The indication for prostate biopsy represents the key interface between prostate-specific antigen (PSA)-based early detection and primary diagnostic evaluation in patients with suspected prostate cancer. The aim is to reduce overdiagnosis while ensuring detection of clinically significant prostate cancer (csPCa; International Society of Urological Pathology [ISUP] grade ≥ 2). PSA remains the most important initial test but is limited by low specificity; digital rectal examination provides no relevant additional value. In cases of clinical suspicion, diagnostic work-up includes multiparametric magnetic resonance imaging (MRI) for risk stratification and reduction of unnecessary biopsies. Diagnostic performance depends on image quality and reader expertise. Biparametric MRI may be an alternative under appropriate conditions but does not match the full diagnostic scope of mpMRI. In the presence of suspicious MRI findings, the combination of targeted and systematic biopsy remains the reference standard, with higher detection rates for csPCa but also increased detection of clinically insignificant tumors. Alternative approaches such as perilesional sampling are under investigation. PSA density, serum biomarkers (e.g., 4KScore, Stockholm-3), and risk calculators may further improve prebiopsy selection. This review provides an evidence-based overview and outlines a guideline-conform, risk-adapted diagnostic pathway for biopsy indication.

INTRODUCTION:Testicular cancer (TC) is the most common malignancy in young men and is highly curable with platinum-based chemotherapy. With growing survivorship rates, treatment-related symptom burden and quality of life (QoL) have become increasingly important. This study evaluates the impact of different TC treatments on symptom burden and QoL. MATERIAL AND METHODS:Of 715 patients with TC and primary or postchemotherapy retroperitoneal lymph node dissection (RPLND) treated at the University Hospital Düsseldorf between 2010 and 2024, 486 eligible survivors were contacted, and 124 (25.5 %) completed a standardized questionnaire. Treatment-related symptoms, including QoL and mental health status, were assessed using the EORTC QLQ-C30 and PHQ-9 questionnaires, respectively. Results were compared with age-matched reference values from the general population. A subgroup comparison of clinical stage (CS) II patients treated with primary RPLND versus first-line chemotherapy followed by RPLND was performed to identify chemotherapy-specific effects. RESULTS:The median time between last treatment and survey response was 55 months. Twenty-four patients were treated with primary RPLND, 80 patients with adjuvant or first-line chemotherapy and RPLND, and 20 patients with multiple lines of chemotherapy and RPLND. Overall, TC survivors reported high global QoL scores comparable to age-matched normative data. The most frequent treatment-related symptoms were polyneuropathy, tinnitus, retrograde ejaculation, and circulatory disorders, particularly among patients receiving multiple lines of chemotherapy. Subgroup analysis showed that CS II patients treated with a single first-line chemotherapy reported lower social functioning and greater financial distress compared with those managed with surgery alone. Despite the physical impact, depression rates were low and similar to the general population, indicating preserved psychological well-being. CONCLUSION:TC survivors maintain good QoL comparable to the general population despite therapy-related symptoms. While persistent side effects such as polyneuropathy and tinnitus are common, their impact on QoL is limited. However, even first-line chemotherapy affects sexual health, social functioning, and financial well-being, highlighting the importance of the development of new treatment approaches and clinical studies focusing on surgery as a QoL-preserving option in selected low-metastatic cases.

Supplementary Table S1 lists potential reasons for initial non-identification of articles through the systematic literature search, but were identified by screening reference lists of included articles.

Abstract Background Diagnostic pathways based on PSA, digital rectal examination (DRE), and systematic biopsy (SB) may miss clinically significant prostate cancer (csPCa) and lead to overdiagnosis of indolent disease. Multiparametric MRI (mpMRI) and MRI-targeted biopsy (TB) improve detection of csPCa; however, the additional diagnostic value of routine SB in biopsy-naïve men with suspicious MRI findings remains controversial. Methods PRIMA is a randomized, prospective, multicenter non-inferiority diagnostic accuracy trial in eight German hospitals. Biopsy-naïve men aged 50–75 years with PSA ≥ 3 ng/ml and/or suspicious DRE undergo mpMRI (PI-RADS v2.1, PI-QUAL v2). Men with PI-RADS 4–5 or PI-RADS 3 with PSA density > 0.15 are randomized 1:1 to TB only (Arm A) or TB + SB (Arm B). Persistent PI-RADS 4–5 lesions with negative biopsy undergo MRI in-bore biopsy. Outcomes Co-primary endpoints are csPCa (ISUP ≥ 2) detection and detection of clinically insignificant cancer (ISUP 1). Secondary endpoints include patient-reported outcomes (EORTC-QLQ-C30, EPIC-26, VAS), biopsy-related complications, biopsy approach, MRI in-bore yield, AI/radiomics validation and follow-up cancer incidence. Sample size One thousand nine hundred eight men were allocated to achieve 1590 analyzable patients (> 80% power; non-inferiority margin δ = 13%). Discussion PRIMA will provide high-level evidence whether systematic biopsy can be safely omitted in MRI-positive biopsy-naïve men, potentially reducing diagnostic morbidity and overtreatment. Trial registration ClinicalTrials.gov NCT04993508. Registered on 2 December 2022.

