Prostate-specific Antigen Cutoff Research Articles

Whole-body tumour burden on [18F]DCFPyL PET/CT in biochemical recurrence of prostate cancer: association with tumour biology and PSA kinetics.

The objective was to assess the association between molecular imaging (mi) variables on [18F]DCFPyL-PET/CT with clinical and disease characteristics and prostate specific antigen (PSA) related variables in patients with biochemical recurrence of prostate cancer (BRPC). We analysed patients with BRPC after radical treatment. We obtained clinical and PSA variables: International Society of Urology Pathology (ISUP) grade group, European Association of Urology (EAU) risk classification, PSA (PSA≤1ng/ml, 1<PSA≤2, PSA>2), PSA doubling time (PSAdt) and PSA velocity (PSAvel). All PET/CT scans were reviewed with the assistance of automated Prostate Molecular Imaging Standardized Evaluation (aPROMISE) software and lesions' segmentation in positive scans was performed using this platform. Standardized uptake value (SUV) derived variables; tumour burden variables [whole-body tumour volume (wbTV), whole-body tumour lesion activity (wbTLA) and whole-body mi PSMA (wbPSMA)] and miTNM staging were obtained. Cut-off of PSA and kinetics able to predict PET/CT results were obtained. Associations between disease and mi variables were analysed using ANOVA, Kruskal-Wallis and Spearman's correlation tests. Multivariate analysis was also performed. Two hundred and seventy-five patients were studied. [18F]DCFPyL-PET/CT were positive in 165/275 patients. In multivariate analysis, moment of biochemical recurrence, ISUP group, PSA level and PSAvel showed significant association with the detection rate. miTNM showed significant association with PSA level (p<0.001) and kinetics (p<0.001), being higher in patients with metastatic disease. Both PSA and PSAvel showed moderate correlation with wbTV, wbTLA and wbPSMA (p<0.001). A weak correlation with SUVs was found. Mean wbTV, wbTLA and wbPSMA values were significantly higher in PSA > 2ng/ml, PSAdt ≤ 6 months and PSAvel ≥ 0.2ng/ml/month groups. Also, wbTV (p=0.039) and wbPSMA (p=0.020) were significantly higher in patients with ISUP grade group 5. PSA and PSAvel cut-offs (1.15 ng/ml and 0.065 ng/ml/month) were significantly associated with a positive PET/CT. Higher PSA values, unfavourable PSA kinetics and ISUP grade group 5 were robust predictive variables of larger tumour burden variables on [18F]DCFPyL PET/CT assessed by aPROMISE platform.

Screening for prostate cancer in a city in Japan: age-specific prostate-specific antigen cutoff thresholds.

Older men have higher prostate-specific antigen levels than younger men. However, the current Japanese Urological Association guidelines recommend secondary screening at a cutoff value of 4.0ng/mL, even in older men. Here, we reexamined the cutoffs for older men using a prostate screening cohort in Japan and first performed an analysis to determine the indication cutoffs for detecting positive biopsies. Data from 68,566 prostate cancer screenings in the city in 2018 were combined with cancer registration data. The optimal prostate-specific antigen levels to predict prostate cancer in different age groups were calculated using receiver operating characteristic curves after determining whether a cancer was registered within one year of screening. At the conventional prostate-specific antigen threshold of 4.0ng/mL, the sensitivity, specificity, and negative predictive value were 94.9%, 91.7%, and 91.7%, respectively. The optimal prostate-specific antigen cutoff values for patients aged 50-59years, 60-69years, 70-79years, and over 80years were 3.900ng/mL, 4.014ng/mL, 4.080ng/mL, and 4.780ng/mL, respectively. The sensitivity and specificity of prostate cancer screening in the city were high, indicating a highly accurate screening. The prostate-specific antigen threshold was 4.78ng/mL in patients older than 80years. A higher prostate-specific antigen threshold may be useful in men over 80years of age to avoid excess biopsy and reduce costs. Our results suggest that the current Japanese method of using PSA 4.0ng/mL as a cutoff regardless of age may not be preferable for older men.

Age-specific percentile-based prostate-specific antigen cutoff values predict the risk of prostate cancer: A single hospital observation.

Testing for prostate-specific antigen (PSA) is often recommended for men with a potential risk of prostate cancer (PCa) before requiring advanced examination. However, the best PSA cutoff value remains controversial. We compared the predictive performance of age-specific percentile-based PSA thresholds with a conventional cutoff of >4 ng/mL for the risk of PCa. We included men who received PSA measurements between 2003 and 2017 in a medical center in Taiwan. Logistic regression modeling was used to assess the association between age-specific percentile-based PSA thresholds and PCa risk in age subgroups. We further applied C-statistic and decision curve analysis to compare the predictive performance of age-specific percentile-based PSA with that of a conventional cutoff PSA. We identified 626 patients with PCa and 40 836 patients without PCa. The slope of PSA in patients >60-year-old was almost 3 times that of those <60-year-old (0.713 vs 0.259). The risk effect sizes of the 75th percentile PSA cutoff (<60-year-old: 2.19; 60-70-year-old: 4.36; >70-year-old: 5.84 ng/mL) were comparable to those observed based on the conventional cutoff in all age groups. However, the discrimination performance of the 75th percentile PSA cutoff was better than that of the conventional cutoff among patients aged <60-year-old (C-statistic, 0.783 vs. 0.729, p < 0.05). The 75th percentile cutoffs also correctly identified an additional 2 patients with PCa for every 100 patients with PSA screening at the threshold probability of 20%. Our data support the use of the 75th percentile PSA cutoff to facilitate individualized risk assessment, particularly for patients aged <60-year-old.

