Variation In Prostate-specific Antigen 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.

Angiotensin II Receptor Blockers Cause Changes in Prostate-specific Antigen Levels: A Retrospective Cohort Study.

We previously reported a decrease in prostate-specific antigen (PSA) levels in patients with castration-resistant prostate cancer treated with angiotensin II receptor blockers (ARBs). However, no studies have reported the effect of ARBs on PSA variability in patients without a history of prostate cancer. Therefore, we conducted a population-based, retrospective study to determine whether ARBs have an inhibitory effect on elevated PSA levels in Japanese patients without a history of prostate cancer. This study was conducted using a large-scale Japanese claim database, including male patients aged ≥60 years who had two or more PSA measurements with an interval between measurements of 3 months to 2 years between April 2008 and June 2019. Patients who had been prescribed ARBs were grouped into the ARB group, and those who were prescribed antihypertensive drugs other than ARBs were grouped into the non-ARB group. We compared the proportions of patients with second PSA levels greater than the first. The numbers of eligible patients in the ARB and non-ARB groups were 777 and 527, respectively. Multivariate logistic regression analysis revealed that the proportion of patients with elevated PSA levels was significantly lower in the ARB group than in the non-ARB group (adjusted odds ratio=0.80, 95% confidence interval=0.64-0.99, p=0.047). ARBs may suppress elevated PSA levels in patients without a history of prostate cancer. This contributes to the prevention of prostate cancer.

Association of PSA variability with prostate cancer development using large-scale medical information data: a retrospective cohort study

BackgroundProstate cancer is one of the most common cancers among men worldwide and the fourth most common cause of death. The number of prostate cancer cases and deaths is increasing every year because of population aging. This study aimed to clarify the risk of developing prostate cancer due to fluctuations in Prostate Specific Antigen (PSA) levels in patients without a history of prostate cancer using large medical information data.ResultsThis retrospective cohort included 1707 male patients aged 60 years or older who had a PSA level measurement date (2-PSA) within 3 months or more and 2 years from the first PSA level measurement date (1-PSA) in the database between 2008 and 2019. We subtracted 1-PSA from 2-PSA and designated patients with a higher 2-PSA than 1-PSA to the “up” group (n = 967) and patients with a lower 2-PSA than 1-PSA to the “down” group (n = 740). By using Cox proportional hazards model, a significant increase in prostate cancer risk was observed in the up group compared with the down group (adjusted hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.21–2.72; adjusted for patient background factors). Subgroup analysis showed that patients with PSA levels < 4 ng/mL had a significantly increased risk of developing prostate cancer if the next PSA level increases by approximately 20% (adjusted HR = 2.94, 95% CI = 1.14–7.58), and patients with PSA levels of 4 ng/mL or higher if the next PSA level is decreased by approximately 20% had a significantly reduced risk of developing prostate cancer (adjusted HR = 0.36, 95% CI = 0.18–0.74), compared to that with no change.ConclusionsThis is the first study to clarify the association between PSA variability and risk of developing prostate cancer in patients without a history of prostate cancer. These results suggest that the suppression of elevated PSA levels may lead to the prevention of prostate cancer and that it would be better to perform a biopsy because the risk of developing prostate cancer may increase in the future if the PSA value increases above a certain level.

HSD105 Sociodemographic Variations in PSA Screening Use: A Cross-Sectional Analysis of Data from the National Health Interview Survey

To assess sociodemographic variations in prostate specific antigen (PSA) screening outside the U.S. Preventive Services Task Force (USPSTF) recommended age range.

