Prostate-specific Antigen Velocity Research Articles

Kinetics differences between PSA bounce and biochemical failure in patients treated with 125I prostate brachytherapy.

To determine the helpful factors to distinguish prostate-specific antigen failure from prostate-specific antigen bounce with large magnitude. From October 2004 to December 2009, 242 patients with prostate cancer treated with (125)I brachytherapy were analyzed, 88 patients were excluded because the follow-up durations were shorter than 5 years. Their median follow-up was 80.4 months (60.0-123.9). Prostate-specific antigen failure was determined using the Phoenix definition. Prostate-specific antigen bounce was defined as an increase ≥0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Prostate-specific antigen bounce +2 was defined as a prostate-specific antigen rise by 2.0 ng/ml or more above the nadir. The 5-year biochemical relapse-free survival rate was 90.2%. Prostate-specific antigen failure and prostate-specific antigen bounce +2 were seen in 23 patients (14.9%) and 12 patients (7.8%), respectively. On univariate analysis, age at implant (P = 0.028), T stage (P = 0.020), time to prostate-specific antigen failure or prostate-specific antigen bounce (time to onset) (P = 0.0008), prostate-specific antigen velocity (P = 0.0003) and prostate-specific antigen doubling time (P = 0.0004) were significant for the distinction between prostate-specific antigen failure and prostate-specific antigen bounce +2. On multivariate analysis, no factor was the statistically significant factor. On receiver operating characteristic curve analysis, time to onset with a cutoff value of 29.8 months, prostate-specific antigen velocity of 0.18 ng/ml/month and prostate-specific antigen doubling time of 6.3 months had the highest accuracy of 82.9, 82.9 and 82.9% for prostate-specific antigen failure, respectively. Time to onset, prostate-specific antigen velocity and prostate-specific antigen doubling time would be helpful for distinction between prostate-specific antigen failure and prostate-specific antigen bounce +2.

Biomarkers for Evaluation of Prostate Cancer Prognosis

Prostate cancer, with a lifetime prevalence of one in six men, is the second cause of malignancy-related death and the most prevalent cancer in men in many countries. Nowadays, prostate cancer diagnosis is often based on the use of biomarkers, especially prostate-specific antigen (PSA) which can result in enhanced detection at earlier stage and decreasing in the number of metastatic patients. However, because of the low specificity of PSA, unnecessary biopsies and mistaken diagnoses frequently occur. Prostate cancer has various features so prognosis following diagnosis is greatly variable. There is a requirement for new prognostic biomarkers, particularly to differentiate between inactive and aggressive forms of disease, to improve clinical management of prostate cancer. Research continues into finding additional markers that may allow this goal to be attained. We here selected a group of candidate biomarkers including PSA, PSA velocity, percentage free PSA, TGFβ1, AMACR, chromogranin A, IL-6, IGFBPs, PSCA, biomarkers related to cell cycle regulation, apoptosis, PTEN, androgen receptor, cellular adhesion and angiogenesis, and also prognostic biomarkers with Genomic tests for discussion. This provides an outline of biomarkers that are presently of prognostic interest in prostate cancer investigation.

PD46-03 PROSTATE CANCER DETECTION AFTER THREE NEGATIVE SCREENS WITH A 4-YEAR INTERVAL. ERSPC ROTTERDAM

You have accessJournal of UrologyProstate Cancer: Detection and Screening V1 Apr 2015PD46-03 PROSTATE CANCER DETECTION AFTER THREE NEGATIVE SCREENS WITH A 4-YEAR INTERVAL. ERSPC ROTTERDAM Monique Roobol, Daan Nieboer, and ERSPC study group Rotterdam Monique RoobolMonique Roobol More articles by this author , Daan NieboerDaan Nieboer More articles by this author , and ERSPC study group RotterdamERSPC study group Rotterdam More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2734AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Whether or not repeated PSA based screening has an effect on reduction of advanced disease/PC mortality or merely contributes to over diagnosis is still unclear. In ERSPC Rotterdam men (55 to 74 yrs)are screened with a 4-year interval. Depending age at 1st screen 5 screens are possible. Here we report on cancer detection rate (CDR), tumor characteristics and screening history of/before 4th screening round (S-round, i.e. 12 years after 1st screening and completed 3 previous screens) and assess the possibility of selective detection of potentially aggressive PC. METHODS So far 3,253 men completed 4th screening (80%). A PSA >= 3.0 ng/ml triggered sextant biopsy (Bx). PC detected were subdivided according to d'Amico classification. Baseline age and PSA, PSA and PSA density at 4th S-round and PSA velocity ((PSA-V) from 0 – 4, 0-8 and 0-12 yr) and the risk count ( # intervals that PSA-V > 0.4 ng/ml/yr) were related to PC detection at 4th screening. RESULTS Median age at 4th screening was 70.3 (67.0-75). Eligible for Bx were 666 men (20.5%) and 566 men had a Bx (85%), 59% had a previous negative Bx. A total of 133 PC cases were detected (PPV = 133/566 = 23.5% and CDR = 133/3252 = 4.1%). 107 men (80.5%) had low, 15 (11.3%) intermediate and 11 (8.3%) high risk PC (table). PSA-density and having had a previous negative Bx were significant predictors in a multivariable regression analysis (including age at 4th screening and PSA-V4) with outcome noPC+low risk PC vs. intermediate + high risk PC (AUC 0.811). At 92% sensitivity (but including all high risk PC) 221 Bx could be avoided (39%) including the diagnosis of 24 low risk PC. Risk count did not have any added value in this screening setting. CONCLUSIONS After 3 previous S-rounds, each with an interval of 4 yr, overall PPV and CDR at 4th screening are comparable to earlier S-rounds. Most PC detected are however low risk and, considering the age of men, potentially over diagnosed. However, taking into account a life expectancy of at least 10 years selective detection of potentially aggressive PC is still warranted. Especially in a repeat screening setting a multivariate risk assessment including PSA density and previous Bx status should be used in the decision to biopsy in order to avoid unnecessary testing and potential over diagnosis. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e957 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Monique Roobol More articles by this author Daan Nieboer More articles by this author ERSPC study group Rotterdam More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP86-11 PROSTATE SPECIFIC ANTIGEN VELOCITY AS A PREDICTIVE BIOMARKER IN A PROSPECTIVE PROSTATE CANCER SCREENING STUDY OF MEN WITH GENETIC PREDISPOSITION