Prostate specific antigen-age volume score in predicting prostate cancer among the Indonesian population

Link of Video Abstract: https://youtu.be/ZNusQRjFEH0 Introduction: Several methods have been explored to increase the effectiveness of prostate-specific antigen (PSA) for prostate cancer screening. A lower prostate-specific antigen-age volume (PSA-AV) score is associated with higher cancer risk. This study aimed to evaluate the value of PSA-AV scores in the detection of prostate cancer among the Indonesian population. Methods: A retrospective study was conducted on 844 prostate biopsies performed at our center between January 2015 and December 2019. The score of PSA-AV was derived by multiplication of the patient's age and prostate volume and then division with PSA level. A ROC curve analysis was conducted to determine the cutoff for the PSA-AV score. The sensitivities and specificities of the PSA-AV score were contrasted with total PSA, PSA density, and age-adjusted PSA. Results: The mean age of the patient was 63.63±8.6 years, with a mean PSA of 16.3±13.9 ng/mL and a mean volume of 42.7±16.0 cm3. Among 844 biopsies, 25.5% tested positive for prostate cancer. Prostate cancer patients had significantly higher mean age, PSA levels, and positive digital rectal examinations (P&lt;0.05). In predicting prostate cancer, the PSA-AV score demonstrated a higher AUC of 0.772, surpassing the AUC of 0.762 achieved by the total PSA. The analysis identified a cutoff of 700 for the PSA-AV score, which showed significant sensitivity (94%) and sufficient specificity (8.4%). These values outperformed the total PSA cutoff of 4 ng/mL (sensitivity 91.6%; specificity 5.4%), PSA density cutoff of 0.15 (sensitivity 85.1%; specificity 30.0%), and age-adjusted PSA cutoff (sensitivity 88.4%; specificity 11.8%). The superiority of the PSA-AV score of &lt;700 was more prominent in the subgroup analysis of patients below 70 years of age and those with a low-moderate prostate volume (&lt;60 cm3). Conclusions: The PSA-AV score demonstrated superior sensitivities and specificities compared to total PSA, PSA density, and age-adjusted PSA. Therefore, it is recommended to utilize a PSA-AV score of &lt;700, particularly for men below 70 years of age with low-moderate prostate volumes (&lt; 60 cm3).

Re-evaluating the diagnostic efficacy of PSA as a referral test to detect clinically significant prostate cancer in contemporary MRI-based image-guided biopsy pathways.

Modern image-guided biopsy pathways at diagnostic centres have greatly refined the investigations of men referred with suspected prostate cancer. However, the referral criteria from primary care are still based on historical prostate-specific antigen (PSA) cut-offs and age-referenced thresholds. Here, we tested whether better contemporary pathways and biopsy methods had improved the predictive utility value of PSA referral thresholds. PSA referral thresholds, age-referenced ranges and PSA density (PSAd) were assessed for positive predictive value (PPV) in detection of clinically significant prostate cancer (csPCa - histological ⩾ Grade Group 2). Data were analysed from men referred to three diagnostics centres who used multi-parametric magnetic resonance imaging (mpMRI)-guided prostate biopsies for disease characterisation. Findings were validated in a separate multicentre cohort. Results: Data from 2767 men were included in this study. The median age, PSA and PSAd were 66.4 years, 7.3 ng/mL and 0.1 ng/mL2, respectively. Biopsy detected csPCa was found in 38.7%. The overall area under the curve (AUC) for PSA was 0.68 which is similar to historical performance. A PSA threshold of ⩾ 3 ng/mL had a PPV of 40.3%, but this was age dependent (PPV: 24.8%, 32.7% and 56.8% in men 50-59 years, 60-69 years and ⩾ 70 years, respectively). Different PSA cut-offs and age-reference ranges failed to demonstrate better performance. PSAd demonstrated improved AUC (0.78 vs 0.68, p < 0.0001) and improved PPV compared to PSA. A PSAd of ⩾ 0.10 had a PPV of 48.2% and similar negative predictive value (NPV) to PSA ⩾ 3 ng/mL and out-performed PSA age-reference ranges. This improved performance was recapitulated in a separate multi-centre cohort (n = 541). The introduction of MRI-based image-guided biopsy pathways does not appear to have altered PSA diagnostic test characteristics to positively detect csPCa. We find no added value to PSA age-referenced ranges, while PSAd offers better PPV and the potential for a single clinically useful threshold (⩾0.10) for all age groups. IV.

