and Cathy Eng1
(1)
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Chapter Overview
An estimated 96,830 new cases of colon cancer and 40,000 new cases of rectal cancer occurred in 2014, according to the most recent estimates from the American Cancer Society. The Centers for Disease Control and Prevention found that the number of survivors of all types of cancer increased from 9.8 million in 2001 to 11.7 million in 2007, and about 10% of these were survivors of colorectal cancer (CRC). By the year 2030, the number of patients with CRC is estimated to increase by as much as 30%. Given these overwhelming demographic changes, it is extremely important to improve our understanding of the essential health care needs and management issues of long-term CRC survivors. The term “cancer survivor” is now commonly used to describe a person from the time of cancer diagnosis through the remaining years of life. This chapter addresses CRC survivorship care and management issues, including risk evaluation, proper staging, available treatment options, surveillance recommendations, quality of life concerns, and prevention of recurrence.
Components of Survivorship Care
Four components are essential to comprehensive survivorship care: proper treatment and prevention, surveillance, intervention, and coordination of care. Prevention means using efficacious methods to prevent recurrence of the original cancer and occurrence of new cancers or late effects. Surveillance indicates monitoring for cancer spread, recurrence, or second cancers, as well as for medical and psychosocial late effects. Intervention means using sensible methods to address the consequences of cancer and its treatment. Coordination of care includes the arrangement and integration of necessary follow-up care between specialists and primary care providers to ensure that the survivor’s health needs are met.
Noninterventional Risk Evaluation
Researchers have found that the following noninterventional risk factors may increase a person’s chance of developing colorectal polyps or CRC:
Age: about 90% of people diagnosed with CRC are older than 50 years
Ethnicity: in the United States, African Americans have the highest incidence of CRC and CRC-related mortality (American Cancer Society 2011)
Personal history of colorectal polyps or CRC
Personal history of inflammatory bowel disease (ulcerative colitis or Crohn disease)
Family history of CRC: Table 6.1 shows the relationship between family history and relative risk of developing CRC
Table 6.1
Relative risk of developing colorectal cancer (CRC) with a family history of the disease
Family history
Relative risk (95% confidence interval)
No family history
1
1 first-degree relative with CRC
2.3 (2.0–2.5)
>1 first-degree relative with CRC
4.3 (3.0–6.1)
1 first-degree relative diagnosed with CRC before age 45 years
3.9 (2.4–6.2)
1 first-degree relative with colorectal adenoma
2.0 (1.6–2.6)
Inherited syndromes: the two most common inherited syndromes linked with CRC are familial adenomatous polyposis and hereditary non-polyposis CRC (Lynch syndrome)
Patient Reactions to a Colorectal Cancer Diagnosis
A CRC diagnosis can be very challenging for the patient. Some patients with CRC have found the following actions helpful for managing the difficult feelings they experienced after hearing of their diagnosis:
Finding a physician that the patient feels comfortable with
Working with the physician to establish a treatment plan, which helps the patient feel more settled and regain a sense of control over their life
Trying to do as many usual activities as possible
Joining CRC support group(s) though organizations such as www.CCAlliance.org, www.acor.org, www.cancercare.org, www.cancer.org, or www.fightcolorectalcancer.org
Survival Rates and Staging
According to the American Cancer Society (2011), only 39% of patients diagnosed with CRC between 1999 and 2006 had localized disease, for which the 5-year relative survival rate was 90%; 5-year relative survival rates for patients diagnosed with regional and distant CRC were 70% and 12%, respectively. The 5-year relative survival rate for CRC in general has increased from 51% for patients diagnosed in the mid-1970s to 67% for patients diagnosed between 1999 and 2006 (National Cancer Institute 2011). The following are 5-year relative survival rates according to the location of the cancer (Gatta et al. 2003):
Rectum: 59%
Right colon: 59%
Transverse colon: 59%
Rectosigmoid junction: 62%
Ascending colon: 63%
Left colon: 65%
Descending colon: 66%
Stages are often labeled using Roman numerals I through IV. According to the American Joint Committee on Cancer (2009), CRC is staged as follows:
Stage 0: very early cancer on the innermost layer of the intestine
Stage I (T1-2, N0, M0): cancer is in the inner layers of the colon
Stage II (T3-4b, N0, M0): cancer has spread through the muscle wall of the colon
Stage III (any T, N1-N2a-b, M0): cancer has spread to the lymph nodes
Stage IV (M1a-b with any T or N): cancer has spread to other organs
Treatment Modalities
Surgery
Surgery is the only definitive treatment modality for cure of nonmetastatic disease (stage I-III). For patients undergoing curative surgical resection of CRC, overall survival with surgery alone mimics that of the general population.
