OBJECTIVE
Active surveillance (AS) is the preferred management for individuals with low-risk prostate cancer (PCa), but its role in intermediate-risk (IR) disease remains underreported. Given growing interest and published data, we performed an updated systematic review and meta-analysis to evaluate AS outcomes in selected patients with Gleason Grade Group (GG) 1-2 IR PCa.
METHODS
A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD420251138532). PubMed/MEDLINE, Embase, and Web of Science databases were searched for studies published up to September 2025 reporting outcomes of AS in IR PCa. Primary outcomes were AS discontinuation-free survival and GG ≥3 upgrade-free survival.
RESULTS
In total, 18 studies, including 3783 selected patients with IR PCa, were analyzed. Pooled AS discontinuation-free survival rates were 70% (95% confidence interval [CI] 62-78) at 3 years, 63% (95% CI 58-68) at 5 years, and 53% (95% CI 38-67) at 10 years. In analyses restricted to GG 2 cohorts, corresponding pooled estimates were 72% at 3 years, 56% at 5 years, and 40% at 10 years. GG ≥3 upgrade-free survival was 84% (95% CI 76-92) at 3 years and 78% (95% CI 65-91) at 5 years in all cohorts and 92% (95% CI 86-98) and 87% (95% CI 78-95) at 3 and 5 years in cohorts screened using multiparametric magnetic resonance imaging. No significant difference in AS discontinuation was observed between biopsy GG 1 and 2 (hazard ratio 1.08; 95% CI 0.86-1.35). Limitations include moderate risk of bias and heterogeneity across AS protocols.
CONCLUSIONS
Although long-term data are lacking, particularly regarding robust oncological outcomes, growing evidence suggests that AS appears oncologically safe in well-selected patients. Magnetic resonance imaging will play a key role in the appropriate selection and follow-up of patients.
Alessandro Uleri, L. Cella, T. Long-Depaquit et al.· BJU International· 0 citations
Lineage plasticity has emerged as a central mechanism through which cancer cells adapt to therapeutic pressure, evade immune surveillance, and acquire aggressive phenotypes. Although recognized across tumor types, the regulatory principles governing how cancer cells reprogram cellular identity remain incompletely understood. In this review, we propose that lineage plasticity in cancer reflects the redeployment of regulatory frameworks established during normal development. Rather than representing a stochastic byproduct of genomic instability, cancer plasticity frequently unfolds within gene regulatory architectures that also govern cell fate specification, lineage commitment, and controlled state transitions during embryogenesis and tissue homeostasis. Developmental transcription factors, including members of the SOX family, FOXA1, ASCL1, NKX2-1, and epithelial-mesenchymal transition regulators, function as lineage gatekeepers during development but are repurposed in cancer to destabilize lineage commitment and enable phenotypic switching. Similarly, epigenetic regulators that guide developmental trajectories, including chromatin remodeling complexes, Polycomb group proteins, and DNA methylation machinery, are frequently dysregulated or redistributed in tumors, altering the repression of lineage-stabilizing and alternative lineage programs and thereby weakening epigenetic barriers to lineage transitions. Together, these observations support a model in which development and cancer operate as mirror regulatory systems: one establishing and stabilizing cellular identity, the other exploiting the same regulatory architecture to permit adaptive reprogramming under selective pressure. We further discuss how emerging single-cell and spatial multi-omics technologies, integrated with artificial intelligence-based modeling, enable mapping of cell state landscapes and transitional trajectories, transforming lineage plasticity from a descriptive phenomenon into a measurable and predictable property of tumor evolution.
Melanie Fraidenburg, Longjun Li, Rosa Kwon et al.· Cancer Letters· 0 citations