You have accessJournal of UrologyProstate Cancer: Detection and Screening VII1 Apr 2015MP86-11 PROSTATE SPECIFIC ANTIGEN VELOCITY AS A PREDICTIVE BIOMARKER IN A PROSPECTIVE PROSTATE CANCER SCREENING STUDY OF MEN WITH GENETIC PREDISPOSITION Christina G. Selkirk, Christos Mikropoulos, Sibel Saya, Elizabeth Bancroft, Tokhir Dadaev, Charles Brendler, Elizabeth Page, Daniel A. Leongamornlert, Natalie Taylor, Edward J. Saunders, Clara Cieza-Borrela, The IMPACT study collaborators, Sue Moss, Zsofia Kote-Jarai, Brian T. Helfand, and Rosalind A. Eeles Christina G. SelkirkChristina G. Selkirk More articles by this author , Christos MikropoulosChristos Mikropoulos More articles by this author , Sibel SayaSibel Saya More articles by this author , Elizabeth BancroftElizabeth Bancroft More articles by this author , Tokhir DadaevTokhir Dadaev More articles by this author , Charles BrendlerCharles Brendler More articles by this author , Elizabeth PageElizabeth Page More articles by this author , Daniel A. LeongamornlertDaniel A. Leongamornlert More articles by this author , Natalie TaylorNatalie Taylor More articles by this author , Edward J. SaundersEdward J. Saunders More articles by this author , Clara Cieza-BorrelaClara Cieza-Borrela More articles by this author , The IMPACT study collaboratorsThe IMPACT study collaborators More articles by this author , Sue MossSue Moss More articles by this author , Zsofia Kote-JaraiZsofia Kote-Jarai More articles by this author , Brian T. HelfandBrian T. Helfand More articles by this author , and Rosalind A. EelesRosalind A. Eeles More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1920AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It has been shown that carriers of BRCA1/2 mutations are more likely to develop prostate cancer (PrCa) and that BRCA2 carriers are at risk for aggressive disease. It is unclear whether any of these men exhibit altered PSA kinetics prior to diagnosis. We therefore assessed the clinical application of prostate specific antigen velocity (PSAV) in the IMPACT study (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in men at higher genetic risk and controls). METHODS IMPACT is a case-control PrCa screening study for men with a known genetic predisposition to PrCa; participants with a single PSA reading above 3ng/ml are offered diagnostic TRUS prostate biopsy (PB). We calculated PSAV using three validated methods, including the arithmetic mean(a), the linear regression(b) and the first and last readings(c) equations. Pearson chi-square test was used to compare PSAV between four genetic groups: BRCA1 carriers and BRCA1 negative controls and BRCA2 carriers and BRCA2 negative controls in those that underwent PB. Binary Logistic Regression was used to compare PSAV between carriers who were and were not diagnosed with cancer. RESULTS PSAV was available for 191 men who underwent a PB with a total of 57 PrCas diagnosed. There was no significant difference in the median PSAV between BRCA1 carriers and non-carriers who were diagnosed with cancer (0.24 vs. 0.37 ng/ml/yr, respectively). In comparison, BRCA2 carriers who were diagnosed with cancer showed a significantly higher PSAV when compared to non-carriers (1.36 vs. 0.50 ng/ml/yr, respectively, p=<0.05). BRCA2 carriers with a PSAV over 0.75ng/ml/yr were 5 times more likely to be diagnosed with PrCa compared to non-carriers [95%CI=1.5-14; P value=0.003]. In addition, BRCA2 carriers with cancer were 3 times more likely to have a high-grade disease (Gleason score ≥7) phenotype compared to non-carriers with cancer [95% CI: 1.006-11.107; P value=0.045]. CONCLUSIONS This is the first study to document that BRCA2 carriers who develop cancer have different PSA kinetics compared to non-carriers. This increased PSAV most likely reflects prior associations with disease susceptibility, aggressive disease and PrCa specific mortality. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1079-e1080 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christina G. Selkirk More articles by this author Christos Mikropoulos More articles by this author Sibel Saya More articles by this author Elizabeth Bancroft More articles by this author Tokhir Dadaev More articles by this author Charles Brendler More articles by this author Elizabeth Page More articles by this author Daniel A. Leongamornlert More articles by this author Natalie Taylor More articles by this author Edward J. Saunders More articles by this author Clara Cieza-Borrela More articles by this author The IMPACT study collaborators More articles by this author Sue Moss More articles by this author Zsofia Kote-Jarai More articles by this author Brian T. Helfand More articles by this author Rosalind A. Eeles More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD34-06 THE EFFECT OF NSAID USE ON DISEASE PROGRESSION IN PATIENTS ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized IV1 Apr 2015PD34-06 THE EFFECT OF NSAID USE ON DISEASE PROGRESSION IN PATIENTS ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER Gautum Agarwal, Joseph Spuches, Adam Luchey, Trushar Patel, and Julio Pow-Sang Gautum AgarwalGautum Agarwal More articles by this author , Joseph SpuchesJoseph Spuches More articles by this author , Adam LucheyAdam Luchey More articles by this author , Trushar PatelTrushar Patel More articles by this author , and Julio Pow-SangJulio Pow-Sang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2242AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Up to 50% of patients with low risk prostate cancer (CaP) on an active surveillance (AS) protocol will have disease progression. There is a growing body of literature demonstrating that nonsteroidal anti-inflammatory drugs (NSAIDS) can be utilized in the prevention and treatment of different malignancies. We investigated the relationship of NSAID use on disease progression in AS patients. METHODS We reviewed the Institutional Review Board approved Moffitt Cancer Center Oncology database for patients enrolled in an AS protocol for prostate cancer from 1994-2000. Inclusion criteria for AS were: < cT2a disease, PSA < 10 ng/ml, <50% of single core involvement, and gleason score < 7, as well as sufficient follow-up for evaluation (at least 1 subsequent transrectal ultrasound guided biopsy after initial diagnosis). The medication lists for all patients were investigated for NSAID use. Progression was estimated with patients stratified by NSAID use using the Kaplan-Meier method. RESULTS One-hundred and two patients met the inclusion criteria with median age of 70 years (IQR 68-73) and a median follow up of 9.25 years (IQR 6.1 - 12.2). The median time to progression was 4.7 years (IQR 2.8 - 7.9). Among the 102 patients, 51 (50%) were found to be NSAID users. There were no significant differences between the two groups on univariate analysis with respect to the median values for Age, PSA velocity, PSA doubling time, Gleason score, and follow up time. However, the non NSAID users were found to have higher median initial PSA, PSA density and lower body mass index. On multivariate analysis using binary logistic regression models taking into account NSAID use, initial PSA, age, PSA velocity, PSA doubling time, PSA density, and BMI; only NSAID use was significantly associated with stability of disease (OR 14.4, p=0.027). CONCLUSIONS NSAID use was associated with stability of disease on long term follow up in patients on AS for prostate cancer. This is consistent with previous studies suggesting antineoplastic properties of NSAID use. Further prospective trials of NSAID use for the prevention and treatment of prostate cancer are warranted. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e756-e757 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gautum Agarwal More articles by this author Joseph Spuches More articles by this author Adam Luchey More articles by this author Trushar Patel More articles by this author Julio Pow-Sang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP60-07 CONFIGURATION AND VALIDATION OF A NOVEL PROSTATE DISEASE NOMOGRAM PREDICTING PROSTATE BIOPSY OUTCOME: A PROSPECTIVE STUDY CORRELATING CLINICAL INDICATORS AMONG FILIPINO ADULT MALES WITH ELEVATED PSA LEVEL

