OBJECTIVE: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Nevertheless real-world data are limited. The aim of this multicenter study was to generate real-world data from nmCRPC patients treated with ADT plus apalutamide.
METHODS: In this observational cohort based investigator initiated trial data of nmCRPC patients receiving apalutamide plus ADT were collected focusing on patient demographic data, prostate-specific antigen (PSA) declines, safety profile including dose modification/discontinuation as well as subsequent therapy and metastasis-free survival (MFS).
RESULTS: Data from a total of 31 nmCRPC patients were documented. Compared to the Phase III study Spartan real-world patients are older, showed a higher ECOG-PS and more aggressive tumors. In the cohort PSA decreased about 98.1%, 74% of patients showed a PSA decrease over 90% and 54.8% reached a PSA-level < 0.2ng/ml. Apalutamide was well tolerated in real world patients: adverse events occurred in 67.7% but were in the majority mild (≥ grade 3: 6.5%). Dose reduction was necessary in 38.7% and 32.2% discontinued apalutamide treatment. MFS was 43 months and majority of patients were subsequently treated with abiraterone.
CONCLUSIONS: In real world more comorbid nmCRPC patients with a higher ECOG-PS and more aggressive tumors are treated with apalutamide plus ADT. Nevertheless efficacy results as well as side effects are similar in real-world compared to Spartan trial showing also a rapid, durable and deep PSA response with a median MFS of 43 months.

OBJECTIVE: The prognostic value of declining prostate-specific antigen (PSA) levels is under investigation in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) receiving PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-617 (177Lu-PSMA-617). This post hoc analysis of the phase 3 VISION trial aimed to evaluate associations between PSA decline and clinical and patient-reported outcomes in patients receiving 177Lu-PSMA-617.
METHODS: Of 831 enrolled patients with PSMA-positive progressive mCRPC treated previously with one or more androgen receptor pathway inhibitors and one to two taxanes, 551 were randomised to 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC). Radiographic progression-free survival, overall survival, radiographic objective response rate, and patient-reported health-related quality of life (HRQoL) and pain were analysed in subgroups of patients categorised by the magnitude of unconfirmed PSA decline from baseline.
UNASSIGNED: Patients randomised to 177Lu-PSMA-617 with the best PSA declines of ≥0-<50% (96/551 [17%]), ≥50-<90% (152/551 [28%]), and ≥90% (83/551 [15%]) up to and including week 12 had 61%, 72%, and 88% reduced risks of radiographic disease progression or death, and 51%, 70%, and 87% reduced risks of death, respectively, versus those with increased PSA levels (160/551 [29%]), based on hazard ratios in a multivariate Cox proportional hazard model. In patients with greater PSA declines, radiographic responses were more frequent and median time to worsening in HRQoL and pain scores were longer.
CONCLUSIONS: The magnitude of PSA decline was associated with improvement in clinical and patient-reported outcomes in patients with mCRPC receiving 177Lu-PSMA-617 plus SoC in VISION. PSA decline therefore appears to have a prognostic value during 177Lu-PSMA-617 treatment in this population.

OBJECTIVE: To provide a baseline comparative assessment of the main epidemiological features of prostate cancer in European populations as background for the proposed EU screening initiatives.
METHODS: Population based study.
METHODS: 26 European countries, 19 in the EU, 1980-2017. National or subnational incidence data were extracted from population based cancer registries from the International Agency for Research on Cancer\'s Global Cancer Observatory, and mortality data from the World Health Organization.
METHODS: Men aged 35-84 years from 26 eligible countries.
RESULTS: Over the past decades, incidence rates for prostate cancer varied markedly in both magnitude and rate of change, in parallel with temporal variations in prostate specific antigen testing. The variation in incidence across countries was largest around the mid-2000s, with rates spanning from 46 (Ukraine) to 336 (France) per 100 000 men. Thereafter, incidence started to decline in several countries, but with the latest rates nevertheless remaining raised and increasing again in the most recent quinquennium in several countries. Mortality rates during 1980-2020 were much lower and less variable than incidence rates, with steady declines in most countries and lesser temporal differences between countries. Overall, the up to 20-fold variation in prostate cancer incidence contrasts with a corresponding fivefold variation in mortality. Also, the inverse U-shape of the age specific curves for incidence contrasted with the mortality pattern, which increased progressively with age. The difference between the highest and lowest incidence rates across countries ranged from 89.6 per 100 000 men in 1985 to 385.8 per 100 000 men in 2007, while mortality rates across countries ranged from 23.7 per 100 000 men in 1983 to 35.6 per 100 000 men in 2006.
CONCLUSIONS: The epidemiological features of prostate cancer presented here are indicative of overdiagnosis varying over time and across populations. Although the results are ecological in nature and must be interpreted with caution, they do support previous recommendations that any future implementation of prostate cancer screening must be carefully designed with an emphasis on minimising the harms of overdiagnosis.

