Is Adjuvant Chemotherapy Beneficial To Early Stage Colorectal Patients?

An original article called “Is Adjuvant Chemotherapy Beneficial To High Risk Stage II Colon Cancer” ( Lin C-C, et al. Int J Colorectal Dis; 2009, 24:665-676. reported results from an analysis in a single institute. It also investigated the benefit of adjuvant therapy for high-risk, stage II colon cancer patients. In particular, the study was designed to identify “the pattern of treatment failure in stage II colon cancer in a single institute.” The research was conducted from May 1998 through August 2004, and examined 375 stage II colon cancer patients who received surgery for the disease, from a total pool of 1,169 patients who received resection for colon cancer during the research period.

Stethoscope and Map

Colorectal cancer (CRC) is the third most common cancer worldwide. Around 1.2 million cases of colorectal cancer were recorded in 2008, accounting for around 10 per cent of all new cancer cases. It is predicted that the number of cases will rise to 2.2 million
by 2030.  CRC is the fourth leading cause of cancer death worldwide (608,000 deaths, 8% of the total) with the highest mortality rates in Central and Eastern Europe, while the lowest is found in Middle Africa (World Cancer Research Fund International (http://www.wcrf.org/cancer_facts/bowel_cancer_rates.php).  The National Comprehensive Cancer Network (NCCN) guidelines (http://www.nccn.com/files/cancer-guidelines/colon/index.html#/48/) recommend adjuvant therapy for all stage III CRC patients and for high risk Stage II only.

The question has been raised as to whether adjuvant therapies can improve overall survival outcomes by reducing the risk of recurrence when administered to all stage II colorectal patients. According to Dr. Axel Grothey at the Mayo Clinic, while most stage II patients will be cured by surgery alone, “a subset of patients will experience tumor recurrence, mainly in the form of metastatic disease.” (http://clincancerres.aacrjournals.org/content/17/10.toc). Even though surgical resection will cure the majority of such patients, investigators have utilized a variety of approaches in recent years to identify those patients who are at highest risk for recurrence. Identification of patients with higher (and lower) risk profiles has been deemed important in guiding postoperative adjuvant treatment decisions.

The authors report that “after (the) potentially curative operation, the decision of whether administration of adjuvant chemotherapy depended on the clinical judgment of the attending physicians, which includes the general performance of the patients, the pathologic features, and operative condition.” The prescribed 5-FU based adjuvant chemotherapy was administered to 66 patients for six-months with follow-up visits at three-month intervals for the first two years, six-month intervals for the following three years, and annually afterward. The results of the study showed that “high risk patients (n=102), but not other patients with stage II colon cancer, benefited from 5-FU-based adjuvant therapy (3-year disease-free survival 96.4% vs. 84.7%, p=0.045; 5-year overall survival (100% vs. 86.4%, p=0.015.”

A pooled analysis of seven studies of Fluorouracil-Based Adjuvant Therapy for Stage II and III Colon Cancer, including 1,440 node-negative patients (http://jco.ascopubs.org/content/22/10/1797.full.pdf), indicated “adjuvant chemotherapy for stage II colon cancer significantly improves 5-year disease-free survival.” The authors called for a randomized study “to clarify the role of adjuvant therapy in stage II colon cancer,” and cited one limitation of their study as the decision to administer adjuvant chemotherapy “depended on clinical judgment of corresponding attending physicians.”

At the time of the study, routine use of adjuvant chemotherapy was not indicated in all stage II colon cancer patients following curative resection. However, the study concluded “adjuvant chemotherapy is beneficial in high-risk stage II patients,” and recommended that “adjuvant therapy should be considered in this group of patients.”

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