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Purpose of Review: Many prostate cancer active surveillance protocols mandate serial monitoring at defined intervals, including but certainly not limited to serum PSA (often every 6 months), clinic visits, prostate multiparametric MRI, and repeat prostate biopsies. The purpose of this article is to evaluate whether current protocols result in excessive testing of patients on active surveillance., Recent Findings: Multiple studies have been published in the past several years evaluating the utility of multiparametric MRI, serum biomarkers, and serial prostate biopsy for men on active surveillance. While MRI and serum biomarkers have promise with risk stratification, no studies have demonstrated that periodic prostate biopsy can be safely omitted in active surveillance. Active surveillance for prostate cancer is too active for some men with seemingly low-risk cancer. The use of multiple prostate MRIs or additional biomarkers do not always add to the prediction of higher-grade disease on surveillance biopsy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate how blood levels of prostate-specific antigen (PSA) relate to prostate volume of benign tissue, Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancer., Methods: The cohort included 2209 consecutive men undergoing radical prostatectomy at 2 academic institutions with pT2N0, Grade Group 1-4 prostate cancer and an undetectable postoperative PSA. Volume of benign, GP3, and GP4 were estimated. The primary analysis evaluated the association between PSA and volume of each type of tissue using multivariable linear regression. R 2 , a measure of explained variation, was calculated using a multivariable model., Results: Estimated contribution to PSA was 0.04/0.06 ng/mL/cc for benign, 0.08/0.14 ng/mL/cc for GP3, and 0.62/0.80 ng/ml/cc for GP4 for the 2 independent cohorts, respectively. GP4 was associated with 6 to 8-fold more PSA per cc compared to GP3 and 15-fold higher compared to benign tissue. We did not observe a difference between PSA per cc for GP3 vs. benign tissue (P = 0.2). R 2 decreased only slightly when removing age (0.006/0.018), volume of benign tissue (0.051/0.054) or GP3 (0.014/0.023) from the model. When GP4 was removed, R 2 decreased 0.051/0.310. PSA density (PSA divided by prostate volume) was associated with volume of GP4 but not GP3, after adjustment for benign volume., Conclusion: Gleason pattern 4 cancer contributes considerably more to PSA and PSA density per unit volume compared to GP3 and benign tissue. Contributions from GP3 and benign are similar. Further research should examine the utility of determining clinical management recommendations by absolute volume of GP4 rather than the ratio of GP3 to GP4., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Recent advances in our understanding of genetic factors that contribute to prostate cancer (PCa) susceptibility have the potential to improve disease screening, diagnosis, and treatment. Genetic risk scores in particular can more accurately inform patients of their risk of being diagnosed with PCa, which may help in decisions on whether to undergo prostate-specific antigen screening or prostate biopsy. Genetic information may also be useful in helping patients understand the etiology of their PCa and whether their family members should undergo more intensive screening. PATIENT SUMMARY: This mini review discusses recent advances in our understanding of how genetic factors influence a man's risk of developing prostate cancer. This information has the potential to improve screening, diagnosis, and patient counseling following a diagnosis of prostate cancer., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

To evaluate whether prostate volume (PV) would provide additional predictive utility to the prostate health index (phi) for predicting prostate cancer (PCa) or clinically significant prostate cancer, we designed a prospective, observational multicenter study in two prostate biopsy cohorts. Cohort 1 included 595 patients from three medical centers from 2012 to 2013, and Cohort 2 included 1025 patients from four medical centers from 2013 to 2014. Area under the receiver operating characteristic curves (AUC) and logistic regression models were used to evaluate the predictive performance of PV-based derivatives and models. Linear regression analysis showed that both total prostate-specific antigen (tPSA) and free PSA (fPSA) were significantly correlated with PV (all P < 0.05). [-2]proPSA (p2PSA) was significantly correlated with PV in Cohort 2 (P< 0.001) but not in Cohort 1 (P= 0.309), while no significant association was observed between phi and PV. When combining phi with PV, phi density (PHID) and another phi derivative (PHIV, calculated as phi/PV 0.5 ) did not outperform phi for predicting PCa or clinically significant PCa in either Cohort 1 or Cohort 2. Logistic regression analysis also showed that phi and PV were independent predictors for both PCa and clinically significant PCa (all P < 0.05); however, PV did not provide additional predictive value to phi when combining these derivatives in a regression model (all models vs phi were not statistically significant, all P > 0.05). In conclusion, PV-based derivatives (both PHIV and PHID) and models incorporating PV did not improve the predictive abilities of phi for either PCa or clinically significant PCa., Competing Interests: None

