Even with a greater emphasis on prevention of colon cancer, it is still high on the radar of policy makers, practitioners, and the biopharmaceutical industry. This is related to the impact it continues to have on our society.
The number of deaths caused by colon cancer has trended significantly lower since 1998, with the greatest decline seen in women.1 Even accounting for the decrease in deaths, about 103,000 persons will be diagnosed with colon cancer this year and about 52,000 will die of either colon or rectal cancer in 2012,2 making it the second-leading cause of cancer-related deaths in the United States.3
The incidence of disease rises with age, and the decile group most affected by colon cancer remains those between the ages of 65 and 74 years, followed by those 55 to 64 years of age. The median age of patients with colon cancer is 69 years, and the highest frequency of diagnoses is among African Americans, followed by Caucasians.1
As is the case with many oncologic disorders, the 5-year survival is greater for those diagnosed at earlier stages of disease (Table). Greater use of screening is believed to be the key reason for declining colon cancer mortality, resulting from earlier diagnosis.4 This may be related to the availability of new screening technologies as well, such as capsule endoscopy or virtual colonoscopy
National guidelines recommend screening beginning at age 50 years and continuing until 75 years, with people at higher risk beginning screening at a younger age.5 The government estimates that as many as 60% of colorectal cancer deaths could be prevented if the screening guidelines were followed.6 Even though death rates associated with colon cancer are falling, there is much room for improvement: screening remains underutilized, with less than 60% of age-eligible patients being fully compliant with screening test guidelines.7 Many patients have not had any appropriate colorectal screening or only underwent a single screening.
Current Treatment Options
As mentioned earlier in this article, patients with an earlier diagnosis have better 5-year survivals. Treatment strategies for colon cancer are guided by the stage of the disease with surgery, chemotherapy, targeted biologic therapy, radiation therapy, and combined therapies most often employed.8
Colon cancers are classified by stage 0, I, II, III, or IV and recurrent disease.9 This refers to the depth of the tumor through the intestinal wall and of course the extent of its spread. Surgery for Stage 0 and I disease is considered curative, and adjuvant chemotherapy is not required. Stage II disease is treated with surgery, with about 80% of patients being considered cured with surgery alone.10 The need for adjuvant chemotherapy is usually limited to high-risk stage II disease11; adjuvant chemotherapy in this setting is thought to reduce the risk of death by only 5%.10 Approximately 50% of patients with stage III disease are cured with surgery alone, and adjuvant chemotherapy reduces the risk of death by 15% to 20%.10 Therefore, for stage III colon cancer, chemotherapy beyond surgery is prescribed for most patients. Depending on the patient’s health, surgery may not be performed in patients with stage III disease. Surgery may or may not be performed in patients with stage IV disease. Some of these patients may require chemotherapy before surgery (ie, neoadjuvant) can be performed, in an attempt to reduce the size of the tumor and increase the probability of a successful, complete resection.
Common therapies for colon cancer include the traditional chemotherapy agents 5-fluorouracil, capecitabine, irinotecan, leucovorin, and oxaliplatin, with the targeted biologic agents bevacizumab, cetuximab, and panitumumab being utilized for metastatic colon cancer. In July 2012, the US Food and Drug Administration (FDA) expanded the indication for cetuximab for use in combination with FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) for firstline treatment of patients with K-RAS mutation-negative (wild-type), EGFRexpressing metastatic colorectal cancer.12
A new therapeutic entity, an angiogenesis inhibitor, ziv-aflibercept, was approved by the FDA in August 2012 for use in combination with FOLFIRI for metastatic colorectal cancer that is resistant to or has progressed following an oxaliplatin-containing regimen.13 The median overall survival was 13.5 months in the group receiving ziv-aflibercept plus FOLFIRI compared with 12.1 months in patients receiving FOLFIRI only (hazard ratio [HR], 0.82). The ziv-aflibercept plus FOLFIRI group also had an improved median progression-free survival, 6.9 versus 4.7 months (HR, 0.77). Both measures were found to be statistically significant.14
Treatment Options on the Horizon
Although only 2 medications have been approved to date in 2012 for colon cancer, more than 100 medications for colorectal cancer are being currently investigated for this indication, with the majority being targeted agents.15 In June 2012, priority review was given to the new drug application for regorafenib, an oral multikinase inhibitor, for patients whose disease has progressed after approved standard therapies. The FDA approved regorafenib on September 27, 2012.16 In a clinical trial, the median overall survival was 6.4 months for the regorafenib group compared with 5.0 months in the standard treatment group (HR, 0.77). Progressionfree survival was also improved in the regorafenib group (HR, 0.49).17
Most colon cancer begins as a neoplastic polyp that progresses slowly over 10 to 15 years.18,19 Because of the slow growth, colon cancer can effectively be screened, resulting in patients avoiding a diagnosis of colon cancer or having their cancer diagnosed at an early stage.