Genetically adjusted PSA levels for prostate cancer screening

Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P < 5 × 10−8) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGSPSA) that explains 9.61% of constitutive PSA variation. We found that, in men of European ancestry, using PGS-adjusted PSA would avoid up to 31% of negative prostate biopsies but also result in 12% fewer biopsies in patients with prostate cancer, mostly with Gleason score <7 tumors. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR) = 3.44, P = 6.2 × 10−14, area under the curve (AUC) = 0.755) than unadjusted PSA (OR = 3.31, P = 1.1 × 10−12, AUC = 0.738) in 106 cases and 23,667 controls. Compared to a prostate cancer PGS alone (AUC = 0.712), including genetically adjusted PSA improved detection of aggressive disease (AUC = 0.786, P = 7.2 × 10−4). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.

Assessing volatile organic compounds exposure and prostate-specific antigen: National Health and Nutrition Examination Survey, 2001–2010

BackgroundVolatile organic compounds (VOCs) are a large group of chemicals widely used in people's daily routines. Increasing evidence revealed the VOCs' accumulating toxicity. However, the VOCs toxicity in male prostate has not been reported previously. Thus, we comprehensively evaluated the association between VOCs and prostate-specific antigen (PSA).MethodsA total of 2016 subjects were included in our study from the National Health and Nutrition Examination Survey with VOCs, PSA, and other variables among U.S. average population. We constructed XGBoost Algorithm Model, Regression Model, and Generalized linear Model (GAM) to analyze the potential association. Stratified analysis was used to identify high-risk populations.ResultsXGBoost Algorithm model identified blood chloroform as the most critical variable in the PSA concentration. Regression analysis suggested that blood chloroform was a positive association with PSA, which showed that environmental chloroform exposure is an independent risk factor that may cause prostate gland changes [β, (95% CI), P = 0.007, (0.003, 0.011), 0.00019]. GAM observed the linear relationship between blood chloroform and PSA concentration. Meanwhile, blood chloroform linear correlated with water chloroform in the lower dose range, indicating that the absorption of water may be the primary origin of chloroform. Stratified associations analysis identified the high-risk group on the chloroform exposures.ConclusionThis study revealed that blood chloroform was positively and independently associated with total PSA level, suggesting that long-term environmental chloroform exposure may cause changes in the prostate gland.

Prostate-Specific Antigen Variation as a Predictor of Prostate Cancer in Patients With Prostate-Specific Antigen ≤20 ng/mL Who Underwent Magnetic Resonance Imaging-Targeted Prostate Biopsy

Purpose: We investigated the role of prostate-specific antigen (PSA) variation as a predictor of prostate cancer in patients who underwent prebiopsy multiparametric magnetic resonance imaging (MRI).Materials and Methods: The clinicopathological data of 266 patients with PSA ≤20 ng/mL who underwent prebiopsy MRI and prostate biopsy between September 2019 and February 2021 were included. PSA variation was defined as the difference in PSA values taken when a prostate biopsy was recommended and performed (median 20 days). Receiver operating characteristic (ROC) curves and area under the ROC curves (AUCs) for predicting prostate cancer were analyzed through 4 models that considered conventional clinical variables and PSA variation.Results: Of the 258 patients, 166 (64.3%) were diagnosed with prostate cancer. The prostate cancer (+) group had a lower median PSA variation (-0.09 mg/mL vs. -0.27 ng/mL, p=0.006) and higher proportion of patients with PSA variation within -0.54 to 0.05 ng/mL (40 ng/mL [range, 24.1%] vs. 9 ng/mL [9.8%], p=0.002) than the prostate cancer (-) group. There was no significant difference in the duration between the 2 PSA measurements. When PSA variation and conventional variables, such as age, PSA density, prostate biopsy history, number of target lesions, were considered, the highest AUC value was 0.870. In a subgroup analysis of patients with PSA ≤10 ng/mL, the highest AUC value was 0.860 when PSA variation and conventional variables were considered.Conclusions: A large PSA variation within 1 month was a negative predictor of prostate cancer among patients who underwent prebiopsy MRI.