Background: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort., Methods: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV., Results: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml -l , PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers., Conclusions: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

Purpose of Review: To provide an overview of how genetic, serum, and urine biomarkers can help identify men at high risk for prostate cancer (PCa) and aggressive disease and men who would benefit from prostate biopsy., Recent Findings: Screening for PCa is controversial because of concerns about overdiagnosis and overtreatment of nonlife-threatening tumors. Therefore, an approach to screening that includes a detailed family history with genetic testing of risk single nucleotide polymorphisms and high-penetrance genetic variants should be considered. After an elevated serum prostate-specific antigen (PSA) level has been confirmed, obtaining additional information (family history, biomarkers, and imaging) should be considered before recommending a prostate biopsy., Summary: There are now genetic tests that can help identify men who would benefit from PSA testing. Additional biomarker and imaging tests should be offered to those men who are confirmed to have elevated PSA values. These new biomarkers and imaging tests can improve the specificity of PSA testing while missing a small percentage of high-grade tumors. The path forward involves a multiparametric risk assessment based on clinical data and these new tests.

Background: The performance of prostate health index (phi) in predicting prostate biopsy outcomes has been well established for patients with prostate-specific antigen (PSA) values between 2 and 10 ng/mL. However, the performance of phi remains unknown in patients with PSA >10 ng/mL, the vast majority in Chinese biopsy patients. We aimed to assess the ability of phi to predict prostate cancer (PCa) and high-grade disease (Gleason Score ≥7) on biopsy in a Chinese population., Methods: This is a prospective, observational, multi-center study of consecutive patients who underwent a transrectal ultrasound guided prostate biopsy at four hospitals in Shanghai, China from August 2013 to December 2014., Results: In the cohort of 1538 patients, the detection rate of PCa was 40.2%. phi had a significantly better predictive performance for PCa than total PSA (tPSA). The areas under the receiver operating characteristic curve (AUC) were 0.90 and 0.79 for phi and tPSA, respectively, P < 0.0001. A considerable proportion of patients in the cohort had PSAs >10 ng/mL (N = 838, 54.5%). The detection rates of PCa were 35.9% and 57.7% in patients with tPSA 10.1-20 and 20.1-50 ng/mL, respectively. The AUCs of phi (0.79 and 0.89, for these two groups, respectively) were also significantly higher than tPSA (0.57 and 0.63, respectively), both P < 0.0001. If a phi ≤35 was used as the cutoff, 599/1538 (39%) biopsies could have been avoided at a cost of missing small numbers of PCa patients: 49 (7.93%) PCa patients, including 18 (3.69%) high-grade tumors., Conclusions: Results from this study suggest that phi can be used to predict PCa and high-grade disease in Chinese men with high PSA levels (>10 ng/mL)., (© 2017 Wiley Periodicals, Inc.)

