Survival Rates Increasing in Metastatic Colorectal Cancer

Roxanne Nelson

May 26, 2009

May 26, 2009 — Survival rates for patients with metastatic colorectal cancer have dramatically increased since 1990, owing primarily to advances in pharmaceutical and surgical interventions. Median overall survival is now nearly 30 months, compared with only 14.2 months for patients diagnosed in 1990, according to a study published online May 26 in the Journal of Clinical Oncology.

In addition, overall 5-year survival increased to 19.2% in the period from 2001 to 2003, up from 9.1% in period from 1990 to 1997. The improved outcomes in the period from 1998 to 2004 were primarily due to an increase in hepatic resection, which was performed in 20% of the patients, the researchers note; survival gains after 2004 are most likely attributable to advances in medical therapy. During this general time period, several new drugs were launched in the United States for the treatment of metastatic colorectal cancer, including oxaliplatin (Eloxatin, Sanofi-Aventis, 2002), bevacizumab (Avastin, Genentech/Roche, 2004), and cetuximab (Erbitux, Bristol-Myers Squibb, 2004).

A high quality of life is now also possible for many of these patients, despite the fact that they are not disease free, explained lead author Scott Kopetz, MD, assistant professor in the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston.

"We have results from various studies of chemotherapy and surgery that suggest that these approaches improve patients' quality of life," he told Medscape Oncology. "The treatments are better tolerated now than in the past, and there have been additional improvements in supportive medications that reduce the symptoms for patients on therapy."

Although the number of new biologic and chemotherapeutic agents has greatly increased over the past few years, these agents are more expensive than older drugs. The high cost of treatment can be a barrier to patients receiving optimal therapy.

"The cost of these chemotherapy agents and surgery is high, and we need to continue to research ways that we can be just as effective with the treatment but with less expense," said Dr. Kopetz. "As the research progresses, less expensive options are being developed, including pills that may one day replace many of the expensive intravenous chemotherapies."

He pointed out that costs tend to decrease as drug patents expire, as has happened with the chemotherapeutic agent irinotecan. "However, the problems that cancer patients face go beyond the cost of IV chemotherapy and surgery, as costs for supportive-care medications or pills that replace IV medications tend to be too expensive for uninsured and underinsured patients, despite the fact that the use of these agents are 'cost-saving' treatments for the broader health system," he said. "This is an area to which we need to pay close attention in any planned health reform."

Indirect Evidence of Improvement

Improvements in survival observed in phase 3 trials and excellent outcomes after hepatic resection in surgical series represent only indirect evidence of improvements in outcomes for the broader population of patients with metastatic colorectal cancer. In addition, the authors note, data from population-based studies are limited. Thus, the goal of the current analysis was to evaluate the changes in survival using both multi-institutional and population-based databases, and to assess the impact that hepatic resection and improvements in chemotherapy had on survival.

Dr. Kopetz and colleagues performed a retrospective review of patients with newly diagnosed metastatic colorectal cancer who received treatment at either MD Anderson or the Mayo Clinic in Rochester, Minnesota, from 1990 through 2006. They also conducted an additional survival analysis using data from the Surveillance, Epidemiology, and End Results (SEER) database from 1990 through 2005.

A total of 2470 patients with metastatic colorectal cancer received treatment at the Mayo Clinic (n = 856) or at MD Anderson (n = 1614) during the designated time period. Overall survival in the institutions was similar (hazard ratio [HR], 1.03; P = 0.58).

The median overall survival times from 1990 through 1997 were relatively similar, and were pooled for a median overall survival of 14.2 months (95% confidence interval [CI], 13.3 - 15.2). Conversely, significant improvements in overall survival were observed for the later time periods.

Overall Median Survival From 1998 to 2006

Time Period Median Survival Time 95% CI
1998–2000 18 months 15.8 - 20.2
2001–2003 18.6 months 16.4 - 20.8
2004–2006 29.2 months 24.3 - 34.2

 

The researchers also observed an increase in the 5-year overall survival rate during later time periods.

Overall 5-Year Survival Rates

Time Period 5-Year Survival Rate
1990–1997 9.1%
1998–2000 13.0%
2001–2003 19.2%
2004–2006 Data not yet available

 

Hepatic Resection and Chemotherapy

During the 17-year time period, 231 patients underwent hepatic resection and, beginning in 1998, hepatic resections were performed with increasing frequency. From 2000 through 2006, the proportion of patients who underwent hepatic resection remained relatively unchanged, at approximately 20% of the population.

Among patients diagnosed in the period from 1998 to 2006, the 5-year survival rate for those who had previously undergone hepatic resection was 55.2%, compared with 19.5% for patients who had unresected disease during the same time period. The median overall survival for these 2 groups was 65.3 months and 26.7 months, respectively.

The researchers also estimated the impact of changes in pharmaceutical treatments, and repeated the survival analyses after censoring patients with hepatic resection at the time of surgery, to exclude the effects of liver resection. Compared with patients diagnosed before 1998, the overall survival rates for those who did not undergo hepatic resection failed to improve from 1998 to 2000.

They also note that although improvement was only minimal from 2001 to 2003, patients diagnosed from 2004 to 2006 experienced a significant improvement in overall survival.

Confirmation with SEER Data

To confirm their findings, the researchers used the SEER database to identify 49,459 patients diagnosed with metastatic colon cancer between 1990 and 2005. Similar survival trends were evident, even though the database represented a different population than the registries from the 2 institutions.

The increase in median overall survival time was minimal from 1990 to 2003 (from 8 to 9 months), but survival rates rose among patients diagnosed in 2004 and 2005 (to 11 months). The 5-year overall survival rate also significantly increased, beginning in 1998, but more recent follow-up data are not yet available.

"The discordance in median overall survival between the population and institutional databases reflects several inherent limitations of institutional results," the authors write. "Although we limited our analysis of the institutional data to patients undergoing primary therapy in the academic institutions to prevent inclusion of traveling, high-performance-status, second-opinion patients, a referral bias likely remains."

Even though metastatic colorectal cancer remains an incurable disease for the majority of patients, these findings suggest that patients are living longer with the disease. "Indeed, according to the proportional-hazards model derived from the institutional databases, we predict that over 30% of patients diagnosed with metastatic colorectal cancer after 2004 will be alive at 5 years," they conclude. "This prediction, if realized, will represent a continued and significant change in the demographics of metastatic colorectal cancer.

The study was supported by the National Cancer Institute.

J Clin Oncol. Published online May 26, 2009.

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