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Swaminathan Murugappan, William P. Harris, Christopher G. Willett and Edward Lin

Although tumor biology and genomics of colon and rectal cancer are no different, patients with locally advanced rectal cancer (LARC) require neoadjuvant fluoropyrimidine-based chemoradiation and total mesorectal excision. In addition to known clinical risk factors, improved algorithms integrating molecular tools are needed to stratify patients with LARC to improve treatment outcomes and reduce acute and long-term toxicities. Simply combining newer systemic or targeted agents with standard treatment in all patients yielded little success but added toxicities. This article reviews the historical data, current standards of care, and ongoing research efforts regarding biomarkers, molecular imaging, and personalized genomic information.

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Paul F. Engstrom, Juan Pablo Arnoletti, Al B. Benson III, Jordan D. Berlin, J. Michael Berry, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Raza A. Dilawari, Dayna S. Early, Peter C. Enzinger, Marwan G. Fakih, James Fleshman Jr., Charles Fuchs, Jean L. Grem, James A. Knol, Lucille A. Leong, Edward Lin, Mary F. Mulcahy, Eric Rohren, David P. Ryan, Leonard Saltz, David Shibata, John M. Skibber, William Small Jr., Constantinos Sofocleous, James Thomas, Alan P. Venook and Christopher Willett

Overview An estimated 5290 new cases (2100 men and 3190 women) of anal cancer (involving the anus, anal canal, or anorectum) will occur in the United States in 2009, accounting for approximately 1.9% of digestive system cancers, and an estimated 710 deaths due to anal cancer. 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 (see Risk Factors, facing page). This manuscript summarizes the NCCN Clinical Practice Guidelines in Oncology for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. Other types of cancers occurring in the anal region are addressed in other NCCN guidelines (i.e., anal adenocarcinoma and anal melanoma are managed according to the NCCN Clinical Practice Guidelines in Oncology on Rectal Cancer and Melanoma, respectively). Except where noted, the recommendations in these guidelines are classified as category 2A, meaning that uniform NCCN consensus was present among the panel based on lower-level evidence that the recommendation is appropriate. The panel unanimously endorses patient participation in a clinical trial over standard or accepted therapy. Risk Factors 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 HIV infection; and smoking. Currently, the association between anal carcinoma and persistent infection with a high-risk form...
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Paul F. Engstrom, Juan Pablo Arnoletti, Al B. Benson III, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Anne Covey, Raza A. Dilawari, Dayna S. Early, Peter C. Enzinger, Marwan G. Fakih, James Fleshman Jr., Charles Fuchs, Jean L. Grem, Krystyna Kiel, James A. Knol, Lucille A. Leong, Edward Lin, Mary F. Mulcahy, Sujata Rao, David P. Ryan, Leonard Saltz, David Shibata, John M. Skibber, Constantinos Sofocleous, James Thomas, Alan P. Venook and Christopher Willett

Colon Cancer Clinical Practice Guidelines in Oncology NCCN Categories of Evidence and Consensus Category 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus. Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus. Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement). Category 3: The recommendation is based on any level of evidence but reflects major disagreement. All recommendations are category 2A unless otherwise noted. Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Overview Colorectal cancer is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. In 2009, an estimated 106,100 new cases of colon and 40,870 cases of rectal cancer will occur. During the same year, it is estimated that 49,920 people will die from colon and rectal cancer.1 Despite these statistics, mortality from colon cancer has decreased slightly over the past 30 years, possibly due to earlier diagnosis through screening and better treatment modalities. This manuscript summarizes the NCCN Clinical Practice Guidelines in Oncology for managing colon cancer. The guidelines begin with clinical presentation to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, adjuvant treatment, management of recurrent and metastatic disease, and patient surveillance. When reviewing these guidelines, clinicians should be aware of...
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Paul F. Engstrom, Juan Pablo Arnoletti, Al B. Benson III, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Anne Covey, Raza A. Dilawari, Dayna S. Early, Peter C. Enzinger, Marwan G. Fakih, James Fleshman Jr., Charles Fuchs, Jean L. Grem, Krystyna Kiel, James A. Knol, Lucille A. Leong, Edward Lin, Mary F. Mulcahy, Sujata Rao, David P. Ryan, Leonard Saltz, David Shibata, John M. Skibber, Constantinos Sofocleous, James Thomas, Alan P. Venook and Christopher Willett

Rectal Cancer Clinical Practice Guidelines in Oncology NCCN Categories of Evidence and Consensus Category 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus. Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus. Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement). Category 3: The recommendation is based on any level of evidence but reflects major disagreement. All recommendations are category 2A unless otherwise noted. Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Overview In 2009 an estimated 40,870 new cases of rectal cancer will occur in the United States (23,580 cases in men; 17,290 cases in women). During the same year, an estimated 49,920 people will die from rectal and colon cancers.1 Although colorectal cancer is ranked as the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States, mortality from colorectal cancer has decreased during the past 30 years. This decrease may be due to earlier diagnosis through screening and better treatment modalities. The recommendations in these clinical practice guidelines are classified as category 2A except where noted, meaning that there is uniform NCCN consensus, based on lower-level evidence (including...
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Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Clair Beard, Sam Bhayani, Graeme B. Bolger, Sam S. Chang, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Shilpa Gupta, Steven L. Hancock, Jenny J. Kim, Timothy M. Kuzel, Elaine T. Lam, Clayton Lau, Ellis G. Levine, Daniel W. Lin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Elizabeth R. Plimack, Edward N. Rampersaud, Bruce G. Redman, Charles J. Ryan, Joel Sheinfeld, Brian Shuch, Kanishka Sircar, Brad Somer, Richard B. Wilder, Mary Dwyer and Rashmi Kumar