Objective: To evaluate whether genetic correction using the genetic variants prostate-specific antigen (PSA)-single nucleotide polymorphisms (SNPs) could reduce potentially unnecessary and/or delayed biopsies in African-American men., Subjects and Methods: We compared the genotypes of four PSA-SNPs between 964 Caucasian and 363 African-American men without known prostate cancer (PCa). We adjusted the PSA values based on an individual's PSA-SNP carrier status, and calculated the percentage of men that would meet commonly used PSA thresholds for biopsy (≥ 2.5 or ≥ 4.0 ng/mL) before and after genetic correction. Potentially unnecessary and delayed biopsies were defined as those men who were below and above the biopsy threshold after genetic correction, respectively., Results: Overall, 349 (96.1%) and 354 (97.5%) African-American men had measured PSA levels <2.5 and <4.0 ng/mL. Genetic correction in African-American men did not avoid any potentially unnecessary biopsies, but resulted in a significant (P < 0.001) reduction in potentially delayed biopsies by 2.5% and 3.9%, based on the biopsy threshold level., Conclusions: There are significant differences in the influence of the PSA-SNPs between African-American and Caucasian men without known PCa, as genetic correction resulted in an increased proportion of African-American men crossing the threshold for biopsy. These results raise the question of whether genetic differences in PSA might contribute to delayed PCa diagnosis in African-American men., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objectives: In May 2012, United States Preventive Services Task Force (USPSTF) finalized its recommendation against prostate-specific antigen (PSA) screening in all men. We aimed to assess trends in PSA screening frequency amongst primary care physicians (PCPs) surrounding the May 2012 USPSTF recommendation., Methods and Materials: The electronic data warehouse was used to identify men aged between 40 and 79 years with no history of prostate cancer or urology visit who were evaluated by an internal medicine or family practice physician between 2007 and 2012. Analyses were directed toward PSA testing within 6-month time period from June to November, with particular focus on the 2011 (pre-USPSTF recommendation) and 2012 (post-USPSTF recommendation) cohorts. The primary outcome measure was proportion of men with at least 1 PSA test during the 6-month pre- and post-USPSTF recommendation periods., Results: A total of 112,221 men met inclusion criteria. There was a significant decrease in screening frequency between the 2011 and 2012 cohorts (8.6% vs. 7.6%, P = 0.0001; adjusted odds ratio 0.89, 95% confidence interval 0.83-0.95). This decrease was most evident amongst patients aged 40 to 49 years (5.6% vs. 4.6%, P = 0.004) and 70 to 79 years (7.9% vs. 6.2%, P = 0.01). A significant decrease was also observed in patients with highest previous PSA value<1.0 (P<0.0001) and 1.0 to 2.49 ng/ml (P = 0.0074)., Conclusions: Since the USPSTF recommendation was finalized, there is evidence of continuing decreases in PSA testing by PCPs. PCPs may be shifting toward more selective screening practices, as decreases in screening are most pronounced in the youngest and oldest patients and in those with history of PSA values<2.5 ng/ml., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Recent studies have identified genetic variants associated with increased serum prostate specific antigen concentrations and prostate cancer risk, raising the possibility of diagnostic bias. By correcting for the effects of these variants on prostate specific antigen, it may be possible to create a personalized prostate specific antigen cutoff to more accurately identify individuals for whom biopsy is recommended. Therefore, we determined how many men would continue to meet common biopsy criteria after genetic correction of their measured prostate specific antigen concentrations., Materials and Methods: The genotypes of 4 single nucleotide polymorphisms previously associated with serum prostate specific antigen levels (rs2736098, rs10788160, rs11067228 and rs17632542) were determined in 964 healthy Caucasian volunteers without prostate cancer. Genetic correction of prostate specific antigen was performed by dividing an individual's prostate specific antigen value by his combined genetic risk. Analyses were used to compare the percentage of men who would meet commonly used biopsy thresholds (2.5 ng/ml or greater, or 4.0 ng/ml or greater) before and after genetic correction., Results: Genetic correction of serum prostate specific antigen results was associated with a significantly decreased percentage of men meeting biopsy thresholds. Genetic correction could lead to a 15% or 20% relative reduction in the total number of biopsies using a biopsy threshold of 2.5 ng/ml or greater, or 4.0 ng/ml or greater, respectively. In addition, genetic correction could result in an 18% to 22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses., Conclusions: Our results suggest that 4 single nucleotide polymorphisms can be used to adjust a man's measured prostate specific antigen concentration and potentially delay or prevent unnecessary prostate biopsies in Caucasian men., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Several reports suggest that a combination of risk alleles may be associated with prostate cancer (CaP) risk and tumor features. However, their ability to detect CaP and tumor characteristics in patients with a "normal" PSA (<4 ng/ml) and non-suspicious digital rectal examination (DRE) remains to be determined., Methods: We examined 203 men of European ancestry with clinical stage T1c CaP diagnosed at a "normal" PSA and 611 healthy volunteer controls. The genotypes for 17 different risk alleles were compared between CaP cases and controls. Additional analyses were used to compare the pathologic features between carriers and non-carriers (defined using best-fit genetic model) of these variants., Results: All risk alleles were present at an increased frequency in cases with "normal" PSA values and DRE compared to controls. Amongst CaP patients, carriers of an increasing number of genetic risk factors (i.e., alleles and positive family history) were at a significantly increased risk of CaP (P-trend <0.001). Specifically, men with >10 genetic risk factors had an 11.2-fold risk (95% CI 4.3-29.2) of having the disease compared to men with ≤5 variants. There also was a higher frequency of many the variants amongst men with adverse pathologic features., Conclusions: A substantial proportion of biopsy-detectable CaP occurs in men with "normal" PSA levels and negative DRE. In this population, CaP risk alleles and family history are significantly associated with CaP risk and may help predict aggressive disease. Future studies are warranted to determine the utility of incorporating these variants into CaP screening programs., (Copyright © 2010 Wiley-Liss, Inc.)

Measuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.

