Surgery a Mainstay in Colorectal Cancer Treatment

William R. Jarnagin, MD

Over time, novel surgical approaches have led to a shift and evolution in treatment for patients with colorectal cancer (CRC), especially for those who have liver-metastatic disease, according to William R. Jarnagin, MD. These include portal vein embolization, segmental-type resections, and selective internal radiation therapy (SIRT)—albeit, a less common approach.

“Surgery is the most effective treatment for this disease in patients who have liver-confined disease,” Jarnagin said. “And, as the safety of the operations have improved over time, the boundaries have expanded in terms of who should have an operation or who is a candidate for an operation.”

OncLive: What did you focus on in your presentation on CRC?

Jarnagin, surgeon, chief, Hepatopancreatobiliary Service, Benno C. Schmidt Chair in Surgical Oncology, Memorial Sloan Kettering Cancer Center, spoke about the necessary role of surgery and novel techniques in patients with CRC in an interview during the 2017 OncLive^® State of the Science Summit^TM on Gastrointestinal Cancers.Jarnagin: I gave some historical perspective about how things have changed over time. There have also been advances with chemotherapy that have seen tremendous progress, which has also changed the nature of who should get an operation and who is a candidate for surgery. I spoke about how more can be currently expected of surgery in a contemporary setting and in a high-volume center, and how we are looking at ways to improve the results of surgery as we go forward.

How have you noticed that surgery has changed in this landscape?

I spoke about SIRT a little bit only because the data in CRC is just not as strong as it is in hepatocellular carcinoma, and its place [in CRC] is a little less well-defined.The operation has become safer over time. We tend to do fewer big resections so we don’t take as much liver as we did in the past, which made it safer. We do things before surgery to help improve the safety, particularly something called portal vein embolization…which increases the amount of functional liver left behind. We are doing a lot of segmental-type resections, which allows us to take patients to the operating room who have more advanced disease with larger tumors and, in doing that more effectively, we remove more of the disease and leave more functioning liver behind. Those are the major safety points that need to be emphasized.

What are some other common sites of metastasis in patients with CRC? Is surgery in these areas trickier?

The effectiveness of chemotherapy has changed the way we practice. More patients have been getting chemotherapy before surgery, which is good and bad. It is good because they respond¬—much better than they ever had in the past. There is damage to the liver that happens, which can adversely affect regeneration of the future liver remnant, and can potentially increase the morbidity. It emphasizes more than ever the need for surgeons and medical oncologists to work together to decide how much treatment to give before surgery, when surgery should be given, when to give chemotherapy first, and when not to.It is not so much the difficulty of the operation, and that is an important point to understand. It is not that we can’t take these other sites out, it’s more of a question of, “Should we?” When they are spread to the liver plus other sites, the results of surgery on the liver becomes worse; the risk of recurrence is much higher.

You have a patient with liver-metastatic CRC come into your clinic. What factors are you looking for to determine whether they’re a good candidate for surgery?

There are some people who will benefit from resection of liver, plus lymph nodes and lung, but the majority will not benefit. It is up to the surgeons and medical oncologists to determine who should get an operation and who shouldn’t. We have to be careful. Once there is more advanced disease, the result of surgery in the liver becomes more difficult to predict and most patients don’t benefit.There are several things to consider. The first step is to know whether or not the disease in the liver can be removed from a technical standpoint. If you have 1 or 2 tumors in favorable locations, then resection is certainly possible and that is the first jumping-off point. If they have much more advanced disease, then surgery is not an option and the conversation changes quite dramatically to more palliative measures.

Looking at the future of surgery, while taking SIRT into consideration, what lies ahead?

If the tumors are technically resectable, then the question is, “Should we do it?” That involves consideration of the biology of the tumor, the behavior, and what other factors are there that would suggest not as good of outcomes as someone else. If their disease has spread to the liver, or there are a large number of lymph nodes in the primary tumor—things of that nature—then we consider their fitness for an operation. Are they healthy enough to go through an operation of this magnitude? Do they have comorbid disease? Liver disease? Those are important factors to know about ahead of time and can, in many cases, prevent an operation from happening.Right now, the use of SIRT is limited to patients who have nonresectable disease and who have failed at least 1 line of chemotherapy. The likelihood of success with almost any regimen is going to be limited, possibly except for liver-directed pump chemotherapy, or something like that.

SIRT has also been looked at as upfront treatment combined with chemotherapy and it hasn’t really shown a benefit there. It is hard to know exactly where it will fit in. Using it earlier in the course of someone's disease, before they have exhausted all of their chemotherapy options, may be the right thing to do. Combining SIRT and resection—I know people do that and have done it in selected situations—is not going to be a common event, where we are going to use SIRT to shrink tumors and then go to the operating room. I don’t think SIRT, right now, has the capability of bringing about those kinds of responses that we can get with chemotherapy.