Evolution of European prostate cancer screening protocols and summary of ongoing trials

Population-based organised repeated screening for prostate cancer has been found to reduce disease-specific mortality, but with substantial overdiagnosis leading to overtreatment. Although only very few countries have implemented a screening programme on a national level, individual prostate-specific antigen (PSA) testing is common. This opportunistic testing may have little favourable impact, while stressing the side-effects. The classic early detection protocols as were state-of-the-art in the 1990s applied a PSA and digital rectal examination threshold for sextant systematic prostate biopsy, with a fixed interval for re-testing, and limited indication for expectant management. In the three decades since these trials were started, different important improvements have become available in the cascade of screening, indication for biopsy, and treatment. The main developed aspects include: better identification of individuals at risk (using early/baseline PSA, family history, and/or genetic profile), individualised re-testing interval, optimised and individualised starting and stopping age, with gradual invitation at a fixed age rather than invitation of a wider range of age groups, risk stratification for biopsy (using PSA density, risk calculator, magnetic resonance imaging, serum and urine biomarkers, or combinations/sequences), targeted biopsy, transperineal biopsy approach, active surveillance for low-risk prostate cancer, and improved staging of disease. All these developments are suggested to decrease the side-effects of screening, while at least maintaining the advantages, but Level 1 evidence is lacking. The knowledge gained and new developments on early detection are being tested in different prospective screening trials throughout Europe. In addition, the European Union-funded PRostate cancer Awareness and Initiative for Screening in the European Union (PRAISE-U) project will compare and evaluate different screening pilots throughout Europe. Implementation and sustainability will also be addressed. Modern screening approaches may reduce the burden of the second most frequent cause of cancer-related death in European males, while minimising side-effects. Also, less efficacious opportunistic early detection may be indirectly reduced.</p

Evolution of European prostate cancer screening protocols and summary of ongoing trials

Population-based organised repeated screening for prostate cancer has been found to reduce disease-specific mortality, but with substantial overdiagnosis leading to overtreatment. Although only very few countries have implemented a screening programme on a national level, individual prostate-specific antigen (PSA) testing is common. This opportunistic testing may have little favourable impact, while stressing the side-effects. The classic early detection protocols as were state-of-the-art in the 1990s applied a PSA and digital rectal examination threshold for sextant systematic prostate biopsy, with a fixed interval for re-testing, and limited indication for expectant management. In the three decades since these trials were started, different important improvements have become available in the cascade of screening, indication for biopsy, and treatment. The main developed aspects include: better identification of individuals at risk (using early/baseline PSA, family history, and/or genetic profile), individualised re-testing interval, optimised and individualised starting and stopping age, with gradual invitation at a fixed age rather than invitation of a wider range of age groups, risk stratification for biopsy (using PSA density, risk calculator, magnetic resonance imaging, serum and urine biomarkers, or combinations/sequences), targeted biopsy, transperineal biopsy approach, active surveillance for low-risk prostate cancer, and improved staging of disease. All these developments are suggested to decrease the side-effects of screening, while at least maintaining the advantages, but Level 1 evidence is lacking. The knowledge gained and new developments on early detection are being tested in different prospective screening trials throughout Europe. In addition, the European Union-funded PRostate cancer Awareness and Initiative for Screening in the European Union (PRAISE-U) project will compare and evaluate different screening pilots throughout Europe. Implementation and sustainability will also be addressed. Modern screening approaches may reduce the burden of the second most frequent cause of cancer-related death in European males, while minimising side-effects. Also, less efficacious opportunistic early detection may be indirectly reduced.</p

False positives in PIRADS (V2) 3, 4, and 5 lesions:relationship with reader experience and zonal location

PURPOSE: To investigate the effect of reader experience and zonal location on the occurrence of false positives (FPs) in PIRADS (V2) 3, 4, and 5 lesions on multiparametric (MP)-MRI of the prostate. MATERIALS AND METHODS: This retrospective study included 139 patients who had consecutively undergone an MP-MRI of the prostate in combination with a transrectal ultrasound MRI fusion-guided biopsy between 2014 and 2017. MRI exams were prospectively read by a group of inexperienced radiologists (cohort 1; 54 patients) and an experienced radiologist (cohort 2; 85 patients). Multivariable logistic regression analysis was performed to determine the association of experience of the radiologist and zonal location with a FP reading. FP rates were compared between readings by inexperienced and experienced radiologists according to zonal location, using Chi-square (χ2) tests. RESULTS: A total of 168 lesions in 139 patients were detected. Median patient age was 68 years (Interquartile range (IQR) 62.5-73), and median PSA was 10.9 ng/mL (IQR 7.6-15.9) for the entire patient cohort. According to multivariable logistic regression, inexperience of the radiologist was significantly (P = 0.044, odds ratio 1.927, 95% confidence interval [CI] 1.017-3.651) and independently associated with a FP reading, while zonal location was not (P = 0.202, odds ratio 1.444, 95% CI 0.820-2.539). In the transition zone (TZ), the FP rate of the inexperienced radiologists 59% (17/29) was significantly higher (χ2P = 0.033) than that of the experienced radiologist 33% (13/40). CONCLUSION: Inexperience of the radiologist is significantly and independently associated with a FP reading, while zonal location is not. Inexperienced radiologists have a significantly higher FP rate in the TZ

Unanswered questions in prostate cancer : Findings of an international multi-stakeholder consensus by the PIONEER Consortium

Acknowledgements PIONEER is funded through the IMI2 Joint Undertaking and is listed under grant agreement No. 777492. This joint under- taking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.Peer reviewedPostprin

Predictive Models for Assessing Patients’ Response to Treatment in Metastatic Prostate Cancer:A Systematic Review

Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients’ response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.</p

Predictive Models for Assessing Patients’ Response to Treatment in Metastatic Prostate Cancer:A Systematic Review

Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients’ response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.</p

Predictive Models for Assessing Patients’ Response to Treatment in Metastatic Prostate Cancer : A Systematic Review

Peer reviewe

Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management : a PIONEER Analysis Based on Big Data

Funding statement PIONEER is funded through the IMI2 Joint Undertaking and is listed under grant agreement No. 777492. This joint undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations EFPIA. The European Health Data & Evidence Network has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 806968. The Joint Undertaking is supported by the European Union’s Horizon 2020 research and innovation programme and EFPIA, a large association which represents the biopharmaceutical industry in Europe. The views communicated within are those of PIONEER. Neither the IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained hereinPeer reviewe