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

Muneer J Al-Husseini,Omar Abdel-Rahman,Mohamad A Alkhayat,Mohamad Bassam Sonbol,Anas M Saad,Hadeer H Mohamed

doi:10.1186/s12885-019-6074-6

Abstract

BackgroundMost 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.MethodsCRC 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.ResultsA 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.ConclusionA 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.

Highlights

Most clinical trials on colorectal cancer (CRC) exclude cases who have history of a prior malignancy
After adjustment for age, sex, race, marital status, stage of CRC, grade of CRC, radiation, and surgery, we found that a non-leukemic malignancy was associated with better colorectal-cancer specific outcomes, with a subhazard ratio (SHR) of
When we compared the overall survival of stage IV Left colon cancer (LCRC) with stage IV Microsatellite instability (RCRC) based on having a history of prior malignancy, we found that stage IV LCRC without a history of a prior malignancy has the best overall survival, followed by stage IV LCRC with a history of a prior malignancy, stage IV RCRC without a history of a prior malignancy, and the worst survival with stage IV RCRC with a history of a prior malignancy (Additional file 2)

Summary

Introduction

Most clinical trials on colorectal cancer (CRC) exclude cases who have history of a prior malignancy. No prior research studied this history’s actual impact on the survival of CRC. We study the effects of having a malignancy preceding CRC diagnosis on its survival outcomes. Colorectal cancer (CRC) is the third most common cancer in men and women in the US. Among individuals older than 50 years, incidence rates of CRC have been decreasing starting from the mid1980s reaching a progressive decline in the past 5 years. According to American cancer society colorectal cancer statistics 2017, the 5-year relative survival rate for CRC patients diagnosed from 2006 to 2012 was 65% [2]

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