Hello, my name is Susan Urba. I'm the medical oncologist specializing in the treatment of esophageal cancer. I'm also a palliative care physician specializing in pain and symptom management. I've prepared six modules from the medical oncologist perspective on the treatment of esophageal cancer. This module is called clinical presentation and staging. The objectives of this discussion are to recognize the typical clinical presentation for patients with esophageal cancer. Describe the staging modalities, identify the importance of testing for HER@ status in tumor tissue. And also to understand the principle elements of the TNM or tumor node metastatic site staging for esophageal cancer. So let's start with a pre-lecture question. Why should adenocarcinoma of the esophagus be tested for HER2 status? Number 1, it predicts a better prognosis. Number 2, it indicates that the tumor will be more sensitive to platinum chemotherapy. Number 3, it means that an antibody treatment can be given. And number 4, it indicates sensitivity to radiation therapy. So, take a moment to write down your answer. And then, if you know it great, and if not, let's see if we can find it in the lecture that I'll be giving right now. Clinical presentation almost always is from dysphagia. The esophagus is very distensible, and the circumference can really get quite narrow before a patient notices that food is getting stuck. Usually the opening is about 13 millimeters before they start complaining of food not going down. Often they'll present with weight loss, almost always. And there's an increasing number of cases in young white males with adenocarcinoma. And they are often well nourished or even obese at the time of presentation. Sometimes we'll see patients present with hematemesis, I'm always surprised we don't see that more often. Because the tumor is just sitting right in the esophagus, but it bleeds somewhat, sometimes microscopically. But once in awhile someone will present with vomiting of blood. So there are several staging modalities. First of all, of course, if you look on the right of the slide, is an endoscope. Looking down there, finding the tumor, biopsying it, and then certainly doing CT scans and trying to make sure if the tumor has spread. So talking about the endoscopy, the lighted tube, the endoscope is put down into the esophagus. On picture a you can see a fungating mass in the upper left part. That would be an esophageal tumor and almost certainly that's going to be malignant. b is a more normal esophagus. There's not really an abnormality. Every now and then on endoscopy, the endoscopist will see like an ulcer or sort of a flat lesion and they will biopsy that, that can also be cancer. But the more common is that sort of fungating pendulous tumor that's pictures in a there. Histology is most typically adenocarcinoma, either with or without Barrett's esophagus or squamous cell cancer. After that determination has been made, the grade, meaning how aggressive it looks, how bad the cells look so to speak. And then also the depth of tumor invasion, I'll show some pictures of that in a minute. But, for example, the very earliest invasion, T1a goes into the very, most superficial area of the mucosa, or the muscularis mucosae. T1b goes a little bit further in, in the submucosa. Other principles of pathology is testing for HER2 amplification, the Human Epidermal Growth Factor Receptor. It can be either amplified or overexpressed. Now this occurs in many breast cancer patients. And only relatively recently have we discovered that about 20% of patients with adenocarcinomas also express this receptor. It's of unclear significance as far as does the tumor grow quickly or slowly. It may correlate with tumor invasion and lymph node metastases. But what's the significance of it, why do we even care to know? Because there is a treatment called trastuzumab, or herceptin is a brand name, and this is an antibody to the HER2 receptor. So if that receptor is there, then we want to give the antibodies so it can hook up with the antigen and hopefully kill off the cell. The pictures here, one in purple shows the Herceptin, which is the drug, the antibody, blocking the receptor. So the EGF, the epidermal growth factor, that would normally hook up with the receptor and stimulate the growth, is blocked. So it can't hook up with it, and it can't stimulate the growth. Therefore it seems to have a good effect on trying to help kill off the cancer cells. Here's a picture of the esophageal wall. The top part is what is seen in the endoscope. That's the inner part of the esophagus, which is really the mucosa. And then as you go farther down, you start getting into the submucosa and then into the muscle wall. Which is a very common place for the tumors to invade. If it goes through that wall and into local areas, then that makes resection more difficult. You can see the regional lymphatics in green, low down on the screen there. And if they become involved, you can see that tumor would have moved from the esophagus to the lymph nodes, and therefore, will have a propensity to move even further. The slide might be a little bit too much to see and break down. But just to give you a general overview of what it looks like, from left to right is a very earliest tumor to the more advanced tumor. The earliest tumor, which is really the carcinoma in site 2. And then T1 just goes in the very superficial layers. And then you could see it gets lower and lower into the esophagus. By the time you get to the end there, T4, it's actually gone all the way through the esophagus. And in this picture is invading the aorta and it can invade any adjacent organ. And as you can imagine that would be very difficult or impossible to resect, because they have to resect part of the organ with it. So that usually will make a tumor unresectable. So after we've made that diagnosis then we assess for distant metastases, usually with a CT scan. Unfortunately, a good two thirds of patients at time of diagnosis will have metastatic disease, primarily in the lung or liver. We usually try to get a biopsy if we can to prove that. If not, we do a PET scan, and if the PET scan lights up or takes up sugar in that area, that's also pretty convincing for spread of the cancer. Other options that are sometimes done, are laparoscopy. Where they put a lighted tube just right into the abdomen and look around the surface of the abdomen to make sure there aren't any deposits on the outside surface of the bowel. Bone scan if there's pain or if the alkaline phosphatase is elevated. And sometimes bronchoscopy is done. Sometimes on the CT scan, they see the esophageal tumor and it's not clear if it actually invades the trachea, which would make them unacceptable. So sometimes a bronchoscope is done to make sure it hasn't gone into the trachea. And also if a patient complains of coughing every time they swallow, then that's inferring that something's getting in the trachea. And then we have to suspect a connection there. This is a very difficult to read slide, I apologize, but once you get into a clinical rotation that's looking at esophageal cancer, all cancer staging is done this way. You figure out involvement of the tumor, involvement of the lymph nodes and whether there are any metastatic sites. You piece them together and it gives you a stage. However, even though that does exist, there's a more practical staging for esophageal cancer, and that really comes into three categories. Number one is the resectable, can surgery be part of the treatment? Number two, is it localized disease but just not resectable? Because maybe the tumor is so big it involves an adjacent organ. Or number three, has it spread throughout the body? And the survival for those patients is very poor. As a matter of fact 5-year survival, even for the best localized disease, is only about 40%. If regional disease occurs, so the lymph nodes are involved, that goes down to 21%. And if there's distant disease, only approximately 4% would be alive in 5 years. So we've talked now about the clinical presentation. So let's go back to our question about the HER2 status. Why should adenocarcinoma of the esophagus be tested for HER2 status? Does it predict a better prognosis? Does it indicate that the tumor will be more sensitive to platinum therapy? Does it mean that there's antibody treatment that can be given? Or does it indicate sensitivity to radiation? The answer is, it means there's an antibody treatment that can be given, and that's the drug Herceptin, or trastuzumab is the generic name for it. So, in summary the take home points for this module are that the most common presenting symptoms are dysphagia and weight loss. Patients with adenocarcinoma should have their tumor tested for HER2 because it may alter treatment, either you'll give the Herceptin or you won't. And also endoscopy, endoscopic ultrasound, CT scan, and PET scan are core elements for the staging of esophageal cancer. So, I thank you very much. And please join me in the following modules that will complete the discussion on esophageal cancer.