MP58-18 REAL WORLD APPLICATION AND EXPERIENCE OF A PROSTATE SPECIFIC ANTIGEN (PSA) MACHINE LEARNING MODEL IN A SCREENING POPULATION

You have accessJournal of UrologyCME1 May 2022MP58-18 REAL WORLD APPLICATION AND EXPERIENCE OF A PROSTATE SPECIFIC ANTIGEN (PSA) MACHINE LEARNING MODEL IN A SCREENING POPULATION Marlon Perera, Lewis Smith, Peter Swindle, Anthony Costello, and Elliot Smith Marlon PereraMarlon Perera More articles by this author , Lewis SmithLewis Smith More articles by this author , Peter SwindlePeter Swindle More articles by this author , Anthony CostelloAnthony Costello More articles by this author , and Elliot SmithElliot Smith More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002641.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Machine learning algorithms may be beneficial in the setting of prostate cancer screening. Our group has developed one such algorithm based on PSA, age, free:PSA and other variables based on the data sets from the Prostate, Lung, Colorectal and Ovarian Cancer and PCPT trials. Limited data exists examining the effect of machine learning algorithms on prostate cancer diagnosis prospectively. We aimed to report our early experience using this algorithm in prostate cancer screening on an Australian cohort. METHODS: 1223 men without previous history of prostate cancer were tested using an AI clinical decision support tool in a digital health clinical setting. Clinicians assessed demographic factors as well as PSA, Free-PSA, Prostate Health Index and MRI results alongside an AI based clinical decision support tool. Men determined to be high risk were referred for urologic assessment and potential biopsy. When results were discordant with guidelines but flagged by AI the case was reviewed by a second clinician. The results of those men who underwent biopsy were collected and compared to statistics in a recent publication from the Australian Prostate Cancer Outcomes Registry. RESULTS: Of the 1223 men tested prospectively, 49 were referred to a urologist on the basis of their clinical parameters and AI risk score. These men underwent MRI which was then assessed. Of those that underwent MRI 26 continued to a prostate biopsy. Of the 26 biopsies completed 19 were found to have prostate cancer, 17 of the 19 (89%) cancers were found to be Gleason 7 or above on surgical histopathology. This is above a recently published rate of 74%. The median PSA at diagnosis was 2.3 µg/L, lower than the published median of 7.3 µg/L. No biopsied men were found to have metastatic disease compared to a published rate of 7%. Overall initial results show early detection of clinically significant disease with a reduced rate of biopsies in low risk men. CONCLUSIONS: Our machine learning model appears to reduce the need for biopsy and reduces the diagnosis of low-risk prostate cancer. Further, we highlight that PSA at the time of diagnosis was considerably lower than comparable screening cohorts. We provide a proof-of-principal highlighting the utility of machine-learning algorithms for prostate cancer screening in a real-world population. Source of Funding: MP is funded by a Fulbright scholarship through the Australian-America Fulbright Association © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e999 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marlon Perera More articles by this author Lewis Smith More articles by this author Peter Swindle More articles by this author Anthony Costello More articles by this author Elliot Smith More articles by this author Expand All Advertisement PDF DownloadLoading ...

Effects of chronic intermittent hypobaric hypoxia on prostate-specific antigen (PSA) in Chilean miners

ObjectiveThe aim was to determine the effects of chronic intermittent hypobaric hypoxia (CIHH) on prostate-specific antigen (PSA) levels in Chilean miners who work at different altitudes.MethodsA cross-sectional study was conducted...

The Effect of Payer Status on Survival of Patients With Prostate Cancer.

