b-T2b N0M0 disease, Gleason ≤7, and prostate-specific antigen ≤15 ng/mL (Choo R et al. J Urol. 2002;167:1664-1669), or (3) T1c PCa (Mohler JL et al. World J Urol. 1997;15:364-368.). Results: 3959, 3536, and 2330 RRP patients, respectively, would have met these AS criteria. At surgery, 3%-4% had a Gleason score of 8-10, 16%-19% had positive surgical margins, 15%-18% had extracapsular tumor extension, 3%-5% had seminal vesicle invasion, and 0.4%-1% had lymph node metastasis. The 5-year progression-free survival rate ranged from 84%-89%. Metastasis occurred in 0.1%-1.2%, and 0.1%-0.9% died of PCa. On multivariate analysis, Gleason score >6 was the strongest predictor of biochemical progression. Conclusions: A substantial proportion of men who might have been considered potential AS candidates had aggressive tumor features at RRP and/or progression. Biopsy Gleason score >6 was the strongest predictor of adverse outcomes, highlighting the importance of limiting AS to patients with Gleason ≤6. Overall, the accurate identification of patients with truly indolent PCa at the time of diagnosis remains challenging. [Copyright &y& Elsevier]

Objectives: Conflicting evidence has been reported on the association of prostate-specific antigen velocity (PSAV) with Gleason score in prostate needle biopsy specimens. The Gleason score is an important prognostic indicator for men with prostate cancer, and, in modern practice, it frequently affects treatment decisions. To our knowledge, the relationship between preoperative PSAV and Gleason score in the radical prostatectomy specimen has not been formally demonstrated. Methods: A total of 1049 men treated with radical prostatectomy had data on PSAV and Gleason score. Statistical analysis was performed to examine the relationship between the preoperative PSAV and the prostatectomy Gleason score and other adverse tumor features. Results: The median preoperative PSAV was 0.84, 0.97, and 1.39 ng/mL/y in men with a Gleason score of 6, 7, and 8-10, respectively (P = .05). A PSAV greater than 2 ng/mL/y was significantly associated with a prostatectomy Gleason score of 7 or greater on univariate and multivariate analysis. In addition, the preoperative PSAV was significantly lower in men with organ-confined disease (0.82 vs 1.17 ng/mL/y, respectively, P = .002). Conclusions: Our results have further validated PSAV as a marker for prostate cancer aggressiveness. The preoperative PSAV was a significant independent predictor of the Gleason score and non–organ-confined disease in the radical prostatectomy specimen. Thus, PSAV could be useful in treatment decision-making and in assessing the likelihood of long-term cancer control in men with prostate cancer. [Copyright &y& Elsevier]

Objectives: With the widespread use of prostate-specific antigen (PSA)-based screening, there is now concern about the overdiagnosis and overtreatment of men with low-risk prostate cancer (PCa). One of the most difficult aspects of PCa management is a balance of the often-competing goals of cancer control with functional outcomes and quality of life. To address this issue, we examined the potency, continence and overall complication rates associated with radical prostatectomy (RP), specifically in potential candidates for active monitoring. Methods: From a large RP database, we compared potency, continence, and complication rates among men meeting one of the following active monitoring criteria from the literature: clinically localized, Gleason score of 7 or less, and no significant comorbidities; T1b-T2b NOMO, Gleason score of 7 or less, and PSA of 15 ng/mL or less; and T1c PCa. Results: There were 3458, 3533, and 2338 men who met the above criteria, respectively. After 18 months of follow-up, potency was preserved in 70% to 74%. At least 93% of patients were continent, and the rate of surgical complications ranged from 5% to 7%. Increasing age was significantly associated with a greater risk of all complications. Conclusions: Men with newly diagnosed low-risk PCa must carefully weigh the risks and benefits of treatment. In young men with low-risk PCa, RP was associated with a relatively low complication rate and good long-term functional outcomes. However, with increasing age, RP was associated with significantly higher complication rates. These results can be used to help guide management decisions for men with low-risk disease. [Copyright &y& Elsevier]