The currently available screening tools include colonoscopy, flexible sigmoidoscopy, barium enema, and fecal occult blood testing. Traditional colonoscopy is generally considered the gold standard, as polyps can be directly observed and removed as needed. However, there is some difference of opinion as to the best procedural preparation (which can discourage patients from having repeat colonoscopies at their recommended intervals) and to the need and insurance coverage of anesthesia during the procedure. Another more recent development has been the use of virtual colonoscopy and capsule colonoscopy.
In virtual colonoscopy, a 3-dimensional image is generated using multiple x-rays. To prepare for a virtual colonoscopy exam, the patient must use laxatives or enemas to empty the colon before the procedure. This noninvasive screening tool is considered to be more cost-effective than the standard colonoscopy when polyps are smaller than 6 mm in diameter. Clinical guidelines consider polyps below this size not to be clinically significant. The cost per life-year gained was found to be $4361 for a virtual colonoscopy versus $9180 for a standard colonoscopy.20
Another screening tool option being explored is a capsule colonoscopy. With capsule colonoscopy, patients use a standard lavage regimen before swallowing a capsule with imaging equipment aboard. The capsule takes images of the bowel wall as it transits and sends the images generally through radio frequency transmission to a receiving device worn around the patient’s waist, which stores the images for later review.21 A study in Germany showed that capsule colonoscopy helped increase the patient uptake of colon cancer screening, although the sensitivity for detecting cancerous lesions was not considered to be acceptable.22 Another study confirmed these sensitivity results for capsule endoscopy for detecting colon polyps.23 Clearly, improved accuracy will need to be proved before capsule endoscopy acceptance for colon cancer screening in the United States. A second-generation product does suggest the potential for improved accuracy, but additional studies are needed to confirm this finding.24
In either capsule or virtual colonoscopy, a traditional procedure may also be required to remove any polyps visualized on the images, but it may somewhat reduce the need for difficult preparations and possible costs associated with the endoscopic procedure. Stool DNA testing would also be a non-invasive strategy for screening for colon cancer; however, the US Preventive Services Task Force does not recommend the use of this type of screening, nor does Medicare pay for this screening test. Currently, there is 1 such test available, ColoSure, which is not approved by the FDA. A recent study, however, has found that colorectal cancer can be detected with a high level of accuracy using a stool DNA test.25 A test developed by Exact Science is projected to be available in 2012 or 2013 that will comprise several key markers including stool DNA.18
Economics of Colon Cancer
The direct costs for treating colorectal cancer in 2010 were $14.1 billion, with the majority of costs in the initial phase of care followed by the last year of life care and continuing care (42%, 30%, and 28%, respectively).26,27 It should be noted that these costs do not include screening and prevention costs. Costs for treating the different stages of colon cancer vary greatly, with early stage costing less than late-stage cancer ($30,000 vs $120,000 per patient based on 2007 data).28 Hence, the burden of disease for patients and society is much less when colon cancer is found at the earliest possible stage. Indirect costs, specifically the loss of productivity due to colon cancer—related illness and death, were estimated to be $10.7 billion in 2005.29
Advances in drug discovery have contributed to the improved overall survival of patients with metastatic colon cancer.30 Economic evaluations of traditional chemotherapy agents have demonstrated that they are costeffective for treating metastatic colon cancer.31-36 Recently, an evaluation was performed of published cost-effectiveness analyses with the 3 targeted biologic agents, bevacizumab, cetuximab, and panitumumab. For first-line therapy, the authors concluded that these agents can be cost-effective when predictive biomarkers are utilized before initiating therapy; however, additional studies are needed for patients who have proven refractory to other treatments.37 Clinical guidelines/pathways have been developed by oncology organizations (ASCO, NCCN, US Oncology) to reduce the variation in practice and improve the quality of care based on the existing evidence supporting each regimen. They found that adherence to Level I Pathways utilized by US Oncology yielded shorter durations of therapy, lower rates of chemotherapy- related hospital admissions, and reduced costs.38