BackgroundDisparities in access to care and proper treatment can have significant implications in patient survival outcome and mortality. This retrospective study of prostate cancer patients from the National Cancer Database (NCDB) between the years 2004 and 2014 and follow-up to the end of 2015 analyzed such effects that variation in payer status might have on outcome.MethodsThis study used the data of 696,321 diagnosed prostate cancer patients from the NCDB for the years 2004 to 2014 and follow-up to the end of 2015 to analyze the effect that payer status would have on prostate cancer survival. Multivariable cox regression was used to study the hazard ratios (HRs) of payer status and other variables along with the Charlson Comorbidity Index to analyze their associated increased risk of death. Statistical software SAS 9.4 for Windows was used to analyze the overall survival (OS) of patients on different insurance plans along with variations in prostate-specific antigen (PSA) levels and treatment type.ResultsWhen looking at OS, those with private insurance had the greatest overall survivability while those on Medicare were the only ones who reached the median OS. In contrast to those who had private insurance, those who had Medicare, the uninsured, and those with Medicaid demonstrated significantly greater risks of death at 43%, 58%, and 69% increased risk of death, respectively. In addition to payer status, other variables were also significant predictors of OS, including demographic factors (age, race), comorbidities, socioeconomic status (income, education), distance traveled to facility, type of facility, treatment delay, treatment modality, PSA levels at diagnosis, and cancer stage at diagnosis.ConclusionPayer status is intricately linked to a number of other variables that might affect survival. Even after adjustment for a number of these factors, insurance status was shown to have a significant effect on prostate cancer survivorship. In contrast to those who had private insurance, those who had Medicare, the uninsured, and those with Medicaid demonstrated significantly greater risks of death at 43%, 58%, and 69% increased risk of death, respectively. Studies have suggested that those without insurance or on Medicaid are less likely to undergo screening and have worse health-related quality of life, while those on Medicare may be deterred from continuing treatment due to high out-of-pocket costs. However, the complete mechanism behind the improved survivorship of those on private insurance is unclear. The effect of payer status on quality of life may be an interest that needs to be further studied. Further research will be required to provide definite reasons for these observations and mediation analysis of other factors could prove to be valuable.

A general class of calibration estimators under stratified random sampling in presence of various kinds of non-sampling errors

This paper addresses the issue of estimating the population variance of a study character in the joint presence of random non-response and measurement errors and its application for estimating variations in biological data. Additional information on two highly positively correlated auxiliary variables has been incorporated to develop a general class of estimators under stratified two-phase sampling scheme. Its properties, in terms of bias and mean square error, have been examined. Optimum strata weights have been determined by employing suitable calibration techniques. Simulations using artificial data, as well as real data involving the variation in prostate specific antigen in different age groups when information about prostrate cancer volume and prostate weight is available, demonstrate the performance of the proposed class of estimators with respect to a contemporary estimator. Relevant R codes have been provided as Appendix.

Relationship of Prostate-Specific Antigen (PSA) and Prostate Volume in Patients with Biopsy Proven Benign Prostatic Hyperplasia (BPH)

Abstract Benign prostatic hyperplasia (BPH) is one of the most common benign tumors in men with prevalence ranging from 50% for men in their 60s to 90% for men in their 80s. The researcher sought to determine the relationship of prostate-specific antigen (PSA) and prostate volume in patients with benign prostatic hyperplasia. This study was based on 33 cases of benign prostatic hyperplasia in the Department of Urology, RSUD Dr. Soetomo Surabaya that diagnosed by histopathology examination. Cases with malignancy, acute urinary retention and prostatitis were excluded. The variables of prostate-specific antigen and prostate volume were examined. The results of this study found that 33 men were enrolled with mean PSA 16,04 ng/ml and a mean prostate volume of 49,13 ml. Overall, 84,8% had PSA level &gt;4 ng/ml and 90,9% had prostate volume &gt;25 ml. Prostate-specific antigen has significant correlation with prostate volume (p=0,019; r=0,362). This study concluded that prostate-specific antigen and prostate volume showed a significant correlation. Keywords : benign prostatic hyperplasia, prostate specific antigen, prostate volumeCorrespondence : anny_sr@fk.unair.ac.id

Comparison of changes in serum prostate specific antigen in prostate cancer patients treated either with flutamide or stilboestrol monotherapy