You have accessJournal of UrologyProstate Cancer: Detection and Screening II1 Apr 2015MP60-07 CONFIGURATION AND VALIDATION OF A NOVEL PROSTATE DISEASE NOMOGRAM PREDICTING PROSTATE BIOPSY OUTCOME: A PROSPECTIVE STUDY CORRELATING CLINICAL INDICATORS AMONG FILIPINO ADULT MALES WITH ELEVATED PSA LEVEL Michael Chua, Patrick Tanseco, Jonathan Mendoza, Josefino Castillo, Marcelino Morales, and Saturnino Luna Michael ChuaMichael Chua More articles by this author , Patrick TansecoPatrick Tanseco More articles by this author , Jonathan MendozaJonathan Mendoza More articles by this author , Josefino CastilloJosefino Castillo More articles by this author , Marcelino MoralesMarcelino Morales More articles by this author , and Saturnino LunaSaturnino Luna More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2209AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To configure and validate a novel prostate disease nomogram providing prostate biopsy outcome probabilities from a prospective study correlating clinical indicators and Prostate specific antigen (PSA) derivatives among Filipino adult male with elevated serum total PSA level. METHODS A prospective study of all men with an elevated serum total PSA underwent initial prostate biopsy at a tertiary institution from January 2011 to August 2014. Clinical indicators, diagnostic parameters, PSA level and PSA derivatives, were collected and considered as predictive factors for biopsy outcome. Multiple logistic regression analysis involving a backward elimination selection procedure was used to select independent predictors. A nomogram model was developed that was based on independent predictors to calculate the probability of the biopsy outcomes. A receiver-operating characteristic (ROC) curve was used to assess the accuracy of the nomogram and PSA levels alone in predicting differential biopsy outcome. External validation of the nomogram was done using separate set of patients' data from another center for determination of sensitivity and specificity. The protocol of this study was reviewed and approved by the Institutional Scientific Review Board (ISRB), Institutional Ethics Review Board (IERB), and registered at Clinicaltrial.gov (Identifier: NCT01826617) RESULTS A total of 552 patients were referred to our institution for initial prostate biopsy. 191 (34.6%) patients had benign prostatic hyperplasia, 165 (30%) had prostatitis, particularly chronic type. The remaining 196 patients (35.5%) had prostate adenocarcinoma. Number of patients according to Gleason scoring classification of the prostate cancer ≥8, 7 and 6, were 82 (42%), 66 (33.7%), 48 (24.5), respectively. The significant independent variables used to predict biopsy outcome were age, family history of prostate cancer, prior prostatitis, PSA level, PSA density, PSA velocity, echogenic findings on ultrasound and DRE status. The areas under the ROC curve for prostate cancer using PSA alone and the nomogram were 0.688 and 0.804, respectively. CONCLUSIONS The nomogram configured based on routinely available clinical parameters and PSA derivatives, provides high predictive accuracy with good performance characteristics in predicting the prostate biopsy outcome such as presence of prostate cancer, high Gleason prostate cancer, benign prostatic hyperplasia and chronic prostatitis. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e740 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Chua More articles by this author Patrick Tanseco More articles by this author Jonathan Mendoza More articles by this author Josefino Castillo More articles by this author Marcelino Morales More articles by this author Saturnino Luna More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP42-01 NO SIGNIFICANT IMPROVEMENT IN PATIENT OUTCOMES WHEN STRICTER ACTIVE SURVEILLANCE CRITERIA ARE APPLIED: A COMPARISON OF CONTEMPORARY ACTIVE SURVEILLANCE PROTOCOLS

