Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 51-year-old man is evaluated for a 6-month history of increased fatigue and decreased exercise tolerance. He is otherwise well with no significant medical history.

On physical examination, temperature is 37.3 °C (99.1 °F), blood pressure is 115/75 mm Hg, pulse rate is 76/min, and respiration rate is 14/min. The abdomen is soft with no distention or organomegaly, and bowel sounds are normal. The remainder of the physical examination is normal.

Fecal occult blood testing results disclose brown, guaiac-positive stool.

Laboratory studies indicate a hemoglobin level of 8.4 g/dL (84 g/L) and a mean corpuscular volume of 80 fL.

Colonoscopy is performed, and a 5-cm mass is identified in the cecum. A biopsy of the mass reveals moderately differentiated adenocarcinoma. A contrast-enhanced CT scan of the chest, abdomen, and pelvis demonstrates the cecal mass and no evidence of metastatic disease. The patient undergoes a right hemicolectomy from which he recovers uneventfully. Final pathology reveals a tumor penetrating into the pericolonic fat, with 3 of 28 lymph nodes positive for cancer (T3N1M0; stage III). All margins of resection are clear of tumor.

Which of the following is the most appropriate management?

A: 5-Fluorouracil and leucovorin
B: 5-Fluorouracil, leucovorin, and oxaliplatin (FOLFOX)
C: Radiation therapy
D: Radiation therapy plus 5-fluorouracil followed by FOLFOX

MKSAP Answer and Critique

The correct answer is B: 5-Fluorouracil, leucovorin, and oxaliplatin (FOLFOX).

This patient has stage III colon cancer with the tumor invading the pericolonic fat and three lymph nodes involved (T3N1M0), and the preferred treatment is a chemotherapy regimen of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX). Stage III colon cancer is potentially curable, and the rate of cure is statistically significantly increased by the use of adjuvant chemotherapy. 5-FU plus leucovorin was established as an appropriate standard adjuvant treatment for stage III colon cancer in the mid-1990s; however, in 2004, a large, randomized trial comparing adjuvant 5-FU plus leucovorin versus the FOLFOX regimen showed that the FOLFOX regimen led to a greater disease-free survival at both 3 and 5 years after surgery. Thus, the FOLFOX regimen, or some modification of it, is the current accepted standard for postoperative management of stage III colon cancer.

Because local recurrence is not a common event with colon cancer, and because it can be difficult to isolate the small bowel from the radiation field, radiation therapy, alone or in combination with chemotherapy, does not have a role in the routine management of stage III colon cancer (radiation to the small bowel can cause substantial toxicity). However, in the rectum, local recurrence is a greater problem, and it is far easier to isolate the small bowel out of the radiation field; therefore, the combination of radiation and chemotherapy, usually preoperatively, is routinely used in stage II and III rectal cancer.

Key Point

• An adjuvant chemotherapy regimen of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) has been shown to improve disease-free survival in patients with stage III colon cancer.

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