For surgically resectable metastatic lesions (limited in number, satisfactory organ preservation possible), a course of stage IV neoadjuvant chemotherapy or chemoradiation (for rectal cancer) is usually considered. Surgery can be performed safely 4 weeks after the last cycle of chemotherapy, assuming no anti–vascular endothelial growth factor (VEGF) agents were used (Van Cutsem et al. 2010).
Chemotherapy
Adjuvant chemotherapy for 6 months is indicated for stage III CRC but not for stage II CRC. However, chemotherapy may be considered for high-risk stage II CRC that includes any of the following: T4 primary tumor, histologic findings of poor differentiation, lymphovascular invasion, perineal invasion, bowel obstruction or perforation, fewer than 12 regional lymph nodes in the surgical specimen, positive margin(s), or microsatellite instability (Wolpin et al. 2007). Chemotherapy is also used to improve symptoms and prolong survival in patients with stage IV colon cancer.
Several chemotherapeutic agents are available for the treatment of metastatic CRC. Conventional agents include fluoropyrimidine, capecitabine (Xeloda), oxaliplatin, and irinotecan. Targeted agents include bevacizumab (anti-VEGF), cetuximab (HER monoclonal antibody), and panitumumab (HER monoclonal antibody).
Radiation
Radiation alone has a limited role in the treatment of CRC; it is usually combined with chemotherapy for patients with locally advanced rectal cancer. However, radiation may be used for palliation of metastases in certain locations, such as the sacrum or brain.
Chemoradiation
Patients with clinical stage II or stage III rectal cancer who underwent radiation therapy (45–50 Gy in 25–28 fractions of 1.8 Gy over a period of 5.5 weeks) and chemotherapy (fluorouracil or capecitabine) before surgery were found to have fewer problems after treatment was completed and a lower risk of cancer recurrence in the rectum than patients who underwent radiation and chemotherapy after surgery (Bosset et al. 2006). The patients who underwent neoadjuvant chemoradiation also underwent more sphincter-sparing procedures, experienced fewer toxic effects during therapy, and adhered better to the chemotherapy than patients in the other group.
Other
For patients with stage IV disease that has spread to the liver, various treatments other than surgery that are directed specifically at the liver can be used. These may include radiofrequency ablation. For additional details, see http://www.mdanderson.org/education-and-research/resources-for-professionals/clinical-tools-and-resources/practice-algorithms/ca-treatment-colon-web-algorithm.pdf.
Surveillance
The proportion of CRC patients undergoing resection with curative intent increased from 6.7% during the 1976–1984 period to 23.7% during the 1994–2003 period (P < 0.001) for those with distant metastases and from 15.9% to 58.1% (P < 0.001) for those with local recurrence (Guyot et al. 2005). According to another study, patients with hepatic CRC metastases detected at follow-up were significantly more likely to have a potentially curative operation than patients with hepatic CRC metastases who did not receive regular follow-up (Child et al. 2005).
In 2000, the American Society of Clinical Oncology (ASCO) introduced clinical practice guidelines for follow-up care and recurrence prevention for patients with stage II and III CRC (Benson et al. 2004). These guidelines were updated in 2005 (Desch et al. 2005). The ASCO Colon Cancer Survivorship Care Plan is a 1-page document that outlines the components of follow-up care (physician visit, carcinoembryonic antigen test, computed tomographic scan, and colonoscopy). Surveillance recommendations for colon (Table 6.2) and rectal (Table 6.3) cancer were developed at MD Anderson using the ASCO guidelines.
