Leveraging Surgical Oncology to Treat Gastrointestinal Cancers

Michael Choti, MD, MBA, FACS, is a surgical oncologist of the hepatobiliary tract and the pancreas; division chief of surgery at Banner MD Anderson Cancer Center at Banner Gateway Medical Center in Gilbert, Arizona, and co-chair of the 7th Annual School of Gastrointestinal Oncology® Conference hosted by Physicians’ Education Resource, LLC (PER®).

Q: Can you begin by discussing how surgery is evolving, aside from advancements in technique?

A: What’s exciting is this area of integration, the timing of surgery, [and use of] molecular genetics [to indicate when] surgery has benefit rather than just rushing into surgery. We’re using innovative areas to give preoperative chemotherapy, and in some cases [we] molecularly study the nuances of the cancer to know which patients may benefit more from surgery or not, or which patients get chemotherapy prior to surgery versus surgery up front. The most exciting area, besides technical robotic and other techniques, is related to understanding the biology of cancer and knowing when surgery is [appropriate]. So that’s an area [to focus on].

A couple of other areas [where] there’s work going on now is in ctDNA. We’re looking at the ongoing studies where after the surgery, we can measure residual [disease] in the bloodstream when we think we “got it all out.” We can then measure whether there may be residual cancer DNA in the bloodstream, and that can dictate whether there’s residual cancer and whether to [give chemotherapy] after [surgery]. This may not be a surgical question, but it’s very important to the surgical oncologist in understanding the completeness of the surgery and so forth.

On the imaging side, more sophisticated imaging that can either detect cancer sooner or earlier, in which case patients can undergo surgery or [the imaging], can help guide surgery. I pivot away from the pure technical question as to how we stitch and how we sew and how we take out a cancer. Yes, there are some innovations—as I mentioned, in robotics and so forth—but I would say the most exciting area is regarding these other aspects.

Q: Are there any specific cancers where surgery has changed for use in conjunction with other modalities?

A: I would say the concept [began] 2 decades ago and started with rectal cancer where the standard 20 years ago was to remove the cancer and give chemo-radiation therapy after that. Now, most [patients] except [those with] very early-stage rectal cancer is treated with chemotherapy, and/or sometimes radiation therapy first. The innovative thing now in rectal cancers is to give [chemotherapy] prior to radiation therapy. Rather than giving someone chemo-radiation first and then the surgery and then [chemotherapy] after the surgery, we’re giving more or all the chemotherapy prior to surgery, maybe with radiation, and then surgery later. The preoperative [area] has been there a long time but [continuously giving more chemotherapy,] not just chemoradiation, and giving more of it up front is what’s innovative in the rectal cancer space.

In other areas such as pancreatic cancer if it’s an operable pancreatic cancer, many around the country are still doing surgery first. [Banner Health] was one of the first centers [to do this] and now the NCCN [National Comprehensive Cancer Network] guidelines and others are finally recognizing that [patients should receive] preoperative chemotherapy for all pancreatic adenocarcinomas should get chemotherapy prior to surgery, not so much radiation.

The other area is stomach cancer or gastric cancer. The pendulum is moving fast towards giving chemotherapy prior to surgery, and the research is going on to continue that trend. The surgical management of cancer is giving more and more systemic chemotherapy prior to surgery rather than the standard [of care] which is take [the cancer] out and then give it after. I mentioned rectal cancer, pancreas, stomach, and now the areas of study are to continue that expansion to liver cancer, biliary cancer, cholangiocarcinoma, where now there is research going on [regarding which] patients we should be giving chemotherapy to prior to surgery. The standard now for cholangiocarcinoma, or bile duct [cancer, is] if it’s operable, to do surgery first, just as it was with stomach cancer or pancreatic cancer. There are ongoing studies to see if it will become the standard now to consider chemotherapy [prior to surgery for] GI cancers such as bile duct cancers and so forth.

Q: Has the coordination between surgeons and other oncology professionals evolved? Or does it need improvement?