INTRODUCTION AND OBJECTIVES: Activesurveillance (AS) is of growing interest as an alternative to radical treatment of low-risk prostate cancer (PCa). However various surveillance eligibility criteria and protocols exist with no consensus among stakeholders as to which criteria and protocol yield the best results for the most patients. Our aim is to discern between the outcomes of stricter versus more inclusive AS protocols and elucidatewhether oneprovidesmore favorable outcomes formost patients. METHODS: Between 1998-2014, 912 men enrolled in an AS program at Princess Margaret Cancer Centre (PM) between, with the following inclusioncriteria:PSA 10, clinical stage cT2,Gleasonsum 6, number of positive cores 3, no single core>50% involved, age 75 years. All patients who met the set criteria were retrospectively reviewed and assessed for entry eligibility into: Prostate Cancer Research International: Active Surveillance (PRIAS), John Hopkins Medical Institute (JH), University of Miami (UM), University of California, San Francisco (UCSF), Memorial Sloan-Kettering Cancer Center (MSK) and University of Toronto (UT).We also considered how the use of the various protocols would alter the timing and utilization of curative intervention. Univariate and multivariate statistics with Cox proportional hazards were used for comparisons. Logistic regression was used to determine any significant associations. All statistical analysis was done using SAS . RESULTS: From 912 men enrolled over the 16 year period, 712 met PM inclusion criteria. When JH, PRIAS, and UM criteria were applied to these patients 13.7%, 11.5%, and 8.8% of these men were excluded from AS. However, when we compared outcomes such as grade or volume progression there were no significant differences between men who met the PM criteria and those who met stricter AS criteria. No significant differences in PSA velocity, or the number of patient who proceeded to seek treatment (p>0.1). Time to treatment and follow-up were also not significantly different between men who were followed on a more inclusive versus more exclusive AS protocols. CONCLUSIONS: While there are differences in inclusion criteria for AS, our results demonstrate that more strict criteria do not significantly improve patient outcomes when considering relative risk of Gleason Score upgrading, or biochemical failure after treatment. In an era of heightened awareness regarding over-diagnosis and overtreatment of prostate cancer, we believe that these stricter entry criteria should be reconsidered.

Association of ERG-PTEN expression profile of prostate biopsy with PSA velocity.

92 Background: Although ERG and PTEN expression has demonstrated to have a role in prostate carcinogenesis, its association with important clinical markers such as PSA velocity (rate of prostate specific antigen [PSA] change over time) is currently unknown. This novel pilot study presents the results of the above association with the aim of understanding its clinical utility. Methods: Data for this study was obtained from men enrolled in a phase 2 clinical trial conducted to determine the effect of selenium supplementation on prostate cancer progression. All men in this trial were diagnosed with prostate cancer and opted for watchful waiting as their treatment modality. Biopsy tissue collected at randomization was stained for ERG and PTEN using immunohistochemistry techniques. PSA was measured at baseline and at each follow-up visit (every three months). PSA velocity was calculated using mixed effects regression models and the study group was divided into three tertiles. Results: Data from 77 subjects indicates ERG and PTEN expression is independently associated with lower PSA velocity (p = 0.02 and 0.037 respectively). Joint effect of ERG and PTEN expression on PSA velocity was also analyzed using logistic regression. As compared to the wild type (ERG+/PTEN-), ERG-/PTEN- and ERG-/PTEN+ subjects demonstrated increased risk for high PSA velocity. Odds ratios (95% confidence intervals) are: 4.05 (0.68, 24.1) and 1.71 (0.12, 23.1), respectively. These models were adjusted for age, race and Gleason score. Conclusions: This is the first study to report on an association between ERG-PTEN expression and PSA velocity, an important clinical marker of aggressive prostate cancer. Results of this study are counterintuitive to the current understanding of ERG-PTEN mechanism in prostate carcinogenesis indicating presence of yet undiscovered molecular pathways. Hence further research is needed to delineate these pathways and determine clinical utility of ERG and PTEN expression in prostate cancer.

