T he National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have become the most widely used guidelines in oncology practice. The Guidelines cover 97% of all patients with cancer and are continually updated by expert panels. The following is a synopsis of the 2010 updates and key points made by panel representatives at the NCCN 15th Annual Conference. For the complete guidelines, visit NCCN at www.nccn.org.

Breast Cancer

"A positive PET scan in a woman with localized breast cancer is as likely to be a false positive as a true positive, and as likely to lead to an incorrect treatment decision as a correct one." Robert W. Carlson, MD, Stanford Cancer Center, Palo Alto, California

• Sentinel node biopsy is recommended as the standard of care for nodal evaluation, with axillary dissection reserved for positive findings, in most cases.
• PET and PET/CT scans should not be used for the initial staging of early breast cancer, or for monitoring metastatic cancer in most patients. They may be useful for locally advanced disease.
• Paclitaxel should be administered every 2 weeks or weekly, but not every 3 weeks.

Colorectal Cancer

"The panel wrestled with whether MSI testing should always be done" in patients with stage II colorectal cancer, and reached consensus that it should be recommended for patients ≤ 50 years of age." Paul F. Engstrom, MD, Fox Chase Cancer Center, Philadelphia, Pennsylvania

• Bevacizumab (Avastin), cetuximab (Erbitux), panitumumab (Vectibix), and irinotecan should not be used in the adjuvant setting for patients with stage II or III disease, outside of a clinical trial.
• Testing for microsatellite instability (MSI), or mismatch repair gene status, is recommended for patients with stage II colorectal cancer ≤ 50 years of age.
• Testing for BRAF mutations should be considered for KRAS wild-type tumors.
• Chemotherapy-free intervals should be avoided in the metastatic colorectal cancer setting.
• The use of transanal resection in rectal cancer should be limited.

Gastrointestinal Stromal Tumor

"Patients with a low risk of recurrence who have no mitotic activity might not need adjuvant imatinib (Gleevec), even for a reasonably sized GIST." George D. Demetri, MD, Dana-Farber Cancer Institute, Boston, Massachusetts

• An entirely new page of recommendations for managing patients with very small gastric GISTs (< 2 cm) has been added.
• To assess response to therapy, CT is the sole recommendation, and PET is no longer included.
• Two new pages provide principles of pathologic assessment and principles of surgery for GIST.
• Adjuvant imatinib should be considered in patients with intermediate- to high-risk GIST but may not be required for patients with a low risk of recurrence and no mitotic activity.

Esophageal Cancer

"Our recommendations are to try to use new techniques, and to use uniform staging and long-term follow-up to make sure that additional treatment can actually benefit these patients." Jaffer A. Ajani, MD, The University of Texas M. D. Anderson Cancer Center, Houston

• The updated guidelines advocate for precise staging of patients.
• The initial workup should include esophagogastroduodenoscopy and multidisciplinary team collaboration; endoscopic ultrasound is a minimum requirement.
• Tis and T1a tumors are potentially curable with endoscopic mucosal resection, as an alternative to esophagectomy.
• For T1b and higher, the primary treatment is definitive chemoradiation, preoperative chemotherapy, or preoperative chemoradiation before esophagectomy.

Multiple Myeloma

"The old regimens are no longer acceptable first-line options." George Somlo, MD, City of Hope Comprehensive Cancer Center, Duarte, California

• Initial treatment is important: induction chemotherapy, followed by autologous stem cell transplant, followed by maintenance therapy is the new standard.
• For induction therapy, triple regimens that include novel agents are superior to standard doublets.
• Maintenance therapy with lenalidomide (Revlimid) is the most important addition to the guidelines.

Prostate Cancer

"The NCCN Panel on Prostate Cancer is the first cancer-treatment panel to recommend not treating cancer." James L. Mohler, MD, Roswell Park Cancer Institute, Buffalo, New York

• Annual prostate-specific antigen (PSA) screening is recommended only for men at high risk according to family history, African-American race, and PSA > 1 ng/mL.
• A new risk category was defined: very-low-risk prostate cancer.
• Active surveillance is now the only recommendation for men with low-risk cancer and life expectancy < 10 years, and very-low-risk cancer and life expectancy
• < 20 years.
• Active surveillance is more fully described in the guidelines.
• Daily image-guided radiation therapy (IGRT) is required for high-dose radiotherapy (≥ 78 Gy).
• External-beam radiation therapy (EBRT) failure workup and treatment is clarified.
• Chemotherapy algorithms have been simplified.
• Docetaxel is the only recommended first-line chemotherapy regimen, and there is no best second-line regimen.

