Chapter 5 92 Discussion This study, performed in a large cohort of 349 surgically treated LRRC patients, evaluated whether the oncological outcomes in highly selected LRRC patients with a history of metastases or with synchronous metastases were comparable to the oncological outcomes in LRRC patients without metastases. We observed an inferior MFS in patients with a history of metastases or synchronous metastases compared with patients without metastases, with a trend towards a worse OS in patients with synchronous metastases. The 3-year MFS was worse in patients with a history of metastases (33 percent) than in patients without metastases (52 percent), although this difference was not statistically significant. Nonetheless, the clinical impact of this inferior MFS is high, as newly developed metastases potentially require (invasive) treatment. Despite the poor MFS, patients with a history of metastases showed a 3-year OS comparable to that in patients without metastases. The lack of impact of the inferior MFS on OS possibly indicates a relatively favourable tumour biology in patients with a history of curatively treated metastases, as the previous distant metastases were curatively treatable and allowed a sufficiently long disease-free interval to develop an LRRC that was considered feasible for curative treatment. It is reasonable to assume that distant metastases developing during post-treatment follow-up of m-LRRC have a similar favourable tumour biology. The 3-yearMFS in patients with synchronousmetastases (13 percent) was significantly worse compared to patients without synchronous metastases. In contrast to patients with a history of metastases, this poor MFS tended to result in a poor OS compared to patients without metastases, suggesting aggressive tumour behaviour. As patients with LRRC and synchronous metastases were historically considered incurable and usually offered palliative treatment, there is limited scope for comparisons with the literature. Some institutions have reported findings from (sub)groups of LRRC patients with synchronous metastases who underwent intentionally curative treatment. Hagemans et al. recently reported on 193 surgically treated LRRC patients of whom 12 percent had treatable synchronous metastases, and observed a 3-year OS of 65 percent, which is slightly superior to that in our study.12 Kishan et al. observed a more similar 3-year OS rate to our study (51.6 percent) in their retrospective review of 25 patients, wherein 40 percent of patients had synchronous metastases.15 Kishan et al. also found that the presence of synchronous distantmetastaseswas not associatedwithOS, whichwas also reportedbySchurr et al. in a study on 38patientswith synchronousmetastases, and is in linewith the present study.15,16 However, the relatively small patient population in these studies could have resulted in less statistical power. A few small studies reported on the
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