Higher Prostate-specific Antigen Values Research Articles

Clinical and histopathological parameters in transrectal ultrasound-guided biopsies associated with tumor upgrading after radical prostatectomy: A comparative analysis of risk groups.

Thanks to technological advances, prostate cancer (PCa) can be diagnosed at a younger age. It is known that most of these patients are in the low-intermediate risk group, and the histological grade of the tumor increases in half of those undergoing radical prostatectomy (Rp) compared to their diagnostic biopsies. This is especially important in terms of active surveillance (AS) and/or the timely evaluation of curative treatment options in patients diagnosed at an early age. Our aim was to investigate clinical and histopathological parameters that may be associated with an increase in the histological grade of the tumor in patients with acinar adenocarcinoma who were diagnosed by transrectal ultrasound-guided biopsy (TRUS-Bx) and underwent Rp. A total of 205 patients with classical acinar adenocarcinoma diagnosed by TRUS-Bx without metastasis and who underwent Rp were grouped according to the D'Amico risk classification. Age at diagnosis, serum prostate-specific antigen (PSA), PSA density, prostate volume, Prostate Imaging Reporting and Data System (PI-RADS) score, clinical stage, Gleason Grade Group (GGG), high-grade intraepithelial neoplasia in tumor-free cores (HGPIN) (single and ≥2 cores), perineural invasion (PNI), and lymphovascular invasion (LVI) was obtained. Additionally, GGG, pathological stage, lymph node metastasis, surgical margin positivity, and tumor volume obtained from Rp were evaluated. Comparisons were made between the case groups in which the tumor grade increased and remained the same, in terms of age, serum PSA, PSA density, HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI in all biopsies (with or without tumors), as well as risk groups. In addition, the relationships of HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI on TRUS-Bx with age, serum PSA and PSA density, tumor volume, surgical margin positivity, pathological stage, lymph node metastasis, and risk groups were examined separately. Of the patients, 72 (35.1%) were in the low-risk group, 95 (46.3%) in the intermediate-risk group, and 38 (18.5%) in the high-risk group. Most of the patients with an increased histological grade (n = 38, 48.1%) were in the low-risk group (p < 0.05) and had an advanced median age. HGPIN in single and ≥2 tumor-free cores and PNI were more common in these patients (p < 0.01, p < 0.001, and p < 0.05, respectively). According to the multivariable analysis, advanced age (odds ratio [OR]: 1.087, 95% confidence interval [CI]: 1.029-1.148, p < 0.05), high serum PSA (OR: 1.047, 95% CI: 1.006-1.090, p < 0.05), HGPIN in ≥2 tumor-free cores (OR: 6.346, 95% CI: 3.136-12.912, p < 0.001), and PNI (OR: 3.138, 95% CI: 1.179-8.356, p < 0.05) were independent risk factors for a tumor upgrade. Furthermore, being in the low-risk group was an independent risk factor when compared to the intermediate- and high-risk groups (OR: 0.187, 95% CI: 0.080-0.437, p < 0.001 and OR: 0.054, 95% CI: 0.013-0.230, p < 0.001, respectively). The HGPIN diagnosis was more common in the low- and intermediate-risk groups. Advanced age at diagnosis, high serum PSA and PSA density values were associated with PNI on TRUS-Bx. High serum PSA and PSA density values were associated with LVI on TRUS-Bx. Surgical margin positivity was higher in cases with PNI and LVI detected by TRUS-Bx. HGPIN in ≥2 tumor-free cores, PNI, and LVI on TRUS-Bx were associated with a higher rate of lymph node metastases. In patients diagnosed with acinar adenocarcinoma, the presence of HGPIN even in a single tumor-free core on TRUS-Bx was found to be significant in terms of showing an increase in the histological tumor grade in Rp. The diagnosis of HGPIN in ≥2 tumor-free cores on TRUS-Bx was determined as an independent risk factor for an increased Gleason score after Rp. Furthermore, an advanced age, a high serum PSA value, being in the low-risk group, and the presence of PNI were associated with a tumor upgrade. HGPIN in ≥2 tumor-free cores, PNI, and LVI were also associated with lymph node metastasis. Therefore, the diagnosis of HGPIN should be signed out on pathological reports.

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.