Acute Myeloid Leukemia

"Over the past 7 to 10 years, several new molecular markers have emerged that appear to offer more prognostic information for patients with AML…it is important to think about testing for these mutations at the time of diagnosis." Douglas Smith, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland

• Bone marrow with cytogenetics is a mandatory part of the workup for acute myeloid leukemia (AML) and is the gold standard of outcome predictors.
• Not all mutations confer a poor prognosis: "good" mutations are NPM1 and CEBPA, and a "bad" mutation is FLT3/ITD.
• The revised Guidelines have added CEBPA mutations to the recommended markers.
• The treatment recommendations for acute promyelocytic leukemia (APL) now contain risk stratification based on white blood cell counts.
• Cytarabine plays a prominent role in the induction regimen for patients with APL.
• Performance status is now a criterion on which to base treatment recommendations for older patients with AML.
• Azacitidine (Vidaza), decitabine (Dacogen), and  clofarabine (Clolar) are now category 2B recommendations for the treatment of older patients with AML.

Cervical Cancer

"Not much has changed over the past year or two regarding the treatment of cervical cancer." Benjamin E. Greer, MD, Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, Washington

• Few changes were made in the 2010 Guidelines, but major staging revisions are expected for endometrial cancer in the 2011 edition.
• Nodal information and the use of more contemporary imaging are recommended additions to the FIGO staging system.
• MR and PET are useful methods of functional imaging for advanced cervical tumors
• Chemoradiation therapy may be more effective than radiation alone.
• Cisplatin/paclitaxel remains the standard treatment of recurrent or metastatic disease.

Non-Small Cell Lung Cancer

"A significant revision is the inclusion of erlotinib (Tarceva) for patients with EGFR-positive disease across all levels of performance status. If you have the EGFR mutation, response rates are higher than 60%." David S. Ettinger, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins School of Medicine, Baltimore, Maryland

• Erlotinib is recommended as a first-line option for epidermal growth factor receptor (EGFR) mutation-positive disease.
• Pemetrexed (Alimta) and bevacizumab (Avastin) have emerged as treatment options for nonsquamous non-small cell lung cancer (NSCLC).
• There are many benefits to neoadjuvant therapy, but whether it prolongs survival is uncertain.
• The issue of concurrent vs sequential chemoradiotherapy for unresectable stage III NSCLC continues to be debated.

Malignant Pleural Mesothelioma

"There are limited data on the prognostic significance of serum markers and the best second-line treatment options. Therefore, the Panel found it challenging to arrive at a consensus regarding the best approach to managing patients with mesothelioma." Lee M. Krug, MD, Memorial Sloan-Kettering Cancer Center, New York, New York

• Mesothelioma should be managed by a multidisciplinary team with experience in treating this rare cancer.
• CT of the chest with contrast is the recommended method for the initial workup.
• Patients with the epithelioid subtype are more likely to respond to chemotherapy.
• Because surgery alone may be an inadequate treatment, combined-modality therapy is recommended for certain patients.
• The standard chemotherapy regimen is the combination of pemetrexed and cisplatin.

Cancer of Unknown Primary

"More effective therapies are emerging that produce a significantly good quality of life and long-term survival in patients with epithelial tumors.  This makes it especially important to identify the specific tumor type." David S. Ettinger, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland

"The clinicians' decisions can raise the cost of evaluation tenfold. We should think about the efficiency of care-not what we can do, but what we should do. Furthermore, the pathology evaluation is useless unless it is fully integrated with clinical management." Charles Handorf, MD, PhD, University of Tennessee Cancer Institute, Memphis, Tennessee

• Most patients with cancer of unknown primary have metastases that limit life expectancy, but some have a treatable tumor that may respond well to treatment.
• The pathologic evaluation is critical to diagnosis, and is detailed in the updated guidelines.
• Guidelines recommend additional tests according to site of occurrence.
• Surgery should be considered for some lung nodules.