Table 6.2
Colon cancer observation/surveillance recommendations used at MD Anderson
Surveillance technique | Stage I, stage II (low risk) | Stage II (high risk), stage III | Stage IV/no evidence of disease |
|---|---|---|---|
Physical examination | Every 3–6 months for the first 2 years, then every 6 months for 3 years | Every 3 months for 3 years, then every 6 months for 2 years | Every 3–4 months for 2 years, then every 6 months for 3 years |
Carcinoembryonic antigen test | Every 3–6 months for 1–2 years, then every 6 months for 3 years | Every 3 months for 3 years, then every 6 months for 2 years | Every 3–4 months for 3 years, then every 6 months for 3 years |
Contrast-enhanced computed tomographic scan of the chest and contrast-enhanced computed tomographic scan or magnetic resonance imaging of the abdomen/pelvis | Every 12 months for 5 years | Every 12 months for 5 years | Every 3 months as needed to monitor therapy; upon reaching no evidence of disease, every 3–6 months for 2–3 years, then yearly as dictated by primary site, response, and site of metastasis if clinically appropriate |
Colonoscopy | After 1 year, then (if normal) after 3 years, then every 5 years | After 1 year, then (if normal) after 3 years, then every 5 years | For patients with unresected, intact primary tumors, endoscopic surveillance is recommended every 3–6 months to ensure luminal patency |
Table 6.3
Rectal cancer observation/surveillance recommendations used at MD Anderson
Surveillance technique | Stage I | Stage II (low risk) | Stage II (high risk), stage III | Stage IV/no evidence of disease |
|---|---|---|---|---|
Physical examination | Every 3–6 months for 3 years, then every 6 months for 2 years | Every 3–6 months for 3 years, then every 6 months for 2 years | Every 3 months for 3 years, then every 6 months for 2 years | Every 3–4 months for 2 years, then every 6 months for 3 years |
Carcinoembryonic antigen test | Every 3–6 months for 3 years, then every 6–12 months for 2 years | Every 3 months for 3 years, then every 6 months for 2 years | Every 3 months for 3 years, then every 6 months for 2 years | Every 3–4 months for 3 years, then every 6 months for 3 years |
Contrast-enhanced computed tomographic scan of the chest and contrast-enhanced computed tomographic scan or magnetic resonance imaging of the abdomen/pelvis | Every 12 months for at least 3 years | Every 12 months for at least 5 years | Every 12 months for at least 5 years | Every 3 months; upon reaching no evidence of disease, every 6 months, then yearly as dictated by primary site, response, and site of metastasis if clinically appropriate |
Proctoscopy | Every 6 months for 3 years, then every 6–12 months for 2 years | Every 6 months for 3 years, then every 6–12 months for 2 years | Every 6 months for 3 years, then every 6–12 months for 2 years | |
Colonoscopy | After 1 year, then (if normal) after 3 years, then every 5 years | After 1 year, then (if normal) after 3 years, then every 5 years | After 1 year, then (if normal) after 3 years, then every 5 years |
Genetic Tests Predicting Recurrence
Nonmetastatic Disease
Currently, about 75–85% of patients with stage II CRC can be cured with surgery alone (Donna 2007), but there is no way to identify these patients. Moreover, the absolute survival benefit of chemotherapy is relatively small, about 3–6%, whereas the risk of serious side effects is about 25% (Laino 2009). According to reports from the 45th annual ASCO meeting in 2009, new molecular tools can help physicians identify patients who might benefit most from chemotherapy. To date, 3 gene expression tests for CRC have been or are being studied: Oncotype DX (Genomic Health, Redwood City, CA), Coloprint (Agendia, Irvine, CA), and OncoDefender-CRC (Everist Genomics, Ann Arbor, MI). Oncotype DX is currently the only gene expression test out of the 3 that is approved by the US Food and Drug Administration (FDA).