Prostate cancer is a disease of males. Though commoner in the elderly, cases are beginning to be reported in the younger population. It is thecommonest cancer diagnosed in males. Risk factors include ageing, genetic/familial factors, racial predilection, increased fat diet, and hormonal imbalance. It is a slow-growing tumour but can be associated with severe morbidity. The commonest histologic type is adenocarcinoma (>95%). When detected early, cure may be possible. Prostate-specific antigen (PSA) is the major serum marker used to monitor progress of the disease and its' response to therapy. Several treatment modalities have been used in the management of prostate cancer. This includes watchful waiting, prostatectomy, radiotherapy, hormone therapy, and chemotherapy. These treatment options are not without devastating and sometimes life-threatening adverse effects; hence the choice of therapy depends on patient's age, stage of disease, other co-morbidities, and even patient's choice.Aims and Objectives: This study aimed at establishing the variation in PSA among patients with advanced CaP treated either with Flutamideor Stilboestrol monotherapy in UCTH, Calabar. This helped in choosing an agent with better patient compliance, better therapeutic effect, minimal side-effects, and cost-effectiveness.Method: All newly diagnosed prostate cancer patients in the Division of Urology, Department of Surgery, UCTH, Calabar that met certain inclusion criteria were treated either with Flutamide or Stilboestrol monotherapy over a period of one year. Patients enrolled into the study were shared into two equal groups based on certain considerations. Response to therapy was monitored by conducting a three-monthly PSA check and results from the groups compared.Results: Fifty patients were enrolled into the study. The mean age was 70.12±8.93, and age range was 51-93 years. The peak age range was 61-70 years constituting 40.0% of total number of patients. The decline in serum PSA caused by flutamide and stilboestrol during each quarter of the year was 8.0%, 12.0%, 12.0%, 4.0% and 28.0%, 4.0%, 28.0%, 4.0% respectively. Overall flutamide caused a 36.0% reduction and stilboestrol 64.0% reduction in serum PSA over the period. In all, stilboestrol caused a greater decline in serum PSA compared to flutamide, and this became statistically significant at 9 months (p=0.044) and one year (p=0.048) of therapy.Conclusion: Patients who are on androgen deprivation therapy for CaP have their serum PSA reduced by either flutamide or stilboestrol monotherapy. However, over time, the PSA is more rapidly reduced by stilboestrol monotherapy compared to flutamide monotherapy. Keywords: Prostate Cancer, Flutamide, Stilboestrol, PSA.

The value of prostate-specific antigen monitoring during salvage radiotherapy: a retrospective study and systematic review with meta-analysis

Use of salvage radiotherapy (SRT) after cancer surgery has a low disease control rate. Low prostate-specific antigen (PSA) levels in the blood pre-SRT seem to be the best predictor of success. Our study used PSA monitoring during and after treatment to investigate if PSA levels during SRT can give further information about its chances of success. In a retrospective cohort of 78 patients submitted to salvage radiotherapy (SRT) for biochemical relapse after cancer surgery, we assess PSA values at start of the treatment, 1 week before the end of treatment, and every 3 months for at least 2 years. Post-treatment PSA in our series and the systematic review of the literature aimed to investigate the prognostic value of PSA variation for biochemical disease-free survival. The results suggest that a decline in PSA levels after at least 45 Gy of radiation therapy dosage or a decrease of at least 0.2 ng/mL compared with the start value may be a favorable prognostic factors for biochemical disease-free survival. These results need confirmation using prospective data before being applied to clinical practice and could help physician to choose the correct therapeutic strategy.

Observational study comparing the accuracy/variability between the ERSPC and the PCPT risk calculators for the prediction of significant prostate cancer in patients with PSA

IntroductionRisk calculators (RCs) are easy-to-use tools considering available clinical variables that could help to select those patients with risk of prostate cancer (PCa) who should undergo a prostate biopsy.ObjectiveTo perform...