BACKGROUND:The 2025 update of the German S3 guideline on prostate cancer introduces major revisions in early detection and diagnostic strategies, marking a paradigm shift in the management of localized prostate cancer. METHODS:This review summarizes the main evidence-based recommendations on early detection derived from the systematic evidence synthesis conducted for the 2025 guideline update. RESULTS:The revised guideline establishes a risk-adapted, prostate-specific antigen (PSA)-based screening strategy starting at age 45, with individualized follow-up intervals (2 or 5 years) and indication-based diagnostic clarification using short-term PSA retesting, multiparametric magnetic resonance imaging (mpMRI), and targeted biopsy where appropriate. Digital rectal examination is no longer recommended for screening purposes. The structured integration of mpMRI increases the detection of clinically significant prostate cancer while reducing unnecessary biopsies and overdiagnosis. Active surveillance (AS) is a key component of the updated early detection and management strategy. For men with low-risk disease (ISUP 1), the guideline issues a strong "should" recommendation for AS, whereas for men with favorable intermediate-risk disease (ISUP 2 without cribriform or intraductal growth and with a limited proportion of Gleason pattern 4), AS carries a weaker "may" recommendation. Recent 15-year long-term results from the international Prostate Cancer Research International: Active Surveillance (PRIAS) cohort confirm the oncological safety of AS and highlight the pivotal role of mpMRI in patient selection and longitudinal monitoring. CONCLUSION:Combining individualized PSA-based early detection with high-quality MRI diagnostics enables precise, risk-adapted, and patient-centered prostate cancer management. This approach minimizes overdiagnosis and overtreatment while ensuring timely intervention for clinically relevant disease.

Supplementary Figure S2 shows Deeks’ Funnel Plots used to assess publication bias across the included studies.

Risk-adapted prostate cancer screening is urgently needed to reduce overdiagnosis and overtreatment in the general population while allowing intensified risk adapted early detection in high-risk individuals. Clear eligibility criteria for genetic testing, professional education, and structured early detection programs must be established.

BACKGROUND:The diagnostic performance of prostate magnetic resonance imaging (MRI) critically depends on image quality and reader expertise. The PROBASE trial is a prospective population- and prostate-specific antigen (PSA)-based prostate cancer (PCa) screening study enrolling men aged 45 yr. OBJECTIVE:In this predefined substudy, we evaluated the impact of MRI quality and expert reference reading on clinically significant PCa (csPCa; International Society of Urological Pathology grade ≥2) detection. DESIGN, SETTING, AND PARTICIPANTS:This analysis included 516 participants who underwent multiparametric MRI and combined MRI-targeted biopsy and systematic biopsy after screening with PSA ≥3 ng/ml. Local Prostate Imaging Reporting and Data System (PI-RADS) scores were compared with reference readings by experienced uroradiologists. MRI quality was assessed using Prostate Imaging Quality (version 1; PI-QUAL [v1]). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Detection rates, positive predictive values (PPV), and negative predictive values (NPV) were calculated at an underlying biopsy threshold of PI-RADS score of ≥4. Image quality was compared between the study sites. RESULTS AND LIMITATIONS:Reference reading yielded higher NPV (92% vs 86%), PPV (57% vs 50%), and sensitivity (83% vs 69%) than local reading. Local reading missed substantially more csPCa in PI-RADS 1-2 (17.1% vs 2.9%) and resulted in more false-positive MRI findings in PI-RADS 4-5 (n = 76 vs n = 59) than reference reading. Lower MRI quality (PI-QUAL 1-3/5) was associated with reduced csPCa detection (46% vs 62%) and true negative rate (84% vs 95%). PI-QUAL differed between the study sites. PI-RADS classification of reference reading missed small or diffusely infiltrative csPCa, often in lower quality scans. Limitations include using local interpretations to define biopsy targets, limiting retrospective comparison, and possibly underestimating reference-reader performance. CONCLUSIONS:Expert reference MRI reading substantially improves csPCa detection and can reduce unnecessary biopsies in a screening setting. High-quality imaging, standardized protocols, and experienced reading should be considered essential components of future MRI-based screening strategies. TRIAL REGISTRATION:The trial is registered with the ISRCTN (International Randomized Controlled Trial Number) registry, registration number ISRCTN37591328, and can be accessed at https://www.isrctn.com/ISRCTN37591328. The study protocol can be accessed at doi: 10.1016/j.eururo.2013.05.022.