A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

SummaryBackgroundLynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants.MethodsThe IMPACT study is an international, prospective study. Men aged 40–69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This study is registered with ClinicalTrials.gov, NCT00261456, and is now closed to accrual.FindingsBetween Sept 28, 2012, and March 1, 2020, 828 men were recruited (644 carriers of mismatch repair pathogenic variants [204 carriers of MLH1, 305 carriers of MSH2, and 135 carriers of MSH6] and 184 non-carrier controls [65 non-carriers of MLH1, 76 non-carriers of MSH2, and 43 non-carriers of MSH6]), and in order to boost the sample size for the non-carrier control groups, we randomly selected 134 non-carriers from the BRCA1 and BRCA2 cohort of the IMPACT study, who were included in all three non-carrier cohorts. Men were predominantly of European ancestry (899 [93%] of 953 with available data), with a mean age of 52·8 years (SD 8·3). Within the first screening round, 56 (6%) men had a PSA concentration of more than 3·0 ng/mL and 35 (4%) biopsies were done. The overall incidence of prostate cancer was 1·9% (18 of 962; 95% CI 1·1–2·9). The incidence among MSH2 carriers was 4·3% (13 of 305; 95% CI 2·3–7·2), MSH2 non-carrier controls was 0·5% (one of 210; 0·0–2·6), MSH6 carriers was 3·0% (four of 135; 0·8–7·4), and none were detected among the MLH1 carriers, MLH1 non-carrier controls, and MSH6 non-carrier controls. Prostate cancer incidence, using a PSA threshold of higher than 3·0 ng/mL, was higher in MSH2 carriers than in MSH2 non-carrier controls (4·3% vs 0·5%; p=0·011) and MSH6 carriers than MSH6 non-carrier controls (3·0% vs 0%; p=0·034). The overall positive predictive value of biopsy using a PSA threshold of 3·0 ng/mL was 51·4% (95% CI 34·0–68·6), and the overall positive predictive value of a PSA threshold of 3·0 ng/mL was 32·1% (20·3–46·0).InterpretationAfter the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings.FundingCancer Research UK, The Ronald and Rita McAulay Foundation, the National Institute for Health Research support to Biomedical Research Centres (The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; Oxford; Manchester and the Cambridge Clinical Research Centre), Mr and Mrs Jack Baker, the Cancer Council of Tasmania, Cancer Australia, Prostate Cancer Foundation of Australia, Cancer Council of Victoria, Cancer Council of South Australia, the Victorian Cancer Agency, Cancer Australia, Prostate Cancer Foundation of Australia, Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), the Institut Català de la Salut, Autonomous Government of Catalonia, Fundação para a Ciência e a Tecnologia, National Institutes of Health National Cancer Institute, Swedish Cancer Society, General Hospital in Malmö Foundation for Combating Cancer.

A novel screening strategy for clinically significant prostate cancer in elderly men over 75 years of age.

A standard modality for prostate cancer detection in men 75 years and older has not been established. A simple screening method for elderly patients is needed to avoid unnecessary biopsies and to effectively diagnose prostate cancer. A retrospective study was conducted on elderly patients who had prostate biopsy at Kanazawa University Hospital (Kanazawa, Japan) between 2000 and 2017. Of the 2251 patients who underwent prostate biopsy, 254 had clinically significant prostate cancer (CSPC) with a Gleason score (GS) of ≥7 and 273 had a GS of <7 or no malignancy. In this study, patients aged 75 years or older were classified as elderly patients. GS ≥7 was characterized by a prostate-specific antigen (PSA) of the maximum area under the curve of 12 ng ml−1 with a sensitivity of 76.2% and a specificity of 73.2%. For PSA levels between 4 ng ml−1 and 12 ng ml−1, based on the maximum area under the curve, patients with three or four of the following factors may present a GS of ≥7: percent free PSA >24, PSA density ≥0.24 ng ml−2, positive findings on digital rectal examination, and transrectal with 90.0% sensitivity and 67.4% specificity. In this study, we found that raising the PSA cutoff to 12 ng ml−1 for CSPC in elderly individuals can significantly reduce unnecessary prostate biopsies. Furthermore, CSPC could be efficiently discovered by combining the four supplementary markers in patients with a PSA level of 4–12 ng ml−1. By performing this screening for elderly men over 75 years of age, unnecessary biopsies may be reduced and CSPC may be detected efficiently.

