Case-Based Review

Adjuvant Chemotherapy in the Treatment of Colon Cancer


 

References

INTRODUCTION

Colorectal cancer (CRC) is one of the most prevalent malignancies and is the fourth most common cancer in the United States, with an estimated 133,490 new cases diagnosed in 2016. Of these, approximately 95,520 are located in the colon and 39,970 are in the rectum.1 CRC is the third leading cause of cancer death in women and the second leading cause of cancer death in men, with an estimated 49,190 total deaths in 2016.2 The incidence appears to be increasing,3 especially in patients younger than 55 years of age;4 the reason for this increase remains uncertain.

A number of risk factors for the development of CRC have been identified. Numerous hered-itary CRC syndromes have been described, including familial adenomatous polyposis,5 hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome,6 and MUTYH-associated polyposis.7,8 A family history of CRC doubles the risk of developing CRC,9 and current guidelines support lowering the age of screening in individuals with a family history of CRC to 10 years younger than the age of diagnosis of the family member or 40 years of age, whichever is lower.10 Patients with a personal history of adenomatous polyps are at increased risk for developing CRC, as are patients with a personal history of CRC, with a relative risk ranging from 3 to 6.11 Ulcerative colitis and Crohn’s disease are associated with the development of CRC and also influence screening, though evidence suggests good control of these diseases may mitigate risk.12 Finally, modifiable risk factors for the development of CRC include high red meat consumption,13 diets low in fiber,14 obesity,13 smoking, alcohol use,15 and physical inactivity16; lifestyle modification targeting these factors has been shown to decrease rates of CRC.17 The majority of colon cancers present with clinical symptoms, often with rectal bleeding, abdominal pain, change in bowel habits, or obstructive symptoms. More rarely, these tumors are detected during screening colonoscopy, in which case they tend to be at an early stage.

SURGICAL MANAGEMENT

A critical goal in the resection of early-stage colon cancer is attaining R0 resection. Patients who achieve R0 resection as compared to R1 (microscopic residual tumor) and R2 (macroscopic residual tumor)18 have significantly improved long-term overall survival.19 Traditionally, open resection of the involved colonic segment was employed, with end-end anastomosis of the uninvolved free margins. Laparoscopic resection for early-stage disease has been utilized in attempts to decrease morbidity of open procedures, with similar outcomes and node sampling.20 Laparoscopic resection appears to provide similar outcomes even in locally advanced disease.21 Right-sided lesions are treated with right colectomy and primary ileocolic anastomosis.22 For patients presenting with obstructing masses, the Hartmann procedure is the most commonly performed operation. This involves creation of an ostomy with subtotal colectomy and subsequent ostomy reversal in a 2- or 3-stage protocol.23 Patients with locally advanced disease and invasion into surrounding structures require multivisceral resection, which involves resection en bloc with secondarily involved organs.24 Intestinal perforation presents a unique challenge and is associated with surgical complications, infection, and lower overall survival (OS) and 5-year disease-free survival (DFS). Complete mesocolic excision is a newer technique that has been performed with reports of better oncologic outcome at some centers; however, this approach is not currently considered standard of care.25

STAGING

According to a report by the National Cancer Institute, the estimated 5-year relative survival rates for localized colon cancer (lymph node negative), regional (lymph node positive) disease, and distant (metastatic) disease are 89.9%, 71.3%, and 13.9%, respectively.1 However, efforts have been made to further classify patients into distinct categories to allow fine-tuning of prognostication. In the current system, staging of colon cancer utilizes the American Joint Committee on Cancer tumor/node/metastasis (TNM) system.20 Clinical and pathologic features include depth of invasion, local invasion of other organs, nodal involvement, and presence of distant metastasis (Table 1). Studies completed prior to the adoption of the TNM system used the Dukes criteria, which divided colon cancer into A, B, and C, corresponding to TNM stage I, stage IIA–IIC, and stage IIIA-IIIC. This classification is rarely used in more contemporary studies.

Table 1

APPROACH TO ADJUVANT CHEMOTHERAPY

Adjuvant chemotherapy seeks to eliminate micrometastatic disease present following curative surgical resection. When stage 0 cancer is discovered incidentally during colonoscopy, endoscopic resection alone is the management of choice, as presence of micrometastatic disease is exceedingly unlikely.26 Stage I–III CRCs are treated with surgical resection with

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