Historically, the treatment of patients with metastatic solid tumours has been based on systemic therapies that aim to delay progression and extend life, but not to eradicate the disease completely.1, 2 The oligometastatic paradigm, formally defined in the 1990s3 but anecdotally reported as early as the 1930s,4 suggests that in some patients, metastatic disease is not widespread, but is constrained to develop in only a small number of sites because of anatomical and physiological factors.3 This paradigm suggests that patients with oligometastases should be amenable to a curative treatment approach.3
Clinical evidence to support improved treatment outcomes in the oligometastatic state has generally been limited to non-randomised observational studies.5 Many of these studies, but not all, suggest that the treatment of oligometastatic disease with ablative therapies can lead to better-than-expected survival, compared with a general population of patients with metastatic disease.6, 7 However, these promising results could be due to selection bias, with the inclusion of fit patients with low-burden, indolent cancers.5, 7 Nevertheless, the use of ablative therapies has increased in many jurisdictions worldwide, albeit with substantial geographical variability in practice.8, 9 Interest in treating oligometastatic disease is also increasing because of improvements in systemic therapy, as has been observed with molecular targeted therapies10 and immune checkpoint inhibitors.11
Research in context
Evidence before this study
Several recent systematic reviews examined the effect of ablative therapies in patients with oligometastatic cancers. No previous randomised trials were identified in patients with oligometastases, in which the primary endpoint was a comparison of overall survival between an ablative treatment group (eg, stereotactic ablative radiotherapy [SABR] or surgery) and a group that did not receive ablative therapy. In patients with one to nine hepatic metastases from colorectal cancer, a secondary analysis of a randomised trial assessing systemic therapy with or without radio-frequency ablation showed an overall survival benefit with the use of radio-frequency ablation to all hepatic lesions. Three randomised trials using surrogate endpoints, such as progression-free survival, have shown benefits of ablative therapies in oligometastatic prostate and lung cancers. Findings are based on a search of PubMed from inception to Aug 1, 2018, using search terms related to “oligometastatic” (eg, “limited metastatic”, “solitary metastasis”, and “oligometastatic”), and common cancer types (eg, “breast cancer”, “prostate cancer”, and “lung cancer”), limited to English language randomised trials. A similar search for systematic reviews was undertaken and their reference lists were hand-searched.
Added value of this study
This study found that the use of SABR in patients with controlled primary tumours and one to five oligometastases achieved a 13-month improvement in overall survival, with a doubling of progression-free survival, at the cost of increased risk of toxicity, including a 4·5% risk of grade 5 toxicity. These findings represent the strongest level of evidence, thus far, in support of the existence of an oligometastatic state.
Implications of all the available evidence
Although further trials are needed, the emerging evidence supports the existence of an oligometastatic state, and that patients with a limited number of metastases might be amenable to curative-intent treatment strategies.
Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy, is a modern radiation technique that delivers high doses of radiation to small tumour targets with use of highly conformal techniques (appendix p 2).12 SABR is non-invasive, delivered on an outpatient basis, and is used to target lesions in the lungs, brain, liver, adrenals, and bone, among other locations.
To our knowledge, the oligometastatic paradigm has not been directly tested before in a randomised trial; namely, no trial has evaluated whether eradicating oligometastases that have propagated through the systemic circulatory system improves overall survival. In this randomised controlled trial, we aimed to assess standard of care palliative treatments with or without SABR in patients with a controlled primary tumour and up to five metastatic lesions.