SABR-COMET: a new paradigm of care lights up the twilight of metastatic disease

Not so long ago, the diagnosis of haematogenous metastases in a patient with a solid organ malignancy was synonymous with incurability and palliation. It was assumed that the appearance of the metastatic phenotype, even if at only one site, was the tip of the iceberg, and that it would only be a matter of time before synchronous but microscopic deposits would become clinically evident macroscopic metastases. As surmised by Hellman and Weichselbaum (1), on the balance of probabilities, in a population of patients with stage IV cancer, there could be a wide distribution of metastatic deposit numbers from one to many. If so, the ablative treatment of one or limited metastases (“oligometastases”) in addition to control of the primary might achieve long term disease control, or perhaps even cure. Further, if the metastasis was not solitary but in a life-limiting location such as the brain, ablation of the metastasis could at least prolong survival before the appearance of other competing metastatic risks for death. The first evidence in support of the oligometastatic concept was reported by Churchill and Barney in 1939, where they showed that a patient with synchronous metastatic kidney cancer was cured by nephrectomy and pulmonary metastasectomy (2). Later, randomized evidence in the setting of solitary brain metastasis demonstrated that surgical extirpation in addition to whole brain radiotherapy increased survival compared with radiotherapy alone (3). Ablation of brain oligometastases is a now well-established standard of care, and the concept might have gained widespread acceptance beyond the brain if it were not for potential morbidity of surgery in certain body sites (e.g., bone) or in the context of co-existing medical conditions (e.g., lung metastasectomy in a patient with limited cardiorespiratory reserve). The development of stereotactic ablative body radiotherapy (SABR), which is effective, non-invasive, relatively safe, convenient and widely applicable thus represented an attractive alternative to surgery in the oligometastatic setting. However high-level evidence to support its use to prolong survival has until now not been available