18F-fluciclovine PET CT detection of biochemical recurrent prostate cancer at specific PSA thresholds after definitive treatment

ObjectivesTo evaluate various Prostate-Specific Antigen (PSA) thresholds at which a 18F-fluciclovine PET scan could be considered in the setting of biochemical recurrent prostate cancer after definitive treatment. MethodsWe analyzed available records of men who underwent a 18F-fluciclovine PET scan after definitive therapy at a single academic institution between November 2016 to May 2018. The primary outcome was the rate of positive imaging findings at specific PSA thresholds. We then employed empiric strategies including a ROC curve and decision curve analysis to identify a specific threshold for which obtaining a positive result would be optimized. ResultsA total of 115 men underwent imaging with 18F-fluciclovine PET. No concerning lesions were identified in 25 (21.7%) patients, 32 (27.8%) had a solitary lesion identified, 45 (39.1%) had 2 to 5 lesions, and 13 (11.3%) had greater than 5 suspicious lesions identified. At PSA thresholds of less than 0.5, 0.5 to 2.0, and greater than 2, lesions were detected in 55.5% (12/22), 70.6% (24/34), and 91.5% (54/59) of patients respectively [P < 0.001]. Our ROC analysis yielded a PSA threshold of 2.10 while our decision curve analysis provided a PSA cutoff of 1.38. ConclusionThis study constitutes an early single institution series evaluating the use of 18F-fluciclovine PET scans in the assessment of biochemically recurrent prostate cancer after definitive treatment. The probability of having positive imaging findings and increasing numbers of suspicious lesions rises with increasing PSA. Utilization of a lower PSA threshold of 0.5 may allow earlier intervention with salvage therapies in biochemical recurrence. However, using a threshold below 1 carries a higher risk of negative scans. Employing a higher PSA threshold of 1 to 2 carries greater sensitivity and specificity and may maximize identifying individuals with early BCR who may benefit from early intervention, while minimizing negative scans.

Significance of Serum Prostate Specific Antigen Levels in Evaluating Prostatic Lesions with Histopathological Correlation

Background: Prostate cancer is one of the commonest forms of cancer among men. Serum prostate specific antigen (PSA) used in the diagnosis of prostate cancer is also elevated in other benign and non-malignant diseases of prostate. Objectives: The objectives of the study were to determine the relationship of serum f(PSA) and t(PSA), its correlation with histopathological findings and to assess the PSA cut off variable in various pathological conditions of prostate with clinical relevance. Materials and methods: This study included 141 patients admitted for transurethral resection of prostate and 141 control cases. fPSA was determined on blood samples by sandwich enzyme linked immunosorbent assay and total PSA by Enzyme Linked Fluroscent Assay method. The samples were processed and stained with haematoxylin and eosin. Results: The mean t(PSA) values for benign, premalignant and malignant lesions were 10.3 ng/ml, 20.36 ng/ml and 75.92 ng/ml respectively. The mean serum fPSA values for benign, premalignant and malignant lesions were 3.2 ng/ml, 9 ng/ml and 13.2 ng/ml respectively. The cut off value for tPSA was 12.25 ng/ml and that of fPSA was 9.4ng/ml. The p value(<0.0001) was highly significant in determining premalignant and malignant lesions. Conclusion: Total PSA is raised in premalignant, malignant, inflammatory and benign neoplastic lesions of prostate. In cases where the t(PSA) values are between four - ten ng/ml, f(PSA) is useful marker in cases of malignancies, which were confirmed on histopathology.

Sensitivity of fluorine-18-fluoromethylcholine PET/CT to prostate-specific antigen over different plasma levels: a retrospective study in a cohort of 192 patients with prostate cancer.

Several factors have been identified that predict positive fluorine-18-fluoromethylcholine (F-FCH) PET/CT result in patients with prostate cancer undergoing PET/CT for biochemical failure. Among these factors, prostate-specific antigen (PSA) is the single factor most consistently associated with the prediction of positive F-FCH PET/CT. In this study, we wished to confirm this finding and expand it in a large series of patients. We retrospectively analyzed 192 patients with prostate cancer who were recruited from the Nuclear Medicine Department of the Sant'Andrea Hospital of La Spezia, Italy, from March 2013 to March 2018 and who underwent F-FCH PET/CT owing to biochemical failure after radical prostatectomy. Median trigger PSA was 2.57 ng/ml. The overall positive detection rate of F-FCH PET/CT was 60.9%. The percent of positive scans was 30.5% for PSA less than 1 ng/ml, 59.4% (38/64) for PSA between 1 and 5 ng/ml, and 88.4% for PSA greater than 5 ng/ml (P<0.001). On univariate regression analysis, high PSA levels, biochemical failure during antiandrogenic therapy at the time of PET/CT, and older age significantly (P<0.05) predicted positive F-FCH PET/CT result. On multivariate regression analysis, only high PSA levels and biochemical failure during antiandrogenic therapy maintained the statistical significance (P<0.05). However, when the analysis was restricted to patients with PSA less than 1 ng/ml, PSA lost the statistical significance. Receiver operating characteristic analysis revealed an area under the curve of 0.795. The PSA cutoff value that best distinguished PET/CT-positive from PET/CT-negative patients was 2.57 ng/ml. Sensitivity and specificity at this PSA value were 66.7 and 76.0%, respectively. This study confirms that PSA robustly predicts positive PET/CT result with radiolabeled choline. Unfortunately, this study also confirms the limited sensitivity of F-FCH PET/CT for PSA less than 1 ng/ml, which currently represents the weakest point of the technique.

