Local Control of Distant Disease: Yes, but Where to Next?

Throughout most of the modern era of cancer therapeutics, the standard dogma of metastatic disease, at least among medical oncologists, has run something like this: before initial surgery for the primary tumor, micrometastases have fled the organ of origin, successfully colonized distant sites, and grown there—eventually to a size capable of robbing the patient of life. If, this dogma also attests, systemic therapy is incapable of eradication of distant metastases, then other therapeutic modalities are futile and should be reserved for palliation. This basic dogma has guided therapy for most metastatic disease. Yet we know that this dogma, like most, is riddled with exceptions. As discussed by Boffa1 in his overview, randomized controlled trials in colorectal cancer have demonstrated survival benefits for patients with oligometastatic disease, and collections of anecdotes abound in the medical literature that attest to the existence of long-term survivors after local therapy in other cancer types. Such observations (which range from level-1, randomized, controlled trial data to “I once saw a case” anecdotes) raise the question of whether we might be underusing local therapies for metastatic disease. I certainly could add to the pile of anecdotes: Most cancer doctors know long-term survivors whose tumors failed to respond to systemic therapy, only to disappear into formalin or to be ablated by radiation. Yet data are not the plural of anecdote. What do we require to suggest local therapy to patients with metastatic disease? Boffa1 has offered an interesting approach, and there is much wisdom in this offering. At the risk of presumption, let me add a few of my own thoughts. Biology is still destiny. Use of local therapy with curative intent presumes that, in the setting of oligometastatic disease (a term in which the meaning varies among both researchers and disease types), anatomy is destiny; that is, lump removal trumps all else. However, local control of oligometastatic disease does not work in all cancers, nor in all patients with diseases in which we consider metastatectomy an option. The presence of disseminated micrometastatic disease refractory to systemic therapy still dooms most patients. If this is indeed the case, then it follows that improvement in technology to detect “bad actor” micrometastases represents one potential means of patient selection for local control with distant metastasis. Such technologies might include imaging with submillimeter resolution, circulating tumor DNA, and circulating tumor cell analyses. Use of such technologies