Background/Objectives: Prostate cancer (PCa) is the second most common malignancy among men worldwide and a leading cause of cancer-related mortality. In 2022, over 1.4 million new cases were reported globally, with a prevalence exceeding 5 million. Despite its widespread occurrence, the incidence and mortality of PCa show substantial geographic variation, influenced by factors such as genetic predisposition, healthcare access, lifestyle, and the adoption of screening programs. Regions with high PCa incidence, such as Northern America and Oceania, often have lower mortality rates due to early detection and advanced healthcare infrastructure. Conversely, areas with limited access to medical resources, such as parts of Africa and Latin America, experience higher mortality rates. Methods: This review explores non-modifiable risk factors such as age, family history, and race, emphasizing their role in PCa development and progression. Results: Modifiable factors, including diet, physical activity, alcohol consumption, and smoking, are also addressed, with evidence suggesting their potential in mitigating risk. Emerging data on medications such as 5-alpha reductase inhibitors and statins, as well as dietary supplements such as vitamins D, indicate their potential for chemoprevention, though further research is needed to solidify these findings. Healthcare disparities, especially in low- and middle-income regions, highlight the need for equitable access to diagnostic tools and treatment options. The review underscores the significance of tailored screening approaches, particularly in high-risk populations, to optimize outcomes while minimizing overdiagnosis and overtreatment. Conclusions: The review concludes with recommendations for future research, including the need for standardized screening protocols and the exploration of novel biomarkers for early detection. By synthesizing epidemiological data and current evidence, this review aims to enhance understanding of PCa risk factors, geographic disparities, and preventive strategies, ultimately contributing to improved global PCa management and outcomes.

Low-risk prostate cancer usually has an indolent course, and in this scenario, active surveillance (AS) is currently the preferred management, reducing overtreatment without compromising oncologic outcomes in well-selected patients. Two pillars of this strategy are patient selection and adequate monitoring strategy to detect early progression, leading to active treatment in the window of curability. The aim of this review is to assess the novel available tools and their role in AS. We conducted a comprehensive review of the current literature addressing the risk of reclassification and studies evaluating traditional and emerging diagnostic and prognostic tools, including imaging modalities, biomarkers, and genomic classifiers, which could decrease reclassification rates and minimize the burden of serial exams during follow-up and, especially, the frequency of biopsies, which are still necessary to evaluate progression. The most significant follow-up cohorts demonstrate long-term treatment rates ranging from 30% to 45%, and 36% of low-risk prostate cancer patients have an upgrade in radical prostatectomy specimens. Despite the emergence of new diagnostic and prognostic tools, few of them have been validated or included in the assessment of eligible patients for AS. In the current guidelines, a combination of cT stage, Gleason score, prostate-specific antigen value, prostate-specific antigen density, and number of positive cores in biopsy is used to select patients for AS. However, various risk factors have been associated with the risk of reclassification, which reveals the need to incorporate better tools that may contribute to better risk stratification of patients eligible for AS. Although AS is feasible and safe, the risk of progression is of great concern for patients and physicians, and monitoring is also an important part of the therapeutic strategy. Novel risk stratification tools are promising but need further validation to improve results and decrease the burden and anxiety that monitoring can bring to patients.