Colorectal Cancer

Four years ago, at least five years of statin use was found to be associated with a 53% reduction in the risk of colorectal cancer and that association still stands, according to a coauthor of one of the initial studies to make the statin-cancer connection.

A primer on managing the chemorefractory patient from Eric Van Cutsem, MD, PhD.

In this supplement to Oncology, guest editor Axel Grothey from the Mayo Clinic, explores adjuvant therapy considerations in stage II colon cancer from different angles.

In the treatment of colon cancer today, the decision-making involved in the treatment of stage II disease is probably the most challenging aspect. The major question is whether or not these patients should receive postoperative adjuvant chemotherapy. Approximately 75% of stage II colon cancer is cured by surgery alone. For the remaining 25% of cases, there is great debate over whether adjuvant chemotherapy is sufficiently effective in enough patients to warrant the exposure to potentially toxic treatments. In the important QUASAR clinical trial, stage II patients were randomized to either fluorouracil (5-FU)-based therapy or observation. The results demonstrated an approximate 3% improvement in outcome for the 5-FU–treated patients. This leads to the assumption that treating all stage II patients with adjuvant chemotherapy is gross overtreatment, when essentially 97% of these patients will not benefit. Clearly the only way to approach this decision is through risk determination. In this article, I will describe the current state of defining high- and low-risk disease, which is mainly through histopathologic characteristics, as well as discuss emerging approaches such as molecular markers and genomic profiling

it is obvious that some patients with stage II cancers have excellent outcomes and do not require additional therapy, whereas other patients have cancers that biologically behave more like stage III tumors.Over the past years, our understanding of stage II colon cancer has made significant advances leading to a refinement in the identification of the patient population and the treatment options considered appropriate as adjuvant therapy in this setting.

Colon cancer is estimated to have accounted for 106,100 new cancer cases and 49,920 cancer-related deaths in 2009. Over half of these new diagnoses and deaths occur in individuals age 70 and older.

Approximately 150,000 new cases of colorectal cancer were expected for the year 2009 in the United States. Moreover, 49,920 deaths related to colorectal cancer were also predicted for the same year. The age-adjusted cancer death rates related to colorectal cancer have steadily declined over the past 2 decades. This improvement is a direct consequence of advances in prevention and treatment, including colorectal cancer screening, diagnostic tests, surgical technique, adjuvant therapies, and medical support.

In this issue of ONCOLOGY, Dr. Czito and colleagues from Duke University School of Medicine and the University of Texas Southwestern describe the potential benefit of incorporating intensity-modulated radiation therapy (IMRT) into the combined-modality treatment of anal canal cancer.[1] As the authors well delineate, the treatment of anal canal cancer has progressed from radical surgery to organ preservation with the use of definitive chemoradiotherapy.

The combined-modality care of the patient with colon or rectal cancer metastatic to the liver demands a team approach. It is little wonder that there is much confusion about this topic, given the number of unique treatment options that are delivered in a sequential and reiterative process. The concept of multidisciplinary approaches to complex cancer challenges has been adopted for a variety of tumor types and situations.

Historically, the treatment of squamous cell carcinoma of the anal canal has been an abdominoperineal resection (APR), resulting in loss of the anus and rectum with need for a permanent colostomy.

BERLIN-The failure of a major colon cancer trial to reach its primary endpoint surprised even the most seasoned gastrointestinal cancer investigators. Overall survival was not improved when cetuximab (Erbitux) was added to a first-line oxaliplatin-based regimen (Eloxatin), according to phase III COIN trial at ECCO/ESMO 2009.

The treatment of older patients with colorectal cancer is not always straightforward. As highlighted in the article by Dr. Ades, the heterogeneity of physiologic aging, the increasing prevalence of comorbid disease with age, and changing preferences with aging make counseling about adjuvant therapy more complex for older patients than for younger patients.

States population will be over 65 years old, with 2% of the population over 84. The corresponding projections for 2050 are 21% and 5%, respectively.[1] These projections underscore the aging of the population, with most recent estimates of life expectancy hitting a record high of 78.1 years.[2] With Americans living longer than ever before, physicians are already seeing larger numbers of elderly patients with cancers whose incidence increases with age, including colon cancer.

