Desley van Zoggel

Summary, discussion and future perspectives 143 CHAPTER 8 numbers with this specific type of local recurrence and even lower numbers of patients who underwent induction chemotherapy. Furthermore, induction chemotherapy was not administered consistently during the inclusion period of this study, which might have led to bias. Although these limitations exist, it is clear that induction chemotherapy should also be considered in patients with lateral local recurrences to improve chances of clear resection margins. Approximately 50 percent of LRRC patients present with distant metastases, making synchronous systemic disease another major issue. Systemic disease is considered an indicator or aggressive tumour biology and treatment options are usually limited to palliative intent. In chapter 5, the treatment principles for metastatic primary rectal cancer are applied in patients with metastatic LRRC. The study provides insight in the outcomes of a curative treatment approach for this specific patient group. The goal of the treatment remains resection with clear margins, combined with resection or ablation of the metastases. All patients who underwent curative resection between 2005 and 2017 were included and classified in three categories; no metastases (261, 75 percent), history of metastases (42, 12 percent) and synchronous metastases (46, 13 percent). The study showed that a history of metastases did not influence overall survival. The 3-year metastasis-free survival however, was worse in patients with a history of metastases than in patients without metastases (33 percent vs 52 percent, not significant), possibly requiring those patients to undergo (repeated) invasive treatment. In patientswith synchronousmetastases the 3-yearmetastasis-free survival was significantlyworse than in patients without synchronousmetastases. This resulted in a trend towards worse overall survival (hazard ratio 1.43; 95 percent CI 0.98-2.11), suggestingmore aggressive tumour behaviour. Using a tailored approach, with attention to natural behaviour of the disease, may enable selection of patients with metastatic LRRC who might benefit from a curative treatment approach. The importance of achieving clear resection margins has been stressed multiple times before. The methods of facilitating downsizing and downstaging have also been discussed. However, in LRRC, assessment of response to different neoadjuvant treatment relies heavily on imaging techniques. Preoperative prediction of the pathological response potentially provides an opportunity to adopt a non-operative treatment strategy in patients with a clinical complete response, which may be very valuable in the light of the complexity and impact on quality of life of LRRC surgery. Chapter 6 investigated the role of an MRI based tumour regression grading (mrTRG) in the treatment decision making for LRRC patients. A retrospective cohort of patients who underwent treatment with induction chemotherapy and neoadjuvant chemo(re)