Serum Prostat-Spesifik Antijen Düzeyi 2,5-10 Ng/Ml Arasındaki Erkeklerde İki Kadeh Testinin Prostat Biyopsisi ve Asemptomatik Prostat İnflamasyonu Varlığı ve Derecesiyle İlişkisinin Araştırılması

Objective: Prostate-specific antigen (PSA) is a marker used to detect prostate cancer. When high PSA values are detected, a prostate biopsy is performed considering the possibility of prostate cancer. PSA elevation is not specific to prostate cancer, but may also be caused by conditions such as benign prostatic hyperplasia (BPH), urinary tract infection, and chronic prostatitis. Prostate cancer is not detected in approximately 66% of patients undergoing a biopsy, and patients are exposed to unnecessary biopsy and biopsy complications. Chronic prostatitis is detected in approximately 40% of these biopsies. The two-glass test is based on examining urine before and after rectal examination, which is used in diagnosing chronic prostatitis. In this study, we aimed to reveal the two-glass test’s effectiveness in predicting the incidence of prostatitis and inflammation in patients with a PSA value of 2.5-10 ng/ml and who underwent prostate needle biopsy.&#x0D; &#x0D; Methods: Fifty-two male patients, aged between 50 and 78 years, with PSA values between 2.5 and 10 ng/ml, who applied to our clinic were included in the study. EPS-two-glass test and prostate biopsy were applied to all patients. EPS; is a sample obtained by removing the fluid from the urethra after a prostate massage; VB-3; shows the urine produced by taking about 10 ml of urine voided after massage. EPS and VB3 detect prostate infection. Under the microscope, ≥10 leukocytes were considered significant for prostate inflammation. According to the pathology results, the patients were divided into 3 groups; prostate cancer, BPH, and chronic prostatitis. The chronic prostatitis group was classified according to the histopathological calcification described by Nickel.&#x0D; &#x0D; Results: In this study, the ratio of chronic prostatitis was found to be 38%. VB3 positivity was found to be statistically significant in the chronic prostatitis group compared to the other groups (p = 0.028). Although there was no statistically significant difference between the prevalence of inflammation and PSA elevation, PSA was found to be higher in the multifocal inflammation subgroup than in the focal inflammation patient group.&#x0D; &#x0D; Conclusion: The relationship between chronic prostatitis and PSA elevation remains a mystery. Although no statistical relationship was found between inflammation and PSA elevation in this study, the significant correlation between chronic prostatitis and VB3 positivity reinforces the possibility of this relationship. We believe that our results will form the basis for further studies to avoid unnecessary biopsies.

Association between patient ethnicity and prostate cancer diagnosis following a prostate-specific antigen test: a cohort study of 730,000 men in primary care in the UK

BackgroundBlack men have higher prostate-specific antigen (PSA) levels and higher prostate cancer incidence and mortality than White men, while Asian men tend to have lower prostate cancer incidence and mortality than White men. Much of the evidence comes from the USA, and information from UK populations is limited.MethodsThis retrospective cohort study used data on patients registered at general practices in England contributing to the Clinical Practice Research Datalink (CPRD) Aurum dataset. Those eligible were men aged 40 and over with a record of ethnicity and a PSA test result recorded between 2010 and 2017 with no prior cancer diagnosis.The aim was to assess the incidence of prostate cancer following a raised PSA test result in men from different ethnic groups. Additionally, incidence of advanced prostate cancer was investigated. Cancer incidence was estimated from multi-level logistic regression models adjusting for potential confounding factors.Results730,515 men with a PSA test were included (88.9% White). Black men and men with mixed ethnicity had higher PSA values, particularly for those aged above 60 years. In the year following a raised PSA result (using age-specific thresholds), Black men had the highest prostate cancer incidence at 24.7% (95% CI 23.3%, 26.2%); Asian men had the lowest at 13.4% (12.2%, 14.7%); incidence for White men was 19.8% (19.4%, 20.2%). The peak incidence of prostate cancer for all groups was in men aged 70–79. Incidence of prostate cancer diagnosed at an advanced stage was similar between Black and White men.ConclusionsMore prostate cancer was diagnosed in Black men with a raised PSA result, but rates of advanced prostate cancer were not higher in this group. In this large primary care-based cohort, the incidence of prostate cancer in men with elevated PSA levels increases with increasing age, even when using age-adjusted thresholds, with Black men significantly more likely to be diagnosed compared to White or Asian men. The incidence of advanced stage prostate cancer at diagnosis was similar for Black and White men with a raised PSA result, but lower for Asian men.

Role of 18F-FCH PET/CT in Detecting Recurrences of Prostate Cancer After Curative Treatments.