UNASSIGNED: This study describes the characteristics of men attending a primary health care screening initiative, determines the proportion of men who have elevated International Prostate Symptom Score (IPSS) scores and prostate-specific antigen (PSA) levels, and determines any correlation between these scores as indicators for benign prostatic hyperplasia (BPH) or prostate cancer.
UNASSIGNED: Data were collected from all patient records during men\'s health screening initiatives that occurred in December 2018, January 2019, and March 2019 in Trinidad and Tobago. A total of 350 medical records were analyzed to record patient demographics, PSA levels, and IPSS scores. Analysis of the data was performed with the use of Statistical Package for the Social Sciences software (version 27).
UNASSIGNED: Most men who attended the screening initiative belonged to the 61-65 age group (20.57%), with more than half of the men being married (57.71%) and employed (52.57%) and of patients with comorbidities (17%), the most prevalent included hypertension (6%) and diabetes mellitus (3.7%). A mean PSA level of 2.94 ng/ml and a mean IPSS of 7.62 were recorded. Moreover, 11.5% of the males had elevated PSA levels (>4 ng/ml) and 32.9% had elevated IPSS levels (>8). There were correlations between PSA and IPSS values (r = 0.161 and P = 0.006). Age was a predictor of both IPSS and PSA values (r = 0.214, P = 0.000 and r = 0.192, P = 0.000, respectively). Among diabetic participants, a small but significant correlation between IPSS and diabetes was shown (r = 0.223, P = 0.028). As a predictor of elevated IPSS, diabetes had an odds ratio of 1.132 (95% confidence interval (CI): 1.021-1.255).
UNASSIGNED: Our findings are similar to those described in previous studies; however, further investigations are required to fully describe the relationship between PSA and IPSS. This may assist in advancing screening measures and improving health outcomes for men with BPH and prostate cancer. Primary care physicians should recognize the possible association between BPH and diabetes mellitus and offer appropriate screening where indicated.

Although overall survival data are still premature, the PROpel study found radiological progression-free survival (PFS) benefits of abiraterone and olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). However, for patients who have not been genetically tested or lack BRCA1/2 mutations (BRCAm), this combination therapy has been questioned as a first-line conventional treatment for mCRPC, mainly due to significant health economics and side effects. In our retrospective study, we found that treatment with low-dose abiraterone plus olaparib as a late-line treatment for mCRPC could lead to prostate-specific antigen (PSA) and symptom PFS in selective cases even without BRCAm. The median PSA-PFS was 8 months (IQR: 6.5-11.5), with a median follow-up duration of 39.0 months (IQR: 27.5-64.5). Gene tests were conducted in all patients, identifying non-BRCA mutations through ctDNA testing (24%), tumor tissue testing (12%), or both (64%). Adverse events occurred in 72% of patients, with 16% experiencing Grade ≥ 3 events. Common adverse events included anemia (64%), decreased appetite (48%), and fatigue (25%). Our findings support low-dose abiraterone plus olaparib as a potential option for mCRPC patients without BRCAm, offering manageable safety and efficacy profiles.

Background Lutetium 177 [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) is a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC). Quantitative PSMA PET/CT analysis could provide information on 177Lu-PSMA-617 treatment benefits. Purpose To explore the association between quantitative baseline gallium 68 [68Ga]Ga-PSMA-11 (68Ga-PSMA-11) PET/CT parameters and treatment response and outcomes in the VISION trial. Materials and Methods This was an exploratory secondary analysis of the VISION trial. Eligible participants were randomized (June 2018 to October 2019) in a 2:1 ratio to 177Lu-PSMA-617 therapy (7.4 GBq every 6 weeks for up to six cycles) plus standard of care (SOC) or to SOC only. Baseline 68Ga-PSMA-11 PET parameters, including the mean and maximum standardized uptake value (SUVmean and SUVmax), PSMA-positive tumor volume, and tumor load, were extracted from five anatomic regions and the whole body. Associations of quantitative PET parameters with radiographic progression-free survival (rPFS), overall survival (OS), objective response rate, and prostate-specific antigen response were investigated using univariable and multivariable analyses (with treatment as the only other covariate). Outcomes were assessed in subgroups based on SUVmean quartiles. Results Quantitative PET parameters were well balanced between study arms for the 826 participants included. The median whole-body tumor SUVmean was 7.6 (IQR, 5.8-9.9). Whole-body tumor SUVmean was the best predictor of 177Lu-PSMA-617 efficacy, with a hazard ratio (HR) range of 0.86-1.43 for all outcomes (all P < .001). A 1-unit whole-body tumor SUVmean increase was associated with a 12% and 10% decrease in risk of an rPFS event and death, respectively. 177Lu-PSMA-617 plus SOC prolonged rPFS and OS in all SUVmean quartiles versus SOC only, with no identifiable optimum among participants receiving 177Lu-PSMA-617. Higher baseline PSMA-positive tumor volume and tumor load were associated with worse rPFS (HR range, 1.44-1.53 [P < .05] and 1.02-1.03 [P < .001], respectively) and OS (HR range, 1.36-2.12 [P < .006] and 1.04 [P < .001], respectively). Conclusion Baseline 68Ga-PSMA-11 PET/CT whole-body tumor SUVmean was the best predictor of 177Lu-PSMA-617 efficacy in participants in the VISION trial. Improvements in rPFS and OS with 177Lu-PSMA-617 plus SOC were greater among participants with higher whole-body tumor SUVmean, with evidence for benefit at all SUVmean levels. ClinicalTrials.gov identifier: NCT03511664 Published under a CC BY 4.0 license. Supplemental material is available for this article.