Purpose: The 5alpha-reductase inhibitors improve urinary symptoms related to benign prostatic hyperplasia, deter benign prostatic hyperplasia progression and provide prostate cancer chemoprevention. Currently there are a number of 5alpha-reductase inhibitor formularies, including Proscar, generic finasteride and dutasteride. While all formularies decrease serum prostate specific antigen (a proxy for prostate volume), they may not accomplish this to the same degree, which may have dramatic effects on prostate specific antigen kinetics in men changing 5alpha-reductase inhibitor formularies. We examined prostate specific antigen velocity after changes in 5alpha-reductase inhibitor formularies., Materials and Methods: We identified patients treated with 2 or more 5alpha-reductase inhibitor formularies who had sufficient prostate specific antigen values to calculate prostate specific antigen velocity during each 5alpha-reductase inhibitor treatment. Patient data were grouped depending on the formularies received. Statistical analysis was done to compare prostate specific antigen velocity at various time points while on different 5alpha-reductase inhibitors., Results: Eight men changed from dutasteride to generic finasteride (group 1), 21 changed from dutasteride to Proscar (group 2), 49 changed from Proscar to dutasteride (group 3) and 77 changed from Proscar to generic finasteride (group 4). We noted a significant increase in prostate specific antigen velocity in groups 1 and 2 (p <0.05), and 4 (p <0.005). The increase was greater than 0.35 ng/ml per year, the common cutoff for prostate biopsy recommendations, in more than a third of patients., Conclusions: Results confirm that changing 5alpha-reductase inhibitors drugs can be associated with a clinically significant change in prostate specific antigen velocity. These prostate specific antigen velocity changes could place patients at risk for unnecessary prostate biopsy. Additional prospective studies are warranted., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Prostate-specific antigen (PSA) is the most widely used marker for prostate cancer (CaP) screening and monitoring benign prostatic hyperplasia (BPH) progression. However, lack of an established abnormal threshold and the presence of other benign processes confound the interpretation of PSA levels. Many factors besides inflammation, trauma, and instrumentation can influence PSA levels; specifically, BPH and its associated medical and surgical therapies frequently complicate the interpretation of this serum blood test. For example, the commonly used 5 alpha reductase inhibitor (5ARI) medications directly affect PSA levels by decreasing prostate volume. The amount of time and potentially even the 5ARI formulary a patient is administered has been implicated to directly impact the degree of reduction in PSA (a proxy for prostate volume). In addition, each of the currently available surgical procedures for BPH appears to remove varying amounts of prostatic adenoma. This directly confounds CaP screening because each procedure is associated with a relatively specific postoperative nadir PSA level, and PSA kinetics are not well described in the literature. Taken together, it is important for clinicians to comprehend that BPH and its associated medical and surgical interventions should directly influence their interpretation of PSA and PSA velocity when screening for CaP or following BPH progression.

Purpose: A controversy of current prostate specific antigen based prostate cancer screening is the over detection of potentially insignificant prostate cancer. Because PSA kinetics were previously linked to prostate cancer specific mortality, we determined whether prostate specific antigen velocity is associated with clinically significant prostate cancer., Materials and Methods: A total of 1,073 men underwent radical prostatectomy from 1992 to 2008 with data available on prostate specific antigen velocity and tumor volume. Insignificant cancer was defined by the Ohori criteria as organ confined, tumor volume 0.5 cc or less and no primary or secondary Gleason pattern 4 or 5. We calculated the proportion of men with pathologically insignificant prostate cancer stratified by prostate specific antigen velocity., Results: Preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year was significantly associated with high grade disease (p = 0.008), positive surgical margins (p = 0.003) and seminal vesicle invasion (p = 0.007) at radical prostatectomy. Median tumor volume was also significantly higher in men with preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year (3.1 vs 2.4 cc, p = 0.0001). Overall 69 men (6%) met the Ohori criteria for insignificant cancer. Patients with preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year were 50% less likely to have insignificant disease (10% vs 5%, p = 0.003)., Conclusions: A prostate specific antigen velocity threshold of 0.4 ng/ml per year was associated with the likelihood of insignificant prostate cancer. This suggests that prostate specific antigen velocity may be a useful adjunct in prostate cancer screening to increase specificity for identifying patients with clinically significant disease.