Risk Prediction of Prostate Cancer with Single Nucleotide Polymorphisms (SNPs) and Prostate-Specific Antigen (PSA)

PurposeCombined information on single nucleotide polymorphisms (SNPs) and prostate-specific antigen (PSA) offers opportunities for improving the performance of screening by risk stratification. We aimed to predict the risk of prostate cancer (PrCa) based on PSA together with SNPs information. Materials and MethodsProspective study of 20,575 men with PSA test and 4,967 men with polygenic risk score for PrCa based on 66 SNPs from the Finnish population-based screening trial for PrCa and 5,269 samples on seven SNPs from the Finnish PrCa DNA study. Bayesian predictive model was built for estimating the risk of PrCa by sequentially combining genetic information with PSA in comparison with PSA alone among study subjects limited with 4 ng/mL or above. ResultsThe posterior odds for PrCa based on seven SNPs together with the PSA level ranged from 3.7 at 4 ng/mL, 14.2 at 6 ng/mL, 40.7 at 8 ng/mL, to 98.2 at 10 ng/mL. The area under receiver operating characteristic curve was elevated to 88.8% (95% CI: 88.6%-89.1%) with PSA in combination with the risk score based on seven SNPs in comparison with 70.1% (95% CI: 69.6%-70.7%) with PSA alone. It was further escalated to 96.7% (95% CI: 96.5%-96.9%) when all prostate cancer susceptibility polygenes were combined. ConclusionsExpedient use of multiple genetic variants together with information on PSA levels better predicts the risk of PrCa than PSA alone and allows higher PSA cut-offs. Combined information also provides a basis for risk stratification that can be used for optimizing the performance of PrCa screening.

Prostate-specific antigen cutoff value for ordering sodium fluoride positron emission tomography/computed tomography bone scan in patients with prostate cancer

The use of F-18 sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) bone scan is increasing because of its higher sensitivity and specificity over standard bone scintigraphy (BS). Studies previously reported a prostate-specific antigen (PSA) cutoff value for ordering standard BS. However, this has not been determined for NaF PET yet. In this study, our goal was to determine a PSA cutoff level for ordering NaF PET/CT bone scan. Newly diagnosed and previously treated prostate cancer patients who had NaF PET/CT scan and PSA measurements within 2 mos of PET study were selected for analysis. When available, other parameters, such as Gleason score (GS), clinical stage, alkaline phosphatase levels, skeletal symptoms, and correlative image findings, were recorded. Receiver operating characteristic (ROC) analysis was performed to determine PSA cutoff values. Sixty-two patients (32 newly diagnosed and 30 previously treated) met the inclusion criteria. Near half of previously treated patients were on hormone therapy. NaF PET/CT was positive in 9 newly diagnosed (PSA mean: 91.6 ng/ml, range: 6.2–226 ng/ml) and in 6 previously treated patients (PSA mean: 146.4 ng/ml, range: 6.6–675 ng/ml). ROC analysis indicated that PSA cutoff value for NaF PET/CT positivity was >20 ng/ml in newly diagnosed and >6 ng/ml in previously treated patients. PSA cutoff value for ordering NaF PET/CT in newly diagnosed patients does not seem significantly different than the previous results for BS (>20 ng/ml). However, we found a lower PSA cutoff value of >6 ng/ml in previously treated patients.

