Select Excerpts from the Interview

Track 1

DR LOVE: Can you discuss the evolution in the treatment of liver-only colorectal metastases?

DR CURLEY: In the late 1980s and early 1990s, patients who presented with synchronous primary and metastatic disease, had more than three or four liver metastases or had small-volume extrahepatic disease were considered incurable. Now we have data for each of those subsets that show an opportunity for long-term survival.

For example, a number of groups have examined the issue of curative surgery for patients with more than four hepatic metastases, including Rene Adam at the Paul Brousse Hospital (Adam 2003). With surgery alone, these patients have a five-year survival rate in the range of 20 to 25 percent.

However, if we add adjuvant or neoadjuvant chemotherapy, their five-year survival rate at MD Anderson is 51 percent (Pawlik 2006; [1.1]). Approximately 20 percent are alive and disease free at five years, while the other 30 percent are alive with disease. Essentially, we have changed the landscape for these patients in that they are living longer.

Track 3

DR LOVE: What is your approach for a patient who presents with primary colorectal cancer and potentially resectable metastatic disease?

DR CURLEY: If the patient presents with an asymptomatic or minimally symptomatic primary tumor, we frequently begin with three months of systemic chemotherapy and then we restage the disease. At MD Anderson, our data from the past five years showed that in 24 percent of these patients the primary tumor essentially disappeared. We still resect the primary tumor. Surgery reveals that although some patients are pathologic complete responders, an even larger number have remaining microscopic disease. We resect the liver metastases because we believe it will impact survival.

If the patient had a symptomatic primary tumor, in most cases I would resect the primary and stage the liver disease with intraoperative ultrasonography. Then I would administer systemic chemotherapy and resect the metastases later.

DR LOVE: What if the liver metastases disappear on imaging after treatment?

DR CURLEY: Data have demonstrated that microscopic disease was still present in 85 percent of such cases (Benoist 2006), which tells us that even though we downsize the tumor, we still need to examine the area where the tumor existed and try to include that in our resection.

DR LOVE: Do you make exceptions for which you still resect the metastatic disease before using chemotherapy?

DR CURLEY: Not all tumors respond to systemic chemotherapy, and some may progress, so I always ask myself whether the tumor would become unresectable if the disease progressed. In those cases, I have performed the liver resection first, followed by systemic chemotherapy and finally resection of the primary tumor.

DR LOVE: Do you ever resect the primary tumor and the liver metastases in the same procedure?

DR CURLEY: It depends on the volume of the liver resection. The liver needs a lot of protein and energy to heal itself. We and others have shown that we can do both if we are not performing a major resection. However, when removing 75 or 80 percent of the liver, it would be too risky to perform the two procedures at once.

Track 6

DR LOVE: How many weeks do you wait between the use of bevacizumab and surgery, when feasible, and have you run into problems with wound healing?

DR CURLEY: We wait six weeks (Kesmodel 2008; [1.2]). Recently, we presented data at the Society of Surgical Oncology meeting showing that when we discontinued bevacizumab six weeks before surgery, the complication rate was not increased after major liver resections. We examined not only wound healing but also liver regeneration because of the experimental data suggesting that bevacizumab impairs regeneration (Zorzi 2008).

DR LOVE: Have you observed problems with bowel perforation in patients who received bevacizumab?

DR CURLEY: Among the patients whom we treated with FOLFOX/bevacizumab for Stage IV disease with an intact primary tumor, a few experienced perforation. We always warn patients to report certain symptoms right away. We are then forced to operate on these patients at an inopportune time, because they’ve received bevacizumab.

Track 7

DR LOVE: Beyond hepatic metastases, what other sites may be considered surgically resectable?

DR CURLEY: Frequently patients with liver metastases also have metastases in the lymph nodes in the porta hepatis, and a lymphadenectomy in those cases has potential for survival benefit. More commonly, we see patients who present with either synchronous or metachronous liver and lung metastases. They may have resectable liver metastases, or they may already have undergone liver resection and then present with one or two lung metastases that are technically resectable. We and several others have data that show surgical treatment of those lung metastases can provide a long-term survival benefit for a subset of patients (Pfannschmidt 2007; [1.3]).

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