Objectives: To determine whether prostate-specific antigen (PSA) values can distinguish those with prostate cancer (CaP) from those with histologic benign prostatic hyperplasia (BPH) only after surgical intervention. Prostatic adenoma inevitably remains after BPH surgery; therefore, patients remain at risk of developing CaP. Although the PSA level can be used for CaP screening in this population, it might be influenced by the efficacies of different BPH procedures., Methods: We performed a review of patients who had undergone transurethral resection of the prostate (TURP; n = 343), holmium laser resection of the prostate (HoLRP; n = 54), or open prostatectomy (OP; n = 68). The PSA and PSA velocity values were collected at regular intervals both pre- and postoperatively for all patients. Only patients with histologic BPH and those with incidental CaP who underwent a watchful waiting strategy were included., Results: The average preoperative PSA values were significantly different between the TURP, HoLRP, and OP groups. Only 1 patient had incidental CaP in the HoLRP group. No differences were present between the preoperative PSA values for patients with histologic BPH and those with incidental CaP undergoing a watchful waiting strategy (P > .05). However, the postoperative PSA values were increased in the patients with CaP (watchful waiting compared with the patient with BPH only (2.4 vs 1.7 ng/mL TURP and 4.1 vs 1.1 ng/mL OP). Similarly, patients with incidental CaP had a significantly elevated postoperative mean PSA velocity compared with patients without CaP (0.38 vs 0.06 ng/mL/y TURP and 0.47 vs -0.13 ng/mL/y OP; P < .05)., Conclusions: Postoperative PSA and PSA velocity measurements can be used to distinguish patients with CaP from those with histologic BPH only.

Purpose: The Prostate Cancer Prevention Trial reported that 15% of men with a prostate specific antigen less than 4 ng/ml and a normal digital rectal examination have biopsy detectable prostate cancer. However, limited published data describe the tumor features of prostate cancer detected at low prostate specific antigen levels (less than 2.5 ng/ml)., Materials and Methods: A total of 1,278 men underwent radical retropubic prostatectomy by 1 surgeon between 2003 and 2008. We describe the clinicopathological features of 77 patients with a preoperative prostate specific antigen of less than 2.5 ng/ml., Results: Of the men with a low prostate specific antigen (less than 2.5 ng/ml) tumor 51 (66%) had findings suspicious for prostate cancer on digital rectal examination. Indications for prostate biopsy in the remainder of men included an increased prostate specific antigen velocity, hematospermia and abnormal transrectal ultrasound findings. Prostate cancer was detected at transurethral resection of the prostate in the remaining 8% of men. Despite having a low prostate specific antigen at diagnosis 8 (10.4%) and 20 (26%) men, respectively, had biopsy and radical retropubic prostatectomy Gleason grade 7 disease or greater, while 7 (9%) and 6 (7.8%), respectively, had extracapsular tumor extension or positive surgical margins. Compared to men with a normal digital rectal examination mean tumor volume was significantly higher in those with a suspicious digital rectal examination (3.3 vs 1.7 cc, p = 0.018)., Conclusions: Despite having a prostate specific antigen of less than 2.5 ng/ml at diagnosis, a considerable proportion of men had aggressive pathological features at radical retropubic prostatectomy. Digital rectal examination remains an important component of early prostate cancer detection.

Purpose: Despite the tremendous stage migration associated with prostate cancer screening to our knowledge it remains unproven whether prostate specific antigen based screening decreases prostate cancer specific mortality. Recent studies have shown that prostate specific antigen velocity more than 2 ng/ml per year in the year before diagnosis is associated with a significantly greater risk of prostate cancer specific mortality after treatment. This may serve as a surrogate marker for prostate cancer outcomes. We compared the prostate specific antigen velocity profile between patients with prostate cancer in whom the tumor was detected in a formal screening study and those who were referred for treatment., Materials and Methods: We evaluated prostate specific antigen velocity in 1,101 men from a prostate cancer screening study and in 368 not enrolled in a screening study who were referred for treatment. All patients underwent radical prostatectomy for clinically localized disease and had multiple preoperative prostate specific antigen measurements to calculate prostate specific antigen velocity., Results: Median prostate specific antigen velocity before diagnosis was significantly higher in referred vs screened men (1.35 vs 0.68 ng/ml per year, p <0.0001). In addition, a significantly greater proportion of referred patients had prostate specific antigen velocity more than 2 ng/ml per year (38% vs 17%, p <0.0001). On multivariate analysis using prostate specific antigen, clinical stage and biopsy Gleason score screened vs referred status was a significant independent predictor of prostate specific antigen velocity more than 2 ng/ml per year (p <0.0004)., Conclusions: Prostate specific antigen velocity more than 2 ng/ml per year has been linked to a significantly greater risk of prostate cancer specific mortality. Patients who underwent serial screening had a more favorable prostate specific antigen velocity profile at diagnosis, suggesting that screen detected prostate cancer may be more likely to be cured with definitive therapy.