Objectives: Prior studies have reported that men with a PSA density (PSAD) less than 0.15, less than 3 positive biopsy cores, 50% or less of any core involved, and a Gleason score 6 or lower are likely to have “insignificant” prostate cancer (CaP) in their radical prostatectomy (RRP) specimen. In this study, we examined the ability of PSAD and biopsy features to predict pathologic outcomes in a contemporary RRP population. Methods: From 1999 to 2005, 274 men underwent RRP and had the required data for our analysis. As our database does not record the percentage or length of cancer in each biopsy core, we examined the relative importance of PSAD, the number of positive biopsy cores, and Gleason grade to predict “insignificant” cancer, defined as organ-confined with a tumor volume less than 0.5 mL and no Gleason pattern 4 or 5. Results: Overall, by these criteria, 24.5% of patients were considered to have potentially “insignificant” cancer preoperatively; whereas, only 2.6% had a so-called “insignificant” tumor in the RRP specimen. Without the percentage of biopsy core involvement, the preoperative model to predict “insignificant” cancer was associated with 57% sensitivity, 76% specificity, 6% positive predictive value, and 99% negative predictive value. Conclusions: A model including Gleason grade, PSAD, and number of positive biopsy cores did not provide an accurate means of selecting patients for active monitoring in our patient cohort. However, it was helpful in identifying men with a high likelihood of “clinically significant” CaP. Knowledge of the percentage of biopsy core involvement with cancer may be a critical prognostic factor. [Copyright &y& Elsevier]

Objectives: For prostate cancer screening, the role of prostate-specific antigen (PSA) velocity (PSAV) in conjunction with total PSA is controversial. We evaluated the relationship of PSAV to histologic findings on biopsy and assessed whether PSAV provides independent predictive information. Methods: From a community-based cohort of 25,276 men screened from 1991 to 2001, 1851 underwent a first biopsy for an elevated PSA and nonsuspicious digital rectal examination with a PSAV available from the year before biopsy. We analyzed the association between PSAV and biopsy histology. Results: The histologic findings on biopsy were cancer in 468 (25%), prostatic inflammation in 135 (7%), and benign prostate tissue in 1248 (68%). The cancer detection rate was associated with PSAV and, depending on PSAV, ranged from 13% to 36% (P <0.001). Among men with a PSAV less than 0.5 ng/mL per year, the cancer rate ranged from 27% to 36%, at a PSAV of 0.5 to 3.0 ng/mL per year was 24% to 28%, and at a PSAV greater than 3.0 ng/mL per year was 13% to 18%. On multivariable analysis adjusting for age and PSA, PSAV was independently associated with risk of cancer on biopsy (P <0.0005). The rate of prostatic inflammation was directly associated with PSAV (PSAV of 3.0 ng/mL per year or less: 5% to 9%; PSAV greater than 3.0 ng/mL per year: 11% to 13%, P = 0.01). Conclusions: In screened men with an elevated PSA undergoing biopsy, PSAV provides independent predictive information for estimating prostate cancer risk. Modest increases in PSA are associated with an increased risk of cancer, whereas more dramatic PSA rises are associated with a diminishing risk of cancer and higher rate of inflammation. [Copyright &y& Elsevier]

Objectives: To examine clinical and pathologic features and postoperative survival outcomes of men with prostate cancer detected by digital rectal examination (DRE) alone, elevated prostate-specific antigen (PSA) level alone, or abnormalities in both. Methods: From 1989 to 2001, approximately 36,000 men participated in a prostate cancer screening study. We recommended biopsy for a PSA level greater than 4.0 ng/mL (until 1995) or greater than 2.5 ng/mL (after 1995) or DRE findings suspicious for cancer. The clinical and pathologic features were compared between patients with cancer detected by DRE alone and those with cancer detected by an elevated PSA level, regardless of DRE findings. We also evaluated progression-free survival, overall survival, and cancer-specific survival. Results: Overall 303 men were diagnosed with prostate cancer by DRE alone, 1426 because of PSA level alone, and 504 by abnormal results on both tests. Of the cancers detected by DRE alone, 60 (20%) were non–organ-confined and 56 (20%) had a Gleason score of 7 or higher. Prostate cancers detected because of abnormalities in both PSA level and DRE results were significantly more likely to have adverse pathologic features, as well as lower rates of progression-free survival, overall survival, and cancer-specific survival than those detected by either test alone (all P <0.0001). Conclusions: A substantial proportion of prostate cancers detected by DRE at PSA levels less than 4 ng/mL have features associated with clinically aggressive tumors. The omission of DRE from screening protocols might compromise treatment outcomes because many of the cancers detected by DRE alone are potentially curable but may have worse outcomes by the time PSA also reaches a higher level. [Copyright &y& Elsevier]