OBJECTIVE: Investigating men\'s perceived lifetime risk of prostate cancer.
METHODS: Survey-based study to men invited for prostate-specific antigen (PSA) screening in the GÖTEBORG-2 trial between September 2015 and June 2020.
METHODS: 38 775 men in the Gothenburg area, Sweden, were invited for PSA-testing and participated in a survey.
METHODS: 17 980 men participated in PSA-testing, of whom 13 189 completed the survey. In addition, 1264 men answered the survey only.
METHODS: Before having the PSA-test, men answered an electronic survey and estimated their lifetime risk of receiving a prostate cancer diagnosis on a visual analogue scale from 0% to 100%.
METHODS: The primary outcome was the median lifetime risk estimation, which was compared with Wilcoxon test to an anticipated lifetime risk of 20% (based on GÖTEBORG-1 trial). The secondary outcome was to determine factors associated with risk estimation in a multivariable linear regression model: previous prostate examination, family history, physical exercise, healthy diet, comorbidity, alcohol consumption, smoking, education level, marital status, urinary symptoms and erectile dysfunction.
RESULTS: Among PSA-tested men, the median estimated lifetime risk of prostate cancer was 30% (IQR 19% to 50%), corresponding to a 10 percentage-points higher estimation compared with the anticipated risk (p<0.001). Family history of prostate cancer, moderate to severe urinary symptoms and mild to moderate erectile dysfunction were associated with >5 percentage-points higher risk estimation. Similar results were obtained for non-PSA-tested men.
CONCLUSIONS: Most men overestimated their prostate cancer risk which underscores the importance of providing them accurate information about prostate cancer.
BACKGROUND: ISRCTN94604465.

Prostate cancer screening using prostate-specific antigen (PSA) testing is controversial but remains prevalent in many countries. There is little information in Sweden or elsewhere on the spatial variation in PSA testing. This study aims to describe the spatio-temporal variation in PSA testing prior to a prostate cancer diagnosis in the Stockholm region at the municipality and small area levels. A population-based register study comprised men aged 40 years and over living in the Stockholm region during 2007-2016. For Stockholm in 2016, we reported the proportion of men who had a PSA test for the preceding one, two, five and ten years by ten-year age groups. The age-standardised proportion of men having a PSA test was reported for municipalities by calendar years. We used spatial smoothing for calculating the age-standardised proportion of men having a PSA test in a small area for each calendar year. In 2016, 74.0% and 77.8% of men aged 60-69 and 70-79 years respectively had taken a PSA test in the previous ten years. The municipalities of Danderyd and Ekerö showed high proportions of PSA testing. A marked heterogeneity in such proportions within each municipality was observed. The odds ratio for having a PSA test for those born in Sweden was 2.22 (95% CI 2.00-2.52). Opportunistic PSA testing is widespread with three quarters of men in their sixties and seventies having had a test in the preceding decade. We found evidence for marked geographical heterogeneity, where more affluent and metropolitan areas had higher levels of testing. Variations in PSA testing was associated with socio-economic position and demographic factors including education, income and country of birth.

UNASSIGNED: Direct evidence for the relationship between a large prostate (≥80 ml) and androgen receptor/PSA signal remains lacking in benign prostatic hyperplasia (BPH). Our aim is to identify whether the cause of a large prostate is related to progesterone receptor (PGR) androgen receptor (AR), oestrogen receptor α, β (ERα,β) and prostate-specific antigen (PSA).
UNASSIGNED: Surgical specimens of BPH in plasmakinetic resection of the prostate (PKRP) with three groups of different prostate-sizes with mean volumes of 25.97 ml, 63.80 ml, and 122.37 ml were collected for immunohistochemical analysis of the tissue microarray with PGR, AR, PSA and ERs. Rats were castrated and treated with testosterone replacement to explore androgen and PGR, AR and ERs expression levels in the prostate. Quantitative real-time reverse transcription polymerase chain reaction (Rt-PCR) for mRNA detection of above genes was conducted.
UNASSIGNED: Immunoblotting, Rt-PCR and immunohistochemistry assays showed that PGR, PSA, AR, ERα expression levels were positively correlated with prostate size and that ERβ expression levels were negatively correlated with prostate volume. Animal experiments have shown that prostate volume is decreased in castrated rats with decreased PGR, AR, ERα and increased ERβ expression levels.
UNASSIGNED: PGR, AR, ERs signals can be regarded as important factors for large-sized prostates in BPH patients (≥100 ml).

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate cancer progression. Additionally, optimized machine learning classifier analysis reveals proteomic signatures capable of detecting the disease prior to biopsy, performing on par with an accepted clinical risk calculator benchmark.