To evaluate the role of 18F-fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) in prostate cancer (PC) patients with biochemical recurrence who were submitted to different curative treatments. Seventy-five patients with PC who underwent 18F-FCH PET/CT for biochemical recurrence were retrospectively analyzed to distinguish patients who were submitted only to prostatectomy (PR group), only to radiotherapy (RT) on prostate with curative intent (RT group), and to both (PR + RT group). Correlations between 18F-FCH PET/CT and outcome and between prostate-specific antigen (PSA) values and sites and the number of metastases were analyzed. The performance of 18F-FCH PET/CT in relation to the PSA value and of maximum standardized uptake value (SUVmax) value in relation to patient outcome were assessed by receiver operating characteristic (ROC) curves. 18F-FCH PET/CT relapses mostly involved lymph nodes, bones, and prostate bed. K-cohen test showed moderate agreement with the outcome in the whole population and in the PR group, whereas in the RT group it was perfect and in PR + RT fair. A statistically significant difference in PSA values was observed in the presence of lymph node metastases and with multiple metastases. ROC curves showed PSA cut-off values of 1.96 ng/dL, 1.95, 1.81, and 2.96, respectively, in the whole population, PR, RT and PR + RT group. SUVmax cut-off values of 3.75, 3.45, and 4.7 were described in the whole population, PR group, and PR + RT group. The study confirms that 18F-FCH PET/CT is still valid in PC patients with suspected biochemical recurrence. Therefore, we can affirm that it still makes sense to perform it both with high PSA values and with lower values when prostate-specific membrane antigen tracers are not available.

Very Long-Term Complete Remission Can Be Achieved in Men With High-Risk Localized Prostate Cancer and a Very High PSA Value: An Analysis of the GETUG 12 Phase 3 Trial.

Serum prostate specific antigen (PSA) is a well-known prognostic parameter in men with prostate cancer. The treatment of men with very high PSA values and apparently no detectable metastases is not fully established. Ancillary analysis from the GETUG 12 phase 3 trial. Patients with non-metastatic high-risk prostate cancer by bone and computerized tomography (CT) scan were randomly assigned to receive androgen deprivation therapy (ADT) and docetaxel plus estramustine or ADT alone. Relapse-free survival (RFS), clinical RFS, metastases-free survival (MFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated using the Kaplan-Meier method for different levels of PSA (50 ng/mL, 75 ng/mL, and 100 ng/mL). The relationship between PSA and outcomes was studied using residual-based approaches and spline functions. The median follow-up was 12 years (range: 0-15.3). Baseline PSA (<50 ng/mL, n=328; ≥50ng/mL, n=85) was associated with improved RFS (P=.0005), cRFS (P=.0024), and MFS (P=.0068). The 12-year RFS rate was 46.33% (CI 40.59-51.86), 33.59% (CI 22.55-44.97), and 11.76% (1.96-31.20) in men with PSA values <50 ng/mL (n=328), 50-100 ng/mL (n=68), and ≥100 ng/mL (n=17), respectively. Exploratory analyses revealed no deviation from the linear relationship assumption between PSA and the log hazard of events. Men with apparently localized prostate cancer and a high baseline PSA value have a reasonable chance of being long-term disease-free when treated with curative intent combining systemic and local therapy.

Diagnosis of high-grade prostate cancer in patients with unexpectedly low prostate specific antigen levels: a rare case series

Link of Video Abstract: https://youtu.be/PfhZ7H4kszQ Background: Prostate cancer is regarded as one of the most common leading causes of male cancer-related death worldwide. Clinicians agree that prostate specific antigen (PSA) is the best prostate cancer predictor. High PSA levels increase prostate cancer risk in most men. However, other research suggests that prostate cancer with low PSA levels is aggressive. In this uncommon case series, we present three high-grade prostate cancer patients with low PSA. Case Description: Between 2018 and 2019, three patients were referred for further therapeutic management after initial evaluation and treatment from secondary hospitals. All patients underwent complete diagnostic procedures including Laboratory examination, Pathological examination, and Radiologic imaging. PSA levels were 0.67 ng/mL, 4.0 ng/ml, and 4.93 ng/mL in the first, second, and third patients, respectively. The first two of three patients had a Gleason score (GS) of 9 (5+4), and one patient presented with GS of 8 (5+3). Distant metastatic disease was not found in our series. All of the patients underwent hormonal therapy, and none of them underwent radical prostatectomy. Follow-ups were completed in all patients, with the survival of 3 months, 4 months, and 12 months respectively. Conclusion: High-grade prostate cancer in patients with low PSA levels emphasizes the need for rigorous history taking and physical examination and quick investigation of new biomarkers and criteria for prostate cancer detection. These patients' prognosis and optimal therapy are unknown. These patients have a worse prognosis than those with high PSA values, according to multiple studies.

