Impact of metastases on survival 93 CHAPTER 5 survival inpatientswithsynchronousmetastases specifically, presenting similarmedian OS rates compared with our study.17,18 Previous work by our group showed a median OS of 27months in LRRC patients with synchronousmetastases.9 In this previous study, all patients were treated with induction chemotherapy, whichmay explain the favourable OS. However, all of the above mentioned studies, including the current study, reported on a selected group of patients, hindering direct interstudy comparison. In particular, most studies did not report on patients who began curative neoadjuvant treatment but did not undergo surgery due to progressive disease, resulting in a highly selected group of patients with a relatively favourable prognosis. In LRRC, local control is imperative in securing quality of life as it relieves patients from tumour- related debilitating symptoms.19 If an R0 resection is achievable, extensive surgical intervention should therefore be considered. However, in the presence of synchronous metastases caution is warranted, as synchronous metastases are associated with a short MFS. This should be counterbalanced against the morbidity of neoadjuvant treatment and surgery. Thus, patient selection is of paramount importance in the presence of synchronous metastases. A possible strategy to ensure a better patient selection might include a prolonged observation of tumour behaviour, in an extended neoadjuvant treatment course comprising induction chemotherapy and chemoradiotherapy. Patients who respond well to the treatment are more likely to benefit from locoregional treatments, whereas extensive surgery may be omitted in patients with rapid progression. This staged approach is comparable to the ‘liver- first’ approach in patients with primary rectal cancer and synchronous liver metastases, wherein resection of liver metastases precedes resection of the primary tumour, thus precluding interruption by possible complications of the latter. A concurrent advantage of this approach is that neoadjuvant chemotherapy is used to treat and observe the response of liver metastases and primary tumour. Since tumour progression of liver metastases under neoadjuvant chemotherapy is associated with poor outcomes, in these patients extensive surgery for the rectal tumour could be avoided.20–22 The retrospective study design confers apparent limitations, although the prospectively maintained database ensured only fewmissing values (≤6.3 percent in Table 1 and ≤0.9 percent in Table 2). Another limitation of the study is that it selected only patients who underwent surgery for the LRRC, excluding patients in whom surgery was omitted due to local or systemic progression during neoadjuvant therapy. Consequently, this study presents a highly selected group. Furthermore, in the group of patients with synchronous metastases a minority also had a history of metastases, who had a worse MFS than patientswith synchronousmetastases. However, due to lowpatient numbers, these groups were not analysed separately. During this study period, the treatment
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