Objectives: Since the initiation of prostate-specific antigen (PSA) screening, the progression-free survival (PFS) rates after radical prostatectomy have markedly improved. However, few studies have evaluated whether PFS has improved for stage and grade-matched patients. Our objective was to examine differences in PFS after radical prostatectomy between the pre-PSA era (before 1992) and the PSA era, controlling for tumor stage and grade. Methods: From 1983 to 2003, 3456 men underwent radical prostatectomy by one surgeon. The 10-year PFS rates were calculated for each era and stratified by pathologic tumor stage and grade. Kaplan-Meier curves were generated to show biochemical PFS over time. Results: The proportion of patients with pathologically organ-confined disease increased from 64% to 69%, consistent with stage migration. The PFS rate in the PSA era was 87%, 63%, 58%, and 31% versus 71%, 63%, 47%, and 19% in the pre-PSA era for Stage pT2R0, pT3R0, pT2-T3R1, and pT3c/N1 disease, respectively. The PFS rate stratified by Gleason grade in the PSA era was 84%, 63%, and 37% versus 66%, 49%, and 32% in the pre-PSA era for Gleason grade less than 7, 7, and 8 to 10, respectively. The 10-year PFS rate for organ-confined disease improved from 70% in the pre-PSA era to 86% in the PSA era. Conclusions: Patients treated with radical prostatectomy in the PSA era have improved survival outcomes when controlling for pathologic stage and grade. This is likely attributed to the earlier detection of cancer through PSA screening, better identification of patients amenable to curative therapy, and the effects of lead-time bias. [Copyright &y& Elsevier]

Objectives: Controversy exists about the preferred treatment of patients with high-risk or locally advanced prostate cancer. We examined the intermediate-term cancer control and quality-of-life outcomes after radical retropubic prostatectomy (RRP) in selected patients. Methods: From 1984 to 2003, 288 men with Stage cT2b (Gleason score 8 to 10 or a prostate-specific antigen level greater than 15 ng/mL) or T3 disease underwent RRP by a single surgeon. The 7 and 10-year actuarial progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), potency, and continence rates were recorded. Results: The actuarial 7-year PFS, CSS, and OS rate after surgery was 39%, 92%, and 91%, respectively. The corresponding actuarial 10-year rates were 35%, 88%, and 74%. Only OS differed significantly by age group. On multivariate analysis, the pathologic stage was a significant independent predictor of progression. Ultimately, 31 men (11%) required hormonal therapy, 58 (20%) underwent postoperative radiotherapy, and 67 (23%) received both. Potency and continence were preserved in 64% and 92%, respectively. Conclusions: Overall, RRP offers excellent intermediate-term cancer control for selected men of all ages who present with high-risk or locally advanced disease. The PFS was significantly greater for men with high-risk Stage cT2b than for those with cT3 disease, but the CSS and OS were similar. Both continence and potency were preserved in most patients, although the potency rates were significantly greater for the younger men. RRP with appropriate postoperative radiotherapy and/or hormonal therapy is a reasonable treatment option for selected men with high-risk or locally advanced disease. [Copyright &y& Elsevier]

Objectives: Numerous commercial assays are available for measuring total and free prostate-specific antigen (PSA) levels in serum. These assays can be referenced to different laboratory standards, and interassay variability occurs. Patients and physicians might be affected by the variability between PSA assays that results from the use of different PSA standards. Methods: We prospectively compared the free and total PSA measurements obtained using two commercially available PSA assays in 103 participants from a prostate cancer screening program in Caracas, Venezuela. We recommended biopsy to men with a total PSA level of 3 to 10 ng/mL and a free/total PSA ratio of 20% or less with either assay. We compared the sensitivity, specificity, and concordance index between the two assays to assess the effects of interassay variability on the cancer detection rate and clinical outcomes. Results: Although the total PSA results were similar between the assays, the free PSA level was significantly greater with one assay. Therefore, the free/total PSA ratio was discordant between the two assays, resulting in different biopsy recommendations and cancer detection rates. Conclusions: Using a free/total PSA ratio of 20% or less as the threshold for biopsy, the differences in assay sensitivity and specificity for detecting prostate cancer are significant. Commercially available assays for PSA and its derivatives are not necessarily interchangeable, and these differences might lead to different clinical outcomes. When using free and total PSA measurements to make clinical decisions, patients and physicians should be aware of the potential standardization bias and which assay is being used. [Copyright &y& Elsevier]

