Aspirin Use Improves Established Colorectal Cancer Survival
Aspirin Use Improves Established Colorectal Cancer Survival
Objective The objective of this meta-analysis was to systematically assess the survival benefit of aspirin use before or after diagnosis for patients with colorectal cancer (CRC).
Design Relevant studies were identified through searching PubMed, Embase and Cochrane databases before May 2014. Two investigators extracted data independently for baseline characteristics and outcomes from the included studies. Either a fixed-effects or a random-effects model was derived to composite the pooled HR for overall mortality and CRC-specific mortality of CRC.
Results Seven studies on postdiagnosis aspirin therapy and seven studies on prediagnosis aspirin use were finally included in this meta-analysis. The overall survival benefit associated with postdiagnosis aspirin use represented an HR of 0.84 (95% CI 0.75 to 0.94). This effect was observed both in colon cancer (HR=0.78, 95% CI 0.64 to 0.96) and in rectal cancer (HR=0.90, 95% CI 0.83 to 0.98). Besides, the survival benefit of postdiagnosis aspirin use appeared to be confined to those patients with positive prostaglandin endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase-2, COX-2) expression (HR=0.65, 95% CI 0.50 to 0.85) and with mutated PIK3CA tumours (HR=0.58, 95% CI 0.37 to 0.90). Aspirin use postdiagnosis was not associated with CRC-specific mortality (HR=0.77, 95% CI 0.52 to 1.14). We observed no evidence of an association between prediagnosis aspirin use and CRC overall mortality (HR=1.01, 95% CI 0.96 to 1.06) or CRC-specific mortality (HR=0.93, 95% CI 0.82 to 1.05).
Conclusions These findings provide further indication that postdiagnosis aspirin therapy improved CRC overall survival, especially for patients with positive PTGS2 (COX-2) expression and mutated PIK3CA tumours.
Colorectal cancer (CRC) remains one of the most common type of cancers and a leading cause of death worldwide. CRC accounts for about 8% of annual cancer-related deaths overall, with over 1.2 million new cancer cases and 608 700 deaths estimated to have occurred in 2008. Although morbidity and mortality from CRC have decreased, and systemic therapy of CRC over the last decades has improved modestly, there is still an urgent need for more effective preventive strategies and adjuvant therapies against CRC.
A significant body of observational and randomised data has indicated that aspirin has anticancer effects. Studies over the past decades have suggested that aspirin use could reduce the risk of colorectal adenomas and cancer. In addition, a meta-analysis of randomised trials designed to evaluate the cardiovascular benefits of aspirin demonstrated that aspirin use reduced the risk of distant metastasis for patients with CRC. Nevertheless, it remains uncertain whether aspirin use can influence the prognosis for established patients with CRC. Recently, several studies assessed the effect of postdiagnosis or prediagnosis aspirin use on survival of established patients with CRC. Although it remains unclear for the optimal time, dose and duration of aspirin use and which type of patients with CRC are most likely to benefit, these data suggest aspirin to be a promising adjuvant therapy for patients with CRC. In this meta-analysis, we assessed the survival benefit of prediagnosis or postdiagnosis aspirin use for patients with CRC. Moreover, we investigated whether the effect of aspirin use differed according to factors such as localisation of tumours and tumour biomarkers. This may provide further insight into the anticancer mechanisms of aspirin and indicate evidence for aspirin therapy in patients with CRC.
Abstract and Introduction
Abstract
Objective The objective of this meta-analysis was to systematically assess the survival benefit of aspirin use before or after diagnosis for patients with colorectal cancer (CRC).
Design Relevant studies were identified through searching PubMed, Embase and Cochrane databases before May 2014. Two investigators extracted data independently for baseline characteristics and outcomes from the included studies. Either a fixed-effects or a random-effects model was derived to composite the pooled HR for overall mortality and CRC-specific mortality of CRC.
Results Seven studies on postdiagnosis aspirin therapy and seven studies on prediagnosis aspirin use were finally included in this meta-analysis. The overall survival benefit associated with postdiagnosis aspirin use represented an HR of 0.84 (95% CI 0.75 to 0.94). This effect was observed both in colon cancer (HR=0.78, 95% CI 0.64 to 0.96) and in rectal cancer (HR=0.90, 95% CI 0.83 to 0.98). Besides, the survival benefit of postdiagnosis aspirin use appeared to be confined to those patients with positive prostaglandin endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase-2, COX-2) expression (HR=0.65, 95% CI 0.50 to 0.85) and with mutated PIK3CA tumours (HR=0.58, 95% CI 0.37 to 0.90). Aspirin use postdiagnosis was not associated with CRC-specific mortality (HR=0.77, 95% CI 0.52 to 1.14). We observed no evidence of an association between prediagnosis aspirin use and CRC overall mortality (HR=1.01, 95% CI 0.96 to 1.06) or CRC-specific mortality (HR=0.93, 95% CI 0.82 to 1.05).
Conclusions These findings provide further indication that postdiagnosis aspirin therapy improved CRC overall survival, especially for patients with positive PTGS2 (COX-2) expression and mutated PIK3CA tumours.
Introduction
Colorectal cancer (CRC) remains one of the most common type of cancers and a leading cause of death worldwide. CRC accounts for about 8% of annual cancer-related deaths overall, with over 1.2 million new cancer cases and 608 700 deaths estimated to have occurred in 2008. Although morbidity and mortality from CRC have decreased, and systemic therapy of CRC over the last decades has improved modestly, there is still an urgent need for more effective preventive strategies and adjuvant therapies against CRC.
A significant body of observational and randomised data has indicated that aspirin has anticancer effects. Studies over the past decades have suggested that aspirin use could reduce the risk of colorectal adenomas and cancer. In addition, a meta-analysis of randomised trials designed to evaluate the cardiovascular benefits of aspirin demonstrated that aspirin use reduced the risk of distant metastasis for patients with CRC. Nevertheless, it remains uncertain whether aspirin use can influence the prognosis for established patients with CRC. Recently, several studies assessed the effect of postdiagnosis or prediagnosis aspirin use on survival of established patients with CRC. Although it remains unclear for the optimal time, dose and duration of aspirin use and which type of patients with CRC are most likely to benefit, these data suggest aspirin to be a promising adjuvant therapy for patients with CRC. In this meta-analysis, we assessed the survival benefit of prediagnosis or postdiagnosis aspirin use for patients with CRC. Moreover, we investigated whether the effect of aspirin use differed according to factors such as localisation of tumours and tumour biomarkers. This may provide further insight into the anticancer mechanisms of aspirin and indicate evidence for aspirin therapy in patients with CRC.