Oncotype DX
The Oncotype DX colon cancer recurrence score for stage II cancer is calculated from the quantitated expression of seven recurrence genes and five reference genes in the tumor tissue and is expressed as an individual recurrence score ranging from 0 to 100 (Oncotype DX 2011). A linear relationship was demonstrated between the recurrence score and colon cancer recurrence risk in the QUASAR validation study (Kerr et al. 2009). The recurrence score also provides information about treatment outcome for patients with stage II and III CRC. In the NSABP C-07 study, it was suggested that the addition of oxaliplatin showed greater benefit in patients with high recurrence scores (i.e., >40%) than in patients with low recurrence scores (i.e., <30%).
Coloprint
Coloprint analyzes 18 genes, compared with 12 genes in Oncotype DX, and identifies patients as either high risk or low risk. In the first validation study, Coloprint was superior to the ASCO criteria in assessing the risk of cancer recurrence without prescreening for microsatellite instability (Salazar 2011).
OncoDefender-CRC
OncoDefender evaluates the expression levels of five specific genes (identified by Everist Genomics as predictors of recurrence). It is the only molecular prognostic test that can predict the risk of recurrence in patients with previously surgically treated stage I/II colon cancer and stage I rectal cancer (for stage I colon cancer: sensitivity 69%, specificity 88%, accuracy 79%; for stage II colon cancer: sensitivity 70%, specificity 55%, accuracy 61%).
Metastatic Disease
The K-RAS gene, a human homolog of the Kirsten rat sarcoma-2 virus oncogene, is linked with cellular signaling pathways, including those involving the epidermal growth factor receptor. A K-RAS mutation on codon 12 has been found to predict unresponsiveness to epidermal growth factor receptor–targeted monoclonal antibodies (cetuximab or panitumumab) in previously treated patients or in patients undergoing first-line therapy for metastatic CRC (Chang et al. 2009).
Quality of Life Management
Quality of life is generally measured by structured questionnaires that can be scored and quantified. For evaluating quality of life after surgery, the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire system is reliable and has been validated in patients with CRC. The European Organization for Research and Treatment questionnaire template (QLC-C30) is a more reliable and valid assessment of quality of life for patients with advanced disease than the FACT-C (Silpakit et al. 2006).
Surgery-Related Issues
Care of Stomata
For patients requiring a stoma, enterostomal therapists or surgical oncology staff nurses provide preoperative support, postoperative education, and state-of-the-art supplies (DeCosse and Cennerazzo 1997).
Most patients with left-sided or sigmoid colostomy learn to perform habitual stomal irrigation. Small security pads or pouches are available for use between irrigations (DeCosse and Cennerazzo 1997). Stomal irrigation is not advised if the patient is substantially obese, has poor vision, or has another disabling factor that limits or precludes personal stomal management (DeCosse and Cennerazzo 1997). Thin-walled translucent or opaque pouches adhere well and are secure, comfortable, odor-proof, non-irritating, and inconspicuous (DeCosse and Cennerazzo 1997). To ensure proper sealing on the cicatricial skin, strategic application of skin barrier paste and powder (Stomahesive) is useful (DeCosse and Cennerazzo 1997). Avoiding foods such as fish, onions, garlic, broccoli, asparagus, and cabbage and eating yogurt or drinking buttermilk may help reduce odor production. It is important that patients manage the stoma with reasonable efficiency because Medicare reimbursement is restricted and provision of stomal supplies is limited (DeCosse and Cennerazzo 1997).
Patients should call the doctor if one or more of the following symptoms occur (www.upmc.com):
Purple, black, or white stoma
Severe cramps lasting more than 6 hours
Severe watery discharge from the stoma lasting more than 6 hours
No output from the colostomy for 3 days
Excessive bleeding from the stoma
Effects of Rectal Surgery
Unsurprisingly, all patients who undergo abdominoperineal resection tend to have a permanent stoma, and patients who undergo low anterior resection are more likely to have a stoma than patients who undergo high anterior resection (Engel et al. 2003). Patients who undergo low anterior resection also are usually less depressed and have better sexual function and social adaptation than patients who undergo high anterior resection (Engel et al. 2003). For patients who undergo a low rectal anastomosis, irregular bowel movements are common for weeks or even months after the surgery (DeCosse and Cennerazzo 1997).
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