Evaluation of 3 T pelvic MRI imaging in prostate cancer patients receiving postprostatectomy IMRT.

242 Background: The purpose of the study was to evaluate the utility of a 3 T pelvic magnetic resonance imaging (MRI) in detecting a local recurrence in post-prostatectomy prostate cancer patients prior to receiving adjuvant or salvage intensity-modulated radiation therapy (IMRT). Methods: Ninety prostate cancer patients status post-prostatectomy with rising prostate-specific antigen (PSA) had a 3 T pelvic MRI prior to IMRT. The following variables were analyzed for predicting positive findings on MRI: initial presenting and initial post-op PSA, PSA at the time of imaging, PSA velocity, surgical margins, Gleason score, pathological stage, pre-RT digital rectal examination, and type of surgical prostatectomy. Results: The only significant variable predictive of a positive MRI was positive margins. Specifically, 15 of 46 (33 %) patients with positive margins had a positive MRI, while 5 of 44 (11 %) patients with negative margins had a positive MRI. In the MRI positive group, the location of the positive findings on MRI corresponded with the pathology report in 9 of 12 (75 %) cases. Conclusions: Post-prostatectomy patients with pathologic positive margins are three times more likely to have positive findings on a 3 T MRI. [Table: see text]

Prostate-specific antigen velocity as a predictive biomarker in a prospective prostate cancer screening study (IMPACT study).

16 Background: We retrospectively assessed the clinical application of Prostate Specific Antigen Velocity (PSA V) in the IMPACT study (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in men at higher genetic risk and controls). This is a case-control prostate cancer (PrCa) screening study for men with a known genetic predisposition to PrCa; participants with a single PSA reading above 3ng/ml are offered diagnostic TRUS prostate biopsies (PB). Methods: We calculated PSA velocity (PSA V) using all three validated methods, including the arithmetic mean, the linear regression and the first and last readings equations. Pearson chi-square test was used to compare PSA V between four genetic groups: BRCA1 carriers and BRCA1 negative controls and BRCA2 carriers and BRCA2 negative controls. Results: PSA V data were evaluated in 191 men who underwent a PB with a total of 57 PrCas diagnosed. PSA V using both a threshold of 0ng/ml/year and 0.75ng/ml/year in any of the three methods was not predictive of PrCa diagnosis in BRCA1/2 controls and BRCA1 carriers. Conversely, BRCA2 carriers with a PSA V over 0.75ng/ml/year (by linear regression) were 5 times more likely to be diagnosed with PrCa [95%CI=1.5-14; p=0.003]. Interestingly PSA V using linear regression was predictive of clinically significant tumours as defined by Gleason Score (GS) &gt;= 7. Regardless of their genetic status, men with a PSA V over 0.75/ng/ml/year were 3 times more likely to have a clinically significant PrCa [95% CI: 1.006-11.107; p=0.045] whereas men with a BRCA2 mutation were 12 times more likely [95%CI: 1.1-98; p=0.039]. Conclusions: PSA V is an important tool for identifying which men with a BRCA2 mutation would benefit from a prostatic biopsy and could be incorporated into a predictive model, along with the total PSA value. PSA V also predicts for tumour aggressiveness regardless of genetic predisposition, but more so for those with a known high risk gene mutation. Clinical trial information: NCT00261456.

Testosterone levels in metastatic castration-resistant prostate cancer (mCRPC).

191 Background: It is common practice to continue anti-androgen therapy in terms of androgendeprivation when performing chemotherapy or androgendeprivation with new second generation therapeutic agents such as enzalutamide or abiraterone acetate. Clinical Studies aiming at the question whether continuation of conventional ADT is necessary in this setting are currently recruiting. In this study we analyzed androgen deprivation in patients with mCRPC under chemotherapy and second generation androgen suppression. Methods: Out of 620 screened patients a total of 36 patients with continuous testosterone monitoring and mCRPC underwent therapy with docetaxel, abiraterone acetate, enzalutamide, carboplatin, carbozantinib or cabazitaxel and were evaluated. Data were gathered from our center over a median follow up period of 27.8 (0.6 - 65.1) month. A cutoff of 0.5 ng/dL was used to discriminate patients according to testosterone castration levels. Statistical evaluation was performed applying Kaplan Meier survival estimates, Cox regression and log rank test. Results: Median follow up was 26.2 month (range 1.4 - 64.8 month). Mean patient age was 70.9 years (range 51 - 86 years). The mean testosterone concentration in our cohort was 0.5 ng/dL. Serum testosterone levels varied greatly: ranging from 0 to 16 ng/dL. A total of 18 patients died during follow up. Median survival over all patients according to Kaplan-Meier survival estimation was 38.7 month (95% CI: 31 - NA month). Median survival for patients with testosterone levels below and above 0.5 ng/dL were 48.67 and 18.13 month respectively (log rank test: p = 0.0029). In Cox regression analysis, the hazard ratio for risk of death for patients with testosterone concentrations &gt; 0.5ng/dL was 6.03 (95% CI: 1.5 - 25, p - 0.0132). For the covariates PSA velocity, patient age and primary Gleason score there was no significant effect on risk of death (p = 0.0597, 0.5006, 0.7354). Conclusions: In patients with mCRPC i.e rising PSA or progression under androgen deprivation, conventional suppression of testosterone levels still represents a vital factor for overall survival even at the mCRPC stage and under therapy with second line anti hormonal therapeutic medication and chemotherapy.