New transperineal ultrasound-guided biopsy for men in whom PSA is increasing after Miles’ operation

ObjectivesCurrently, a prostate biopsy is guided by transrectal ultrasound (US) alone. However, this biopsy cannot be performed in men without an anus. The aim of this study was to show the outcomes of a new transperineal US (TPUS)-guided biopsy technique in patients who underwent Miles’ operation.MethodsBetween April 2009 and March 2022, TPUS-guided biopsy was consecutively conducted in 9 patients (median, 71 years; range, 61–78 years) with high prostate-specific antigen values (22.60 ng/mL; 6.19–69.7 ng/mL). Their anuses were all removed due to rectal cancer. TPUS-guided biopsy was performed according to information on prostate magnetic resonance imaging. The technical success rate, cancer detection rate, and complication rate were recorded. Tumor sizes were compared between benign and cancer groups using an unpaired t-test with Welch’s correction.ResultsThe new TPUS-guided biopsy was successfully performed in all patients. Cancer was detected in 77.8% (7/9) of the patients. These were all categorized as PI-RADS 5. Among them, the detection rate of significant cancer (Gleason score 7 or higher) was 66.7% (6/9). The median tumor size was 2.4 cm (1.7–3.1 cm). However, two patients were diagnosed with benign tissue with PI-RADS 3 or PI-RADS 4. Their median tumor size was 1.0 cm (0.8–1.2 cm). There was significant difference between the cancer and benign groups (p = 0.037) in terms of tumor size. Neither post-biopsy bleeding nor infections occurred.ConclusionsNew TPUS-guided biopsy technique may contribute to detecting large PI-RADS 5 prostate cancer in men after Miles’ operation.

Nadir Prostate-specific Antigen as an Independent Predictor of Survival Outcomes: A Post Hoc Analysis of the PROSPER Randomized Clinical Trial.

This post hoc analysis of PROSPER evaluated the relationship between depth of PSA decline and clinical outcomes in enzalutamide-treated men with nonmetastatic castration-resistant prostate cancer. PROSPER was an international, randomized, double-blind, placebo-controlled, phase 3 trial that demonstrated significantly improved metastasis-free survival and overall survival with androgen deprivation therapy plus enzalutamide vs placebo. A total of 905 enzalutamide-treated men were included in this post hoc analysis. Metastasis-free survival (primary endpoint) and overall survival (secondary endpoint) were evaluated for 4 mutually exclusive subgroups defined by PSA decline: <50% (reference); ≥50% to <90%; ≥90%, nadir ≥0.2 ng/mL; and ≥90%, nadir <0.2 ng/mL. Medians and 95% confidence intervals were determined using a 12-month landmark analysis; hazard ratios and P values were based on an unstratified Cox proportional analysis model. In enzalutamide-treated men, PSA declines of <50%, ≥50% to <90%, ≥90% with nadir ≥0.2 ng/mL, and ≥90% with nadir <0.2 ng/mL were associated with median metastasis-free survival in months (95% confidence intervals) of 22.1 (14.8-not reached), 34.2 (29.4-not reached), 36.6 (33.4-not reached), and not reached, respectively, and overall survival in months (95% confidence intervals) of 40.8 (31.7-44.9), 54.4 (49.0-67.0), 64.3 (63.4-not reached), and not reached, respectively. There was a statistically significant correlation between greater depth of PSA decline and improved clinical outcomes, suggesting a previously underappreciated relationship between changes in PSA levels and clinical outcomes in nonmetastatic castration-resistant prostate cancer.

Confirmation of PSMA expression measured on [68Ga]Ga-PSMA PET/CT by immunohistochemistry in prostate adenocarcinoma.

