Epidemiology, disease Progression, and Economic Burden of Colorectal Cancer

BACKGROUND: Every 3.5 minutes, someone is diagnosed with colorectal cancer (CRC); every 9 minutes, someone dies from CRC; and every 5 seconds, someone who should be screened for CRC is not. The 5-year mortality for people diagnosed with CRC is approximately 40%; however, survival improves substantially if the cancer is diagnosed while still localized. OBJECTIVES: To track and review the rapid progress researchers have made in CRC. SUMMARY: among patients who have CRC, approximately 50% will eventually develop liver metastases. The oncology field's significant advances in the last few years, especially in CRC, challenge clinicians and patients. Multiple facets of care intersect in CRC: medical management, pharmacy management, symptom management, case management, and patient advocacy. CRC develops over many years as environmental and genetic factors interact. The American Cancer Society recommends screening all men and women older than 50 years and those at high risk at an earlier age. In the past, patients presenting with the same stage of CRC were considered similar. The staging criteria of the american joint Committee on Cancer recognizes that subsets of patients with varying survival statistics can be identified and that each patient requires a strategic approach. The U.S. Food and drug administration approval of irinotecan in 1996 and oxaliplatin in 2002 changed the landscape, and ultimately, the oral agent capecitabine and the biologics bevacizumab and cetuximab also significantly expanded treatment options. CONCLUSIONS: Clinicians must consider all available treatment options and regimen sequences across multiple lines of therapy, creating an early plan for each patient to extend survival while minimizing side effects.

OBjECTIvE: To track and review therapid progress researchers have made in CrC.
Numerous studiesh ave examined surgical ratesi np atients with metastaticc olon cancerw ho have hads urgicalr esection, andt he 5-year survival rate (the pointa tw hich oncologists consider ap atient cured) ranges from 25%t on early6 0%, compared with patients with metastaticd isease whoh aven ot hadr esection; their5 -years urvivorship rate is between5 % and1 0%. [27][28][29][30][31][32][33]  Before combination chemotherapy and new treatment strategies were available, researchers identified several adverse prognostic factors that might preclude surgical resection. Prognosis is poorer when • the patients' original tumor is stage III or higher; • patients have multiple lesions; • the lesions are larger than 3 cm, involve satellite lesions, or occur in both lobes of the liver; • metastases occur within the first 12 to 30 months; and/or • metastases occur outside the liver and primary colon site.
Prognostic factors, however, may be evolving with the introduction of modern chemotherapy approaches. 5

■■ Approaches for Liver Metastases
Hepatic artery infusion (HAI) is the infusion of chemotherapy into the hepatic artery via a surgically implanted pump. Chemotherapy drugs can be injected periodically into the chamber of the pump, which then employs a gas-driven bellows to send chemotherapy by a hepatic artery catheter directly into the liver. Fluorodeoxyuridine (FUDR) has been the chemotherapy of choice for many years for HAI; compared with other agents, FUDR has the highest rate of extraction by the liver. Trials have compared HAI to systemic therapy with fluorouracil. [34][35][36][37][38][39][40] They have certain limitations and do not confirm a definitive survivorship benefit, but prior to the introduction of intravenous combination therapy, HAI produced the highest response rate seen in colon cancer: 50% to 60%. Since response rates with FOLFOX and FOLFIRI are similar to HAI, there may be a more limited role for HAI-delivered therapy.
Hepatic artery infusion has been tested for patients whose liver metastases have been resected. [34][35][36][37][38][39][40] These trials are also imperfect; however, they show without question that HAI recipients tend to experience less hepatic recurrence than those who did not.

Case 1: Patient Presentation
A 62-year-old nurse presented 10 months ago with a sigmoid colon lesion. She had a moderately differentiated, ulcerated 3 × 2 cm lesion (Stage II). After successful surgical resection, she received 6 months of adjuvant fluorouracil and leucovorin. Last month her carcinoembryonic antigen (CEA, used as a tumor marker for CRC) was elevated to 6.8 ng/mL. After seeing this individual, how would you proceed? Would you do a colonoscopy, a computed tomography (CAT) scan of the chest and abdomen and pelvis, a positron emission tomography (PET) scan, or an anti-CEA nuclear medicine scan?
A CAT scan is appropriate. This patient's rise in CEA in less than a year suggests the development of metastatic disease. Current surveillance strategies after surgery and adjuvant therapy for CRC are imperfect. Testing for CEA is the most widely used test, and it can be an early warning of metastases. Once it rises, the patient needs a full evaluation for metastatic disease. Colonoscopy is appropriate. In most individuals, the National Comprehensive Cancer Network (NCCN) 26 recommends colonoscopy 1 year after surgery to identify new polyps or a second primary tumor.
Although a PET scan would not be the first tool to evaluate metastatic disease, it can be helpful, particularly if further surgery to resect metastatic disease is being considered. The anti-CEA scan is available but is not widely used in the United States and certainly would not be a first choice.
The patient's colonoscopy was normal, but a CAT scan revealed 2 lesions (3 × 3 cm) in the right lobe of the liver. The PET scan confirmed the 2 lesions and found no other evidence of metastatic disease. The clinical team and patient chose surgical resection following chemother apy. The only opportunity to cure the person is with surgery, although the benefit of postoperative chemotherapy in this setting is unknown.
An updated report including4a dditionalp hase 3t rials( for at otal of 11 studies, N=5,768) validated theinitial analysis. 51 It confirmed thatt he percentage of patients with advanced CRC receiving 3d rugs during thec ourse of theird isease were likely to have longer OS.Again,the researchers gathe reddataonexposure to fluorouracil/leucovorin,irinotecan,and oxaliplatin.They concludedthatastrategyofmakingall active agents available to patients with advanced CRCappears to be more importantthan theu se of an individual therapy, andt hatc ombination therapy should remain thestandardofcarefor first-line treatment.