National Comprehensive Cancer Network

NCCN Guidelines^® & Clinical Resources

JNCCN – The Journal of the National Comprehensive Cancer Network

Table of Contents - Volume 8, Number 1: January 2010

• NCCN Clinical Practice Guidelines in Oncology™
• Colorectal Cancer Screening
• Anal Carcinoma
• Featured Articles
• Does Colonoscopy Work?
• Practical Advances in Stool Screening for Colorectal Cancer
• Risk Assessment, Genetic Testing, and Management of Lynch Syndrome
• Radiation Therapy Advances for Treatment of Anal Cancer
• Anal Carcinoma Therapy: Can We Improve on 5-Fluorouracil/Mitomycin/Radiotherapy?

NCCN Clinical Practice Guidelines in Oncology™

Colorectal Cancer Screening

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and women in the United States. In 2009, an estimated 106,100 new cases of colon cancer and 40,870 new cases of rectal cancer will occur in the United States, and 49,920 people will die of colon and rectal cancers. Patients with localized colon cancer have a 90% 5‑year survival rate. CRC mortality can be reduced through early diagnosis and cancer prevention with polypectomy. Therefore, the goal of CRC screening is to detect cancer at an early, curable stage and to detect and remove clinically significant adenomas. Screening tests that can detect both early cancer and adenomatous polyps are encouraged, although the panel recognizes that patient preference and resource accessibility play a large role in test selection. Current technology falls into 2 broad categories: structural and stool/fecal-based tests. Although some techniques are better established than others, the guidelines panelists agree that any screening is better than none.

Anal Carcinoma

An estimated 5290 new cases (2100 men and 3190 women) of anal cancer (involving the anus, anal canal, or the anorectum) will occur in the United States in 2009, accounting for approximately 1.9% of digestive system cancers, with an estimated 710 deaths caused by the disease. Although considered to be a rare type of cancer, the incidence rate of invasive anal carcinoma in the United States increased by approximately 1.6-fold for men and 1.5-fold for women from 1973–1979 to 1994–2000. Anal carcinoma has been associated with human papilloma virus (HPV) infection (anal-genital warts); history of receptive anal intercourse or sexually transmitted disease; history of cervical, vulvar, or vaginal cancer; immunosuppression after solid organ transplantation or human immunodeficiency virus (HIV) infection; and smoking. This manuscript summarizes the NCCN clinical practice guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease.

Featured Articles

Does Colonoscopy Work?
David G. Hewett, MBBS, FRACP; Charles J. Kahi, MD, MSc; and Douglas K. Rex, MD

Through its impact on the adenoma-carcinoma sequence, colonoscopy has a central role in the detection and prevention of colorectal cancer (CRC). Observational data support a protective effect of colonoscopy and polypectomy on CRC incidence and mortality. However, recent studies suggest that the degree of CRC protection afforded by colonoscopy is dependent on the effectiveness of identification of prevalent cancers or their precursors, particularly in the proximal colon. Biologic variation in tumor genetics and growth likely contribute to diminished protection in the proximal colon. Operator variability is known to be a key factor predicting adenoma detection. Evidence supports the immediate adoption of specific quality improvement initiatives to reduce the failure rate of colonoscopy. Further interventions should target individual, organizational, and health system factors that influence physician behavior.

Practical Advances in Stool Screening for Colorectal Cancer
Jonathan Potack, MD, and Steven H. Itzkowitz, MD

The rationale for colorectal cancer (CRC) screening is well established, and several tests are currently recommended. Colonoscopy has become a popular modality in most of the United States and other countries. Despite colonoscopy being highly accurate and therapeutic, many patients prefer a noninvasive screening test. Testing stool for occult blood by the chemical guaiac reagent (gFOBT) has been available for decades and is effective at reducing mortality from CRC. However, because of limitations in sensitivity and specificity, newer fecal immunochemical tests (FITs) were developed that detect occult blood using enzyme immunoassays. Because of their improved sensitivity and specificity, FITs have replaced gFOBT for screening in many settings. Detecting neoplasia-associated genetic changes in stool has also become feasible. Improvements in stool DNA tests have made them more sensitive and less complex. As performance characteristics for FIT and stool DNA tests continue to evolve, stool-based testing for CRC is expected to become a more reliable component in the armamentarium for CRC screening.