A Multicenter Phase 2 study of Hypofractionated Stereostatic Boost in Intermediate Risk Prostate Carcinoma: A 5-Year Analysis of the CKNO-PRO Trial

The aim of this analysis was to assess the 5-year tolerance and survival in patients undergoing hypofractionated stereotactic boost after external beam radiation therapy (EBRT) for intermediate-risk prostate cancer. Between August 2010 and April 2013, 76 patients with intermediate-risk prostate carcinoma were included in the study. A first course delivered 46 Gy using conventional fractionation. The second course delivered a boost of 18 Gy (3 × 6 Gy) within 10 days using stereotactic body radiation therapy (SBRT). Gastrointestinal and genitourinary toxicities were assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.0. Secondary outcome measures were overall, biochemical relapse-free, and relapse-free survival; prostate-specific antigen kinetics; and patient functional status (urinary and sexual) according to the International Index of Erectile Function and International Prostate Symptom Score questionnaires. Sixty patients (79%) were treated by CyberKnife and 16 (21%) by linear accelerator. Median follow-up was 62 months (range, 29-69). The cumulative incidence of genitourinary and gastrointestinal grade ≥2 toxicities at month 60 after the end of radiation therapy was 1.4% (95% confidence interval [CI], 0.1%-6.6%) and 9.3% (95% CI, 4.1%-17.1%), respectively. Biochemical relapse-free and relapse-free survival rates at 5 years were 87.4% (95% CI, 77.1%-93.2%) and 86.2% (95% CI, 75.8-92.3), respectively. The mean (standard deviation) prostate-specific antigen variation within 3 months and 5 years post-radiation therapy was -1.20 ng/mL/mo (0.79) and -1.30 ng/mL/y (1.05), respectively. There was no significant difference between the International Prostate Symptom quality of life score between inclusion and month 60. For the International Index of Erectile Function, there was a significant difference between inclusion and month 60 (P = .005), with a higher proportion of severe/noninterpretable disorders at 60 months. The results of the trial demonstrate that the EBRT and SBRT combination is well tolerated and yields good efficacy results. These data provide a good basis for comparing EBRT and brachytherapy boost to EBRT and SBRT boost in future prospective studies.

The impact of diurnal variation of PSA on timing of measurement in prostate biopsy.

Prostate-specific antigen (PSA) synthesis is related to testosterone, which has a diurnal rhythm. PSA might have a diurnal variation and the timing of measurement could change the clinical practice for prostate biopsy. Male patients complaining of lower urinary tract symptoms (group 1) and diagnosed with prostate cancer (group 2) were recruited into the study. Morning fasting blood samples were withdrawn between 9.00 and 11.00 am for the determination of biochemical parameters, PSA (PSA1), total testosterone (T1), and estradiol (E1) levels. In the afternoon, between 15.00 and 15.30 pm, blood samples were again obtained from the same participants at the same day and the serum concentration of PSA (PSA2), total testosterone (T2), and estradiol (E2) were measured. A total of 160 and 30 patients were enrolled in groups 1 and 2, respectively. One hundred forty (87.5%) and 26 (86.6%) patients had a decrease in the PSA levels when measured in the afternoon. The Wilcoxon signed-rank test determined a statistically significant difference between the PSA levels measured in the morning and in the afternoon in each group. An analysis of covariance test revealed no statistically significant difference in PSA concentration between the groups after adjustment for baseline concentration (F(1.187) = 0.203, P = .653). There was a weak positive correlation between PSA1/PSA2 and T1/T2, rs (160) = 0.163, P = .034. An extra unit increase in PSA1 concentration leads to a 0.805 (95% confidence interval [CI], 0.781-0.830) and 0.828 (95% CI, 0.807-0.849) ng/mL increase in PSA2 concentration in groups 1 and 2, respectively, that is, patients with and without prostate cancer had a similar decrease in the PSA levels. When measured in the afternoon, 66.6% and 50% patients with a morning PSA level over 3 or 4 ng/mL had a PSA drop below these levels, respectively. PSA has a diurnal variation and the timing of measurement may alter the decision of the clinician for transrectal ultrasound prostate biopsy.

