Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy

Abstract

Purpose: Fluorouracil/leucovorin as the sole therapy for metastatic colorectal cancer (CRC) provides an overall survival of 8 to 12 months. With an increase in surgical resections of metastatic disease and development of new chemotherapies, indirect evidence suggests that outcomes for patients are improving in the general population, although the incremental gain has not yet been quantified.

Methods: We performed a retrospective review of patients newly diagnosed with metastatic CRC treated at two academic centers from 1990 through 2006. Landmark analysis evaluated the association of diagnosis year and liver resection with overall survival. Additional survival analysis of the Surveillance Epidemiology and End Results (SEER) database evaluated a similar population from 1990 through 2005.

Results: Two thousand four hundred seventy patients with metastatic CRC at diagnosis received their primary treatment at the two institutions during this time period. Median overall survival for those patients diagnosed from 1990 to 1997 was 14.2 months, which increased to 18.0, 18.6, and 29.3 months for patients diagnosed in 1998 to 2000, 2001 to 2003, and 2004 to 2006, respectively. Likewise, 5-year overall survival increased from 9.1% in the earliest time period to 19.2% in 2001 to 2003. Improved outcomes from 1998 to 2004 were a result of an increase in hepatic resection, which was performed in 20% of the patients. Improvements from 2004 to 2006 were temporally associated with increased utilization of new chemotherapeutics. In the SEER registry, overall survival for the 49,459 identified patients also increased in the most recent time period.

Conclusion: Profound improvements in outcome in metastatic CRC seem to be associated with the sequential increase in the use of hepatic resection in selected patients (1998 to 2006) and advancements in medical therapy (2004 to 2006).

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.

Median overall survival of previously untreated patients with metastatic colorectal cancer reported in published phase III trials since 1995.

Fig 2.

Overall survival for patients with metastatic colorectal cancer treated at The M.D. Anderson Cancer Center and the Mayo Clinic by year of diagnosis. (A) Kaplan-Meier curve. (B) Median overall survival. Error bars represent 95% CIs. (C) Five-year overall survival. Error bars represent SEM. (*) For 2004 to 2006, this represents a statistical projection of 5-year overall survival (error bars represent 95% CI).

Fig 3.

(A) Percentage of patients undergoing liver resection by date of diagnosis increased significantly for patients diagnosed in 1998 and stabilized around 20% for patients diagnosed in 2000 to 2006. Error bars represent SEM. (B) Overall survival by landmark analysis of patients with metastatic colorectal cancer diagnosed between 1998 and 2006 and treated at the institutions. Of those patients alive at 12 months, median overall survival was 65 months in the population of patients who underwent liver resection during the first year. Error bars represent 95% CIs.

Fig 4.

Overall survival for patients with metastatic colorectal cancer treated at the institutions, after censoring patients who underwent liver resection. (A) Kaplan-Meier curve. (B) Median overall survival. Error bars represent 95% CIs. For 2004 to 2006, median overall survival time was 23.9 months (95% CI, 20 to 27.8 months). (C) Five-year overall survival. Error bars represent SEM. (*) For 2004 to 2006, this represents a statistical projection of 5-year overall survival. Error bars represent 95% CI.

Fig 5.

The use of novel chemotherapeutics increased between 1998 and 2006, with a rapid change in 2004. (*) Compared with irinotecan use in 1998 and normalized by yearly patient volume. Details of normalization under Methods.

Fig 6.

Overall survival for patients with metastatic colorectal cancer in the Surveillance, Epidemiology, and End Results registry. (A) Kaplan-Meier curve. (B) Median overall survival. Error bars represent SEM. (C) Five-year overall survival. Error bars represent SEM. P < .001 for all comparisons of later periods with 1990 to 1997.

Fig A1.

Distribution of the time from date of diagnosis of metastatic disease to hepatic resection (n = 231).