Prostate-specific antigen kinetics after primary stereotactic body radiation therapy using CyberKnife for localized prostate cancer.

PurposeTo assess prostate-specific antigen (PSA) kinetics and report on the oncologic outcomes for patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT) using CyberKnife.MethodsWe extracted the list and data of 39 patients with clinically localized prostate cancer who had undergone primary SBRT using CyberKnife between January 2008 and December 2012 from the Smart Prostate Cancer database system of Seoul St. Mary's Hospital. Changes in PSA over time, PSA velocity, and PSA nadir were evaluated from the completion of SBRT using CyberKnife. Biochemical recurrence (BCR)-free survival after primary SBRT using CyberKnife was determined using Kaplan–Meier analysis.ResultsThe rate of PSA decrease was maximal in the first month (median −3.34 ng/mL/mo), which then fell gradually with median values of −1.51, −0.32, −0.28, −0.20, and −0.03 ng/mL/mo for durations of 3, 6, 9, 12, and 24 months after SBRT using CyberKnife, respectively. The median PSA nadir was 0.31 ng/mL after a median 23 months. Kaplan–Meier analysis calculates an actuarial 5-year BCR-free survival after SBRT using CyberKnife as 80.8%.ConclusionsPSA decline occurred rapidly in the first month, and then the rate of PSA decline fell off steadily over time throughout 2 years after treatment. Also, SBRT using CyberKnife leads to long-term favorable BCR-free survival in localized prostate cancer.

Multiparametric magnetic resonance imaging predicts the presence of prostate cancer in patients with negative prostate biopsy

ObjectiveTo assess the ability of multiparametric prostate magnetic resonance imaging (mpMRI) to detect prostate cancer in patients with prior negative transrectal prostate biopsy (TPB). Materials and methodsmpMRI (TSE-T2-w, DWI and DCE sequences) was performed on 1.5T (Magnetom Avanto; Siemens Healthcare Solutions) in 150 patients suspicious of prostate cancer and with negative TPB. European Society of Urogenital Radiology (ESUR) criteria were used (score 1: clinically significant disease is highly unlikely to be present; score 2: clinically significant cancer is unlikely to be present; score 3: clinically significant cancer is equivocal; score 4: clinically significant cancer is likely to be present; score 5: clinically significant cancer is highly likely to be present). PSA measurement (total and free), digital rectal examination (DRE), transrectal ultrasound (TRU) and a second TPB (at least 14 cylinders) were performed in all patients. Variables were submitted for independent blind analysis. The accuracy of each test was measured. Stepwise selection model for prediction of prostate cancer in second TPB was developed. ResultsMean age was 66.2±5 years (51–77), mean PSA 11.3±9.6ng/mL (0.9–75) and mean prostatic volume 82.2±42 (20–250) cc. DRE was suspicious in 11 (7.3%) patients. The mean number of cylinders per patient sampled in second TRB was 17.6±2.7(14–22). Second TRB was positive in 28 patients (18.7%). mpMRI was positive (score 3–5) in 102 (68%), test sensibility was 92.9% and the NPV was 95.8%. The risk of prostate cancer diagnosis in second TPB is modified by: PSA velocity >0.75 (OR 1.04 [0.99–1.08]; p=0.06), free/total ratio PSA <15% (OR 0.37 [0.13–1.05]; p=0.06), each cc. of prostate volume (OR 0.98 [0.97–1]; p=0.017) and mpMRI 3–5 (OR 7.87 [1.78–34.7]; p=0.006). Multivariate analysis reveals that mpMRI (OR 7.41 [1.65–33.28]; p=0.009) and prostatic volume (OR 0.31 [0.12–0.78]; p=0.01) are independent risk predictors of prostate cancer. ConclusionsAccording to ESUR guidelines and in patients with prior negative prostate biopsy, mpMRI is a valuable tool for the prediction of prostate cancer in second TPB. Lower the prostate volume, the higher the reliability.

Effect of Patient Demographic Characteristics and Radiation Timing on PSA Reduction in Patients Treated With Definitive Radiation Therapy for Prostate Cancer

