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. 2009 Feb 20;27(6):872-7.
doi: 10.1200/JCO.2008.19.5362. Epub 2009 Jan 5.

Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials

Daniel Sargent  1 , Alberto Sobrero, Axel Grothey, Michael J O'Connell, Marc Buyse, Thierry Andre, Yan Zheng, Erin Green, Roberto Labianca, Chris O'Callaghan, Jean Francois Seitz, Guido Francini, Daniel Haller, Greg Yothers, Richard Goldberg, Aimery de Gramont
Affiliations

Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials

Daniel Sargent et al. J Clin Oncol. .

Abstract

Purpose: Limited data are available on the time course of treatment failures (recurrence and/or death), the nature and duration of adjuvant treatment benefit, and long-term recurrence rates in patients with resected stage II and III colon cancer.

Methods: The data set assembled by the Adjuvant Colon Cancer Endpoints Group, a collection of individual patient data from 18 trials and more than 20,800 patients testing fluorouracil-based adjuvant therapy in patients with stage II or III colon cancer, was analyzed.

Results: A significant overall survival (OS) benefit of adjuvant therapy was consistent over the 8-year follow-up period. The risk of recurrence in patients treated with adjuvant chemotherapy never exceeds that of control patients, signifying that adjuvant therapy cures some patients, as opposed to delaying recurrence. After 5 years, recurrence rates were less than 1.5% per year, and after 8 years, they were less than 0.5% per year. Significant disease-free survival (DFS) benefit from adjuvant chemotherapy was observed in the first 2 years. After 2 years, DFS rates in treated and control patients were not significantly different, and after 4 years, no trend toward benefit was demonstrated. This benefit was primarily driven by patients with stage III disease.

Conclusion: Adjuvant chemotherapy provides significant DFS benefit, primarily by reducing the recurrence rate, within the first 2 years of adjuvant therapy with some benefit in years 3 to 4, translating into long-term OS benefit. This reflects the curative role of chemotherapy in the adjuvant setting. After 5 years, recurrence rates in patients treated on clinical trials are low, and after 8 years, they are minimal; thus, long-term follow-up for recurrence is of little value.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Kaplan-Meier plots of overall survival (OS) in treatment arm versus control arm for (A) all patients, (B) stage II patients, and (C) stage III patients. FU, fluorouracil.
Fig 2.
Fig 2.
Hazard rates by time from random assignment and treatment arm. Plots of the hazard rate for (A) overall survival, (B) disease-free survival, and (C) time to recurrence by arm (treatment and control) over the 8-year follow-up period. The y axis plots the risk of recurrence on a daily scale; thus, for example, the value 0.0002 represents an annualized 7.3% risk of an event (0.0002 × 365 = 0.073).
Fig 3.
Fig 3.
Disease-free survival hazard rates by time from random assignment and treatment arm in (A) stage II patients and (B) stage III patients.
Fig 4.
Fig 4.
Continuous time estimate of the log-hazard ratios for (A) overall survival, (B) disease-free survival, and (C) time to recurrence comparing treatment arm with control arm over the 8-year follow-up period, with 95% pointwise CIs. Values less than 0 indicate a benefit from treatment. For example, a value of −0.50 for the log-hazard ratio indicates a hazard ratio of 0.61 comparing treatment with control at that time point (e–0.50 = 0.61), that is, a 39% reduction in the risk of an event.
Fig 5.
Fig 5.
Risk of recurrence in each 6-month interval after random assignment among patients remaining recurrence free at the start of each interval, by time.
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References

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