Given the variance in cost of treating early and late-stage colon cancer, it would be prudent to place emphasis on the early detection of colon cancer. Studies have demonstrated that all colorectal cancer screening strategies are cost-effective versus no screening.38 It has been determined in cost-effectiveness analyses that the estimated average cost per life-year gained ranged from $5700 to $39,000 for colon cancer screening.39,40 With the increasing costs of medications utilized to treat colon cancer, screening may actually double the treatment savings, thereby helping to the reduce the costs of managing colon cancer.41
Payer PerspectiveInterview With Alan Sokolov, MD
EBO: From the payer’s perspective, what are the most effective ways to optimize the value of medications for colon cancer today?
Targeted molecular diagnostics are essential for determining efficacy of immunotherapeutics for treatment of advanced colon cancer. Concomitantly with diagnosis and appropriate aggressive treatment for metastatic colon cancer, patients should be counseled on end-of-life planning and palliative care, since studies show that many patients with advanced metastatic disease mistakenly believe that these therapies are likely to cure them.
EBO: Where do you think we’ve made the greatest strides in colon cancer management over the past decade?
Widespread improvement in colon cancer screening rates and use of FOBT has been achieved over the past decade. Additional effort in this area should be made to address some recent declines in colon cancer screening rates.
EBO: What do you see as the greatest challenges for better colon cancer detection and management in the coming years?
Modifications to health plan coverage and increasing difficulty in access to primary care services may lead to diminished detection of colon polyps and early stage colon cancers. Alternative means of access to cancer screening and additional programs and methods for colon cancer screening should be employed.
EBO: Do you believe that capsule or virtual colonoscopy systems can improve adherence with colon cancer screening guidelines?
Virtual colonoscopy systems can improve colon cancer screening rates in some limited situations, and as the imaging technology continues to improve, virtual colonoscopy may become the screening tool of choice. Its less-invasive nature may lead to some increases in patient compliance with colon screening programs. Capsule systems offer similar advantages of being less invasive, but technological performance of these systems has not yet achieved parity with conventional techniques, although that will likely change with time.
EBO: Do you think that managed care organizations will more closely scrutinize colorectal cancer management in the future because of the increased use of specialty drugs?
The high cost and limited indications for use of targeted specialty drugs will most definitely lead to close scrutiny and management of colorectal cancer treatment in the immediate future.
Dr Sokolov is chief medical officer at AccelusHealth Partners in South San Francisco, CA.
Funding Source: None.
Author Disclosures: Mr Mehr reports receiving payment for involvement in the preparation of this article. Ms Zimmerman reports no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.
Authorship Information: Concept and design (SRM); acquisition of data (MPZ, SRM); analysis and interpretation of data (MPZ, SRM); drafting of the manuscript (MPZ, SRM); critical revision of the manuscript for important intellectual content (MPZ, SRM); and supervision (SRM).1. Surveillance Epidemiology and End Results. SEER Stat Fact Sheets: colon and rectum. National Cancer Institute 2012. www.seer.cancer.gov/stat facts/html/colorect.html. Accessed September 19, 2012.
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