Data from <i>PIK3CA</i> Mutations Predict Local Recurrences in Rectal Cancer Patients

Abstract

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Identifying rectal cancer patients at risk for local recurrence would allow for refinement in the selection of patients who would benefit from preoperative radiotherapy. &lt;i&gt;PIK3CA, KRAS&lt;/i&gt;, and &lt;i&gt;BRAF&lt;/i&gt; mutations are commonly found in colon cancers, but their prevalence has not been clearly assessed in rectal cancer. In this study, we aim to determine the mutation frequencies of &lt;i&gt;PIK3CA, KRAS&lt;/i&gt;, and &lt;i&gt;BRAF&lt;/i&gt; and to investigate whether a mutation may be used as a prognostic parameter in rectal cancer patients.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We evaluated DNA mutations in &lt;i&gt;PIK3CA, KRAS&lt;/i&gt;, and &lt;i&gt;BRAF&lt;/i&gt; in 240 stage I to III rectal tumors obtained from nonirradiated patients from the Dutch Total Mesorectal Excision trial.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt;&lt;i&gt;PIK3CA, KRAS&lt;/i&gt;, and &lt;i&gt;BRAF&lt;/i&gt; mutations were identified in 19 (7.9), 81 (33.9), and 5 (2.1) rectal cancers. Patients with &lt;i&gt;PIK3CA&lt;/i&gt; mutations developed more local recurrences (5-year risks, 27.8 versus 9.4; &lt;i&gt;P&lt;/i&gt; = 0.006) and tended to develop these recurrences more rapidly after surgery (median local recurrence-free interval since surgery: 7.9 versus 19.6 months; &lt;i&gt;P&lt;/i&gt; = 0.07) than patients without &lt;i&gt;PIK3CA&lt;/i&gt; mutations. In multivariate analysis, &lt;i&gt;PIK3CA&lt;/i&gt; mutations remained as an independent predictor for the development of local recurrences (hazard ratio, 3.4; 95 confidence interval, 1.2-9.2; &lt;i&gt;P&lt;/i&gt; = 0.017), next to tumor-node-metastasis stage.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt;&lt;i&gt;PIK3CA&lt;/i&gt; mutations can be used as a biomarker in identifying rectal cancer patients with an increased risk for local recurrences. Currently, our findings suggest that prospective evaluation of &lt;i&gt;PIK3CA&lt;/i&gt; mutation status could reduce overtreatment by preoperative radiotherapy for the low-risk patients who might otherwise only experience the side effects. (Clin Cancer Res 2009;15(22):695662)&lt;/p&gt;&lt;/div&gt;