Published online May 24, 2020. doi: 10.5306/wjco.v11.i5.294
Peer-review started: December 31, 2019
First decision: March 15, 2020
Revised: May 9, 2020
Accepted: May 14, 2020
Article in press: May 14, 2020
Published online: May 24, 2020
Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide. Despite significant advances in screening, surgical management and adjuvant therapies, average 5-year survival seldom exceeds 60% in most developed nations. Metastatic disease represents the primary cause of mortality in patients with CRC, and the liver is the most common location for distant tumour spread. Up to 25% of patients are found to have synchronous liver metastases at the time of diagnosis and a further 30%-40% will develop metachronous disease in the course of follow-up. It has been suggested that primary tumour location [right side versus left side, primary tumour location (PTL)] can influence oncological outcomes in this patient group and that this should be considered in prognostic models and therapeutic decision-making algorithms. This suggestion is not universally accepted and there have been conflicting reports in the literature to date.
To provide a comprehensive summary of the available evidence regarding the impact of PTL on oncological outcomes in patients with colorectal cancer liver metastases (CRCLM).
MEDLINE, EMBASE and COCHRANE were searched for relevant publications using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Data on oncological outcomes was then extracted from full text articles that met the predefined inclusion criteria.
A total of 41 studies were identified that met predefined inclusion criteria for this review. In 21 out of 38 studies that provided data on overall survival, a statistically significant improvement in overall survival was reported in patients with left sided primary tumours. These studies included a total of 13897 patients compared with 4306 patients in the studies that did not show a significant difference. Eight studies noted a similar trend towards improved disease-free or progression-free survival. Several authors observed distinct patterns of relapse after treatment of hepatic metastases according to PTL; for example hepatic recurrence after treatment of CRCLM appears to occur more aggressively with right-sided CRC.
Taken together, the findings of the present review indicate that PTL may have a role as an independent prognostic factor when determining treatment and disease surveillance strategies in CRC. The mechanisms responsible for this variation remain poorly understood, but are likely to relate to molecular, histological and embryological differences, as well as inherent differences in therapeutic sensitivity.
Core tip: Primary tumour location is associated with differing oncological outcomes and patterns of hepatic metastatic behaviour in patients with colorectal cancer liver metastases. Specifically, this systematic review indicates that there is improved overall survival in patients undergoing treatment for colorectal cancer liver metastases with left-sided colorectal cancer (CRC), compared with right-sided CRC. These findings suggest that primary tumour location may have a role in developing more individually-tailored staging, treatment and surveillance strategies for patients with CRC in the future. Current chemotherapeutic regimens may require additional modification(s) to take into account the fundamental molecular and embryological differences that underpin primary tumour sidedness.