Lung metastasectomy paradoxes in practice: reflections on the Catania conference.

Abstract

Senior surgeons and medical students and every grade in between, basic scientists and clinicians, researchers and practitioners from many countries met in Catania, Sicily, in April 2014. This was a focus meeting to share knowledge, experience and opinions centered around one question: how best to manage lung metastases? It is my privilege to have been invited to write some personal reflections by way of introduction to the report of the symposium. t he biological basis of metastasis The presence of metastates in the lung is dependent on a number of steps, all of which must be successfully completed to give rise to a metastatic growing tumor. The tumor cells have to enter the circulatory system directly or indirectly via the lymphatic system. They need to survive in the circulation until they can arrest in the lung. There they have to extravasate from the circulation into the surrounding tissue. Then they have to become established and the cells must continue to replicate until they become discernible on imaging. The fate of cancer cells that have survived to reach the lung is uncertain. Cells may stay quiescent and eventually die, they may grow to form a small nidus of metastatic cells, a nidus may regress or it may through angiogenesis develop its own blood supply and proliferate to eventually form a clinically detectable metastasis. Studies using cancer cells labelled with 125 I-deoxyuridine, which is incorporated into DNA, showed that within 24 h after entry of tumor cells into circulation less than 1% of tumor cells are viable and that one in a thousand of these cells survive to produce metastases. The process of cancer metastasis is thus seen to be highly inefficient. Many hundreds of thousands of cancer cells may be disseminated into the circulatory system, but only a small fraction of these cells will actually form growing metastatic colonies [1]. These observations prompt the question of whether the development of metastases represents the fortuitous survival and growth of very few tumor cells or whether the primary tumor progresses to a more malignant state from which metastases arise. Metastases may not share the properties of the primary cancer and possibly in ways that make them more resistant to chemotherapy [2]. Evidence gained from gene studies in renal cancer showed heterogeneity and branched evolution which suggests that the challenges of implementing personalized or targeted therapies and biomarker development may have been underestimated [3]. t he interval between primary resection & metastasectomy Against the uncertain direction of medical management of metastases, surgical metastasectomy has followed a fairly steady course based on the presumption that if the detected metastases are the only cancerous masses in the body, surgical removal or other local treatment could potentially cure the patient. How can that be other than true? It’s the ‘if’ that’s the problem. Here is an analogy which, like all analogies, cannot be tested too far but let’s see if it helps. When fall/autumn comes, if you stand under a solitary tree, there will probably be a point in time when there is the first leaf