Adjuvant Therapy for Colorectal Cancer

Michael A. Morse, MD:I think for stage 3 patients, almost everybody should be considered for systemic chemotherapy because there are adequate studies showing that single-agent fluoropyrimidine lengthens progression-free survival, and also the combination of oxaliplatin/fluoropyrimidine lengthens progression-free survival compared with fluoropyrimidine alone. Therefore, unless there’s a compelling contraindication or the patient refuses, I think everybody should be offered systemic therapy. The considerations in this case that are really driving us to strongly recommend systemic therapy include the fact that they have a very high risk of recurrence based on the large number of lymph nodes involved.

This patient has stage 3 disease—in fact, stage 3C disease, the worst prognostic category in stage 3. However, if we took a different example, if they had no lymph nodes involved, for example, it would be stage 2. Now stage 2 is an area where we actually have to spend quite a bit of time discussing with patients the pros and cons of taking systemic chemotherapy. The discussion I have with a patient who has stage 2 disease involves, first of all, trying to give them some sense of what their prognosis is, with or without therapy. Here’s where it’s very critical to have information about microsatellite instability.

A stage 2 patient, who has a microsatellite instability-high tumor, has such a good prognosis—and, in fact, they don’t benefit from a fluoropyrimidine regimen—that we recommend they be observed only. But for a patient with a microsatellite stable tumor, there are a number of ways to try to help them decide whether they want to take treatment. In a very simplistic discussion, one could quote the QUASAR trial, where a group of patients who had mostly stage 2 disease was randomized to fluorouracil/leucovorin versus no systemic therapy after surgery. And there was about a 3.6% absolute survival benefit in that population who received the systemic 5-FU—based therapy.

For other patients, they might want additional information about their tumor. Now, if they have a high-risk stage 2—for example, they presented with an obstruction or they had a perforation, they have T4, they have a fully differentiated tumor but are microsatellite stable—for those individuals, we would typically recommend they consider systemic therapy because their risk of recurrence is quite a bit higher than it is for patients without those high-risk features.

But for the more typical patient without any high-risk features, who’s microsatellite stable and who wants a little bit more information about their tumor, then one could perform an Oncotype DX, which would give them information about a recurrent score that correlates with a risk of recurrence. For some individuals, if they had a sufficiently high risk of recurrence, that might drive them to consider systemic therapy.

In patients with stage 2 disease who opt to take systemic therapy, the only real consideration is single-agent fluoropyrimidine—either fluorouracil/leucovorin or fluorouracil/capecitabine. Now I would have to point out that there actually is not a randomized capecitabine study for stage 2 patients. The only data come from stage 3 patients who were randomized to capecitabine versus no systemic therapy after surgery. However, most of the time, we extrapolate from that clinical trial and would allow patients to consider capecitabine or fluorouracil/leucovorin for stage 2 disease. As for exactly how long to treat them, currently the standard is 6 months.

Now in a stage 3 patient, as we mentioned before, there’s a progression-free survival benefit for the addition of oxaliplatin to a fluoropyrimidine-based therapy. Therefore, in almost all stage 3 patients, we do recommend the addition of oxaliplatin. However, for individuals who would have excessive toxicity, or in some elderly individuals who may not tolerate the oxaliplatin particularly well, then capecitabine alone or fluorouracil/leucovorin alone certainly could be considered.

Transcript edited for clarity.

• A 55-year old Caucasian male was admitted to the hospital with severe crampy right lower quadrant pain
  • He had a 2-month history of constipation, general abdominal discomfort, and tiredness
  • PMH remarkable for hyperlipidemia managed with diet and statin therapy
• Laboratory findings remarkable for grade 2 anemia (Hb, 9.0 g/dL) and elevated CEA (6.7 ng/mL)
• CT showed a non-obstructive mass in the sigmoid colon that infiltrated the full thickness of the bowel wall and involved adipose tissue
• Biopsy results indicated poorly differentiated invasive adenocarcinoma
• He opted for sigmoid colectomy and was referred to a surgeon
  • Following surgery, R0 resection with clear margins
  • 9 of 13 lymph nodes sampled were positive for adenocarcinoma