Single-molecule microfluidic assay for prostate-specific antigen based on magnetic beads and upconversion nanoparticles.

Early-stage diagnosis of prostatic carcinoma is essential for successful treatment and, thus, significant prognosis improvement. In laboratory practice, the standard non-invasive diagnostic approach is the immunochemical detection of the associated biomarker, prostate-specific antigen (PSA). Ultrasensitive detection of PSA is essential for both diagnostic and recurrence monitoring purposes. To achieve exceptional sensitivity, we have developed a microfluidic device with a flow-through cell for single-molecule analysis using photon-upconversion nanoparticles (UCNPs) as a detection label. For this purpose, magnetic microparticles (MBs) were first optimized for the capture and preconcentration of PSA and then used to implement a bead-based upconversion-linked immunoassay (ULISA) in the microfluidic device. The digital readout based on counting single nanoparticle-labeled PSA molecules on MBs enabled a detection limit of 1.04 pg mL-1 (36 fM) in 50% fetal bovine serum, which is an 11-fold improvement over the respective analog MB-based ULISA. The microfluidic technique conferred several other advantages, such as easy implementation and the potential for achieving high-throughput analysis. Finally, it was proven that the microfluidic setup is suitable for clinical sample analysis, showing a good correlation with a reference electrochemiluminescence assay (recovery rates between 97% and 105%).

The South African Prostate Cancer Screening Guidelines.

Prostate cancer (PCa) is the most widespread solid organ malignancy in males and ranks as the fifth leading cause of death globally. Identifying and treating men with clinically significant disease while avoiding the over-diagnosis and over-treatment of indolent disease remains a significant challenge. Several professional associations have developed guidelines on screening and early diagnosis of asymptomatic men with prostate-specific antigen testing. With recent updates from several large randomised prospective trials, the South African Urological Association and the Prostate Cancer Foundation of South Africa have developed these evidence-based recommendations to guide clinicians on PCa screening and early diagnosis for South African men.

Analysis of the immune-inflammatory indices for patients with metastatic hormone-sensitive and castration-resistant prostate cancer.

BACKGROUND: Inflammation plays a pivotal role in the progression of prostate cancer (PCa). Several immune-inflammatory indices, including neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), lymphocyte to monocyte ratio (LMR) and platelet to lymphocyte ratio (PLR), lung immune prognostic index (LIPI), systemic inflammation response index (SIRI) and systemic immune inflammation index (SII), have demonstrated their prognostic values in several solid malignancies. However, Comparisons of superiority with these seven indices' predictive efficacy within metastatic hormone-sensitive PCa (mHSPC) and metastatic castration-resistant PCa (mCRPC) remain uncertain. METHODS: We retrospectively included 407 patients diagnosed with mHSPC and 158 patients with mCRPC at West China Hospital from 2005 to 2022. The seven immune-inflammatory indices were computed based on hematological data of mHSPC at initial diagnosis and mCRPC at progression to CRPC. Prognostic value for castration-resistant prostate cancer-free survival (CFS), overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS) and prostate-specific antigen (PSA) response was assessed using Kaplan-Meier curves, Cox regression models, and chi-square tests. The predictive performance of each immune-inflammatory index was assessed using the area under the curve (AUC) in time-dependent receiver operating characteristic curve (ROC) analysis and C-index calculation. RESULTS: All seven immune-inflammatory indices were significantly associated with CFS and OS in the mHSPC cohort, as well as with PSA response, PSA-PFS, and OS in the mCRPC cohort. In the mHSPC cohort, LIPI consistently exhibited higher AUC values compared to NLR, dNLR, LMR, PLR, SII, and SIRI for predicting CFS and OS. This indicates that LIPI had a superior discriminative ability compared to the other indices (C-index of LIPI: 0.643 and 0.686 for CFS and OS, respectively). Notably, the predictive advantage of LIPI over other indices in the mHSPC stage diminished in the mCRPC stage. CONCLUSIONS: This study firstly confirmed the prognostic value of SII, SIRI and LIPI in mHSPC and mCRPC, and revealed that LIPI had a higher predictive power than NLR, dNLR, LMR, PLR, SII and SIRI in mHSPC. These non-invasive indices can enable clinicians to quickly assess the prognosis of patients.

