Biology of colorectal pulmonary metastasis: implications for surgical resection

In colorectal cancer, little high grade evidence for cure, life extension, disease modification or palliation achieved by pulmonary metastasectomy exists. This has prompted the pulmonary metastasectomy in colorectal cancer (PulMiCC) trial. Reappraisal of the biological facts on colorectal metastasis may, however, shed light on an alternative avenue of clinical management. Early onset of metastasis, short doubling time and a short disease-free interval are all associated with poor clinical outcomes. Selecting who will be cured (i.e. no occult metastasis) remains the holy grail for pulmonary metastasectomy surgery. Serial CT scans can be utilized to calculate the tumour doubling time by volumetric analysis. Knowing the doubling time and size of the largest metastasis, which by definition is the first cell that has successfully spread from the primary site, the time of initial metastasis can be predicted. More importantly, using the doubling time, calculating the time interval from the primary surgery to the point at which all pulmonary metastases are visible should be possible. Perhaps watchful waiting, with interval CT scanning, followed by pulmonary metastasectomy should be utilized, rather than clinical opinion or randomization in a trial based upon first presentation.