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Simple Summary: High-risk prostate cancer is an aggressive disease, and its treatment can be complex and require the involvement of several specialists. Advances in imaging and therapies in this field can improve survival and help physicians choose the best personalized approach that maintains quality of life. This article summarizes the most recent publications on this condition and its treatments, aiming to provide an updated guide for managing patients with prostate cancer who experience a higher risk of progression and death. The management of high-risk prostate cancer (PCa) presents a significant clinical challenge, often necessitating treatment intensification due to the potential presence of micrometastases. While radical prostatectomy (RP) constitutes one of the primary treatment modalities, the integration of neoadjuvant and adjuvant therapies suggests a paradigm shift towards more aggressive treatment strategies, also guided by new imaging modalities like positron emission tomography using prostate-specific membrane antigen (PSMA-PET). Despite the benefits, treatment intensification raises concerns regarding increased side effects. This review synthesizes the latest evidence on perioperative treatment intensification and de-escalation for high-risk localized and locally advanced PCa patients eligible for surgery. Through a non-systematic literature review conducted via PubMed, Scopus, Web of Science, and ClinicalTrials.gov, we explored various dimensions of perioperative treatments, including neoadjuvant systemic therapies, adjuvant therapies, and the role of novel diagnostic technologies. Emerging evidence provides more support for neoadjuvant systemic therapies. Preliminary results from studies suggest the potential for treatments traditionally reserved for metastatic PCa to show apparent benefit in a non-metastatic setting. The role of adjuvant treatments remains debated, particularly the use of androgen deprivation therapy (ADT) and adjuvant radiotherapy in patients at higher risk of biochemical recurrence. The potential role of radio-guided PSMA lymph node dissection emerges as a cutting-edge approach, offering a targeted method for eradicating disease with greater precision. Innovations such as artificial intelligence and machine learning are potential game-changers, offering new avenues for personalized treatment and improved prognostication. The intensification of surgical treatment in high-risk PCa patients is a dynamic and evolving field, underscored by the integration of traditional and novel therapeutic approaches. As evidence continues to emerge, these strategies will refine patient selection, enhance treatment efficacy, and mitigate the risk of progression, although with an attentive consideration of the associated side effects. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and Methods The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies).Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129–0.278; p<0.001; I²=83.62%, Egger’s p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474–1.706; p<0.001; I²=97.86%, Egger’s p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526–2.121; p<0.001; I²=97.88%, Egger’s p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318–1.968; p<0.001; I²=98.65%, Egger’s p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%–2.153%; p<0.001; I²=98.97%, Egger’s p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%–1.759%; p<0.001; l2=97.98%, Egger’s p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%–1.211%; p<0.001; I²=97.87%, Egger’s p=0.1864. Conclusions The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele. [ABSTRACT FROM AUTHOR]