ProsTAV, a clinically useful test in prostate cancer: an extension study.

PURPOSE: To assess the clinical performance of ProsTAV®, a blood-based test based on telomere associate variables (TAV) measurement, to support biopsy decision-making when diagnosing suspicious prostate cancer (PCa). METHODS: Preliminary data of a prospective observational pragmatic study of patients with prostate-specific antigen (PSA) levels 3-10 ng/ml and suspicious PCa. Results were combined with other clinical data, and all patients underwent prostate biopsies according to each center's routine clinical practice, while magnetic resonance imaging (MRI) before the prostate biopsy was optional. Sensitivity, specificity, positive and negative predicted values, and subjects where biopsies could have been avoided using ProsTAV were determined. RESULTS: The mean age of the participants (n = 251) was 67.4 years, with a mean PSA of 5.90 ng/ml, a mean free PSA of 18.9%, and a PSA density of 0.14 ng/ml. Digital rectal examination was abnormal in 21.1% of the subjects, and according to biopsy, the prevalence of significant PCa was 47.8%. The area under the ROC curve of ProsTAV was 0.7, with a sensitivity of 0.90 (95% CI, 0.85-0.95) and specificity of 0.27 (95% CI, 0.19-0.34). The positive and negative predictive values were 0.53 (95% CI, 0.46-0.60) and 0.74 (95% CI, 0.62-0.87), respectively. ProsTAV could have reduced the biopsies performed by 27% and showed some initial evidence of a putative benefit in the diagnosis pathway combined with MRI. CONCLUSIONS: ProsTAV increases the prediction capacity of significant PCa in patients with PSA between 3 and 10 ng/ml and could be considered a complementary tool to improve the patient diagnosis pathway.

The impact of positive surgical margin parameters and pathological stage on biochemical recurrence after radical prostatectomy: A systematic review and meta-analysis.

BACKGROUND: To systematically review and perform a meta-analysis on the predictive value of the primary Gleason grade (PGG) at the positive surgical margin (PSM), length of PSM, number of PSMs, and pathological stage of the primary tumor on biochemical recurrence (BCR) in patients with prostate cancer (PCa) after radical prostatectomy (RP). METHODS: A systematic literature search was performed using electronic databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, from January 1, 2005, to October 1, 2023. The protocol was pre-registered in PROSPERO. Subgroup analyses were performed according to the different treatments and study outcomes. Pooled hazard ratios with 95% confidence intervals were extracted from multivariate analyses, and a fixed or random effect model was used to pool the estimates. Subgroup analyses were performed to explore the reasons for the heterogeneity. RESULTS: Thirty-one studies that included 50,028 patients with PCa were eligible for this meta-analysis. The results showed that, compared to PGG3, PGG4/5 was associated with a significantly increased risk of BCR. Compared with PSM ≤3 mm, PSM ≥3 mm was associated with a significantly increased risk of BCR. Compared with unifocal PSM, multifocal PSM (mF-PSM) was associated with a significantly increased risk of BCR. In addition, pT >2 was associated with a significantly increased risk of BCR compared to pT2. Notably, the findings were found to be reliable based on the sensitivity and subgroup analyses. CONCLUSIONS: PGG at the PSM, length of PSM, number of PSMs, and pathological stage of the primary tumor in patients with PCa were found to be associated with a significantly increased risk of BCR. Thus, patients with these factors should be treated differently in terms of receiving adjunct treatment and more frequent monitoring. Large-scale, well-designed prospective studies with longer follow-up periods are needed to validate the efficacy of these risk factors and their effects on patient responses to adjuvant and salvage therapies and other oncological outcomes.

Comparison of digital and analog [68Ga]Ga-PSMA-11 PET/CT for detecting post-prostatectomy biochemical recurrence in prostate cancer patients: a prospective study.

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.

PSA doubling time 4.65 months as an optimal cut-off of Japanese nonmetastatic castration-resistant prostate cancer.