The Hippocratic principle of not harming the patient has remained up to this day an undisputed dogma in medicine. It reminds the physician of the possible detrimental, if not lethal, outcome of the treatment he prescribes and implicitly enforces good medical practice, although the true impact will unlikely be known. Oncology is one subspecialty of Medicine where this dilemma-ie, the pros and cons of treatment-is continuously put to the test, as the physician must decide on treatment for an often life-threatening illness while taking into account individual factors such as the patient’s will, performance status, available standard treatment options, and possible experimental approaches.

Davies/Goldberg Article Reviewed. The past decade has seen exciting developments in the field of colorectal cancer, particularly in the setting of advanced disease.

Colorectal cancer is the third most common cancer in the United States.[1] In 2008, an estimated 148,810 new cases of colorectal cancer will be diagnosed and nearly 50,000 people will die of the disease.

Davies/Goldberg Article Reviewed. The complexity of treatment options that now exist for patients with newly diagnosed metastatic colorectal cancer has increased dramatically over the past decade.

Despite advances in endoscopic and other screening techniques, less than half of US adults at risk for colorectal cancer undergo adequate screening. As a consequence, approximately half of all new cases of colorectal cancer are diagnosed in later stages.

Neoadjuvant chemoradiation has become the favored adjuvant treatment for stages II and III rectal cancer. Compared to postoperative chemoradiation, this modality of treatment has been shown to be superior in terms of toxicity, local relapse, and sphincter-saving.[1] This article will focus on the evolution of neoadjuvant chemotherapy over the past 2 decades, current acceptable neoadjuvant standards, and current investigational regimens.

Pohl and colleagues have provided a concise overview of current treatment options for metastatic colorectal cancer (mCRC). However, the authors do not provide personal insights as to what direction this burgeoning field will take next.

Dr. Pohl and colleagues have provided a comprehensive and well written overview of the current landscape of targeted agents and chemotherapy in advanced colorectal cancer.

Colorectal cancer is one of the leading causes of cancer-related death worldwide, with almost 20% of all patients presenting with metastatic disease at the time of their diagnosis. The treatment regimens and options of metastatic colorectal cancer have significantly changed in the last 10 years, leading to an improvement of response rates to about 50%, progression-free survival of about 10 months, and overall survival reaching over 2 years.

Adjuvant therapy is defined as any treatment administered after surgical resection of a primary tumor with the intent of improving the patient’s outcome by eliminating any occult, viable tumor cells that may have remained after surgery.

To treat, or not to treat-the decision to use adjuvant chemotherapy plagues medical oncologists and patients harnessed with the diagnosis of stage II colon cancer. A look to the literature does not simplify the decision, as significant controversy exists regarding the magnitude of benefit associated with 6 months of adjuvant chemotherapy. Dr. Kopetz and colleagues provide a well-organized review of the current literature examining the benefit of adjuvant chemotherapy in stage II disease, and discuss potential prognostic markers that may help determine who would most likely benefit from treatment.

blood-based marker called colon cancer–specific antigen-2 (CCSA-2) may be an accurate indicator of colorectal cancer

Complete evaluation of the lymph node basin after surgical resection for colon cancer is important for the accurate identification of nodal involvement and for the complete resection of disease.

Targeting the epidermal growth factor receptor (EGFR) has proven to be of clinical benefit in the management of metastatic colorectal cancer (mCRC). While the use of small-molecule tyrosine kinase inhibitors in this setting has not shown any significant activity and has been associated with increased gastrointestinal toxicity when combined with chemotherapy, a different picture has emerged with the use of EGFR-targeting monoclonal antibodies.

Cetuximab (Erbitux) plus best supportive care (BSC) provided significantly better overall survival and progression-free survival, compared with BSC alone, in patients with advanced colorectal cancer who had failed or could not take all approved chemotherapies

multicenter, open-label, randomized phase III trial recently published in the New England Journal of Medicine (357:2040-2048, 2007) demonstrated that cetuximab (Erbitux) as a single agent significantly improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to approved chemotherapy agents.

US Food and Drug Administration (FDA) has granted an expanded clearance for the CellSearch System to be used as an aid in the monitoring of metastatic colorectal cancer