Elsevier

Clinical Colorectal Cancer

Volume 15, Issue 3, September 2016, Pages e125-e132
Clinical Colorectal Cancer

Original Study
Primary Tumor Resection and Overall Survival in Patients With Metastatic Colorectal Cancer Treated With Palliative Intent

https://doi.org/10.1016/j.clcc.2015.12.010Get rights and content

Abstract

Background

The survival impact of primary tumor resection in patients with metastatic colorectal cancer (mCRC) treated with palliative intent remains uncertain. In the absence of randomized data, the objectives of the present study were to examine the effect of primary tumor resection (PTR) and major prognostic variables on overall survival (OS) of patients with de novo mCRC.

Patients and Methods

Consecutive patients from the Australian ‘Treatment of Recurrent and Advanced Colorectal Cancer’ registry were examined from June 2009 to March 2015. Univariate and multivariate Cox proportional hazards regression analyses were used to identify associations between multiple patient or clinical variables and OS. Patients with metachronous mCRC were excluded from the analyses.

Results

A total of 690 patients de novo and 373 metachronous mCRC patients treated with palliative intent were identified. The median follow-up period was 30 months. The median age of de novo patients was 66 years; 57% were male; 77% had an Eastern Cooperative Oncology Group performance status of 0 to 1; and 76% had a colon primary. A total of 216 de novo mCRC patients treated with palliative intent underwent PTR at diagnosis and were more likely to have a colon primary (odds ratio [OR], 15.4), a lower carcinoembryonic antigen level (OR, 2.08), and peritoneal involvement (OR, 2.58; P < .001). On multivariate analysis, PTR at diagnosis in de novo patients was not associated with significantly improved OS (hazard ratio [HR], 0.82; 99% confidence interval [CI], 0.62-1.09; P = .068). PTR at diagnosis did not correlate with outcome in de novo patients with a colon primary (HR, 0.74; 99% CI, 0.54-1.01; P = .014) or a rectal primary (HR, 0.81; 99% CI, 0.27-2.44; P = .621).

Conclusion

For de novo mCRC patients treated with palliative intent, PTR at diagnosis does not significantly improve OS when adjusting for known major prognostic factors. The outcomes of randomized trials examining the survival impact of PTR are awaited.

Introduction

Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide.1 The overall survival (OS) of patients with metastatic CRC (mCRC) treated with palliative intent has continued to improve with the advent of modern cytotoxic drugs and biologic therapies.2 In the absence of data from prospective randomized trials, the optimal approach to the management of the primary tumor continues to be debated.

Multiple series have reported that primary tumor resection (PTR) at diagnosis is associated with improved survival outcomes.3, 4, 5 These retrospective series have often been limited by the lack of data on known major prognostic factors. The reported OS differences have often been substantial, including a recent population-based cohort6 that reported PTR improved the median OS from 7.9 to up to 17.9 months (hazard ratio [HR], 0.56; P = .0007). Faron et al7 also analyzed individual data from patients with mCRC enrolled in first-line chemotherapy trials and reported improved outcomes with PTR, adjusting for multiple prognostic variables.

However, many have questioned the true survival impact of PTR at diagnosis, arguing that the reported benefits likely reflect that patients selected for PTR had more favorable prognostic features. Further concerns include that operative complications can be significant8 and that, for some patients, PTR could delay administration of systemic therapy to the extent that the treatment would be less effective or could not be safely delivered.9 When patients do not undergo PTR at diagnosis, the rates of intestinal complications resulting from the intact primary tumor appear to be very low,10, 11 including a prospective series10 in which the expected OS outcomes for patients with mCRC were achieved.

The present study reports on data from a comprehensive mCRC registry that prospectively captures information on consecutive patients treated in routine clinical practice. The unique aspects of the data set included mandatory and prospective clinician documentation at point of care for: (1) the treatment intent; (2) known major prognostic factors, including documentation of the Eastern Cooperative Oncology Group performance status (ECOG PS) and the Charlson comorbidity index; (3) the primary tumor site; and (4) comprehensive data on further management (including any systemic therapy and later PTR). These aspects allowed researchers to address recurrent limitations of previous retrospective analyses.

Section snippets

Participants and Setting

The present analyses were conducted using data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry, which began in mid-2009 and is ongoing. Data were contributed from 10 private and 13 public hospitals across Australia. The human research ethics committee at each participating hospital approved the study.

TRACC is a clinician-led registry, established with support from Roche Australia.12 Point of care data are entered into an electronic database by clinicians, and key

Patient and Disease Characteristics

Of a total of 1567 patients with mCRC, after excluding patients defined by the treating clinician as having resectable or potentially resectable metastatic disease, 1063 patients (690 with de novo and 373 with metachronous disease) treated with palliative intent were identified. The median follow-up period for all patients with mCRC treated with palliative intent was 30 months.

A total of 20 patients with metachronous disease and a primary site classified as ‘colon NOS’ were excluded during the

Discussion

The optimal management of the primary tumor in patients with de novo mCRC treated with palliative intent remains a clinical dilemma. The inconclusive data in published studies regarding the effect of PTR on OS are likely explained by the retrospective nature of previous studies, the varying definitions of de novo versus metachronous mCRC,16, 17 inconsistent definitions of PTR at diagnosis versus no PTR, and the different patient populations and time periods examined. A recurrent issue in most

Conclusion

We were unable to demonstrate a significant survival gain in association with PTR at diagnosis, after adjusting for major known prognostic variables. The results from the present study are relevant because our patients had access to modern systemic therapies, including cytotoxic chemotherapy, bevacizumab, and EGFR inhibitors. The observed incidence of later PTR was low, in particular, for patients with a primary colon cancer, suggesting that PTR later in the clinical course applies to a limited

Disclosure

H.L. Wong, K.M. Field, S. Kosmider, J. Tie, R. Wong, J. Shapiro, L. Nott, G. Richardson, P. Cooray, and P. Gibbs have received research funding for the study database through Roche Products Pty Limited.

Acknowledgments

Roche Products Pty Limited provided financial assistance for the development and the maintenance of this clinical registry.

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