A multicenter study of nonmetastatic castration-resistant prostate cancer (nmCRPC) was conducted to identify the optimal cut-off value of prostate-specific antigen (PSA) doubling time (PSADT) that correlated with the prognosis in Japanese nmCRPC. Of the 515 patients diagnosed and treated for nmCRPC at 25 participating Japanese Urological Oncology Group centers, 450 patients with complete clinical information were included. The prognostic values of clinical factors were evaluated with respect to prostate specific antigen progression-free (PFS), cancer-specific survival (CSS), and overall survival (OS). The optimal cutoff value of PSADT was identified using survival tree analysis by Python. The Median PSA and PSADT at diagnosis of nmCRPC were 3.3 ng/ml, and 5.2 months, respectively. Patients treated with novel hormonal therapy (NHT) showed significantly longer PFS (HR: hazard ratio 0.38, p < 0.0001) and PFS2 (HR 0.45, p < 0.0001) than those treated with vintage nonsteroidal antiandrogen agent (Vintage). The survival tree identified 4.65 months as the most prognostic PSADT cutoff point. Among the clinical and pathological factors PSADT of < 4.65 months remained an independent prognostic factor for OS (HR 2.96, p = 0.0003) and CSS (HR 3.66, p < 0.0001). Current data represented optimal cut-off of PSADT 4.65 months for a Japanese nmCRPC.

Research on the mean maximum Young's modulus value as a new diagnostic parameter for prostate cancer.

Ultrasound-based shear wave elastography (SWE) can non-invasively assess prostate tissue stiffness for the diagnosis of prostate cancer (PCa). So far, there is no widely recognized standard for the detection process and calculation method of Young's modulus value in transrectal SWE ultrasound imaging (TSWEUI). In our study, the mean maximum Young's modulus value (m-Emax) of the maximum cross-section of prostate is obtained by calculating the mean of 12 measured Emax in the four quadrants. This retrospective study included 209 suspected malignant prostate disease patients with pathological results in our hospital. Among the 209 patients, 75 patients completed TSWEUI, and 63 of the 75 patients completed magnetic resonance imaging (MRI). The area under the receiver operating characteristic (ROC) curve (AUC) of 75 patients for m-Emax was 0.754. The prostate volume, prostate-specific antigen, and m-Emax were used to develop a nomogram (AUC = 0.868). The nomogram could effectively predict the probability of PCa, thereby reducing the needle biopsy rate for diagnosing PCa. The AUC of 63 patients was not statistically different between m-Emax (AUC = 0.717) and MRI (AUC = 0.787) (P = 0.361). These indicate that m-Emax can be used as an innovative parameter in TSWEUI to diagnosis PCa. TSWEUI is more cost-effective than MRI in diagnosing PCa.

[Transperineal versus transrectal ultrasound-guided prostate biopsy in detection of clinically significant and insignificant prostate cancer: A prospective randomized controlled trial].

OBJECTIVE: To compare transperineal prostate biopsy (TPB) with transrectal ultrasound-guided prostate biopsy (TRUSB) in detection of clinically significant prostate cancer (csPCa) and insignificant PCa (insPCa). METHODS: We conducted a prospective randomized clinical study on 279 patients receiving TPB (n = 144) or TRUSB (n = 135) from January 2022 to January 2023, and compared the detection rates of csPCa and insPCa between the two groups. RESULTS: The detection rate of PCa was significantly higher in the TPB than in the TRUSB group (37.50% vs 28.15%, P = 0.026). There were no statistically significant differences between the TPB and TRUSB groups in the detection rates of insPCa (6.94% ï¼»n = 10ï¼½ vs 4.45% ï¼»n = 6ï¼½, P > 0.05) and csPCa (30.56% ï¼»n = 44ï¼½ vs 23.70% ï¼»n = 32ï¼½, P > 0.05), nor in the detection rate of csPCa between different groups of age, PSA concentration and prostate volume (P > 0.05). No statistically significant differences were observed between the TPB and TRUSB groups either in the positive rate of biopsy punctures (ï¼»16.44 ± 2.86ï¼½% vs ï¼»12.48 ± 2.39ï¼½%, P > 0.05) or in the biopsy-related complications of urinary retention, urinary tract infection, hematuria and rectal bleeding (P > 0.05). CONCLUSION: TPB is more effective than TRUSB in detection of PCa, but there is no statistically significant difference between the two approaches in the detection rates of csPCa and insPCa.