Our aim is to determine the accuracy of [68Ga]Ga-PSMA PET/CT in showing PSMA expression in primary prostate cancer and to investigate the relationship between SUVmax and immunohistochemical PSMA expression, Gleason score, and PSA value. We retrospectively analyzed 66 male patients who were diagnosed with primary prostate adenocarcinoma, underwent pre-treatment [68Ga]Ga-PSMA PET/CT examination for staging, and performed radical prostatectomy between March 2018-August 2020. Immunohistochemical staining was applied to the radical prostatectomy specimens of all patients to detect PSMA expression. The results were evaluated as an immunoreactive score (IRS) and a modified IRS was obtained. Gleason score groups and prostate-specific antigen (PSA) serum values of the patients were obtained from the patient files. The high SUVmax of primary prostate tumors was significantly correlated with a high modified IRS score (score 2; 3), high PSA value, high Gleason score, and metastasis. In correlation analysis, a positive correlation was found between SUVmax and PSA value and modified IRS score (r = 0.69, p = 0.001; r = 0.39, p = 0.001). In addition, there was a statistically significant weak correlation between PSA serum concentration and modified IRS scores (r = 0.267; p = 0.03). In regression analysis, the percentage of positive cells had a statistically significant and increasing effect on SUVmax (p = 0.031; std beta = 0.268; 95% CI = 0.231-4.596). In prostate adenocarcinoma, SUVmax of the primary tumor in [68Ga]Ga-PSMA PET/CT correlates with immunohistochemical PSMA expression. In addition, high SUVmax is associated with markers of poor prognoses, such as high PSMA expression, PSA value, and Gleason score.

Risk Evaluation of Bone Metastases and a Simple Tool for Detecting Bone Metastases in Prostate Cancer: A Population-Based Study.

Population-based estimates of the incidence and prognosis of bone metastases in prostate cancer (PC) are lacking. We aimed to characterize the incidence and risk of bone metastases and develop a simple tool for the prediction of bone metastases among patients with PC. Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 75698 patients with PC with confirmed presence or absence of bone metastases at diagnosis between 1975 and 2019 in the United States were used for analysis. Data were stratified by age, race, residence, median income, prostate-specific antigen (PSA) values, tumor size, distant metastatic history, and positive lymph node scores. Multivariable logistic and Cox regressions were performed to identify predictors of bone metastases and factors correlated with all-cause mortality. Classification tree analysis was performed to establish a model. After patients with PC with missing data were excluded, 75698 cases remained. Among these, 3835 patients had bone metastases. Incidence proportions were highest in patients with a high prostate-specific antigen (PSA) value (odds ratio (OR), 2.49; 95% confidence interval (CI), 1.35-4.35; p < 0.002). Multivariable Cox regression and risk analyses indicated that high PSA values (hazards ratio (HR), 19.8; 95% CI, 18.5-21.2; p < 0.001) and high positive lymph node scores (vs. score 0; HR, 8.65; 95% CI, 7.89-9.49; p < 0.001) were significant risk factors for mortality. Meanwhile, in the predication tree analysis, PSA values and lymph node scores were the most significant determining factors in two models. Median survival among the patients with PC was 78 months, but only 31 months among those with bone metastases. Patients with PC with high PSA values or high positive lymph node scores were at a significantly higher risk of bone metastases. Our study may provide a simple and accurate tool to identify patients with PC at high risk of bone metastases based on population-based estimates.

Absolute Prostate Specific Antigen after 6 Months of Androgen Deprivation Therapy Is a Predictor of Overall and Cancer-Specific Mortality in Men with Hormone-Sensitive Prostate Cancer.

We sought to determine if absolute prostate specific antigen (PSA) value after 6 months of androgen deprivation therapy (ADT) is predictive of subsequent survival in patients with prostate adenocarcinoma. We performed a retrospective review of men receiving care within the Veterans Health Administration who initiated ADT for prostate adenocarcinoma. We used low- (≤0.2 ng/ml), intermediate- (>0.2 to 4 ng/ml) and high-risk (>4 ng/ml) absolute PSA values after 6-9 months of ADT, previously described in Southwest Oncology Group trial 9346. The primary endpoints were all-cause mortality and prostate cancer-specific mortality (PCSM). Kaplan-Meier survival curves for each PSA category were estimated and log-rank test was conducted. We employed Cox regression analysis adjusted for covariates and inverse propensity score weights associated with PSA categories to estimate the PSA category association with PCSM and all-cause mortality. We identified 9,170 patients in our cohort. Following ADT induction, 3,508 patients had low, 3,419 had intermediate and 2,243 had high PSA values. Two- and 5-year survival rates for low, intermediate and high PSA groups were 93.9% and 85.2% vs 88.6% and 71.2% vs 63.6% and 38.6%, respectively (p <0.0001). Patients in the high and intermediate PSA categories had a 15-fold and 3-fold higher risk of PCSM compared to those with PSA <0.2 ng/ml (p <0.0001). Absolute PSA in hormone-sensitive prostate cancer after 6-9 months of ADT is a predictor of overall mortality and PCSM. This measure can rapidly assess the efficacy of new interventions in phase 2 clinical trials.

