New Surgical and Systemic Approaches Enable Earlier Intervention in CRC With Liver Metastases

Shikha Jain, MD, FACP

Although patients with colorectal cancer (CRC) and more than 1 liver metastasis were historically limited in terms of treatment options, advances in surgical and preoperative chemotherapy approaches have broadened the paradigm for this patient population to include curative-intent strategies, said Shikha Jain, MD, FACP, and Mario Spaggiari, MD, who added that early intervention and multidisciplinary care remain key aspects of this evolving landscape.

“From an oncologist’s perspective, a lot of change [has occurred] in how we discuss patients with metastatic CRC, especially when they have 1 liver lesion vs multiple. Traditionally, these patients were not necessarily candidates for a curative-intent treatment paradigm if they had more than 1 lesion in the liver; however, that has changed over the years. [Now], there is more discussion as to whether these patients will benefit from up-front chemotherapy or surgery,” said Jain, an assistant professor of medicine and the director of communication strategies in medicine at the University of Illinois (UI) College of Medicine, associate director of oncology communication and digital innovation at the UI Cancer Center, and a medical oncologist at UI Health.

“The key is to have a multidisciplinary approach as early as possible,” said Spaggiari, a transplant surgeon in the Division of Transplantation at UI Health. “Sometimes we see patients who come for a second or third opinion after they progress on second- or third-line chemotherapy. Seeing surgery as a rescue treatment never works, so we have to cure with a biological approach. The chance of a cure starts in a very early stage with a discussion between oncologists and surgeons.”

In an interview with OncLive^®, Jain and Spaggiari highlighted key advancements made in the treatment of patients with CRC and liver metastases, patient and disease factors to consider for surgical and systemic treatment, and the importance of multidisciplinary care for this population.

Mario Spaggiari, MD

OncLive^®: How have treatment approaches for patients with CRC and liver metastases changed based on advancements made in recent years?

Jain: As we see more studies coming out showing the utility and benefit of neoadjuvant chemotherapy or conversion therapy—where we are trying to convert someone from a non-operative candidate to an operative candidate—a lot of advancements have been made on the oncology and surgical sides. We have been able to personalize care a lot more based on what each patient is presenting with, their overall liver function, performance status, and tumor biology. Over the years, we have been able to modify our approach based on our specific patients and how they are presenting vs relegating those patients who have more than 1 liver lesion into a systemic therapy–only approach. We've been able to stratify some of those patients into [being eligible for] surgery plus some type of systemic therapy in the hopes of getting them cancer free and improving their overall survival.

How do you best facilitate communication between the different specialties to optimize multidisciplinary care?

Jain: When it comes to multidisciplinary [care], it is important to have open lines of communication. Part of the reason that is so important is exactly what we are discussing: the utility of some chemotherapy agents preoperatively vs going with a surgical intervention to start. In that discussion, everybody needs to weigh in, including the surgeons, radiation oncologists if they need to be involved, pathologists, radiologists, and medical oncologists.

Tumor boards are a great way to do that. Our tumor board at the University of Illinois meets once a week [to discuss patients with] gastrointestinal malignancies. We have a separate tumor board specific to liver malignancies. Along with having those multidisciplinary discussions at the tumor board, we are also constantly in communication about our patients, especially new patients when we are trying to come up with a treatment paradigm.

I often tell my patients that as a medical oncologist, I will be their quarterback because I will be taking care of them most often and for the longest amount of time. It is up to me to make sure that not only is everybody [who is part of the multidisciplinary team] weighing in, but that we discuss [a patient’s opinions] very thoroughly to make sure that we start with the right treatment plan. It is hard to start down a path and reverse to go down a different route, so it is important to have those open lines of communication. We all talk on the phone, text, [use] MyChart, message each other, whatever way we need to get in touch with each other to make sure that the plan [for the patient] is comprehensive, as well as clear to the patient and the entire care team up front. Communication is key to making sure that happens.

Could you expand on some of the surgical approaches that are recommended for patients with CRC and liver metastases?

Spaggiari: The paradigm of surgery for CRC has changed dramatically in the past 10 to 15 years. Very recently, it has been changing a lot. Basically, now what really matters is what is left in terms of liver remnant. Before, we were talking about how many lesions should be taken out. One or more than 2 lesions was the cutoff for a surgical approach. However, it is not like that anymore because with advancements in chemotherapy, we know that if we are able to make the patient tumor-free with good support from oncologic therapy, we give a curative chance to everybody. Of course, that [possibility] changes according to the burden of disease.

From a purely surgical approach, there are different ways of [resecting liver metastases]. In the past, we used to do big resections, even for small tumors, because we thought that what mattered was the size of the margins. Now, everything has changed dramatically, and we try to do small resections to make sure we have [clear] margins. [Then, we are] able to perform rescue resections.