PD23-07 INCREASED DETECTION OF HIGHER GRADE PROSTATE CANCER WITH MRI-FUSION PROSTATE BIOPSY AT HIGHER PSA

You have accessJournal of UrologyProstate Cancer: Detection & Screening II1 Apr 2018PD23-07 INCREASED DETECTION OF HIGHER GRADE PROSTATE CANCER WITH MRI-FUSION PROSTATE BIOPSY AT HIGHER PSA Nabeel Shakir, Niccolo Passoni, Daniel Wong, Samuel Gold, Graham Hale, Kareem Rayn, Joseph Baiocco, Jonathan Bloom, Vladimir Valero, Maria Merino, Baris Turkbey, Peter Choyke, Bradford Wood, Peter Pinto, Daniel Costa, and Claus Roehrborn Nabeel ShakirNabeel Shakir More articles by this author , Niccolo PassoniNiccolo Passoni More articles by this author , Daniel WongDaniel Wong More articles by this author , Samuel GoldSamuel Gold More articles by this author , Graham HaleGraham Hale More articles by this author , Kareem RaynKareem Rayn More articles by this author , Joseph BaioccoJoseph Baiocco More articles by this author , Jonathan BloomJonathan Bloom More articles by this author , Vladimir ValeroVladimir Valero More articles by this author , Maria MerinoMaria Merino More articles by this author , Baris TurkbeyBaris Turkbey More articles by this author , Peter ChoykePeter Choyke More articles by this author , Bradford WoodBradford Wood More articles by this author , Peter PintoPeter Pinto More articles by this author , Daniel CostaDaniel Costa More articles by this author , and Claus RoehrbornClaus Roehrborn More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1188AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Lower threshold values for undertaking prostate biopsy based on serum prostate-specific antigen (PSA) improve overall cancer detection but conversely may result in overdiagnosis of lower-risk prostate cancer (PCa). Multiparametric magnetic resonance imaging (MP-MRI) fusion biopsy has been demonstrated to detect higher grade PCa as compared to standard template transrectal ultrasound (TRUS) guided biopsy but an optimal PSA threshold for its use is unclear. We evaluated the performance of MRI fusion biopsy stratified across PSA cutoffs. METHODS We reviewed 1913 men undergoing first-time MP-MRI followed by MRI-fusion and standard template transrectal ultrasound guided prostate biopsy at two institutions. Patients were divided into 4 groups by PSA: 0-2.5, 2.5-4, 4-10, and >10 ng/mL. The greatest grade group (GG) from either MRI-fusion or standard biopsy was compared across groups with McNemar's test, with clinically-significant (CS) PCa defined as >GG2. RESULTS A total of 1235/1913 (65%) men were diagnosed with PCa by either biopsy method. MRI-fusion biopsy detected higher grade PCa and specifically more CS PCa than did standard biopsy overall (423/1913 vs 340/1913, and 151/1913 vs 63/1913 respectively, p<0.0001 for both). By PSA groups, significantly more patients with PSA 4-10 and >10 ng/mL had CS PCa found by MRI-fusion vs standard biopsy (Figure 1). However, more patients with PSA 2.5-4 ng/mL had CS PCa found by standard biopsy (9/232 vs 2/232, p=0.03). PSA cutoff remained significantly associated with upgrading to CS PCa by targeted biopsy when controlling for age and MRI volume in multivariable analysis (p<0.0001). CONCLUSIONS The detection of CS PCa by MRI-fusion biopsy may be maximized in patients with PSA 4-10 and >10 ng/mL. Below these threshold values, standard template biopsy may identify slightly more CS PSA, emphasizing the importance of performing standard biopsy in conjunction with MRI-targeted biopsy in this population. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e482-e483 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Nabeel Shakir More articles by this author Niccolo Passoni More articles by this author Daniel Wong More articles by this author Samuel Gold More articles by this author Graham Hale More articles by this author Kareem Rayn More articles by this author Joseph Baiocco More articles by this author Jonathan Bloom More articles by this author Vladimir Valero More articles by this author Maria Merino More articles by this author Baris Turkbey More articles by this author Peter Choyke More articles by this author Bradford Wood More articles by this author Peter Pinto More articles by this author Daniel Costa More articles by this author Claus Roehrborn More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-Term Outcome of a Single Intervention Population Based Prostate Cancer Screening Study

We evaluated the long-term effect of screening for prostate cancer. In 1988 we randomly selected 2,400 men from a background population of 27,464 men. The 2,400 men were invited to undergo screening, of whom 1,779 (74%) accepted and were examined with digital rectal examination, ultrasound and prostate specific antigen measurement. Biopsy was performed if there were suspicious findings on ultrasound or digital rectal examination, or prostate specific antigen was greater than 10 ng/ml. The subpopulations have now been reassessed after 20 years. Participants had a decreased overall mortality rate compared to the source population (IRR 0.93, 95% CI 0.86-0.98). Nonparticipants had an increased overall mortality rate (IRR 1.25, 95% CI 1.14-1.37). There was no difference between the groups in prostate cancer specific survival. The incidence of prostate cancer remained higher in the screened population throughout followup. A single screening intervention in men 50 to 75 years old using prostate specific antigen, digital rectal examination and transrectal ultrasound, and a prostate specific antigen cutoff of 10 ng/ml for biopsy carried a significant risk of prostate cancer detection without a concomitant reduction in prostate cancer specific mortality after 20 years. This intervention should not be considered for public screening. Nonparticipants were at greater risk for death of all causes. In addition to being a single intervention trial, the limitations of this study include an outdated prostate specific antigen cutoff for biopsy. Despite the outdated screening method the source population failed to reach the same level of prostate cancer incidence as the screened population even after 20 years.

TRUS Biopsy Yield in Indian Population: A Retrospective Analysis.