The impact of time to prostate specific antigen nadir on biochemical recurrence and mortality rates after radiation therapy for localized prostate cancer.

To investigate the effect of time to prostate-specific antigen (PSA) nadir (TTN) after radiation therapy (RTx) for prostate cancer (PCa) on biochemical recurrence (BCR) and overall survival (OS) rates. We analyzed 2,506 patients treated with RTx (external beam radiotherapy, brachytherapy or combinations) between years 2000 and 2021. Kaplan Meier and multivariable Cox regression models tested BCR-free survival and OS after stratification according to TTN (≤24 vs. 24.1-60 vs. >60 months). Similar analyses were performed after stratification according to absolute PSA values at nadir (<0.01 vs. 0.01-0.1 vs. 0.11-0.4 vs. >0.4 ng/ml). Finally, we repeated analyses after setting the time point of PSA nadir as the beginning of follow up in survival analyses. 10-year BCR-free survival rates were 55.5, 81.7 and 91.1% and OS rates were 71.5, 79.4 and 96.1% for TTN ≤24 months, 24.1 month-60 month and >60 months, respectively. Longer TTN was an independent predictor for BCR-free survival and OS (all P<0.001). However, after accounting for lead-time bias, in multivariable analyses, this association remained only significant for BCR-free survival (P≤0.03), but not for OS (P≥0.1). Finally, compared to a PSA nadir of <0.01 ng/ml, PSA nadir of 0.01-0.1 ng/ml, 0.11-0.4 ng/ml as well as >0.4 ng/ml were independent predictors for shorter BCR-free survival (P≤0.02), but not OS (P≥0.08). Shorter time to TTN and high PSA values at nadir are indicative of early treatment failure (BCR) and OS. However, after accounting for lead-time bias, this effect only remained valid for BCR.

Do the Prostate-Specific Antigen (PSA) Tests That Are Ordered in Clinical Practice Adhere to the Pertinent Guidelines?

Scientific societies have provided guidelines to reduce PSA-specific harms. We studied the potential non-compliance of PSA testing with current guidelines in general practice. A cross-sectional study of a random sample of 1291 patients with a PSA test was performed between January and April 2018 in primary health care. Patients with a previous prostate cancer diagnosis or those who were being followed-up for previous high PSA values were excluded. Two independent researchers classified whether each test was potentially non-compliant with recommendations. We estimated frequencies of potentially non-compliant PSA determinations and calculated prevalence ratios (PR) to assess their relationship with possible explanatory variables. A total of 66% (95% CI: 62–69%) of PSA requests in asymptomatic patients were potentially non-compliant with the current guideline. This was associated with having a previous diagnosis of neoplasm (PR adjusted by age and life expectancy: 1.18; 95% CI: 1.02–1.37) as well as being a current consumer of tobacco, alcohol, or other drugs (PR: 0.80; 95% CI: 0.67–0.97). Real world data shows that patients are still frequently exposed to overdiagnosis risk with a PSA potentially non-compliant with recommendations. Patients diagnosed with another neoplasm or non-consumers of toxic substances were more exposed, probably due to increased contact with doctors or health-seeking behaviour.

Clinical characteristics and survival outcomes in patients with a high PSA and non-metastatic prostate cancer

To investigate the clinical presentation and survival outcomes of patients with both a high prostate-specific antigen (PSA) value and non-metastatic prostate cancer (PC).In total, 2053 PC patients were managed in our institute between January 2008 and December 2014. A total of 343 (16.7%) patients who presented with PSA values > 100 ng/mL were enrolled. Non-metastatic and metastatic PC were identified in 67 (group 1) and 276 (group 2) patients, respectively. Furthermore, 75 metastatic PC patients with PSA values < 20 ng/mL were included (group 3) for comparison. All demographics and survival outcomes were retrospectively reviewed by a questionnaire.Group 2 patients had a higher PSA level than did group 1 (median: 1095 vs. 283 ng/mL, p < 0.001), and a higher Gleason grade than did groups 1 and 3 (grade group 4 plus 5: 60%, 77%, and 56%, for groups 1, 2, and 3, respectively; p < 0.001). Other demographics were similar among groups. Group 1 patients survived significantly longer than group 2 and 3 in terms of overall and cancer-specific survival rates (5-year overall survival rates: 87.5%, 46.3%, and 66.9%; 5-year cancer-specific survival rates: 94.7%, 52.7%, and 68.7% for groups 1, 2, and 3, respectively). Group 1 patients receiving local definitive treatments, such as radiation therapy or cryoablation, received survival and metastasis-free benefits compared to those without local treatment.Patients with a high PSA value were not destined to have metastatic PC. Non-metastatic PC patients with a high PSA level obtained a survival benefit from local prostate-definitive treatments.

