Exploring miRNA Signature and Other Potential Biomarkers for Oligometastatic Prostate Cancer Characterization: The Biological Challenge behind Clinical Practice. A Narrative Review

SIMPLE SUMMARY: The oligometastatic prostate cancer state is defined as the presence of a number of lesions ≤ 5 and has been significantly correlated with better survival if compared to a number of metastases > 5. In particular, patients in an oligometastatic setting could benefit from a metastates directed therapy, which could control the disease delaying the start of systemic therapies. For this reason, the selection of true-oligometastatic patients who could benefit from such approach is particularly important in this setting. The aim of the present narrative review is to report the current state of the art on the liquid biopsy-derived analytes and their reliability as biomarkers in the clinics for the identification of true-oligometastatic patients. This kind of molecular profiling could refine current developments in the era of precision oncology allowing patients’ stratification and leading to more refined therapeutic strategies. ABSTRACT: In recent years, a growing interest has been directed towards oligometastatic prostate cancer (OMPC), as patients with three to five metastatic lesions have shown a significantly better survival as compared with those harboring a higher number of lesions. The efficacy of local ablative treatments directed on metastatic lesions (metastases-directed treatments) was extensively investigated, with the aim of preventing further disease progression and delaying the start of systemic androgen deprivation therapies. Definitive diagnosis of prostate cancer is traditionally based on histopathological analysis. Nevertheless, a bioptic sample—static in nature—inevitably fails to reflect the dynamics of the tumor and its biological response due to the dynamic selective pressure of cancer therapies, which can profoundly influence spatio-temporal heterogeneity. Furthermore, even with new imaging technologies allowing an increasingly early detection, the diagnosis of oligometastasis is currently based exclusively on radiological investigations. Given these premises, the development of minimally-invasive liquid biopsies was recently promoted and implemented as predictive biomarkers both for clinical decision-making at pre-treatment (baseline assessment) and for monitoring treatment response during the clinical course of the disease. Through liquid biopsy, different biomarkers, commonly extracted from blood, urine or saliva, can be characterized and implemented in clinical routine to select targeted therapies and assess treatment response. Moreover, this approach has the potential to act as a tissue substitute and to accelerate the identification of novel and consistent predictive analytes cost-efficiently. However, the utility of tumor profiling is currently limited in OMPC due to the lack of clinically validated predictive biomarkers. In this scenario, different ongoing trials, such as the RADIOSA trial, might provide additional insights into the biology of the oligometastatic state and on the identification of novel biomarkers for the outlining of true oligometastatic patients, paving the way towards a wider ideal approach of personalized medicine. The aim of the present narrative review is to report the current state of the art on the solidity of liquid biopsy-related analytes such as CTCs, cfDNA, miRNA and epi-miRNA, and to provide a benchmark for their further clinical implementation. Arguably, this kind of molecular profiling could refine current developments in the era of precision oncology and lead to more refined therapeutic strategies in this subset of oligometastatic patients.