[Diagnosis and treatment of small-cell carcinoma of the prostate: A report of 2 cases].

OBJECTIVE: To explore the clinical manifestations, diagnosis, pathological features and treatment of small-cell carcinoma of the prostate (SCCP). METHODS: We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018, and reviewed relevant literature. RESULTS: Both the patients had the symptoms of frequent, urgent and difficult urination, with an elevated level of PSA and gradesⅡ－Ⅲ enlargement of the prostate at palpation. One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor. Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases. One of them was treated by etoposide-platinum (EP) chemotherapy and died of systemic multiple organ failure 20 months after diagnosis, while the other underwent endocrine therapy and has lived with tumor up to the present day. CONCLUSION: The incidence rate of SCCP is low, its malignancy is high, and its prognosis is poor. The average survival of the patient is about 7 to 10 months after diagnosis. Currently there is no effective management of the dissease, except by relying on the experience of the treatment of small-cell lung cancer, with chemotherapy as the main option.

Relationship between prostate-specific antigen, alkaline phosphatase levels, and time-to-tumor shrinkage: understanding the progression of prostate cancer in a longitudinal study.

BACKGROUND: This study delves into the complex interplay among prostate-specific antigen, alkaline phosphatase, and the temporal dynamics of tumor shrinkage in prostate cancer. By investigating the longitudinal trajectories and time-to-prostate cancer tumor shrinkage, we aim to untangle the intricate patterns of these biomarkers. This understanding is pivotal for gaining profound insights into the multifaceted aspects of prostate cancer progression. The joint model approach serves as a comprehensive framework, facilitating the elucidation of intricate interactions among these pivotal elements within the context of prostate cancer . METHODS: A new joint model under a shared parameters strategy is proposed for mixed bivariate longitudinal biomarkers and event time data, for obtaining accurate estimates in the presence of missing covariate data. The primary innovation of our model resides in its effective management of covariates with missing observations. Built upon established frameworks, our joint model extends its capabilities by integrating mixed longitudinal responses and accounting for missingness in covariates, thus confronting this particular challenge. We posit that these enhancements bolster the model's utility and dependability in real-world contexts characterized by prevalent missing data. The main objective of this research is to provide a model-based approach to get full information from prostate cancer data collected with patients' baseline characteristics ( Age , body mass index ( BMI ), GleasonScore , Grade , and Drug ) and two longitudinal endogenous covariates ( Platelets and Bilirubin ). RESULTS: The results reveal a clear association between prostate-specific antigen and alkaline phosphatase biomarkers in the context of time-to-prostate cancer tumor shrinkage. This underscores the interconnected dynamics of these key indicators in gauging disease progression. CONCLUSIONS: The analysis of the prostate cancer dataset, incorporating a joint evaluation of mixed longitudinal prostate-specific antigen and alkaline phosphatase biomarkers alongside tumor status, has provided valuable insights into disease progression. The results demonstrate the effectiveness of the proposed joint model, as evidenced by accurate estimates. The shared variables associated with both longitudinal biomarkers and event times consistently deviate from zero, highlighting the robustness and reliability of the model in capturing the complex dynamics of prostate cancer progression. This approach holds promise for enhancing our understanding and predictive capabilities in the clinical assessment of prostate cancer.

Prescription Medications and Overall Survival in Metastatic Hormone Sensitive Prostate Cancer.