Real-world safety and effectiveness of radium-223 in Japanese patients with castration-resistant prostate cancer (CRPC) and bone metastasis: exploratory analysis, based on the results of post-marketing surveillance, according to prior chemotherapy status and in patients without concomitant use of second-generation androgen-receptor axis-targeted agents

BackgroundBased on results from Japanese post-marketing surveillance, exploratory analyses were performed to investigate real-world outcomes of radium-223 for metastatic CRPC (mCRPC) according to patient characteristics.MethodsThis non-interventional, prospective study enrolled mCRPC patients selected for radium-223 treatment in clinical practice. Six-month safety and effectiveness were evaluated in subgroups who had/had not received prior chemotherapy (prior-chemo/no prior-chemo groups), and a subgroup who had not received concomitant androgen-receptor axis-targeted agents (ARATs).ResultsIn the overall population (n = 296), the prior-chemo group (n = 126) tended to have more bone metastases, more analgesic use, and higher prostate-specific antigen values than the no prior-chemo group (n = 170). Incidences of treatment-emergent adverse events (TEAEs), drug-related TEAEs, and ≥ grade 3 drug-related hematological TEAEs were 47% vs. 53%, 25% vs. 29%, and 4% vs. 7% in the no prior-chemo and prior-chemo groups, respectively. Incidences of TEAEs (61%), drug-related TEAEs (36%), and ≥ grade 3 drug-related hematological events (12%) were numerically higher in 33 patients who had received two lines of prior chemotherapy. Multivariate analysis showed that two lines of prior chemotherapy, and hemoglobin, platelet, and lactate dehydrogenase values were baseline factors significantly related to ≥ grade 2 platelet count decreased. Safety and effectiveness in patients without concomitant ARATs (n = 201) were similar to those in the overall population.ConclusionIn a real-life setting, radium-223 was well tolerated irrespective of prior chemotherapy, but relatively higher incidences of TEAEs and hematotoxicities were suggested in patients with two lines of prior chemotherapy, possibly reflecting more advanced disease. Radium-223 safety and effectiveness in patients without concomitant ARATs were favorable.

The Relationship Between Vitamin D Gene Polymorphisms and the Diagnosis of Prostate Cancer in Patients with High Prostate-Specific Antigen Value

The Relationship Between Vitamin D Gene Polymorphisms and the Diagnosis of Prostate Cancer in Patients with High Prostate-Specific Antigen Value

Infertile Men Have Higher Prostate-specific Antigen Values than Fertile Individuals of Comparable Age

BackgroundInfertile men are at greater risk for oncological and nononcological chronic disease than fertile individuals. ObjectiveTo investigate prostate-specific antigen (PSA) values in men presenting for primary couple’s infertility compared with a cohort of fertile individuals, according to the recommendation of the European Association of Urology guidelines that a first PSA assessment should be done at 40–45 yr of age. Design, setting, and participantsThis is a cross-sectional study. Data from 956 (90%) infertile men and 102 (9.6%) fertile participants were analysed. Circulating hormones, total PSA, and semen parameters were investigated in every man. Outcome measurements and statistical analysisDescriptive statistics, local polynomial smoothing, and linear regression models were used to test potential associations with PSA levels. Results and limitationsOverall, PSA >1 ng/ml was found in 318 (30%) men. Serum PSA was higher (p = 0.02), while serum testosterone (p < 0.01) was lower in infertile than in fertile men. In participants younger than 40 yr, 176 (27%) men had PSA >1 ng/ml; of them, a greater proportion were infertile (28% infertile vs 17% fertile, p = 0.03). At multivariable linear regression analysis, infertile status (coefficient 0.21; 95% confidence interval 0.02–0.39) was associated with higher PSA values, after adjusting for age and serum testosterone level. This was a single-centre study, raising the possibility of selection biases. ConclusionsInfertile men have higher PSA values than fertile individuals. Of all, almost one out of three primary infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. Patient summaryIn this study, we observed that (1) infertile men have higher prostate-specific antigen (PSA) values than fertile individuals and (2) a greater proportion of infertile men younger than 40 yr had total PSA >1 ng/ml at the first assessment. These data might be relevant to study the potential clinical impact of more rigorous screening in primary infertile men.

