Paolo Zaurito

Prostate cancer (PCa) screening has long relied on PSA testing, a strategy that has shaped diagnostic pathways for decades but remains limited by substantial overdiagnosis and downstream overtreatment. As screening practices evolve, the relevance of historical evidence must be reconsidered in the context of contemporary diagnostic workflows that now incorporate imaging, refined biopsy techniques, and risk-adapted management. This narrative review examines the transition from PSA-only screening toward modern, risk-adapted early detection strategies. We synthesize evidence supporting the integration of mpMRI, refined biopsy techniques, and active surveillance (AS) as key components of contemporary screening pathways aimed at improving the detection of clinically significant disease while minimizing unnecessary interventions. Particular emphasis is placed on second-line MRI-based approaches, which consistently reduce the number of avoidable biopsies and enhance the diagnostic precision. In addition, we review the role of blood-based and genomic biomarkers in pre-biopsy risk stratification, discussing established tools within a unified framework of individualized screening. The review also contextualizes very recent regulatory developments, including the FDA approval of a novel structure-based PSA assay, as part of the ongoing evolution of biomarker-supported screening rather than a paradigm shift. Overall, this article provides a timely synthesis of mature randomized evidence and emerging diagnostic innovations, offering a clinically grounded perspective on how PCa screening is being reshaped toward more personalized and harm-aware strategies.

Purpose of Review: In approximately 10–15% of patients with prostate cancer (PCa), pathological lymph node metastases (pN1) are detected at radical prostatectomy (RP). The aim of this review is to describe the various treatment options for pN1 patients, with a focus on the most recent evidence reported in the literature. Evidence Synthesis: Due to the lack of prospective studies, several retrospective analyses were conducted according to different types of treatment. Most common strategies are represented by observation plus early salvage radiotherapy (RT) in case of PSA rising, adjuvant androgen deprivation therapy (ADT) alone, or adjuvant RT with or without ADT. Patients with pN1 disease and favorable disease characteristics (lower T stage and ISUP ≤ 2 at RP, 3) were detected at RP. Lastly, few studies analyzed the rate of adverse events following adjuvant ADT or RT, leaving the issue of treatment-related side effects still open. Summary: There is no clearly established standard of care for men with pN1 PCa, and disease characteristics should guide the choice of optimal post-operative management for these patients. Prospective data and clinical trials are clearly needed to define the most effective therapeutic strategy.

Genomic score testing is increasingly being integrated into the management of prostate cancer (PCa) to overcome the limitations of traditional clinical and pathological parameters. Genomic tools will represent essential components of precision medicine, supporting risk stratification, therapeutic decision-making, and personalized screening strategies. Genomic score tests can be broadly classified into two main categories: polygenic risk scores (PRSs) and tumor-derived genomic classifiers (GCs). While not yet standard in routine practice, several international guidelines recommend their selective use when results are likely to impact clinical management. PRSs estimate an individual’s susceptibility to PCa based on the cumulative effect of multiple low-penetrance germline genetic variants. These scores show promise in enhancing early detection strategies and identifying men at higher genetic risk who may benefit from tailored screening protocols. Tumor-based GCs assays provide prognostic information that complements conventional clinical and pathological parameters, and are used to guide treatment decisions, including eligibility for active surveillance (AS) or adjuvant therapy after treatment of the primary tumor. This review summarizes and analyzes the current evidence on genomic testing in PCa, with a focus on the available assays, their clinical applications, and their predictive and prognostic value across the disease spectrum. When integrated with clinical and pathological parameters, these tools have the potential to significantly enhance personalized care and should be increasingly considered in routine clinical practice.