What is Oligometastatic Disease?

Metastatic cancer (often called Stage IV, though not all Stage IV cancers are metastatic) is cancer that has spread from the original tissue (e.g. breast, prostate, lung, etc.) to a distant part of the body (bones, lungs, brain, liver, etc.). This derives from the Greek words meta- meaning "change", and -stasis meaning "placement" -- a change in the location of disease, a migration from one tissue to another.

Biologically this is a very complex process: the cancer cell must detach from the primary tumor, survive a journey though the body (often the bloodstream), and settle in a distant tissue where it can flourish and grow. This is not a guaranteed process -- cancer cells must have acquired the ability to survive detachment and travel, and they must settle in a tissue that provides the right chemical signals and nutrients for survival.

Given each primary cancer is different, with unique propensities, all metastatic cancer does not behave the same. Over the last several years, we have refined our understanding and approaches to metastatic disease in clinical practice. Ultimately we're trying to identify and classify a form of metastatic disease that is slower in growth, more indolent, and with a favorable/longer prognosis to refine our management approach.

Key Definitions

After appropriate staging and imaging, we describe the extent of disease, whether it is diffuse (poly-metastatic, indicating many sites) or limited (oligo-metastatic, indicating few sites). Is there a numerical cutoff between 'many' versus 'few'? This is somewhat debatable though we've roughly settled on "fewer than 5 sites of metastatic disease" for simplicity in our early understanding of this disease state. The absolute number of metastatic sites is certainly not a comprehensive tool for evaluating disease behavior, but is currently the only tool in broad use. Future iterations could include tumor genomic profiles, blood biomarkers (e.g. circulating tumor DNA), and advanced imaging in machine learning risk-stratification models to evaluate tumor behavior. You may hear physicians use some related terms:

1. Oligoprogressive: most disease is controlled by systemic treatment, but a few spots continue to grow
2. Oligorecurrence: the original cancer has been treated, limited metastatic disease has been discovered afterwards in surveillance
3. Oligopersistence: the bulk of sites have responded well to systemic therapy but a few residual sites remain
4. Synchronous: metastatic disease appears at the same time (within 6 months) as the initial primary cancer diagnosis. An example would be a man with newly diagnosed prostate cancer and single metastatic site in the rib. This would be termed "synchronous oligometastatic prostate cancer to the rib"
5. Metachronous: metastatic disease emerges after a disease-free interval following primary treatment. When this is limited in extent, it is synonymous with oligorecurrence. An example would be a woman who was successfully treated for breast cancer and found to have a lung lesion three years later proven to be breast cancer in origin

Why It Matters

Oligometastatic disease describes a limited form of metastatic cancer, an intermediate stage between localized and widespread disease. This can change treatment goals: rather than relying only on systemic therapy (e.g. chemotherapy, immunotherapy, other pharmaceuticals), physicians may aim to eradicate visible disease with surgery, radiation therapy, or other ablative technologies. Sometimes this is done alongside or sequenced with systemic therapy. Research has shown that in appropriate patients, this approach can improve progression-free survival and overall survival, delay more intensive therapy, and enhance the effectiveness of systemic therapy by eliminating resistant clones.

Important Caveats

The oligometastatic concept suggests metastatic disease exists on a spectrum. Yet we have clinically dichotomized this to "many" versus "few". This designation is not a guarantee of limited biology or cure.

"Few" has no universal meaning

There is no single agreed cutoff. Some trials limit the total sites to 3, others to 5. Some trials limit the total organs involved to 1 or 2. Again we're using a single snapshot of visible to disease to infer biology, but we know this is an incomplete assessment +De novo OMD may represent a patient with truly limited disease, or just an early immature picture of a patient rapidly progressing to widespread polymetastatic disease +Metachronous disease that is substantially delayed from initial treatment likely has a different biology from metachronous disease that appears within a year +Oligoprogressive disease can identify resistant sites, but it is unclear if this reflects overall tumor biology

Imaging can underestimate disease

The oligometastatic designation is assigned from imaging, not from a test that proves the cancer truly has limited capacity to spread. Imaging can miss very small lesions or microscopic deposits; a person may therefore appear to have two treatable lesions but harbor additional microscopic disease elsewhere. Choice of imaging matters as well: bone scans have lower sensitivity than PET scans for example. There is not yet a clinically validated biomarker that reliably identifies indolent biology.

Local treatment is not automatically curative

Surgery, radiation, and ablative technologies can eliminate known lesions but they cannot remove disease that is unseen or circulating. Systemic therapy is often still essential though the goals ay vary from person to person: +Achieve durable disease control +Delay progression or a change in systemic therapy +Prevent symptoms or organ damage from a high-risk lesion +Occasionally, pursue long-term remission and potentially cure in a highly selected setting

Evidence is uneven

The benefit in metastasis-directed therapy (MDT) cannot be assumed across every cancer type. Trials use different definitions, imaging workups, systemic therapies, and endpoints. The heterogeneity in trials coupled with the heterogeneity in biology makes it difficult to extend conclusions to all patients. Selection effects are also important: patients offered aggressive local therapy often have better functional status, smaller-volume disease, lesions in safer locations, slower-growing cancer, and tumors that have already responded to systemic treatment. Those characteristics themselves portend better prognosis, so favorable outcomes after local therapy does not prove the local treatment caused it.

Treatment has tradeoffs

Local treatment is not risk-free, even if it is focused. Risks depend on the lesion's location and may include pain, fatigue, inflammation, and injury to nearby tissues. Treating several sites can compound these risks and may interrupt or delay systemic therapy. With the rapid development in systemic therapies as well, there is limited data to evaluate overlapping or synergistic toxicity risks when combined with local therapies. Though the technology exists, the appropriate question is not simply "Can every lesion be treated?" but rather "Will treating every lesion provide enough expected benefit to justify the combined risk and burden?"