Perioperative or Postoperative?

The use of perioperative therapy

Commentator: NICHOLAS PETRELLI, MD

Comment:

Conversion chemotherapy should be used for patients with borderline resectability. I would use perioperative chemotherapy if a tumor was in close proximity to critical vessels, like the outflow tract of the liver, to downsize the lesion and obtain a negative margin. In that situation, I would use the perioperative EORTC protocol. I rarely recommend perioperative therapy unless the metastasis is borderline resectable — otherwise I go straight to surgery.

In my Journal of Clinical Oncology editorial, I explain why I object to the use of perioperative chemotherapy for patients with risk factors related to their normal liver parenchyma (ie, obesity, severe diabetes, cirrhosis). We know that patients who are obese can have steatosis or steatohepatitis. In those individuals — especially if they have resectable disease up front — I object to administering perioperative chemotherapy because chemotherapy is toxic to the normal liver and compounds the rate of postoperative complications in the obese, diabetics and those with cirrhosis.

Defining pre-, peri- and postoperative chemotherapy

Commentator: NICHOLAS PETRELLI, MD

Comment:

It is important to define the various terms for systemic therapy used for these patients. Neoadjuvant therapy usually refers to administering chemotherapy preoperatively for patients with resectable disease. In the perioperative setting, chemotherapy is administered both pre- and postoperatively. Adjuvant therapy is administered only in the post-operative setting. I see no role for the use of neoadjuvant therapy for patients with initially resectable disease.

Postoperative chemotherapy

Commentator: RENÉ ADAM, MD

Comment:

Combining chemotherapy with surgery — even in two stages or through combining postoperative chemotherapy with radiofrequency — is the only way to provide the patient with a relatively good survival benefit.

Perioperative therapy versus immediate resection

Commentator: RENÉ ADAM, MD

Comment:

In the majority of patients with initially resectable disease, I prefer using perioperative chemotherapy. First of all, it provides additional time to determine who will benefit from surgery. I can learn more about the biology, the evolution of the disease and the efficacy of the chosen chemotherapy. The second reason for the perioperative approach is that it allows me to predict whether the chemotherapy will be efficient in the postoperative setting because all patients receive postoperative chemotherapy. One possible exception to using perioperative chemotherapy is with a patient with a metachronous single metastasis that developed late (ie, two years) after colectomy. I’m not convinced that this type of patient would benefit from perioperative chemotherapy. Although this is debatable, I’m not convinced that this patient would benefit the same way a patient with a synchronous metastasis or with an early recurrence after colectomy would benefit. Conversely, all patients receive postoperative chemotherapy to prevent the recurrence.

Treatment strategies for large yet resectable disease

Commentator: STEVEN ALBERTS, MD

Comment:

In general, I favor using a perioperative approach for patients with large yet resectable disease. I am much more comfortable seeing some control of the disease, and having some sense that the selected chemotherapy regimen is effective.

Use of chemotherapy for patients with initially resectable disease and for patients who are not treatment naïve

Commentator: MICHAEL CHOTI, MD

Comment:

The choice of administering chemotherapy before and/or after surgery to a patient with resectable disease is controversial. This is in contrast to a patient with a tumor that was initially unresectable but convertible, where the choice is clearly to use chemotherapy to convert the disease. Is there any role for chemotherapy in a resectable case? The answer seems to be yes. The EORTC trial showed that patients with liver resection who received chemotherapy before and after surgery did better than those who were naïve to chemotherapy.

However, no data exist describing the benefits of using chemotherapy for patients who have already been treated with FOLFOX chemotherapy. Do you use FOLFIRI or do you use FOLFOX again a year and a half later? It is controversial. The other issue is whether to administer the chemotherapy prior to surgery or after resection.

Use of chemotherapy in the pre- and postoperative settings

Commentator: STEVEN CURLEY, MD

Comment:

We almost always use adjuvant therapy because we don’t administer all of the chemotherapy up front. We don’t treat to maximum response because chemotherapy can cause a number of hepatic toxicities. We will usually administer two to three months (ie, four to six cycles) of chemotherapy as neoadjuvant therapy followed by the resection, and then finish the remaining cycles of chemotherapy after surgery — this is well tolerated. Most patients are able to receive their adjuvant chemotherapy six to eight weeks after the liver resection, and then they are closely followed from there.

Perioperative treatment for synchronous metastatic disease

Commentator: STEVEN CURLEY, MD

Comment:

If we feel a patient with synchronous metastatic disease has resectable disease, we use a perioperative approach and administer two to three months of chemotherapy up front — meaning four to six cycles. We then proceed with resection that may include both the colorectal primary and the metastatic disease, if we feel the patient will tolerate that. We may perform staged resections and then finish with the chemotherapy. Our approach is customized based on the patients and what they are able to tolerate.

FOLFIRI as postoperative adjuvant therapy

Commentator: AXEL GROTHEY, MD

Comment:

When you consider the data presented at ASCO comparing 5-FU versus FOLFIRI in the postoperative setting, they didn’t see any benefit from the addition of irinotecan in these patients who had no prior test for efficacy of irinotecan preoperatively. The benefit of having patients undergo testing before surgery is to see if their disease responds to therapy. If you treat a black box, you’re stuck with the adjuvant data for FOLFIRI, which are not great in Stage III disease and not great in Stage IV disease.

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