Elsevier

Clinical Oncology

Volume 29, Issue 1, January 2017, Pages e29-e38
Clinical Oncology

Original Article
Adjuvant Chemotherapy for Stage II Colon Cancer: Practice Patterns and Effectiveness in the General Population

https://doi.org/10.1016/j.clon.2016.09.001Get rights and content

Highlights

  • One quarter of patients with stage II colon cancer receive adjuvant chemotherapy.

  • Chemotherapy utilisation varies widely by age and geography.

  • Adjuvant chemotherapy is not associated with survival benefit in routine practice.

Abstract

Aims

Although guidelines do not recommend adjuvant chemotherapy (ACT) for stage II colon cancer, many state that ACT may be considered in high-risk disease. Here we describe practice patterns and outcomes associated with ACT in the general population.

Materials and methods

All cases of colon cancer diagnosed in Ontario 2002–2008 were identified using the Ontario Cancer Registry, which was linked to electronic treatment records. Pathology reports were obtained for a 25% random sample of cases. High-risk disease was defined as: T4 tumours, <12 lymph nodes, poorly differentiated histology, lymphovascular invasion. Modified Poisson regression was used to evaluate factors associated with ACT. The Cox proportional hazards model was used to explore the association between ACT and cancer-specific (CSS) and overall survival.

Results

The study population included 2488 patients with stage II colon cancer; 1175 (47%) with high-risk disease. ACT was delivered to 18% of all patients and 24% of patients with high-risk disease. ACT rates were higher among younger patients (51% age 20–49 years versus 16% age 70–79, P < 0.001) and varied considerably across geographic regions (range 10–39%, P < 0.001). Among all patients with stage II colon cancer, ACT was not associated with improved CSS (hazard ratio 1.41, 95% confidence interval 1.09–1.82) or overall survival (hazard ratio 1.16, 95% confidence interval 0.94–1.42). Stratified survival analysis for patients with high-risk disease did not show benefit to ACT (CSS hazard ratio 1.14, 95% confidence interval 0.84–1.55; overall survival hazard ratio 1.02, 95% confidence interval 0.79–1.31).

Conclusion

ACT use varies across age groups and geographic regions. ACT is not associated with improved survival among patients with stage II colon cancer including those with high-risk disease.

Introduction

International guidelines do not recommend adjuvant chemotherapy (ACT) for stage II colon cancer [1], [2], [3]. The pivotal IMPACT meta-analysis reported that ACT improved overall survival in stage III (hazard ratio 0.70, 95% confidence interval 0.53–0.92) but not stage II colon cancer (hazard ratio 0.91, 95% confidence interval 0.63–1.34) [4]. The lack of benefit in stage II disease was confirmed in the follow-up IMPACT B2 meta-analysis and two subsequent meta-analyses [5], [6], [7]. However, international guidelines acknowledge that there are subgroups of stage II colon cancer that are at high risk of disease relapse. On the basis of this higher risk of recurrent disease, guidelines state that ACT may be considered in patients with T4 tumours, poorly differentiated histology, inadequate nodal harvest, perforation/obstruction, lymphovascular invasion or perineural invasion [1], [2], [3]. However, there is no strong evidence upon which to base this recommendation.

It is well known that clinical practice may not mirror evidence and guideline recommendations. Population-based studies provide insight into practice and outcomes in routine clinical practice [8], [9]. By including all cases within a given jurisdiction, these studies minimise selection bias and referral bias that plague traditional institution-based case series. Although a number of studies have previously described the use of ACT for stage II colon cancer in the general population, with one exception [10], these studies are all from the USA [11], [12], [13], [14], [15], [16], [17]. Moreover, several of these studies used the linked SEER-Medicare database and were therefore restricted to patients older than 65 years [11], [14], [15]. Across these studies, ACT utilisation rates for stage II colon cancer ranged from 12 to 38%. Several population-based reports have evaluated the association between ACT and overall survival of stage II colon cancer with mixed results [10], [11], [12], [14], [15], [16]. Only one of these studies evaluated disease-specific survival; it found an association between ACT and overall survival but not disease-specific survival [10]. Given the limitations of the existing literature and the ongoing debate regarding the role of ACT in stage II colon cancer, we undertook a population-based study with the following objectives: (i) to describe the use of ACT for stage II colon cancer; and (ii) to evaluate the effectiveness of ACT for stage II disease (with and without high-risk pathological features).

Section snippets

Study Design and Population

This was a population-based, retrospective cohort study to describe the management and outcome of resected stage II colon cancer in the Canadian province of Ontario. Ontario has a population of about 13.5 million people and a single-payer universal health insurance programme. The study population included patients who underwent resection of stage II colon cancer in Ontario between 2002 and 2008 and survived >30 days after surgery. To identify the study cohort we used the Ontario Cancer Registry

Study Population

Linked administrative datasets identified 25 613 potentially eligible patients who underwent resection of primary colon cancer in 2002–2008 (Figure 1). Surgical pathology reports were reviewed for 7519 randomly selected cases. The age, gender, comorbidity and survival of these randomly selected cases did not differ substantially from the 18 094 unselected cases (Supplementary Table S1, Figure S1). Among the 7519 randomly selected cases, 270 (4%) were excluded, as shown in Figure 1. Among 2599

Discussion

Here we describe the use and effectiveness of ACT for stage II colon cancer in the general population. Several important findings have emerged. First, ACT utilisation rates are 24 and 14% for those patients with, and without, high-risk pathological features. These treatment rates are considerably lower than those reported in the USA. Second, ACT utilisation varies considerably across age groups and geographical regions. Notably, ACT was delivered to 42% of patients aged 20–49 years without

Acknowledgements

The authors gratefully acknowledge the contributions of Tina Dyer, Susan Rohland, Sarah Pickett and Lois Bulch in the conduct of this study. Parts of this material are based on data and information provided by Cancer Care Ontario. However, the analysis, conclusions, opinions and statements expressed herein are those of the authors and not necessarily those of Cancer Care Ontario. This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual

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