IJU this issue

This, the latest issue of the International Journal of Urology, covers a wide range of topics including three Review Articles, 17 Original Articles and eight Urological Notes. In their Review Article, Johnin et al. (Otsu, Japan) reconsider the indications for voiding cystourethrography and the procedure itself in view of the distress and anxiety it causes pediatric patients, despite the fact it is considered essential for investigation of lower urogenital tract diseases in children. The other two reviews provide up-to-date information on upper tract urothelial carcinomas and the endourological management of urolithiasis. In their Original Article, Song et al. (St. Louis, USA) report the utility of urine aquaporin 1 and perilipin 2 as new non-invasive biomarkers for distinguishing benign from malignant small renal masses. The authors have confirmed that the two biomarkers have high sensitivity and specificity for detecting clear cell and papillary renal cell carcinoma. Their results imply that the use of these markers might reduce both the number of operations for benign renal masses and the number of renal biopsies required for diagnosis of malignant renal lesions. The Original Article by Harada et al. (Kobe, Japan) provides detailed data on the treatment patterns and outcomes in patients with unresectable or metastatic renal cell carcinoma (RCC) in a real-world setting in Japan. As few previous studies have summarized such data, this study is noteworthy in clarifying the actual clinical situation in Japan. However, as immune checkpoint inhibitors are becoming a standard form of treatment for advanced RCC in the place of tyrosine kinase inhibitors, data from similar investigations carried out several years later would be interesting. In their Urological Note, Shiraishi et al. (Kobe, Japan) describe a unique case of right RCC involving the inferior vena cava in which the surgical specimen was found to have become completely necrotic after sequential treatment with pazopanib followed by nivolumab, even though the tumor mass was still present in both the right kidney and inferior vena cava extending to just above the diaphragm. This case report provides two important pieces of information. One is that sequential treatment with a tyrosine kinase inhibitor followed by nivolumab might be an optimal form of presurgical neoadjuvant therapy. The other is that a pathological response appeared to have been obtained even though the effect was not clinically complete. Clinicians sometimes encounter patients with metastatic RCC who show a good outcome after immuno-oncology drugs, even though the tumor response might not be complete. The reason for this could be related to this mechanism. Inoue et al. (Kyoto, Japan) report some important results of primary targeted focal cryotherapy for patients with magnetic resonance imaging-visible, magnetic resonance–ultrasound image fusion targeted biopsy-proven clinically localized prostate cancer. The authors found that the combination of both multiparametric magnetic resonance imaging (not only both diffusion-weighted and T2-weighted imaging, but also contrast magnetic resonance imaging) and prostate-specific antigen variables (prostate-specific antigen <4 ng/mL and rate of prostate-specific antigen decrease >50%) might provide possible follow-up criteria for suggesting the technical success of focal therapy and/or indications for follow-up biopsy. Currently, very few data are available for defining what form of biochemical control is appropriate for confirming treatment success when an appreciable proportion of the prostate gland is left untreated by focal therapy. There is also a lack of clarity regarding the optimal selection of imaging sequences for the detection of remaining (insufficiently ablated) or recurrent prostate cancer. Therefore, the authors’ criteria will be useful to other focal therapists. None declared.