A: We call it the multidisciplinary care, and that means historically cancer care was linearly managed. You see a surgeon [after you have received a] diagnosis by a gastroenterologist who refers to surgery, then an oncologist, and then referred for [chemotherapy] after rather than when you have the diagnosis at the beginning. In early-stage cancer [such as] stomach cancer, you may do surgery first or [patients] may never need chemotherapy. Quality of the imaging [and] of the molecular testing [needed to be] a priority before you have this unified plan among the whole team about which weapons or which arrows in your quiver to use to optimize the cancer care of that patient. Up front, that’s a so-called multidisciplinary care.

Candidly, it’s a challenging way in cancer care in America because it’s all fragmented. That’s why there’s a big push toward integrated cancer care, [including] tumor boards and multidisciplinary conferences. We’re building MDCs, multidisciplinary clinics, where not just the care is coordinated but there’s 1 visit for the patient, who shows up and sees everybody at the same time. We’re fortunate to [offer the] integrated cancer center; we can deliver that level of care that our competitors sometimes can’t.

Q: What do surgeons need to know about the genotype of tumors they’re operating on?

A: Oncologists need to have an understanding [that] molecular genetics are not necessarily only in the realm of the medical oncologist; as new targeted therapies are being developed based on the molecular signature of the tumor. They’re drug related, and we don’t have too many models of which molecular signature may change or dictate the nature of the operation itself. There are some selected cases where that may be the case. For example, if it’s a hereditary form of colon cancer that has a molecular signature, it may change the extent or nature of the operation, or it may change the prognosis after surgery based on a certain molecular signature. There may be cases in which a patient has a unique molecular signature, and we may not need to do surgery [because] chemotherapy is so effective. It’s rare at least in solid malignancies, but there are some examples of that.

We may want to change the sequencing of surgery versus [chemotherapy] based on the molecular signature. I do think it’s valuable and [it’s important to] put emphasis on that for anyone caring for patients with cancer. [Clinicians] need to understand the value of the of the molecular analysis of the tumor and how exciting this is as a paradigm shift. [This is] particularly true in the in the realm of immunotherapy. It’s still a minority of patients who may be candidates for immunotherapy, but there’s a lot of research going on into how we can expand immunotherapy drugs in patients who don’t necessarily have an immunogenic form of cancer. [With] ctDNA, which is molecular genetics of not just the tumor or biopsy but of the shed cancer in the bloodstream, you can potentially profile the genetics of a cancer by sequencing in the bloodstream.

It’s like a liquid biopsy from the blood. From a surgical standpoint, what’s particularly exciting is the ability after surgery to take the tumor, measure the molecular genetics in the tumor, and then develop a personalized molecular test for that patient to measure in their blood for minimal residual cancer after surgery, which can then dictate whether to take [chemotherapy]. The ctDNA aspect is going to be increasingly useful across the board. It will expand not just for [chemotherapy], but it will guide the response to therapy, the management of therapy, and whether to give further treatment after surgery.

Q: How close are we to using ctDNA to diagnose or guide treatment for GI cancers?

A: There are already some aspects where it’s currently being used selectively and insurance is paying, but it’s limited. There are a variety of domains. One is to be able to achieve the value of the molecular genetics of the tumor. You can use ctDNA to determine the full genomic profile of a patient with cancer. The other way is the response to therapy. If somebody has advanced cancer and they’re getting chemotherapy, we start [chemotherapy] and we give [chemotherapy] for a month or 2 and see if the spots shrink on scans. A month or 2 later, in theory, you can give 1 dose and see the next day or a week later whether the burden of mutation goes down. You can then nimbly adjust and determine if that therapy is working. You don’t have to be pummeling somebody with an ineffective form of chemotherapy again; [you can use] response to therapy to determine more quickly in real time the efficacy of therapy.

Even now, there are some examples of resistance clones where a patient [has tumor shrinkage initially but it] starts to grow with chemotherapy because there’s a mutation emerging. You must switch the chemotherapy. Those are things that now some medical oncologists are using ctDNA for advanced cancer. The key is to get the word out because the research needs to be done to validate it. The second is to have insurance and [consider] it as part of a standard of practice so that we can then use it.