IntroductionThe purpose of this study was to assess how demographic characteristics and temporal factors including time to treatment (TTT) and elapsed time of treatment (ETT) affect prostate-specific antigen (PSA) levels during and after radiation treatment for low- and intermediate-risk prostate cancer. Patients and MethodsA retrospective review of 1584 patients was conducted on patients diagnosed with prostate cancer between 2005 and 2013, from which 147 patients were found to have completed definitive external beam radiation therapy (EBRT) monotherapy. Demographic data, TTT (days between diagnosis and EBRT start date), ETT (days between EBRT start and stop date), and Gleason score were collected on these patients and analysis of variance was performed to analyze the relationship of these factors with PSA changes. PSA changes were calculated during treatment as the difference between pre- and posttreatment PSA levels and after treatment as 3-year and overall PSA velocities. ResultsPatients who spoke Haitian Creole (P = .039) and those with a longer ETT (P = .029) had significantly greater PSA decline during treatment, primarily as a result of higher pretreatment PSA levels. Patients with Gleason score 4+3 disease had significantly greater 3-year (P = .033) and overall (P = .019) PSA velocities. Race and/or ethnicity, insurance type, marital status, and age were not associated with any PSA variable. ConclusionDisparities in prostate cancer are not reflected in PSA dynamics during or after radiation treatment, but are evident in PSA level at presentation. Timeliness of treatment was not found to affect true PSA change due to EBRT in low- and intermediate-risk prostate cancer patients.

Editorial Comment

The challenge of trying to reduce additional biopsies in men with an elevated prostate-specific antigen (PSA) level and an initial negative biopsy result is nothing new to the clinical urologist. Plausible approaches currently include the use of additional markers (such as free PSA, urinary PCA3, OPKO 4Kscore, or Prostate Health Index testing) and/or magnetic resonance imaging of the prostate. PSA velocity (PSAV) has been shown to be unreliable in untreated men, whereas in men receiving 5α-reductase inhibitor (5ARI), PSAV has been shown to be beneficial. 1 Marberger M. Freedland S.J. Andriole G.L. et al. Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study. BJUI. 2011; 109: 1162-1169 Crossref PubMed Scopus (39) Google Scholar In this study, the authors reanalyzed data from the REDUCE trial to further define the benefit of PSA and PSAV in this group of men. 2 Andriole G.L. Bostwick D.G. Brawley O.W. et al. Effect of dutasteride on the risk of prostate cancer. NEJM. 2010; 362: 1192-1202 Crossref PubMed Scopus (879) Google Scholar Unfortunately, their analysis is not ideal as their assumption that serum PSA level will nadir within 6 months of initiating dutasteride therapy is inaccurate. In fact, only 13% of dutasteride-treated men in REDUCE achieved nadir by 6 months. 1 Marberger M. Freedland S.J. Andriole G.L. et al. Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study. BJUI. 2011; 109: 1162-1169 Crossref PubMed Scopus (39) Google Scholar It is for this reason that our prior analysis of the utility of PSA in dutasteride-treated men considered rise from nadir rather than as rise from a specific time point after initiating therapy. In our analysis, a PSA rise from nadir in a dutasteride-treated man was superior to the then (2011) relevant National Comprehensive Cancer Network PSAV guideline for untreated men. Decision Analysis of Dutasteride Use for Patients With Negative Prostate BiopsyUrologyVol. 85Issue 2PreviewTo determine whether the additional benefits of improved prostate cancer detection associated with 5α-reductase inhibitors are sufficient to warrant chemoprevention in the case where the degree of prostate cancer risk reduction is deemed inadequate. Full-Text PDF ReplyUrologyVol. 85Issue 2PreviewIt may well be true that our analysis “is not ideal” (after all, is any?). The key question is whether taking an alternative approach would change our conclusions. We repeated all analyses measuring change in prostate-specific antigen (PSA) level from nadir instead of change from 6 months. As the authors of the letter point out, this led to different estimates for many individual patients. However, this did not affect our conclusions at the group level. In no case did measuring from nadir instead of from 6 months lead to consistent changes in either inference or estimation. Full-Text PDF

Decision Analysis of Dutasteride Use for Patients With Negative Prostate Biopsy

To determine whether the additional benefits of improved prostate cancer detection associated with 5α-reductase inhibitors are sufficient to warrant chemoprevention in the case where the degree of prostate cancer risk reduction is deemed inadequate. We reanalyzed data from REDUCE, a randomized trial of dutasteride for prostate cancer chemoprevention in men with prior negative biopsy. We evaluated whether statistical models using prostate-specific antigen (PSA) and PSA velocity could help predict the result of repeat prostate biopsy separately for dutasteride and placebo groups. Area under the curve was evaluated by 10-fold cross-validation. PSA velocity improved discrimination at 4 years in the dutasteride group but not at 2 years nor in the placebo group. At 2 years, dutasteride improved discrimination of PSA slightly (0.616 vs. 0.603 for any grade cancer; 0.681 vs. 0.676 for high-grade disease). Between-group differences in cancer rates at 4 years were small. Clinicians who are willing to treat at least 23 patients with dutasteride for 2 years to avoid 1 prostate cancer diagnosis should offer dutasteride after initial negative biopsy. Clinicians not willing to do so might consider dutasteride for its additional benefit of reducing unnecessary biopsy, although this benefit is apparent only under very restrictive conditions. It is difficult to justify extending treatment with dutasteride for >2 years.

MR imaging-guided prostate biopsy: technical features and preliminary results.