The reported cancer detection rate of Trans-Rectal Ultrasonography (TRUS) biopsies (TRUS biopsy yield) has been around 30 percent in western countries. However it is much lower in Asian countries, including India. Hence a larger proportion of patients in India undergo unnecessary biopsies. To find out the cancer detection rate of TRUS biopsy (TRUS biopsy yield) in contemporary Indian population. Also, to study the positive predictive values at different serum Prostate-Specific Antigen (PSA)/PSA Density (PSAD) cut off levels and suspicious Digital Rectal Examination (DRE) findings. This retrospective study was carried out in a tertiary care institute. All symptomatic patients who underwent TRUS guided biopsy for indication of raised serum PSA level (>4 ng/ml) or suspicious DRE findings (nodule, irregularity, hard consistency, immobile rectal mucosa) from January 2012 to December 2014 were included. For serum PSA range (4-10) ng/ml, TRUS guided biopsy was done in patients with percent free/total PSA < 25. Statistical analysis used were Chi-square test, Mann-Whitney U-test, Spearman's rank correlation analysis and Receiver-Operating Characteristic (ROC) curve. Out of the 235 patients included, 60 patients had malignancy (overall cancer detection rate= 25.53%). The cancer detection rate for PSA ranges of (4-10) and (10-20) ng/ml was as low as 5.95% and 13.16% respectively. Patients with malignant disease had significantly smaller prostate gland size than patients with benign disease (53.89 vs 63.06; p-value <0.05). On the other hand, cancer detection rate was 100% for PSA greater than 50ng/ml. The cancer detection rates were only upto 10% for PSA density ranges upto 0.25 ng/ml/cm3. The Area Under the Curve (AUC) for PSA and PSAD was 0.876 and 0.884 respectively. Only one patient (0.43%) had post-biopsy complication (acute bacterial prostatitis) requiring hospital admission. The current serum PSA and PSAD cut offs of 4 ng/ml and 0.15 ng/ml/cm3 need to be raised for Indian population to increase its positive predictive value. Prospective study validation of this finding is lacking.

Improved Metastasis-Free and Survival Outcomes With Early Salvage Radiotherapy in Men With Detectable Prostate-Specific Antigen After Prostatectomy for Prostate Cancer.

Purpose To describe outcomes of salvage radiotherapy (SRT) for men with detectable prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer and identify associations with outcomes. Patients and Methods A total of 1,106 patients received SRT between January 1987 and July 2013, with median follow-up 8.9 years. Outcomes were estimated using Kaplan-Meier for overall survival (OS) and cumulative incidence for biochemical recurrence (BcR), distant metastases (DM), and cause-specific mortality (CSM). Variable associations with outcomes used Cox or Fine-Gray methods, as appropriate. Multiple variable analyses used backward selection with P < .05 for retention. Results In multiple variable analyses, pathologic tumor stage, Gleason score, and pre-SRT PSA were associated with BcR, DM, CSM, and OS; androgen suppression and SRT doses > 68 Gy were associated with BcR; and age was associated with OS. Each pre-SRT PSA doubling increased significantly the relative risk of BcR (hazard ratio [HR], 1.30; P < .001), DM (HR, 1.32; P < .001), CSM (HR, 1.40; P < .001), and all-cause mortality (HR, 1.12; P = .02). Using a pre-SRT PSA cutoff ≤ 0.5 versus > 0.5 ng/mL, 5-year and 10-year cumulative incidences for BcR were 42% versus 56% and 60% versus 68% ( P < .001), DM 7% versus 14% and 13% versus 25% ( P < .001), CSM 1% versus 4% and 6% versus 13% ( P < .001), and OS of 94% versus 92% and 83% versus 73% ( P > .05). Conclusion SRT outcomes are in part affected by factors associated with prostatectomy findings but may be positively affected by using SRT at lower PSA levels, including reductions in BcR, DM, CSM, and all-cause mortality. These findings argue against prolonged monitoring of detectable postprostatectomy PSA levels that delay initiation of SRT.

The Cost-Effectiveness of Prostate Cancer Detection with the Use of Prostate Health Index

BackgroundClinical trial results suggested that prostate-specific antigen (PSA) screening can reduce prostate cancer mortality. Nevertheless, because the specificity of the PSA test for cancer detection is low, it leads to many negative biopsies. The Beckman Coulter Prostate Health Index (PHI) testing demonstrates improved specificity compared with the PSA-only screening and therefore may improve the cost-effectiveness of prostate cancer detection. ObjectiveTo examine the cost-effectiveness of adding PHI testing to improve cancer detection for men with elevated serum PSA. MethodsA microsimulation model, based on the results of the European Randomized Study of Screening for Prostate Cancer trial, was used to evaluate the effects of PSA screening and PHI reflex testing. We predicted the numbers of prostate cancers, negative biopsies, deaths, quality-adjusted life-years gained, and cost-effectiveness of both PSA (cutoff 3 ng/mL) and PHI (cutoff 25) testing methods for a European population, screened from age 50 to 75 years at 4-year intervals. ResultsWhen the PHI test was added to the PSA screening, for men with a PSA between 3 and 10 ng/mL, the model predicted a 23% reduction in negative biopsies. This would lead to a 17% reduction in costs for diagnostics and 1% reduction in total costs for prostate cancer. The cost-effectiveness (3.5% discounted) was 11% better. Limitations found were the modeling assumptions on the sensitivity and specificity of PHI by tumor stage and cutoff values. ConclusionsCompared with PSA-only screening, the use of a PHI test can substantially reduce the number of negative biopsies and improve the cost-effectiveness of prostate cancer detection.

