The biology and treatment of oligometastatic cancer

Abstract

Clinical reports of limited and treatable cancer metastases, a disease state that exists in a transitional zone between localized and widespread systemic disease, were noted on occasion historically and are now termed oligometastasis. The ramification of a diagnosis of oligometastasis is a change in treatment paradigm, i.e. if the primary cancer site (if still present) is controlled, or resected, and the metastatic sites are ablated (surgically or with radiation), a prolonged disease-free interval, and perhaps even cure, may be achieved. Contemporary molecular diagnostics are edging closer to being able to determine where an individual metastatic deposit is within the continuum of malignancy. Preclinical models are on the outset of laying the groundwork for understanding the oligometastatic state. Meanwhile, in the clinic, patients are increasingly being designated as having oligometastatic disease and being treated owing to improved diagnostic imaging, novel treatment options with the potential to provide either direct or bridging therapy, and progressively broad definitions of oligometastasis.

New Strategies in Stereotactic Radiotherapy for Oligometastases

“…Several lines of evidence indicate that individual tumors-and individual clones within tumors-vary in their ability for metastatic spread (28). In order to develop metastases, several processes are required, including loss of cell adhesion, increased motility, and invasiveness, followed by entry into the circulation with colonization of new organs (29,30).…”

“…Cells that are efficient at most, but not all, of these components may therefore be inefficient colonizers of distant sites, resulting in an oligometastatic state. The genes required for the development of metastases have been categorized into three groups: initiation genes, which facilitate entry into the circulation; progression genes, involved in the steps required for colonization; and virulence genes, which provide selective advantages in colonizing metastatic sites (28,31). It follows that variability in each of these factors could lead to tumors with varying potential for metastatic progression, including groups of tumors with a low propensity for metastasis, a premise supported by multiple preclinical models (28).…”

“…The genes required for the development of metastases have been categorized into three groups: initiation genes, which facilitate entry into the circulation; progression genes, involved in the steps required for colonization; and virulence genes, which provide selective advantages in colonizing metastatic sites (28,31). It follows that variability in each of these factors could lead to tumors with varying potential for metastatic progression, including groups of tumors with a low propensity for metastasis, a premise supported by multiple preclinical models (28). Bayesian modeling suggests that in patients with oligometastases, the likelihood of occult metastatic disease increases rapidly with even small increases in metastatic potential (32).…”

Oligometastatic Disease in Upper Gastrointestinal Cancer - How to Proceed

“…At the moment, the 'test of time' is the most convincing indicator of a more favorable biological cancer behavior. However, there is an increasing shift toward individualized, multidisciplinary management of OMD because it is difficult to conduct randomized controlled trials due to the variety of presentations [5].…”

“…Moreover, serum microRNAs could potentially be useful biomarkers [31]. Examples of pro-metastatic microRNAs include microRNA-10b (upregulated in primary metastatic breast cancer) and microRNA-21 (correlates with advanced stage and poor outcomes in breast and pancreatic cancer) [5].…”