Repeatedly negative prostate biopsies in individuals with elevated prostate-specific antigen (PSA) levels can be frustrating for both the patient and the urologist. This study was performed to investigate if magnetic resonance imaging (MRI)-guided transrectal biopsy (MRGB) increases diagnostic performance in individuals with suspected prostate cancer (PCa). Twenty-three consecutive men with a total PSA >4ng/mL, PSA density >0.15, PSA velocity >0.75ng/mL/year and suspicious MRI findings were included (average age 64years; age range 53-75years; total PSA levels ranging from 4.7 to 54ng/mL; median 9ng/mL). MRGB was performed with a closed unit at 1.5Tesla, an MRI compatible biopsy device, a needle guide, and a titanium double-shoot biopsy gun. At prebiopsy MRI, in the 23 patients, a total of 26 suspicious areas to which the MRGB should be directed were found, 23 of them in the peripheral zone and three in the transitional zone. The needle guide was depicted and could be positioned with MRI guidance in all 23 patients. The duration of the procedure ranged from 35 to 55min (mean 40min). MRGB was well tolerated by all patients, and no major complications were observed. The detection rate for the diagnosis of PCa was 80, and 90% of detected PCa were of intermediate aggressiveness. MRGB has the potential to improve cancer detection rates in men with suspected PCa to deliver the relevant treatment as soon as possible.

Significant increase in detection of prostate cancer recurrence following radical prostatectomy with an early imaging acquisition protocol with ¹⁸F-fluorocholine positron emission tomography/computed tomography.

To highlight a new imaging acquisition protocol during (18)F-fluorocholine PET/CT in patients with biochemical recurrence after RP. A total of 146 patients with PSA levels between 0.2 and 1 ng/ml with negative conventional imaging who did not receive salvage treatment were prospectively enrolled. Imaging acquisition protocol included an early dynamic phase (1-8 min), a conventional whole body (10-20 min), and a late phase (30-40 min). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were measured. Univariable and multivariable analyses were performed to identify independent predictors of positive PET/CT. The median trigger PSA was 0.6 ng/ml (IQR 0.43-0.76). Median PSA doubling time (PSA DT) was 7.91 months (IQR 4.42-11.3); median PSA velocity (PSAV) was 0.02 ng/ml per month (IQR 0.02-0.04). Overall, (18)F-fluorocholine PET/CT was positive in 111 of 146 patients (76 %). Out of 111 positive examinations, 80 (72.1 %) were positive only in the early dynamic phase. Sensitivity, specificity, PPV, NPV, and accuracy were 78.9, 76.9, 97.2, 26.3, and 78.7 %, respectively. At multivariable logistic regression, trigger PSA ≥ 0.6 ng/ml [odds ratio (OR) 3.13; p = 0.001] and PSAV ≥ 0.04 ng/ml per month (OR 4.95; p = 0.004) were independent predictors of positive PET/CT. The low NPV remains the main limitation of PET/CT in this setting of patients. The increased sensitivity, thanks to the early imaging acquisition protocol, makes (18)F-fluorocholine PET/CT an attractive tool to detect prostate cancer recurrences in patients with a PSA level <1 ng/ml.

Can Prostate-Specific Antigen Kinetics before Prostate Biopsy Predict the Malignant Potential of Prostate Cancer?

PurposeTo predict the malignant potential of prostate cancer (PCa) according to prostate-specific antigen velocity (PSAV), PSA density (PSAD), free/total PSA ratio (%fPSA), and digital rectal examination (DRE).Materials and MethodsFrom January 2009 to December 2012, 548 adult male patients were diagnosed with PCa by prostate biopsy at four hospitals in Korea. We retrospectively analyzed 155 adult male patients with an initial PSA level ≤10 ng/mL and whose PSA levels had been checked more than two times at least 6 months before they had been diagnosed with PCa, with test intervals of more than 3 months. Patients with a urinary tract infection, and patients who had previously undergone cystoscopy or surgery of the prostate were excluded. We separated patients into two groups according to Gleason sum [Gleason sum ≤7 (n=134) or Gleason sum ≥8 (n=21)] and the presence of extracapsular invasion [organ confined (n=129) or extracapsular invasion (n=26)]. Differences between the groups were compared.ResultsThe group with a Gleason sum ≥8 or extracapsular invasion of PCa showed high PSAV and significantly lower %fPSA. There were no significant differences in PSAD and the presence of an abnormality on DRE between two groups.ConclusionIn PCa patients treated with other therapies besides prostatectomy, a high PSA velocity and a low %fPSA may predict high grade PCa with a Gleason sum ≥8 or the presence of extracapsular invasion.

Prostate Specific Antigen as a Tumor Marker in Prostate Cancer: Biochemical and Clinical Aspects.

In this chapter the use of prostate specific antigen (PSA) as a tumor marker for prostate cancer is discussed. The chapter provides an overview of biological and clinical aspects of PSA. The main drawback of total PSA (tPSA) is its lack of specificity for prostate cancer which leads to unnecessary biopsies. Moreover, PSA-testing poses a risk of overdiagnosis and subsequent overtreatment. Many PSA-based markers have been developed to improve the performance characteristics of tPSA. As well as different molecular subforms of tPSA, such as proPSA (pPSA) and free PSA (fPSA), and PSA derived kinetics as PSA-velocity (PSAV) and PSA-doubling time (PSADT). The prostate health index (phi), PSA-density (PSAD) and the contribution of non PSA-based markers such as the urinary transcripts of PCA3 and TMPRSS-ERG fusion are also discussed. To enable further risk stratification tumor markers are often combined with clinical data (e.g. outcome of DRE) in so-called nomograms. Currently the role of magnetic resonance imaging (MRI) in the detection and staging of prostate cancer is being explored.