BACKGROUND/AIM: With new therapies for metastatic prostate cancer, patients are living longer, increasing the need for better understanding of the impact of comorbid disease. Prescription medications may risk-stratify patients independent of established methods, such as the Charlson Comorbidity Index (CCI) and guide treatment selection. PATIENTS AND METHODS: In a nationwide retrospective study of US Veterans, we used multivariable logistic regression and Cox proportional hazard modeling to evaluate the association between number and class of prescription medications and overall survival (OS) with age, race, body-mass index, prostate specific antigen (PSA), and Charlson comorbidities as covariates in veterans treated for de novo metastatic hormone sensitive prostate cancer (mHSPC) between 2010-2021. RESULTS: Among 8,434 Veterans, a median of nine medications and five medication classes were filled in the year prior to initial treatment with abiraterone or enzalutamide for mHSPC. Veterans on 1-4 medications had an average survival of 38 months compared to 5-9 medicines (33 months), 10-14 medicines (27 months), and 15+ medicines (22 months) (p<0.001). After adjusting for age, race, body mass index (BMI), PSA, CCI, and year of diagnosis, both the number of medications and medication classes were associated with increased mortality. The adjusted hazard ratio (aHR) [95% confidence interval (CI)] was 1.03 (1.02-1.03) for the number of medications and 1.05 (1.04-1.07) for medication classes. Medications within ATC B (blood/blood forming organs), ATC C (cardiovascular), and ATC N (nervous) were associated with worse OS, with aHRs of 1.14 (1.07, 1.21), 1.14 (1.06, 1.22), and 1.12 (1.06, 1.19), respectively. CONCLUSION: The number and class of medications were independently associated with overall survival in patients undergoing treatment for mHSPC. With new therapies for advanced prostate cancer, patients are living longer, highlighting the need for a better understanding of the impact of comorbid diseases. Simple methods to assess disease burden and prognosticate survival have the potential to guide treatment decisions.

The Association between Patient Characteristics and Biochemical Recurrence after Radical Prostatectomy.

Background: Biochemical recurrence (BCR) represents the rise of prostate-specific antigen (PSA) levels after treatment with curative radical prostatectomy (RP) or radiation for prostate cancer. The objective of the current study was to test for the association between patient characteristics, namely age, body mass index (BMI), as well as prostate volume at surgery, and BCR after RP. Material and Methods: Within a tertiary care database, patients with prostate cancer treated with RP between January 2014 and June 2023 were included. Kaplan-Meier survival analyses and Cox regression models addressed BCR after RP according to patient characteristics. Results: Of 821 patients, the median age was 66 years (interquartile range [IQR] 61-71 years), BMI was 26.2 kg/m2 (IQR 24.3-28.8 kg/m2), and prostate volume was 40 cm3 (IQR 30-55 cm3). Median follow-up was 20 months. In survival analyses, the three-year BCR-free survival rates were 81 vs. 84 vs. 81% in patients aged ≤60 vs. 61-69 vs. 70 years (p = 0.1). In patients with BMI < 25.0 vs. 25.0-29.9 vs. ≥30.0 kg/m2, the three-year BCR-free survival rates were 84 vs. 81 vs. 84% (p = 0.7). In patients with prostate volume ≤40 vs. >40 cm3, the three-year BCR-free survival rates were 85 vs. 80% (p = 0.004). In multivariable Cox regression models accounting for patient and pathologic tumor characteristics and adjuvant radiation therapy, a higher prostate volume independently predicted BCR as continuous (hazard ratio 1.012, 95% confidence interval 1.005-1.019; p < 0.001), as well as categorized the variable based on the median (hazard ratio 1.66, 95% confidence interval 1.17-2.36; p = 0.005). Conversely, neither age nor BMI were significantly associated with BCR after RP. Conclusions: The higher prostate volume independently predicted BCR after RP, but not age or BMI at surgery. Consequently, patients with an elevated prostate volume should be considered for closer postoperative follow-up.

Predictive Value of Preoperative PSA Levels Combined with MRI Features for BCR after Radical Prostatectomy: A Retrospective Study.