Factors associated with false negative and false positive results of prostate-specific antigen (PSA) and the impact on patient health: Cohort study protocol.

Introduction:Prostate-specific antigen (PSA) is the main tool for early detection, risk stratification and monitoring of prostate cancer (PCa). However, there are controversies about the use of PSA as a population screening test because of the high potential for overdiagnosis and overtreatment associated. The net benefit of screening is unclear and according to the available recommendations, it should be offered to well-informed men with an adequate health status and a life-expectancy of at least 10 years or to men at elevated risk of having PCa. In addition, the factors that influence test results are unclear, as is impact of false positive or negative results on patient health.Our objective is to assess the clinical and analytical factors associated with the presence of false positive and false negative results and the diagnostic/therapeutic process followed by these patients.Methods and analysis:A prospective observational cohort study will be carried out. We will include a cohort of patients with a positive PSA result (1.081 patients) and a sample of patients with negative results (572 patients); both will be followed for 2 years by reviewing medical records to assess the variables associated with these results, as well as characteristics of patient management after a positive PSA value. We will include those patients with a PSA determination from 2 hospitals in the Valencian Community. Patients who have been previously diagnosed with prostate cancer or who are being followed for previous high PSA values will be excluded.Discussion:The study will estimate the frequency of false positive and false negative PSA results in routine clinical practice, and allow us to quantify the potential harm caused.Study registration:Clinicaltrials.gov (https://clinicaltrials.gov/): NCT03978299, June 7, 2019.

Mean Platelet Volume as an Inflammation Marker, Possible Biomarker of Tumor Detection in Prostate Biopsy

Background: In the diagnosis of prostatic diseases, the need for markers other than prostate specific antigen (PSA) has been increasing in recent years. So, we aimed to determine the predictive value, the neutrophil lymphocyte ratio, platelet-to-lymphocyte ratio and mean platelet volume before prostate biopsy in predicting the results of pathology. Transrectal ultrasound-guided biopsy of the prostate was performed because of high PSA values and compared values of these parameters to predict of pathology results. Methods: 2715 patients who underwent 10 - 12 quadrant transrectal ultrasound-guided prostate biopsies between January 2008 and January 2018 have been evaluated retrospectively. Patients were divided into groups according to the biopsy pathology results by benign (group 1), atypical small acinar proliferation (ASAP) (group 2) and prostate cancer (group 3). A total of 204 patients who were benign prostate hyperplasia in 71 patients (34.8%), atypical small acinar proliferation in 80 (39.21%) and prostate adenocarcinoma (PCa) in 53 patients (25.98%) were included in the study by systematic sampling. Before the biopsy total PSA (tPSA), free PSA (fPSA), rate of percentage of free to total prostate specific antigen (f/tPSA) rate, PSA density (PSA-D), white blood cell (WBC) count, blood neutrophil count (NC), blood lymphocyte count (LC), neutrophil lymphocyte ratio (NLR), mean platelet volume (MPV), platelet count (PLT) and platelet-to-lymphocyte ratio (PLR) were measured and compared in all groups. Differences in continuous variables were assessed using the ANOVA. Logistic regression was used to analyze the linear relationship between predictive variables and pathology results. P Results: NLR and PLR values were lower in group 1 than group 2 and were found statistically significant between in group 1 and group 2 (p: 0.03 and p: 0.02, respectively). MPV value was found 1.7 times higher in patients who were diagnosed with ASAP pathology than those with benign pathologies. Although there was statistically significant increase in MPV values in logistic regression results, no statistically significant diagnostic value was found. In addition MPV value was found 0.5 times higher in patients who were diagnosed patients with ASAP than prostate cancer group. ROC analysis showed that the optimal threshold was 7.65 femtoliter (sensitivity: 51%; specificity: 30%) and was found to be a statistically significant diagnostic value to distinguish groups 2 and 3. The lowest value of MPV was found in group 3. Conclusions: In cases where the PSA value is insufficient in predicting the pathology result, the effect of NLR, PLR and MPV on differential diagnosis can be kept in mind. While NLR and PLR are more useful in the diagnosis of ASAP, MPV is more effective in the diagnosis of malignancy.