Leveraging Locoregional Therapy and Resection in Metastatic CRC

Bassel El-Rayes, MD

Although resection is considered to be standard in the absence of long-term follow-up data regarding locoregional therapy, there are plenty of alternative approaches that, when applied with the utmost scrutiny, can be beneficial to patients with borderline and unresectable colorectal cancer (mCRC) that has metastasized to the liver, explained Bassel El-Rayes, MD.

“Factors that influence our decision regarding surgery versus local regional therapy include patient-related factors, such as whether the patient is in good enough shape to undergo a large surgery on the liver,” said El-Rayes. “Additionally, we consider the anatomy of the tumor; is there enough liver remnant to resect the tumor? The third thing we consider is the biology of the disease. If the cancer is progressing at a rapid rate, do we have systemic control of the cancer? If we do, we can focus on local therapy.”

If a patient is deemed unresectable, the extent of the disease can help inform which locoregional approach should be pursued, explained El-Rayes. For example, ablative therapies are typically reserved for smaller lesions, whereas a transcatheter delivery can affect a larger expanse of disease.

In an interview with OncLive, El-Rayes, chief clinical research scientist, Winship Cancer Institute of Emory University, further discussed the role of locoregional approaches in borderline and unresectable patients with mCRC.

OncLive: How do you determine which patients with metastatic disease should receive local-regional therapy versus those who should undergo resection?

Bassel: Determining which approach to take usually depends on our tumor board discussion. The management of these patients really requires the expertise of multiple specialties, including medical oncology, surgical oncology, interventional radiology, radiation oncology, and radiology. Discussing these cases at a tumor board is key in getting everyone’s input regarding the best approach.

Usually, resection is the gold standard. The patients who are typically considered for an alternative approach are those who do not fit the bill for resection either because they’re not healthy enough physiologically or the anatomy or distribution of the liver lesions is not conducive for resection.

What are some of the locoregional approaches for patients who are ineligible for resection?

Locoregional approaches can be classified into 2 main categories. There are ablative approaches, which include radiofrequency ablation, microwave ablation, or stereotactic body radiation. Then, there are treatments that are delivered through a catheter or transcatheter, which include chemoembolization, radioembolization, and hepatic artery infusion. The decision of which approach to use depends largely on the extent of the area that you want to treat. The ablative treatments are more useful for more discrete lesions, whereas the transcatheter therapies are more useful for disease that involves more of the liver.

Are there any downsides to locoregional therapies?

The downside to locoregional approaches is that we don't have good randomized trials with long-term follow-up that confirm that these approaches yield the same long-term outcomes as surgery. Therefore, a surgical approach is still the preferred approach. With surgery, you get to examine the tumor after resection and be certain that you got the whole tumor and safe margins around it. With ablation, you are usually relying more on imaging to confirm that you [resected] the whole tumor.

Could you discuss the existing data with locoregional therapies?

We have data, but we don't have good randomized trials comparing resection with ablation. We do have a lot of retrospective data, such as published series of patients who undergo ablation. We have some retrospective series which compare the 2 approaches, but we don't have very good prospective randomized trials, which are considered the gold standard in determining a new therapy.

Are there any ongoing or upcoming trials looking at locoregional therapy?

There is a lot of research in this area, especially in the field of radiation, such as stereotactic body radiation therapy and, more recently, proton therapy. Preliminary results from those trials look very encouraging in terms of local control. [Locoregional therapy] is a completely noninvasive approach. We look forward to seeing more data about the use of this modality in the future.

What are some of the remaining challenges and unanswered questions in this space?

There are many challenges in this area. The area that we have yet to really explore is trying to molecularly characterize the subset of patients who benefit from these types of interventions. We don’t know if there is a particular molecular signature that identifies the patients who will benefit more from regional therapy, such as ablation or radiation, versus the those who will benefit more from a systemic approach like chemotherapy. At this point, these decisions are made based on clinical parameters, but it would be great if we had molecular parameters to go along with the clinical picture that would allow us to better identify the patients who benefit from local therapy versus those who really need systemic therapy.

What are the biggest takeaways regarding the use of surgical and local therapeutic interventions in mCRC?

The first thing is the importance of multidisciplinary care. These patients need to be discussed at a tumor board; we really need to have input from multiple specialties in order to design a management plan. The second thing is that there are many treatment options in this space, and it's important to know which therapy has advantages in which setting in terms of surgery, radiofrequency ablation, microwave ablation, radiation, and transcatheter therapies. The third aspect is the importance of patient selection; identifying the patients who really need a systemic therapy versus those who would really benefit from locoregional therapy, or even those who may require aspects of both approaches.