Desley van Zoggel

Introduction and outline 11 CHAPTER 1 Introduction Treatmentofrectalcancerhasundergonemajorchangesovertheyears.Themanagement of primary rectal cancer has evolved from only surgical options to a multidisciplinary treatment with improved chances of cure for every stage of the disease. For every stage treatment goals are set and clear and a paradigm shift from a surgical resection to organ preservation in selected cases has occurred.1 Despite better neoadjuvant and surgical treatment in primary rectal cancer, local recurrence still occurs in 5-10 percent of patients.2,3 For those patients with locally recurrent rectal cancer (LRRC), treatment options and oncological outcomes have not changed as drastically. Still, most of the patients who develop a local recurrence will die of progressive disease and cure is only possible for a minority.4 Surgery with clear resection margins is the single most important factor influencing survival. This often involves extended pelvic resections with significant loss of function.5 Treatment principles for primary rectal cancer cannot simply be extrapolated to LRRC and for a better understanding, it is important to realize the differences between these two conditions. A primary rectal cancer originates de-novo following the well accepted sequence from polyp to carcinoma-in-situ tomalignant tumour. A local recurrence does not follow this natural sequence but is rather an outgrowth of persisting tumour cells after resection of the primary tumour. Whereas in de-novo origination it takes a long time for mutations to lead to malignant cells, in local recurrence malignant cells are already present and can therefore progress to a solid tumour in a relatively short time span. Theoretically, these cells can be more treatment resistant as they already have survived the primary tumour treatment principles. The development of metastases is a late event in primary rectal cancer, leaving a wide windowtoperforma curative treatment beforemetastases occurs. Evenafter successful treatment of the local recurrence, themajority of patients with LRRCwill die because of early development of metastatic disease. A possible explanation could be that in these cases, development of metastases does not happen after invasion of cancer cells into lymphatic tissue and blood vessels, but instead this process may have already started at the time of the primary tumour. It evenmay be argued that LRRC could in some cases be a manifestation of metastatic disease. Locally recurrent rectal cancer is not a new tumour. The aetiology of LRRC can be explained as a failure to eradicate the primary tumour completely, therefore being a failure of treatment. The quality of the primary surgery contributes to the development of LRRC. In the past, recurrence rates approaching 40 percent have been reported.6