Impact of prior malignancies on outcome of colorectal cancer; Revisiting clinical trial eligibility criteria

Abstract

Background: Most clinical trials on colorectal cancer (CRC) exclude cases who have history of a prior malignancy. However, no prior research studied this history's actual impact on the survival of CRC. In the paper, we study the effects of having a malignancy preceding CRC diagnosis on its survival outcomes. Methods: CRC patients diagnosed during 1973-2008 were reviewed using the SEER 18 database. We calculated overall survival and cancer-specific survival of subsequent CRC, and more specifically stage IV CRC, using Kaplan-Meier test and adjusted Cox models. Results: A total 550,325 CRC patients were reviewed, of whom 31,663 had history of a prior malignancy. The most commonly reported sites of a prior malignancy were: prostate, breast, urinary bladder, lung, and endometrium. Patients with history of a prior non-leukemic malignancy or history of a prior leukemia were found to have worse overall survival (HR = 1.165 95%CI = 1.148-1.183, P < 0.001) and (HR = 1.825 95%CI = 1.691-1.970, P < 0.001), respectively. However, CRC patients with history of a prior non-leukemic malignancy showed an improved colorectal cancer-specific survival (HR =.930 95%CI =.909-.952, P < 0.001). Analysis of stage IV CRC patients showed that patients with history of any non-leukemic malignancy did not have a significant change in overall survival. Whereas, patients with a prior leukemia showed a worse overall survival (HR = 1.535, 95%CI = 1.303-1.809, P < 0.001). When analyzed separately, right CRC and left CRC showed similar survival patterns. Conclusion: A prior malignancy before CRC -in general- can be associated with worse clinical survival outcomes. These worse outcomes are not observed in stage IV CRC. Considering these results when including/excluding stage IV CRC patients with prior malignancies in clinical trials may play help improve their generalizability.