Evaluation of prostatic cancer prevalence in patients with prostatic-specific antigen between 4 and 10 and normal digital rectal examination

Background:Prostate cancer is one of the most common male cancers. The prevalence of prostate cancer is different due to genetic and environmental factors. Diagnosis of prostate cancer is by biopsy due to prostate-specific antigen (PSA) and Digital Rectal Examination (DRE). Controversy about decision making for prostate biopsy in PSA between 4 and 10 and normal DRE, is one of the problems in this time. In this study we evaluated the prevalence of prostate cancer in males with PSA between 4 and 10 and normal DRE. We also evaluated the PSA density and percent of free PSA in patients with prostate cancer.Materials and Methods:A total of 121 males with PSA between 4 and 10 and normal DRE, were evaluated. Then, transrectal ultrasonography (TRUS) andprostate biopsy from 12 points of peripheral zone, was done. These data were analyzed by Chi-square, t-test and ANOVA and Roc curve.Results:In this study, the prevalence of prostate cancer in PSA between 4 and 10 and normal DRE, was evaluated, 29.8%. With use of Roc curve, PSA density cutoff point was calculated 0.12 and percent of free PSA cutoff point, was calculated, 18%.Conclusion:In males with PSA between 4 and 10 and normal DRE, PSA density smaller than 0.12-0.15, and percent of free PSA greater than 18%, the prevalence of prostate cancer is very few and we can safely ignore the TRUS and prostate biopsy in these males and eliminate its costs and side effects.

Pathological Outcome following Radical Prostatectomy in Men with Prostate Specific Antigen Greater than 10 ng/ml and Histologically Favorable Risk Prostate Cancer

Active surveillance is now the treatment of choice in men with low risk prostate cancer. Although there is no consensus on which patients are eligible foractive surveillance, prostate specific antigen above 10 ng/ml is generally excluded. In an attempt to determine the validity of using a prostate specific antigen cutoff of 10 ng/ml to counsel men considering active surveillance we analyzed a multi-institution database to determine the pathological outcome in men with prostate specific antigen greater than 10 ng/ml but histologically favorable risk prostate cancer. We queried a prospectively maintained database of men with histologically favorable risk prostate cancer who underwent radical prostatectomy between 2003 and 2015. The cohort was categorized into 3 groups based on prostate specific antigen level, including low-less than 10 ng/ml, intermediate-10 or greater to less than 20 and high-20 or greater. Associations of prostate specific antigen group with adverse pathological and oncologic outcomes were analyzed. Of 2,125 patients 1,327 were categorized with histologically favorable risk disease. However on multivariate analyses the rates of up staging and upgrading were similar between the intermediate and low prostate specific antigen groups. In contrast compared to the intermediate prostate specific antigen group the high group had higher incidences of up staging (p = 0.02) and upgrading to 4 + 3 or greater disease (p = 0.046). Biochemical recurrence-free survival rates revealed no pairwise intergroup differences except between the low and high groups. Patients with preoperatively elevated prostate specific antigen between 10 and less than 20ng/ml who otherwise had histologically favorable risk prostate cancer were not at higher risk for adverse pathological outcomes than men with prostate specific antigen less than 10 ng/ml.

Predictive value of prostate specific antigen in a European HIV-positive cohort: does one size fit all?

It is common practice to use prostate specific antigen (PSA) ≥4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men. A nested case control study of 21 men with PCa and 40 matched-controls within EuroSIDA was conducted. Prospectively stored plasma samples before PCa (or matched date in controls) were measured for the following markers: total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG). Conditional logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 ng/ml to predict PCa was calculated. Receiver operating characteristic curves were used to identify optimal cutoffs in HIV+ men for total PSA. 61 HIV+ men were included with a median 6 (IQR 2-9) years follow-up. Levels of tPSA increased by 13.7% per year (95% CI 10.3, 17.3) in cases, but was stable in controls (-0.4%; 95% CI -2.5, 1.7). Elevated PSA was associated with higher odds of PCa at first (OR for twofold higher 4.7; 95% CI 1.7, 12.9; P<0.01) and last sample (8.1; 95% CI 1.1, 58.9; P=0.04). A similar relationship was seen between fPSA and PCa. Testosterone and SHBG level were not associated with PCa. tPSA level >4 ng/ml had 99% specificity and 38% sensitivity. The optimal PSA cutoff was 1.5 ng/ml overall (specificity =84%, sensitivity =81%). PSA was highly predictive of PCa in HIV+ men; however, the commonly used PSA>4 ng/ml to indicate high PCa risk was not sensitive in our population and use of the lower cutoff of PSA>1.5 ng/ml warrants consideration.