Objectives: No consensus has been reached about the optimal follow-up for patients with an isolated finding of high-grade prostatic intraepithelial neoplasia (HG-PIN) on prostate biopsy. Early studies reported that approximately one half of men with HG-PIN were diagnosed with prostate cancer (CaP) within a few years. However, more recent studies, using extended biopsy protocols, have shown that HG-PIN may be less predictive of CaP on repeat biopsy in the short term. Thus, our objective was to identify the clinical factors that could help predict which men with isolated HG-PIN were at the greatest risk of subsequent CaP detection. Methods: In 190 men from a CaP screening study with an initial biopsy finding of HG-PIN, we compared the prostate-specific antigen velocity (PSAV) between patients who were later diagnosed with CaP and those who were not. Multivariate models were constructed for the ability to predict CaP detection. Results: The median PSAV was significantly greater in the men with HG-PIN who were subsequently diagnosed with CaP (P = 0.03). A PSAV threshold of 0.75 ng/mL/yr predicted which men with HG-PIN would ultimately be diagnosed with CaP (P = 0.007). On multivariate analysis, including PSAV, age, and initial PSA level, PSAV was the only significant predictor of subsequent CaP detection. Conclusions: Among the men with an isolated finding of HG-PIN on prostate needle biopsy, PSAV helps to identify those men who are subsequently diagnosed with CaP. Thus, we advocate the use of the PSAV to help guide the need for repeat biopsy in men with HG-PIN. [Copyright &y& Elsevier]

Abstract: Objective: Screening using a standardized protocol may improve outcomes of patients undergoing treatment for prostate cancer. We compared the 7- year progression-free survival rates after radical retropubic prostatectomy in patients whose prostate cancer was detected through a formal screening program with those of patients referred for treatment by other physicians who did not use a standardized screening/referral protocol. Methods: A single surgeon (W.J.C.) performed radical retropubic prostatectomy in 3,177 consecutive patients between 1989 and 2003. Of these patients, 464 had cancer detected in a screening study, and 2,713 were referred from outside institutions. We compared the screened and referred cohorts for age at surgery, clinical stage, pathologic stage, Gleason sum, preoperative prostate-specific antigen (PSA) levels, and adjuvant radiation therapy. Kaplan-Meier product limit estimates were used to calculate 7-year progression-free probabilities, and Cox proportional hazards models were used to determine the clinical and pathologic parameters associated with cancer progression in each group. Results: The overall 7-year progression-free survival rates were 83% for the screened patients compared with 77% for the referred patients (P = 0.002). Preoperative PSA, Gleason sum, clinical stage, pathologic stage, and adjuvant radiotherapy were all significantly associated with cancer progression. There was a significantly higher proportion of referred patients with a preoperative PSA ≥10, Gleason sum ≥7, and nonorgan-confined disease. Conclusions: Patients with screened-detected prostate cancer have more favorable clinical and pathologic features, and 7-year progression-free survival rates than referred patients. On multivariate analysis, including other clinical variables, screening status was a significant independent predictor of biochemical outcome. [Copyright &y& Elsevier]

Abstract: Objectives: Patients and referring physicians often ask about the significance of lymphovascular invasion (LVI) on pathology reports from radical prostatectomy specimens. However, limited data are available concerning the relationship between LVI and preoperative screening characteristics, pathologic tumor features, and patient prognosis. Methods: LVI was evaluated for its ability to predict elevated prostate-specific antigen velocity, adverse pathologic features, and biochemical progression in 1709 men who underwent radical prostatectomy for clinically localized disease. Results: LVI was present in 118 (7%) of the 1709 men. On univariate analysis, LVI was significantly associated with tumor grade, tumor volume, and other adverse pathologic features. Prostate-specific antigen velocity was not significantly associated with the presence of LVI. Biochemical progression occurred in 34% of those with LVI compared with 10% of those without LVI (P <0.0001). However, on multivariate analysis with other pathologic tumor features, LVI was not an independent predictor of progression. Conclusions: LVI is a relatively uncommon finding in radical prostatectomy specimens for clinically localized disease. Although LVI was seen primarily in large-volume, high-grade tumors, it was not an independent predictor of progression in the multivariate model. [Copyright &y& Elsevier]

