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Long-Term Survival Results of Surgery Alone Versus Surgery Plus 5-Fluorouracil and Leucovorin for Stage II and Stage III Colon Cancer: Pooled Analysis of NSABP C-01 Through C-05. A Baseline from Which to Compare Modern Adjuvant Trials

  • Colorectal Cancer
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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The objective of this study is to conduct a pooled analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) colon trials involving surgery and surgery plus 5-fluorouracil and leucovorin (5-FU/LV) to compare survival and establish a baseline from which to evaluate future studies.

Methods

All patients enrolled in NSABP adjuvant trials C-01 through C-05 with stage II and III disease who were treated with surgery or with surgery plus 5-FU/LV were examined for overall survival (OS), disease-free survival (DFS), and recurrence-free interval (RFI). Time-to-event by treatment group was examined using adjusted Kaplan–Meier estimates and multivariable Cox regression analysis.

Results

There were 2,966 eligible patients: 693 (23%) surgery and 2,273 (77%) surgery plus 5-FU/LV; 1,255 (42%) stage II and 1,711 (58%) stage III. Age ≥60 years [hazard ratio (HR) = 1.36, P < 0.0001], male gender (HR = 1.20, P = 0.0012), and more nodes positive or fewer nodes examined (P < 0.0001) were associated with worse survival. At 5 years, the adjusted OS was 0.62 [confidence interval (CI) = 0.60–0.63] in the surgery group and 0.76 (CI = 0.74–0.78) in the surgery plus 5-FU/LV group. Treatment with 5-FU/LV was associated with improved outcome compared with surgery: OS (HR = 0.62, P < 0.0001), DFS (HR = 0.66, P < 0.0001) and RFI (HR = 0.64, P < 0.0001). Improved OS with adjuvant treatment was seen in both stage II (HR = 0.58, 95% CI = 0.48–0.71) and stage III disease (HR = 0.65, 95% CI = 0.55–0.75).

Conclusions

This analysis demonstrates that treatment of colon cancer patients with 5-FU/LV following surgery provides benefit over surgery alone and can provide anticipated survival outcomes with which to compare modern adjuvant trials.

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Acknowledgment

These studies were supported by: Public Health Service grants U10-CA-12027, U10-CA-69651, U10-CA-37377, and U10-CA-69974, from the National Cancer Institute, Department of Health and Human Services.

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Authors and Affiliations

  1. National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA

    Neal W. Wilkinson MD, MPH, Greg Yothers PhD, Samia Lopa MS, Joseph P. Costantino DrPH, Nicholas J. Petrelli MD & Norman Wolmark MD

  2. Division of Surgical Oncology, University of Iowa, Iowa City, IA, USA

    Neal W. Wilkinson MD, MPH

  3. NSABP Biostatistical Center, Pittsburgh, PA, USA

    Greg Yothers PhD, Samia Lopa MS & Joseph P. Costantino DrPH

  4. Department of Biostatistics, The University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA

    Greg Yothers PhD, Samia Lopa MS & Joseph P. Costantino DrPH

  5. Helen F Graham Cancer Center Newark, Newark, DE, USA

    Nicholas J. Petrelli MD

  6. Allegheny General Hospital, Pittsburgh, PA, USA

    Norman Wolmark MD

Authors
  1. Neal W. Wilkinson MD, MPH
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  2. Greg Yothers PhD
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  3. Samia Lopa MS
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  4. Joseph P. Costantino DrPH
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  5. Nicholas J. Petrelli MD
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  6. Norman Wolmark MD
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Corresponding author

Correspondence to Neal W. Wilkinson MD, MPH.

Additional information

Clinical Trial Registration: NSABP C-01: NCT00427570; NSABP C-02: NCT00427310; NSABP C-03: PDQ: NSABP C-03; NSABP C-04: NCT00425152; NSABP C-05: PDQ: NSABP C-05.

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Wilkinson, N.W., Yothers, G., Lopa, S. et al. Long-Term Survival Results of Surgery Alone Versus Surgery Plus 5-Fluorouracil and Leucovorin for Stage II and Stage III Colon Cancer: Pooled Analysis of NSABP C-01 Through C-05. A Baseline from Which to Compare Modern Adjuvant Trials. Ann Surg Oncol 17, 959–966 (2010). https://doi.org/10.1245/s10434-009-0881-y

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  • DOI: https://doi.org/10.1245/s10434-009-0881-y

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