Influence of KRAS mutation status in metachronous and synchronous metastatic colorectal adenocarcinoma

Abstract

Background: Mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) are present in approximately 30% to 40% of colorectal adenocarcinomas. Wild-type (WT) KRAS mutation status is predictive of tumor response with epidermal growth factor receptor-directed therapies, but the results from studies evaluating the prognostic value of KRAS status in localized disease have been contradictory. The prognostic value of KRAS in metastatic disease, specifically according to whether patients have synchronous or metachronous disease at presentation, is less understood.

Methods: One-hundred ten consecutive patients with metastatic colorectal adenocarcinoma underwent testing for KRAS exon 2 mutations by polymerase chain reaction amplification and direct nucleotide sequencing. The clinical characteristics, treatments, and outcomes of these patients were then analyzed retrospectively, stratified according to whether patients presented with synchronous or metachronous metastasis and according to KRAS mutation status (WT or mutated).

Results: For the entire cohort, the median overall survival from the date of diagnosis of metastatic disease was 34.3 months (95% confidence interval, 28.3-49.4 months) for patients with WT KRAS (n = 70). The median overall survival for patients with mutated KRAS (n = 40) was 40.3 months (95% confidence interval, 27.9-51.1 months; log-rank P = .91). Kaplan-Meier survival analysis indicated that 3-year overall survival and 5-year overall survival were not statistically different. Within the subgroups of patients with synchronous and metachronous metastatic disease, no significant differences were observed in median overall survival, 3-year overall survival, or 5-year overall survival between the WT KRAS and mutated KRAS groups.

Conclusions: In this study, KRAS mutation status did not influence overall survival in either synchronous or metachronous metastatic colorectal adenocarcinoma and, as such, had no prognostic role in this disease setting.

Figure 1

Overall survival is illustrated from the original date of colorectal diagnosis for patients with synchronous metastatic and metachronous metastatic disease, stratified by v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status. WT indicates wild type.

Figure 2

Overall survival is illustrated from the date of diagnosis of metastatic disease for synchronous and metachronous disease, stratified by v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status. WT indicates wild type.

Figure 3

Overall survival is illustrated from the date of diagnosis of metastatic disease for all patients (synchronous and metachronous), stratified by v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status. WT indicates wild type.