Abstract: Objectives: To describe the changes in pathologic outcomes and progression-free survival (PFS) rates after radical retropubic prostatectomy for clinically localized prostate cancer in men whose cancers were detected in a 12-year longitudinal prostate cancer screening study. Methods: Between 1989 and 2001, more than 36,000 men participated in a digital rectal examination-based and prostate-specific antigen (PSA)-based screening program. In 1995, the PSA cutoff for biopsy recommendation was lowered from 4.0 ng/mL to 2.6 ng/mL, and the biopsy protocol was changed from four to at least six-sector biopsies. From the screening study, 2952 men were diagnosed with cancer and 2241 of these men underwent radical retropubic prostatectomy. We analyzed the differences in clinical and pathologic stage and PFS after surgery, according to the greater PSA cutoff era (1989 to 1995) and lower PSA cutoff era (1996 to 2001). Results: A significant downward clinical and pathological stage migration was found toward T1c and organ-confined disease, respectively, in men whose cancer was detected in the lower PSA cutoff era. Furthermore, men with cancer diagnosed in the lower PSA cutoff era had improved PFS rates 5 and 8 years after radical retropubic prostatectomy (P = 0.007). These changes occurred without a significant increase in the proportion of unimportant tumors (organ confined, smaller than 0.5 cm3 without a Gleason pattern of 4 or 5). Conclusions: These findings support the enhanced detection of favorable cancer and improved PFS rates with lower PSA cutoffs and more intensive biopsy regimens, although the follow-up and lead-time and length-time biases, as well as improvements in surgical technique, might also have affected these results. [Copyright &y& Elsevier]

Abstract: Objectives: Limited data are available concerning the extent to which the initial prostate-specific antigen (PSA) measurement in men younger than age 60 predicts for the risk of prostate cancer (CaP) and how this compares to other known risk factors. Methods: From 1991 to 2001, 13,943 men younger than 60 years old participated in a CaP screening study. Men aged 40 to 49 years were eligible for the study if they had a positive family history or African-American heritage, and men older than 50 years were screened without respect to risk factors. The CaP detection rate, PSA velocity, pathologic features, and treatment outcomes were evaluated as a function of the baseline PSA level. Results: The median PSA level was 0.7 ng/mL for men aged 40 to 49 years and 0.9 ng/mL for men aged 50 to 59. A baseline PSA level between the median and 2.5 ng/mL was associated with a 14.6-fold and 7.6-fold increased risk of CaP in men aged 40 to 49 and 50 to 59 years, respectively. A greater baseline PSA value was also associated with a significantly greater PSA velocity, more aggressive tumor features, a greater biochemical progression rate, and a trend toward a greater cancer-specific mortality rate. Conclusions: In men younger than 60, a baseline PSA value between the age-specific median and 2.5 ng/mL was a significant predictor of later CaP and was associated with a significantly greater PSA velocity. A young man’s baseline PSA value was a stronger predictor of CaP than family history, race, or suspicious digital rectal examination findings. A greater baseline PSA level was associated with significantly more adverse pathologic features and biochemical progression. [Copyright &y& Elsevier]

Abstract: Objectives: To compare the pathologic outcomes and prostate-specific antigen (PSA) progression rates of patients who underwent radical prostatectomy because of prostate cancers and whose cancer was detected at a PSA level of 2.6 to 4.0 ng/mL versus those with cancer detected after the PSA level rose to greater than 4.0 ng/mL. Some studies have suggested that clinically significant prostate cancer is detected more frequently in an organ-confined stage with a PSA level between 2.6 and 4.0 ng/mL than with a PSA level greater than 4 ng/mL. However, it is uncertain whether this will affect clinical outcomes. Methods: From 1991 to 2001, 20,788 men enrolled in a prostate cancer screening study had an initial PSA level of less than 2.6 ng/mL. Of these patients, 523 had a PSA level that rose to greater than 2.5 ng/mL and had prostate cancer detected. Of the 297 patients who subsequently underwent radical prostatectomy, 223 had a preoperative PSA level of 2.6 to 4.0 ng/mL and 74 had a preoperative PSA level greater than 4.0 ng/mL. The median follow-up was 4 years. The pathologic stage, mean tumor volume, Gleason score, possibly insignificant cancer rate, possibly rapidly progressive cancer rate, and PSA progression rate were compared between the two groups. Results: The patients with a preoperative PSA level between 2.6 and 4.0 ng/mL had more favorable pathologic outcomes in terms of cancer volume, pathologic stage, and possibly rapidly progressive cancer rate. The possibly insignificant cancer rates were not different between the groups. A trend was noted for patients with a preoperative PSA level between 2.6 and 4.0 ng/mL to have a lower PSA progression rate. Conclusions: Biopsy in men with PSA levels between 2.6 and 4.0 ng/mL may detect clinically significant prostate cancer more frequently at an organ-confined stage, with a lower PSA progression rate. Additional study in a larger population with longer follow-up is needed to confirm this trend. [Copyright &y& Elsevier]