819P - Prognostic associations of early prostate-specific antigen (PSA) changes in patients with metastatic castration-resistant prostate cancer treated with with abiraterone acetate or enzalutamide

Background: The availability of multiple treatments for metastatic castration-resistant prostate cancer (mCRPC) mandates the need to identify prognostic factors applicable to clinical practice. Variations in (PSA) levels are widely used in the monitoring of response to treatment with abiraterone acetate (AA) or enzalutamide, but are not validated as an early biomarker for overall survival (OS). Objective: To evaluate the association between early PSA changes and OS following enzalutamide or AA treatments in mCRPC. Methods: We retrospectively evaluated mCRPC patients treated with AA or enzalutamide, before or after docetaxel, in 11 reference hospitals between 2011 and 2017. A descriptive and multivariate analysis of the data was carried out in order to establish the association of PSA variations at 4 and 12 weeks (expressed as 30% and 50% percentage modifications, respectively, relative to baseline value at the start of AA or enzalutamide) with OS. Association with OS was analyzed using multivariate Cox regression and log-rank analyses. Spearman’s rho correlation coefficient (r) was calculated to evaluate the association between PSA changes at 4 and 12 weeks. Results: We analyzed 450 mCRPC patients with a median follow-up of 16 months (1-65). A 30% PSA decline at 4 weeks was associated with longer OS (30 vs 20 months; hazard ratio [HR] 0.55 (0.42-0.73), p < 0.001), as well as a 50% PSA decrease at 12 weeks (39 vs 19 months; HR 0.42 (0.31-0.56), p < 0.001). We found a detriment in survival in patients with a 30% PSA rise at 4 weeks, with shorter OS (22 vs 26 months; HR 1.5 (1.07-2.21), p = 0.025) and a 50% PSA increase at 12 weeks after starting treatment (14 vs 29 months; 2.66 (1.93-3.67) p < 0.001), in both univariate and multivariable models. The percentage PSA decline at 4 weeks was significantly correlated with the percentage PSA change at 12 weeks (r = 0.635; p < 0.001). Limitations include the retrospective design of this analysis. Conclusions: PSA changes as early as 4 weeks after enzalutamide or AA initiation are highly associated with OS in mCPRC. Prospective multicentre validation studies are needed to confirm these findings. Legal entity responsible for the study: Fernando López Campos. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Prostate-Specific Antigen Trends Predict the Probability of Prostate Cancer in a Very Large U.S. Veterans Affairs Cohort

If prostate-specific antigen (PSA) trends help identify elevated prostate cancer (PCa) risk, they might provide early warning of progressing cancer for further evaluation and justify annual testing. Our objective was to determine whether PSA trends predict PCa likelihood. A biopsy cohort of 361,657 men was obtained from a Veterans Affairs database (1999–2012). PSA trends were estimated for the 310,458 men with at least 2 PSA tests prior to biopsy. Cancer tumors may grow exponentially with cells doubling periodically. We hypothesized that PSA from prostate cancer grows exponentially above a no cancer baseline. We estimated PSA trends on that basis along with five descriptive variables: last PSA before biopsy, growth rate in PSA from cancer above a baseline, PSA variability around the trend, number of PSA tests, and time span of tests. PSA variability is a new variable that measures percentage deviations of PSA tests from estimated trends with 0% variability for a smoothly increasing trend. Logistic regression models were used to estimate relationships between the probability of PCa at biopsy and the trend variables and age. All five PSA trend variables and age were significant predictors of prostate cancer at biopsy (p < 0.0001). An overall logistic regression model achieved an AUC of 0.67 for men with at least 4 tests over at least 3 years, which was a substantial improvement over a single PSA (AUC 0.58). High probability of PCa was associated with low PSA variability (smooth trends), high PSA, high growth rate, many tests over a long time-span and older age. For example, at 4.0 PSA the probability of cancer is 32% for 1 PSA test and increases to 68% for 8 tests over 7 years with smooth, fast growth (0% variability and 50% exponential growth). Our results show that smooth, fast exponential growth in PSA above a baseline predicts an increased probability of PCa. The probability increases as smooth (low variability) trends are observed for more tests over a longer time span, which makes annual testing worth considering. Worrisome PSA trends might be used to trigger further evaluation and continued monitoring of the trends—even at low PSA levels.