Germ cell tumors (GCTs) account for 95% of testicular cancers. Testicular GCTs constitute the most common solid tumor in men between the ages of 20 and 34 years, and the incidence of testicular GCTs has been increasing in the past 2 decades. Testicular GCTs are classified into 2 broad groups—pure seminoma and nonseminoma—which are treated differently. Pure seminomas, unlike nonseminomas, are more likely to be localized to the testis at presentation. Nonseminoma is the more clinically aggressive tumor associated with elevated serum concentrations of alphafetoprotein (AFP). The diagnosis of a seminoma is restricted to pure seminoma histology and a normal serum concentration of AFP. When both seminoma and elements of a nonseminoma are present, management follows that for a nonseminoma. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Testicular Cancer outline the diagnosis, workup, risk assessment, treatment, and follow-up schedules for patients with both pure seminoma and nonseminoma.

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Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Clair Beard, Sam Bhayani, Graeme B. Bolger, Sam S. Chang, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Shilpa Gupta, Steven L. Hancock, Jenny J. Kim, Timothy M. Kuzel, Elaine T. Lam, Clayton Lau, Ellis G. Levine, Daniel W. Lin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Elizabeth R. Plimack, Edward N. Rampersaud, Bruce G. Redman, Charles J. Ryan, Joel Sheinfeld, Brian Shuch, Kanishka Sircar, Brad Somer, Richard B. Wilder, Mary Dwyer and Rashmi Kumar

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These NCCN Guidelines Insights highlight the recent updates/changes in these guidelines, and updates include axitinib as first-line treatment option for patients with clear cell renal carcinoma, new data to support pazopanib as subsequent therapy for patients with clear cell carcinoma after first-line treatment with another tyrosine kinase inhibitor, and guidelines for follow-up of patients with renal cell carcinoma.

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Al B. Benson III, J. Pablo Arnoletti, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Raza A. Dilawari, Paul F. Engstrom, Peter C. Enzinger, James W. Fleshman Jr., Charles S. Fuchs, Jean L. Grem, James A. Knol, Lucille A. Leong, Edward Lin, Kilian Salerno May, Mary F. Mulcahy, Kate Murphy, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, William Small Jr., Constantinos T. Sofocleous, Alan P. Venook and Christopher Willett

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Al B. Benson III, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Marwan G. Fakih, Charles S. Fuchs, Jean L. Grem, Steven Hunt, Lucille A. Leong, Edward Lin, Michael G. Martin, Kilian Salerno May, Mary F. Mulcahy, Kate Murphy, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, William Small Jr, Constantinos T. Sofocleous, Alan P. Venook, Christopher G. Willett, Deborah A. Freedman-Cass and Kristina M. Gregory

These NCCN Clinical Practice Guidelines in Oncology provide recommendations for the management of rectal cancer, beginning with the clinical presentation of the patient to the primary care physician or gastroenterologist through diagnosis, pathologic staging, neoadjuvant treatment, surgical management, adjuvant treatment, surveillance, management of recurrent and metastatic disease, and survivorship. This discussion focuses on localized disease. The NCCN Rectal Cancer Panel believes that a multidisciplinary approach, including representation from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology, is necessary for treating patients with rectal cancer.

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Anal Carcinoma, Version 2.2012

Featured Updates to the NCCN Guidelines

Al B. Benson III, J. Pablo Arnoletti, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Raza A. Dilawari, Paul F. Engstrom, Peter C. Enzinger, Marwan G. Fakih, James W. Fleshman Jr., Charles S. Fuchs, Jean L. Grem, Lucille A. Leong, Edward Lin, Kilian Salerno May, Mary F. Mulcahy, Kate Murphy, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, William Small Jr., Constantinos T. Sofocleous, Alan P. Venook, Christopher Willett and Deborah A. Freedman-Cass

The workup and management of squamous cell anal carcinoma, which represents the most common histologic form of the disease, are addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Anal Carcinoma. These NCCN Guidelines Insights provide a summary of major discussion points of the 2012 NCCN Anal Carcinoma Panel meeting. In summary, the panel made 4 significant changes to the 2012 NCCN Guidelines for Anal Carcinoma: 1) local radiation therapy was added as an option for the treatment of patients with metastatic disease; 2) multifield technique is now preferred over anteroposterior-posteroanterior (AP-PA) technique for radiation delivery and the AP-PA technique is no longer recommended as the standard of care; 3) PET/CT should now be considered for radiation therapy planning; and 4) a section on risk reduction was added to the discussion section. In addition, the panel discussed the use of PET/CT for the workup of anal canal cancer and decided to maintain the recommendation that it can be considered in this setting. They also discussed the use of PET/CT for the workup of anal margin cancer and for the assessment of treatment response. They reaffirmed their recommendation that PET/CT is not appropriate in these settings.

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Metastatic Colon Cancer, Version 3.2013

Featured Updates to the NCCN Guidelines

Al B. Benson III, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Marwan G. Fakih, Moon J. Fenton, Charles S. Fuchs, Jean L. Grem, Steven Hunt, Ahmed Kamel, Lucille A. Leong, Edward Lin, Kilian Salerno May, Mary F. Mulcahy, Kate Murphy, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, William Small Jr, Constantinos T. Sofocleous, Alan P. Venook, Christopher G. Willett, Kristina M. Gregory and Deborah A. Freedman-Cass

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions surrounding metastatic colorectal cancer for the 2013 update of the guidelines. Importantly, changes were made to the continuum of care for patients with advanced or metastatic disease, including new drugs and an additional line of therapy.