KRAS mutation in patients undergoing hepatic resection for colorectal liver metastasis: A biomarker of cancer biology or a byproduct of patient selection?

Abstract

Patients with colorectal cancer have experienced remarkable progress in a range of surgical and oncologic management strategies over the past few years, with a corresponding improvement in survival. The KRAS mutation may be a biomarker of cancer biology and prognosis, but also reflects patient selection.

Activating KRAS mutation is prognostic only among patients who receive preoperative chemotherapy before resection of colorectal liver metastases

“…The prognostic value of the KRAS genotype among patients with CRLM has been controversial [18]. While several investigators have reported that KRAS status has prognostic value, other investigators have failed to note an association of mut KRAS with worse survival [11][12][13][14][15].…”

“…end, Soreide et al have criticized previous studies for possible bias due to the highly selective manner in which patients were included in these study cohorts [18]. In fact, Soreide et al questioned whether the apparent prognostic impact of KRAS status was a by-product of patient selection or would persist among a more "unselected" cohort [18].…”

“…In fact, Soreide et al questioned whether the apparent prognostic impact of KRAS status was a by-product of patient selection or would persist among a more "unselected" cohort [18]. Indeed, the answer to this query has been difficult to answer as most studies have included select cohorts of patients who had received some type of preoperative chemotherapy [14,15].…”

“…Specifically, virtually all previously published studies have included only patients who had received some type of perioperative chemotherapy [13][14][15]. In a recent editorial, Soreide et al suggested that the reported prognostic effect of KRAS might be a by-product of patient selection due to the inclusion of mostly patients who were pretreated with systemic chemotherapy [18]. Therefore, the objective of the current study was to assess the prognostic role of KRAS status in an unselected cohort of patients who did and did not receive preoperative treatment.…”

The Prognostic Yield of Biomarkers Harvested in Chemotherapy-Naive stage II Colon Cancer: Can We Separate the Wheat from the Chaff?

“…Vogelaar et al also confirmed a trend toward poorer prognosis in patients with mutant KRAS or BRAF (12). The negative impact of these mutations has been noted by others in both early-and late-stage colorectal cancer (CRC) (11,(14)(15)(16). Strikingly, the high mutation rate of BRAF in the study by Vogelaar et al (19%) should be noted, as this rate is usually reported as a single-digit percentage, typically at 5-8% (17).…”