BACKGROUND: Existing models for predicting that biochemical recurrence (BCR) will occur in patients after radical prostatectomy (RP) vary in their predictive results from magnetic resonance imaging (MRI). This study aimed to assess the predictive value of preoperative prostate-specific antigen (PSA) levels combined with MRI features in determining BCR following radical prostatectomy. METHODS: A retrospective analysis was conducted on a cohort comprising 102 patients who underwent radical prostatectomy at our hospital between January 2019 and December 2019. On the basis of the outcomes observed during a 4-year follow-up after surgery, the patients were categorised into BCR group (n = 52) and non-BCR group (n = 50). Differences in preoperative PSA levels and MRI characteristics between the two groups were compared, and factors influencing postoperative BCR were analysed. The receiver operating characteristic curve was drawn, and the sensitivity, specificity, area under the curve (AUC) and Youden index were calculated to observe the predictive value of the combination of preoperative PSA level and MRI features for BCR following radical prostatectomy. RESULTS: Logistic regression analysis showed that preoperative PSA level, postoperative Gleason score, data system (Prostate Imaging-Reporting and Data System (PI-RADS)) score and clinical T stage were independent risk factors for BCR in patients following radical prostatectomy, with odds ratio (OR) greater than 1. The AUC value of preoperative PSA level combined with PI-RADS score was 0.921, surpassing the AUC values of 0.783, 0.822, 0.617 and 0.608 predicted by preoperative PSA level, postoperative Gleason score, PI-RADS score and clinical T stage alone, respectively. CONCLUSIONS: Postoperative BCR in patients with prostate cancer undergoing radical prostatectomy is associated with preoperative PSA level, postoperative Gleason score, PI-RADS score and clinical T stage. The combination of preoperative PSA level and MRI features can improve the predictive efficiency for postoperative BCR.

Bi-Parametric Magnetic Resonance Imaging Analysis of Biochemical Recurrence of Prostate Cancer after Radical Surgery and Its Predictive Value: A Retrospective Study.

OBJECTIVE: This study aimed to analyse the characteristics of biochemical recurrence after radical prostatectomy via bi-parametric magnetic resonance imaging. METHODS: A total of 200 patients with radical prostatectomy admitted to our hospital from January 2016 to January 2021 were retrospectively enrolled as observation objects. According to whether there was biochemical recurrence after surgery, the patients were divided into the abnormal group (n = 62) and normal group (n = 138). Clinical data, encapsulation infiltration, seminal vesicle infiltration and prostate imaging report and data system (PI-RADS) were collected and compared between the two groups. Propensity score matching (PSM) was used to balance the baseline data of the two groups. Student's t-test and Chi-square test were used to analyse the data. RESULTS: PSM was performed in a 1:1 ratio, and a total of 72 patients were included in the abnormal and normal groups. The baseline data of the patients in each group were not statistically significant. The incidence of extraperitoneal invasion and seminal vesicle invasion was higher in the abnormal group than in the normal group, and we observed a significant difference in PI-RADS scores between the two groups (p < 0.05). Extracapsular invasion, seminal vesicle invasion, PI-RADS score and biochemical recurrence were significantly correlated (p < 0.05). The PI-RADS score has a high value for predicting biochemical recurrence, with an area under the curve value of 0.824, sensitivity of 0.667, specificity of 0.861 and Youden index of 0.528. CONCLUSIONS: Bi-parametric magnetic resonance imaging has a high predictive value in biochemical recurrence after radical prostatectomy, which can provide reference for early intervention measures.

Optimising the use of the prostate- specific antigen blood test in asymptomatic men for early prostate cancer detection in primary care: report from a UK clinical consensus.

BACKGROUND: Screening is not recommended for prostate cancer in the UK. Asymptomatic men aged ≥50 years can request a prostate-specific antigen (PSA) test following counselling on potential harms and benefits. There are areas of clinical uncertainty among GPs, resulting in the content and quality of counselling varying. AIM: To produce a consensus that can influence guidelines for UK primary care on the optimal use of the PSA test in asymptomatic men for early prostate cancer detection. DESIGN AND SETTING: Prostate Cancer UK facilitated a RAND/UCLA consensus. METHOD: Statements covering five topics were developed with a subgroup of experts. A panel of 15 experts in prostate cancer scored (round one) statements on a scale of one (strongly disagree) to nine (strongly agree). Panellists met to discuss statements before rescoring (round two). A lived experience panel of seven men scored a subset of statements with outcomes fed into the main panel. RESULTS: Of the initial 94 statements reviewed by the expert panel, a final 48/85 (56%) achieved consensus. In the absence of screening, there was consensus on proactive approaches to initiate discussions about the PSA test with men who were at higher-than-average risk. CONCLUSION: Improvements in the prostate cancer diagnostic pathway may have reduced some of the harms associated with PSA testing; however, several areas of uncertainty remain in relation to screening, including optimal PSA thresholds for referral and intervals for retesting. There is consensus on proactive approaches to testing in higher-than-average risk groups. This should prompt a review of current guidelines.