The concept of a more limited, potentially treatable form of metastatic disease is one that has some support, including anecdotal evidence spanning decades. In the study of malignancies at other sites, there has been confirmation from randomized clinical trials (eg, in non-small cell lung cancer) that local therapies may, indeed, prolong the progression-free survival of patients with 3 or fewer metastases after first-line systemic therapy. As for prostate cancer, multiple prospective randomized trials to investigate the role of metastasis-directed therapy are ongoing. These trials may also serve to further the understanding of the biology of oligometastatic disease.

Historically, patients with metastatic castration-resistant prostate cancer (mCRPC) were believed to harbor microscopic metastases in radiographically silent areas, regardless of the number of metastases. Generally, therefore, systemic therapy alone has been offered to all patients with metastatic disease. Tumor-directed therapy such as radiation or surgery has been reserved for patients with localized disease, or cases of symptomatic metastatic disease. Owing to the lack of prospective randomized trials, metastasis-directed therapy for oligometastatic disease remains somewhat controversial.

The current understanding of how, molecularly, a primary tumor might progress to oligometastasis rather than polymetastases is not well developed. And, although many sources refer to a range of approximately 3-5 metastases in describing oligometastatic disease, no formal cut-off for ‘‘oligo’’ has been defined in the literature. One area of interest has been the potential role of micro-RNAs. Uppal and colleagues found in their review of the known functions of oligometastatic-specific micro-RNAs that there might be regulatory action in the metastatic cascade, including epithelial-mesenchymal transition, tumor invasion, intravasation, distant vascular extravasation, and proliferation in a distant organ.

A better understanding of the molecular characteristics of oligometastatic disease would be especially helpful in concert with other advances in the field such as more sensitive imaging techniques and emerging forms of focal treatment. Indeed, a molecular signature to discriminate between metastatic disease destined to remain oligometastatic and disease destined to progress to polymetastatic disease will inform therapeutic decisions. More sensitive imaging will likely identify more metastases in many patients previously classified as ‘‘oligometastatic’’ by conventional modalities such as computed tomography and bone scintigraphy. Likewise, many patients determined to have M0 disease via conventional imaging may be reclassified as having M1 disease, with an oligometastatic presentation, especially where lower PSA thresholds lead to imaging.