Clinicopathological features and outcome in advanced colorectal cancer patients with synchronous vs metachronous metastases

Abstract

Background:Synchronous metastases of colorectal cancer (CRC) are considered to be of worse prognostic value compared with metachronous metastases, but only few and conflicting data have been reported on this issue.Methods:We retrospectively investigated patient demographics, primary tumour characteristics and overall survival (OS) in 550 advanced CRC patients with metachronous vs synchronous metastases, who participated in the phase III CAIRO study. For this purpose only patients with a prior resection of the primary tumour were considered.Results:The clinical and pathological characteristics associated with poor prognosis that we observed more often in patients with synchronous metastases (n=280) concerned an abnormal serum lactate dehydrogenase (LDH) concentration (P=0.01), a worse WHO performance status (P=0.02), primary tumour localisation in the colon (P=0.002) and a higher T stage (P=0.0006). No significant difference in median OS was observed between patients with synchronous metastases and metachronous metastases (17.6 vs 18.5 months, respectively, P=0.24).Conclusion:Despite unfavourable clinicopathological features in patients with synchronous metastases with a resected primary tumour compared to patients with metachronous metastases, no difference in the median OS was observed. Possible explanations include a (partial) chemoresistance in patients with metachronous disease because of previous adjuvant treatment, whereas differences between the two groups in screening procedures resulting in a lead time bias to diagnosis or in prognostic molecular markers remain speculative.

FOLFOX as Adjuvant Chemotherapy after Curative Resection of Distant Metastases in Patients with Colorectal Cancer

“…By contrast, according to the subgroup analysis of the CAIRO study described above, metachronous metastases originated from smaller primary CRC, and smaller T and N numbers than synchronous metastases. They also described that extrahepatic organs were more frequently involved in metachronous metastases [19]. These results are in accordance with our observation.…”

“…One plausible reason is that previous chemotherapy, most frequent in the FOLFOX group (71%), had a good chance to confer chemoresistance to tumor cells, therefore multiple micrometastases were more likely to grow into clinically overt metastases heterochronically. In a subgroup analysis of the CAIRO study, a randomized phase III trial of capecitabine, irinotecan, and oxaliplatin for unresectable CRC, the authors suggested this possibility as an explanation for the lower response rate in CRC patients with metachronous metastases compared to those with synchronous metastases [19]. However, in our series, both the 2 chemotherapy-naïve patients who underwent FOLFOX after curative resection of metachronous metastases developed metastases again (data not shown); thus, distinct scenarios must be considered.…”

Mitochondrial DNA alteration in primary and metastatic colorectal cancer: Different frequency and association with selected clinicopathological and molecular markers

“…According to a definition by Mekenkamp et al, 36 18 DM were synchronous (onset within 6 months after primary diagnosis of Figure 1) was significantly more frequently seen in LN than in PT and DM, considering both the number of included patients (p = 0.0248 and p = 0.0082) or the number of investigated tumor samples (p = 0.0183 and p = 0.0005). The distribution of mtMSI in the three different loci is displayed in Table 1.…”

Managing synchronous liver metastases from colorectal cancer: A multidisciplinary international consensus

“…Although, by definition, all metastases are synchronous (occult or detectable at diagnosis), most definitions include detection at or before diagnosis or surgery of the primary tumour [13], whilst some also include metastases detected up to 3 [14,15], 4 [16] or 6 months [17,18] following diagnosis.…”