PIK3CA mutations linked to local recurrences of rectal cancer

NEW YORK (Reuters Health) - PIK3CA mutations in tumors from patients with rectal cancer predict local recurrences, according to a report in the November 15th Clinical Cancer Research.

Previous studies have shown PIK3CA mutations to be associated with poor prognosis among patients with resectable stage I to III colon cancer and poor survival in colorectal cancer patients, the authors explain, but the prognostic value of PIK3CA mutations in rectal cancer patients has not been reported.

Dr. Youji He from Leiden University Medical Center, the Netherlands and colleagues investigated the frequency of PIK3CA, KRAS, and BRAF mutations in tumors from 240 patients with rectal cancer and assessed whether such mutations could be used as prognostic markers.

PIK3CA mutations were found in 19 (7.9%) rectal tumors, KRAS mutations in 81 (33.8%), and BRAF mutations in 5 (2.1%) tumors, the authors report.

Overall, 95 cases (39.6%) had mutations in at least one gene, and 10 (4.2%) had mutations in two genes (PIK3CA and KRAS). There were no tumors with mutations in both KRAS and BRAF.

None of the mutations in PIK3CA, KRAS, or BRAF showed any correlation with clinicopathological or molecular features, the researchers note.

The presence of PIK3CA mutations was associated with a 3-fold increase in the local recurrence rate and a tendency to shorter intervals from surgery to recurrence, but PIK3CA mutations were not associated with distant metastases, overall recurrences, or overall survival.

In multivariate analysis, PIK3CA mutation remained an independent predictor of local recurrences, along with TNM stage.

KRAS and BRAF mutations were not associated with local recurrences, distant metastases, or overall survival.

"Our findings suggest that prospective evaluation of PIK3CA mutation status could reduce overtreatment by preoperative radiotherapy for the low-risk patients who might otherwise only experience the side effects," the investigators conclude.

"These results are a timely contribution to the goal of using molecular profiles to personalize cancer care," write Dr. Andrea P. Myers from Dana Farber Cancer Institute, Boston, and colleagues in a related commentary. "The hope is to characterize molecular details of individual tumors for both prognostic and predictive means, allowing providers to further optimize treatment regimens."

"With continued studies such as this," the editorial concludes, "we can treat rectal cancer more effectively, more safely, and with fewer untoward side effects."

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