What matters is the remnant, or how much liver is left [after surgery]. We have different approaches that [can] increase the size of the liver in preparation for surgery. The traditional approach is portal vein embolization. In this case, usually after 2 to 3 weeks [of time], we can restage the liver, recalculate the [tumor] volumes, and go back to surgery. We [also have] very aggressive surgical procedures that allow us to do the same thing in a shorter period if we think that it is very important to do the resection sooner rather than later. Very recently, we have [started to use] a combined approach between surgery and interventional radiology that allows us, in a matter of 7 to 15 days, to have a spectacular increase in the liver remnant while performing big surgeries in a single step.

Some patients are considered to have no surgical options, such as those in which there is no segment of the liver that can be spared. However, in those cases, there could be some surgical options. One of the potential surgical options is the use of a hepatic artery infusion pump. It is an aggressive liver-targeted chemotherapy that, in about 50% of cases, allows us to downstage the tumor and bring the patient back as a surgical candidate. Of course, nothing can be achieved without a chemotherapy that works because doing a very aggressive surgery in the setting of progression on chemotherapy, unfortunately, never works. That is why we have to start very early in the process.

What factors do you consider when determining what treatment approach is optimal for patients?

Spaggiari: From a surgical standpoint—because for this question we have to divide what surgery is and what oncology is—what really matters is whether I am able to leave at least 30% of the liver behind. The size of the liver is going to grow, but soon after surgery you need at least 30% of the liver back because it is going to [fulfill] metabolic needs. We need to do some calculations in terms of volume using the same strategies that we apply for normal liver transplants. If we see that the remnant is too small, we can adopt one of the strategies [for downstaging], such as portal vein embolization, double vein embolization, associating liver partition and PV ligation in staged hepatectomy surgery, or two-stage hepatectomy. When we clear one site of the liver, we do the embolization, we increase the size that has been already cleared, and then we go back in the second stage to remove the bigger part of the liver. From a surgical standpoint that is what matters. If we can achieve R0 resection in a safe way, [we can] prevent small-for-size syndrome and liver insufficiency because of small size.

Jain: From a medical oncology standpoint, we look at performance status especially; that is the most important [factor]. We want to make sure the patient can tolerate whatever systemic therapy they may need.

We also want to make sure they have the support system at home that they need. If they don't, we try to provide whatever resources we can to make sure that if they have complications or adverse effects [AEs] that they are able to manage them at home. Performance status is really the biggest component of how we decide what type of therapy to put a patient on.

Also, we talk about comorbidities and other possible medical issues that may contribute or make their AEs or symptoms worse. For example, if somebody is going to be started on oxaliplatin, we want to make sure they don’t have underlying neuropathy beforehand. There are a lot of different aspects of their other medical problems that we want to make sure are well controlled or addressed before we put them on a particular path.

We want to make sure also that if the patient is planning on going for any type of surgery that, just as Dr Spaggiari said, they can recover. [We need to make sure] they have enough reserve in their systems to make sure that after they go through a surgery they will be able to recover. They also need to be aware [beforehand] that adjuvant therapy might be required after they complete their surgical intervention and whatever other local interventions we plan for.

Are there emerging approaches that you are keeping your eye on?

Spaggiari: [We have] a new opportunity that will come into our field very soon, which is liver transplantation for CRC liver metastases. The reason I mention this is because the message that should [be conveyed] is that no matter how bad the cancer is inside the liver, there could be options. Those options should be explored in the early-stage setting.

A couple of trials are [looking at liver transplantation]. Our big trial is in the process of enrollment right now in the United States and Europe. It [could show] that liver transplant [may] be very beneficial in the setting of nonresectable liver metastases. That is something that will happen. I saw preliminary results [from the large study] and studies that are very promising. Don’t think that options [don’t exist,] because maybe in a cancer center at an academic center there [could be] options for [patients].

What role do clinical trials play amid these new therapeutic approaches?

Jain: We see across the board that there are huge disparities in who is enrolling on clinical trials. A lot of that is because the time isn’t spent talking to patients and explaining to them what a clinical trial entails. A part of it is that there are many individuals, especially in those communities that are often underserved in clinical trials, who don’t trust the health care system.

I want to encourage everyone that we need to make sure that our patients in these trials are heterogenous and diverse so that we are providing the best care for all our patients. We are seeing a big rise in CRC in our younger populations, especially among African American populations. I would strongly recommend encouraging patients regardless of their background or history to consider clinical trials, taking the time to answer their questions, and explaining to them why [clinical trials] might be the best option for their care. We need to try to get some of these patients into these trials who would benefit from them and who are often hesitant because they [may not] necessarily understand what going into a clinical trial entails.