Original Study
Primary Tumor Location and Survival in the General Population With Metastatic Colorectal Cancer

https://doi.org/10.1016/j.clcc.2017.11.001Get rights and content

Abstract

Background

Recent evidence from clinical trials suggests that primary tumor location in patients with metastatic colorectal cancer correlates with differential outcomes, and patients with tumors originating in the right side of the colon have inferior survival. We conducted a large population-based cohort study using individual patient data to confirm the prognostic importance of primary tumor location in the general population with metastatic colorectal cancer.

Methods

A cohort of 1947 patients who were diagnosed with metastatic colorectal cancer from 1992 to 2010 was studied. Ascending and transverse colon cancers were defined as right-sided tumors. Cox proportional multivariate analyses were done to determine prognostic significance of primary tumor location.

Results

The median age was 70 years (interquartile range, 60-78 years), and the male to female ratio was 1.3:1. Twenty-nine percent had World Health Organization performance status of > 1. Seven-hundred and seventy (39%) patients had right-sided tumors, and 908 (47%) received chemotherapy. The median overall survival of patients with right-sided tumors was 14 months (95% confidence interval [CI], 12.7-15.3 months) compared with 20.5 months (95% CI, 18.5-22.5 months) of patients with left-sided tumors (P < .001). On multivariate analysis, right-sided tumors (hazard ratio [HR], 1.40; 95% CI, 1.20-1.60), no metastasectomy (HR, 2.40; 95% CI, 1.90-2.90), intact primary tumor (HR, 1.60; 95% CI, 1.32-1.90), an elevated carcinoembryonic antigen level (HR, 1.54; 95% CI, 1.30-1.90), lack of combination chemotherapy (HR, 1.52; 95% CI, 1.31-1.80), stage IVb disease (HR, 1.50; 95% CI, 1.17-1.86), leukocytosis (HR, 1.44; 95% CI, 1.28-1.73), and World Health Organization performance status > 1 (HR, 1.30; 95% CI, 1.10-1.55) were correlated with inferior survival.

Conclusions

Our results confirm that individuals with metastatic colorectal cancer and right-sided tumors who received chemotherapy have inferior survival independent of other known prognostic variables. Future studies are required to understand the underlying pathophysiology.

Introduction

Various clinical and pathologic markers and interventions are known to affect the outcomes of patients with metastatic colorectal cancer. Among them, the patient’s age, performance status, and extent of the metastatic disease (for example, number of metastases sites) have been identified as important prognostic markers that correlate with survival.1, 2 Furthermore, molecular profiles of the tumors such as the presence of the BRAF mutation (noted in about 5% to 11% of metastatic colorectal cancer) are associated with differential outcomes.3 Various interventions such as chemotherapy, biological agents, metastasectomy, and possibly primary tumor resection have contributed to prolonging the longevity of patients with metastatic colorectal cancer.1 Emerging data suggests that that the primary tumor location may impact the outcomes of patients with metastatic colorectal cancer.4, 5, 6, 7, 8 Several reports have shown that patients with tumors originating in the right side of the colon tend to have inferior survival.5, 6, 7, 8 For example, a retrospective analysis of a large randomized trial that evaluated cetuximab or bevacizumab as a first-line therapy in combination with chemotherapy, for patients with metastatic colorectal cancer, revealed that patients with KRAS wild-type right-sided primary tumors had a median overall survival (OS) of 19.4 months compared with an OS of 34.3 months of patients with left-sided tumors (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.32-1.84).5, 9 Likewise, retrospective analyses of CRYSTAL (Cetuximab Combined with Irinotecan in First-line Therapy for Metastatic Colorectal Cancer) and FIRE-3 (FOLFIRI plus cetuximab vs. FOLFIRI plus bevacizumab for metastatic colorectal cancer) trials that examined first-line cetuximab-based combination therapy showed that patients with right-sided tumors had inferior survival compared with the patients with left-sided metastatic disease.6

It is important to know that most emerging information about the prognostic significance of the location of the primary tumor came from retrospective analyses of first-line clinical trials in patients with metastatic colorectal cancer. There is limited information available about the prognostic significance of the primary tumor location in real-world patients. We conducted this large population-based cohort study using individual patient data to confirm the prognostic importance of the primary tumor location in the general population with metastatic colorectal cancer.

Section snippets

Study Population

The University of Saskatchewan’s Research Ethics Board approved the study. Patients with newly diagnosed synchronous metastatic adenocarcinoma of the colon and rectum, from January 1992 to December 2010, living in the province of Saskatchewan, Canada, comprised the study cohort. Patients with neuroendocrine tumors, melanoma, lymphoma, gastrointestinal stromal tumors, and other histologic malignant diagnoses of colon and rectum were excluded. Ascending and transverse colonic tumors (up to the

Demographic Information

A total of 1947 eligible patients were identified (Figure 1). Thirty-nine percent of patients had right-sided tumors, and 61% had left-sided tumors (Table 1). The median age was 70 years (interquartile range, 60-78 years), and the male to female ratio was 1.3:1. Twenty-nine percent of patients had WHO performance status of > 1, 37% had stage IVb disease, and 47% received chemotherapy. Fifty percent of women, compared with 38% of men, were diagnosed with a right-sided primary tumor (P < .001).

Discussion

In agreement with the previous published observations, our study showed that patients with right-sided primary tumors had inferior survival compared with patients having left-sided primary tumors. The correlation between survival and location of the primary tumor was maintained after adjusting for important prognostic factors in a multivariate analysis. Patients with right-sided tumors had a 40% increased risk of mortality compared with patients whose tumor originated in the left colon and

Disclosure

The authors have stated that they have no conflicts of interest.

Acknowledgment

The study was supported by a research grant from Saskatchewan Cancer Agency. The authors would like to thank Dr Haider, Dr Zaidi, Mr Riaz Alvi, Mrs Carla Woites, Dr Tong Zhu, and the Saskatchewan Cancer Agency for their support for this project.

References (14)

  • J.W. Holch et al.

    The relevance of primary tumour location in patients with metastatic colorectal cancer: a meta-analysis of first-line clinical trials

    Eur J Cancer

    (2017)
  • M.K. Boisen et al.

    Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer

    Ann Oncol

    (2013)
  • S. Ahmed et al.

    Advances in the management of colorectal cancer: from biology to treatment

    Int J Colorectal Dis

    (2014)
  • D. Elias et al.

    Hepatic and extrahepatic colorectal metastases: when resectable, their localization does not matter, but their total number has a prognostic effect

    Ann Surg Oncol

    (2005)
  • T. Yokota et al.

    BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer

    Br J Cancer

    (2011)
  • A.P. Venook et al.

    Impact of primary tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): analysis of CALGB/SWOG 80405 (Alliance)

    J Clin Oncol

    (2016)
  • S. Tejpar et al.

    Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials

    JAMA Oncol

    (2017)
There are more references available in the full text version of this article.

Cited by (19)

  • Effect of primary colorectal cancer tumor location on survival after pulmonary metastasectomy

    2021, Journal of Thoracic and Cardiovascular Surgery
    Citation Excerpt :

    Our findings, in addition to those from previous investigators, have also raised the important issue of the differential risk of pulmonary occurrence. Although we acknowledge that our cohort was defined by the existence of pulmonary metastatic disease, previous studies have established that right-sided colorectal cancer cases have an increased propensity for the development of extrahepatic metastases, most commonly lung, and that left-sided tumors are most likely to spread to the liver.6 Although yet absent from consensus screening recommendations, separate screening processes for lung metastases according to colorectal cancer tumor location could be seen in future management of this disease.

View all citing articles on Scopus
View full text