Abstract Background The current national and international guidelines recommend the use of PSMA imaging in proven BCR including very low levels of PSA (< 0.5 ng/ml), which is associated with a certain rate of false-negative results in regular clinical care. To address this issue, research efforts have focused on improving acquisition protocols via the implementation of delayed images or alternative reconstruction algorithms. One of the mainstays of this approach is the use of standardized reporting systems in regular clinical care and research setting to enhance reliability and reproducibility compared with unstructured confidence assessment. Thus, we aimed to investigate the added benefit of delayed imaging and the utility of reconstruction algorithms for the discrimination of equivocal [18F]PSMA-1007 findings in prostate bed. Results This monocentric, retrospective study enrolled 36 biologically male patients who underwent dual-time contrast-enhanced [18F]PSMA-1007 PET/CT scan between October 2021 and February 2024 due to BCR at a tertiary referral hospital. Histopathology after salvage surgery was considered as the gold standard, while clinical, biochemical, and radiological follow-up served as composite reference standards after reviewing the follow-up information. The minimum follow-up per patient was 15 months. The retrospective reading of the early-phase images revealed equivocal PSMA findings, i.e. PSMA-RADS 3 A, in the prostate bed in 12/36 patients (33%), with a total median SUVmax of 5.1 (3.7–6.7). The favourable results with delayed [18F]PSMA-1007 imaging led to upgrading of reporting in 8 out of 12 patients (75%) from PSMA-RADS 3 A to PSMA-RADS 4/5. Conclusion In conclusion, based upon the study results, we suggest the introduction of a new algorithm to enhance and streamline the imaging decision-process, which would prevent avoidable follow-up scans or further imaging modalities and spare economic resources. Yet, further large-scale studies are warranted to validate the additive effect of this algorithm in regular clinical care.

Smart prostate cancer screening means screening better: risk stratification, prostate-specific antigen confirmation, expert magnetic resonance imaging, and prostate-specific antigen density-guided biopsy reduce harm without compromising detection of significant disease.

Supplementary Table S4 summarizes diagnostic test performance measures for PCR-based cfDNA assays, which were not stratified by disease stage (localized/metastatic PCa).

OBJECTIVE:Men with a family history of prostate cancer (PCa) or a pathogenic germline variant (PGV) face increased PCa risk. However, structured PCa early detection and insights into the experiences of affected men remain limited. This qualitative analysis explored (i) why men with familial or genetic PCa risk attended a risk-adapted prevention clinic, (ii) which elements they found helpful, and (iii) how early detection services could be tailored to their needs. METHODS:This study was part of the psychosocial mixed-methods study ProFam-Psych, run alongside the ProFam-Risk prevention clinic. Semi-structured interviews were conducted in a subgroup (13/86 study participants). The clinic offered PSA testing, mpMRI, genetic counselling and panel testing followed by risk-adapted recommendations. Participants were men without PCa who had a family history or previously detected PGV, and men with PCa who had a family history. Participants were selected using maximum variation sampling. Data were analysed by two researchers using Kuckartz's qualitative content analysis. RESULTS:Seven motivators were identified: (1) clarify risk/PGV status, (2) information needs, (3) benefits for the family, (4) support others, (5) external recommendation, (6) access to structured screening, and (7) preventive recommendations. Participants with a family history were primarily motivated by (1) and (3), men with PGVs by (5) and (6), with (6) and (7) unique to this group. Perceptions of elements most helpful to participants varied, but the integrated setting with time for questions, clear guidance, and a reliable point of contact was valued. Suggested improvements were mostly organisational, including reminder systems to support long-term adherence. CONCLUSION:Interdisciplinary early detection for PCa was accepted by participants, with motivators such as screening access and information needs highlighting the need for the implementation of structured screening programs for high-risk men. PRACTICE IMPLICATIONS:Results may inform future outreach efforts and design of screening strategies for familial and genetic PCa risk. TRIAL AND PROTOCOL REGISTRATION:DRKS.de, DRKS00032350. Prospectively registered with the German Clinical Trials Register (DRKS) on 14 September, 2023 SELECTED HEADING: Patient and User Perspectives and Characteristics.

Supplementary Table S3 shows the results of the risk of bias and applicability concerns assessment of all evaluated diagnostic tests according to the QUADAS2-framework.

Abstract Current diagnostic pathways for prostate cancer have unsatisfactory specificity (SPE) and rely heavily on magnetic resonance imaging, underscoring the need for novel diagnostic biomarkers. This article provides a systematic review of the evidence on using blood-derived cell-free DNA (cfDNA)–based biomarkers for prostate cancer diagnosis. A structured review was conducted according to the Preferred Items for Systematic Reviews and Meta-Analyses guidelines. Original peer-reviewed research articles published before August 2025 were identified from PubMed/Medline, Web of Science, and Embase using keyword combinations related to prostate cancer, cfDNA, and diagnostic test performance. Studies that compared blood-derived cfDNA-based diagnostic biomarkers in men with and without prostate cancer were included. Fifty-nine articles were identified and analyzed. Most articles reported qualitative cfDNA assays relying on PCR (N = 37) or next-generation sequencing (NGS; N = 10). Diagnostic test performance improved for aggressive and metastatic prostate cancer. However, evidence about clinical validity in localized disease is scarce, particularly for NGS-based methods (three studies). GSTP1 promoter hypermethylation, the most frequently investigated biomarker, showed an average sensitivity and SPE of 35.1% and 91.2%, respectively, for the detection of localized prostate cancer. Overall, circulating tumor DNA represents a promising diagnostic biomarker for prostate cancer early detection. High-quality discovery and validation research in the intended-use setting are essential to fully understand clinical validity and utility.

Supplementary Table S2 shows extended study characteristics of all included studies.