Risk Assessment, Genetic Testing, and Management of Lynch Syndrome
Shilpa Grover, MD, MPH, and Sapna Syngal, MD, MPH

Of the estimated 150,000 colorectal cancer (CRC) cases diagnosed annually, approximately 30% have a familial basis and 3% to 5% are from high-penetrance inherited cancer syndromes. Lynch syndrome, or hereditary nonpolyposis colorectal cancer, caused by inherited germline mutations in mismatch repair (MMR) genes, is the most commonly inherited CRC syndrome. It is characterized by young-onset CRC and an increased risk for extracolonic tumors, including gynecologic, urinary tract, and other gastrointestinal cancers. Commercial testing is available for mutations in the MMR genes, but testing all patients with CRC would be economically prohibitive. Therefore, a comprehensive evaluation of a multigenerational family cancer history is essential for the identification of at-risk individuals. The presence of tumors diagnosed at a young age, multiple first- and second-degree relatives with cancer, or 2 or more primary cancers may be indicative of an inherited cancer syndrome and these individuals should undergo genetic evaluation. Genetic test results, when conclusive, can guide management for patients and their families. However, indeterminate test results may provide false reassurance to patients who should be managed as being at higher-than-average risk. Online risk assessment tools and commercial genetic testing offer the potential to identify a greater number of at-risk individuals at an earlier age. However, for these measures to improve outcomes, patients must receive screening recommendations and counseling appropriate for their cancer risk.

Radiation Therapy Advances for Treatment of Anal Cancer
Joseph M. Pepek, MD; Christopher G. Willett, MD; and Brian G. Czito, MD

Radiation therapy (RT) is established as the primary treatment of squamous cell carcinoma of the anus. Multiple randomized trials have shown that combined modality therapy with RT, 5-fluorouracil, and mitomycin-C results in high rates of local control, disease-free survival, and sphincter preservation. However, treatment-related toxicity using conventional radiation approaches remains high and may compromise therapeutic efficacy because of prolonged treatment breaks and inability to deliver adequate radiation dose. Recent developments, including the use of PET for staging, radiation planning, and response assessment, and advanced RT planning using intensity-modulated radiation therapy (IMRT), may decrease acute and late treatment-related toxicity, provide high-dose target conformality, and permit safe radiation dose escalation. This article reviews the basic principles of IMRT and highlights current literature on these recent advances and the application of new RT techniques.

Anal Carcinoma Therapy: Can We Improve on 5-Fluorouracil/Mitomycin/Radiotherapy?
Yixing Jiang, MD, PhD; Heath Mackley, MD; Hua Cheng, MD, PhD; and Jaffer A Ajani, MD

In the West, use of definitive chemoradiation as primary therapy for locoregional squamous cell carcinoma of the anal canal has been the standard approach since the 1980s. Over the past several years, phase III studies have shown that combination mitomycin C and 5-fluorouracil (5-FU) concurrent with radiotherapy had better outcomes than radiotherapy alone or 5-FU with radiotherapy. Two recent phase III studies using diverse treatment strategies showed that cisplatin and 5-FU were not superior to 5-FU and mitomycin C; the use of cisplatin-based chemoradiation resulted in a higher rate of colostomy compared with mitomycin-based chemoradiation. Mitomycin C and 5-FU concurrent with radiotherapy remains standard care. Further improvement is likely depending on an increased understanding of the molecular biology of anal carcinoma and the addition of relevant biologic agents to chemoradiation to overcome chemoradiation resistance.