Superior Overall Survival in Patients with Colorectal Cancer, Regular Aspirin Use, and Combined Wild-Type PIK3CA and KRAS-Mutated Tumors

Leonie Gebauer,Marco Mernberger,Kathleen Stabla,Uwe Klinge,Roland Moll,Cornelia Brendel,Elisabeth Mack,Andrea Nist,Andreas Neubauer,Thorsten Stiewe

doi:10.3390/cancers13194959

Abstract

Simple SummaryThe impact of aspirin use after the diagnosis of colorectal cancer is unknown. Among others, PIK3CA mutational status was proposed as a molecular biomarker for the response to adjuvant aspirin therapy. The aim of this study was to retrospectively analyze whether the PIK3CA and KRAS mutational status had an impact on overall survival in patients with colorectal cancer and aspirin use. In a retrospective study, we obtained KRAS and PIK3CA mutational status in a cohort of 153 patients with a first diagnosis of colorectal cancer receiving tumor surgery with curative intent. Clinicopathological data and survival data were assessed using patient records and reporting registers. We observed a significant 10-year overall survival benefit in patients with aspirin use and combined wild-type PIK3CA and mutated-KRAS tumors (HR = 0.38; 95% CI = 0.17–0.87; p = 0.02). Our data indicated a benefit of aspirin usage particularly for patients with combined wild-type PIK3CA and mutated-KRAS tumor characteristics.The impact of aspirin use after the diagnosis of colorectal cancer is unknown. Among others, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutational status was proposed as a molecular biomarker for the response to adjuvant aspirin therapy. However, prognostic data on aspirin use after a colorectal cancer diagnosis in relation to KRAS mutational status is limited. In a single-center retrospective study, we obtained KRAS and PIK3CA mutational status in a cohort of 153 patients with a first diagnosis of colorectal cancer receiving tumor surgery with curative intent. PIK3CA mutational status was determined by pyrosequencing, and KRAS mutational status was determined by next-generation sequencing. Clinicopathological data and survival data were assessed using patient records and reporting registers. We observed a significant 10-year overall survival benefit in patients with aspirin use and combined wild-type PIK3CA and mutated-KRAS tumors (HR = 0.38; 95% CI = 0.17–0.87; p = 0.02), but not in patients without aspirin use. Our data indicate a benefit of aspirin usage particularly for patients with combined wild-type PIK3CA and mutated-KRAS tumor characteristics.

Highlights

With 1.4 million new cases per year, colorectal cancer is one of the most common cancers worldwide
When reviewing the combined PIK3CA and KRAS mutational status of patients with regular aspirin use, a significant overall survival benefit for patients with combined wildtype PIK3CA and mutated-KRAS tumors was observed (HR = 0.38; 95% CI = 0.17–0.87; p = 0.02; Figure 3C, Table 2)
We found that patients with regular aspirin use after the diagnosis of colorectal cancer and combined wild-type PIK3CA and mutated-KRAS tumors showed a significant survival benefit

Summary

Introduction

With 1.4 million new cases per year, colorectal cancer is one of the most common cancers worldwide. Colorectal cancer is one of the most common causes of cancer-related death, with almost 700,000 deaths per year [1]. Retrospective analyses suggest a superior clinical outcome for patients with regular use of aspirin after diagnosis of colorectal cancer [2,3,4,5,6,7]. Several possible biomarkers have been suggested, including the PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutational status [13,14,15,16,17]. Prognostic data on aspirin use after diagnosis of colorectal cancer in relation to KRAS mutational status is limited

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