So I'm Greg Kalemkerian, Professor of Medicine at the University of Michigan. And this lecture is going to cover the treatment, and overview, and surveillance of patients with lung cancer. The objectives of this talk are to review the stage-specific goals of care, and the treatment options for patients with non-small cell and small cell lung cancer, and to review the recommended surveillance after definitive treatment of patients with lung cancer. The care of patients with lung cancer involves a multidisciplinary team of providers, frequently involving radiologists, pathologists, pulmonologists, medical oncologists, radiation oncologists, thoracic surgeons. Although there are guidelines for the management of patients with lung cancer, all decision making must be individualized based on the patient's performance status, comorbidities, and their own goals of care. The appropriate diagnostic in staging procedures are required to allow for optimal therapeutic decision making. So we'll start with a pre-lecture question. In which of the following patient scenarios is treatment given with palliative intent? An 81-year-old with stage IIA NSCLC undergoing surgery. A 42-year-old woman with an EGFR-mutant stage IV NSCLC on erlotinib. 66-year-old woman with limited-stage SCLC receiving chemoradiotherapy. Or a 75-year-old man with stage IIIB NSCLC on chemoradiotherapy. And we'll come back to this question at the end of the lecture and talk about the answer. So we'll start off non-small cell lung cancer just giving you an overview of the treatment by stage. Of note, all of these stages and treatment strategies are taken into more depth in other lectures within this course, which I think you should be referred to if you have an interest in knowing more. So for stages I and II non-small cell lung cancer, that's disease either confined to a nodule within the lung, or a nodule in the lung including local lymph nodes within the hilum of the lung surgery is the treatment of choice. And the goal of treatment is to cure the patient of the disease. The primary surgical procedures are lobectomy, or if necessary, a pneumonectomy. And we know that that type of procedure is better for long term outcomes than lesser resection, such as wedge or segment resection. The surgeon needs to sample the mediastinal lymph nodes at the time of surgery in order to give optimal staging information, as well as to guide us as far as whether the patient needs any further therapy, such as adjuvant chemotherapy. We know that post-operative or adjuvant chemotherapy does improve survival in people with completely resected stage II or III non small cell lung cancer. Overall, the five year survival rates, which essentially is a curate in this disease, for state I disease is 60 to 70%, and stage II disease is 40 to 50%. You'll notice that these numbers are not as high was we would like to see for early stage disease, due to the general aggressiveness and variability of spread of lung cancer compared to some other common tumors, such as breast, colon, or prostate, where the stage specific survivals are significantly higher. For people at stage I or II disease, they're are a number of contraindications to primary surgery. If the stage is higher due to hematogenous metastases, or malignant pleural or pericardial effusions, that would be stage IV disease. If there's biopsy-proven mediastinal lymph nodes, that would be stage III disease. Or invasion of vital structures, such as the spine, or the heart, or the esophagusm, that also would be stage III disease. If people are unable to tolerate surgery, then we call that medically inoperable. And in that situation, the primary treatment would be definitive radiotherapy, or stereotactic body radiation therapy, or radiofrequency ablation. Again, the goal of these interventions is to achieve cure. For people at stage III non-small cell lung cancer, generally meaning that we have spread to the mediastinum and lymph nodes or we have invasion of the tumor into local structures, the goal is still cure. Most people are treated with concurrent chemotherapy and definitive radiation therapy. Though, some people could be considered for chemo with or without radiation, followed by surgery. Immunotherapy after chemoradiation may improve outcomes, and we'll talk a little bit more about that. And in this situation, with multimodality therapy, chemoradition plus/minus surgery, a five year survivor rate is generally around 15 to 25%. For people with stage IV non small cell lung cancer, it is a little bit of a different story. Here, the goal is to improve quality of life and quantity of life. This is not generally considered a curable disease. Systemic therapy is the standard treatment, though radiation and surgery can be used for palliation if necessary. Molecular therapy for tumors that harbor driver mutations, such as EGFR, ALK, ROS1, or BRAF abnormalities, leads to a very high response rate of 60 to 70% and can be very beneficial for those patients. Chemotherapy only benefits patients who are fit, patients with a good performance status of zero to one, and perhaps two. Response rates with chemotherapy are lower, about 20% to 30%. Immunotherapy has a clear clinical benefit, and we have a lecture later in the series on the immunotherapy for non-small cell lung cancer. It talks about the scenarios where that is useful. All patients undergoing treatment for stage IV disease need to understand the potential benefits and the potential risks in order for them to make good decisions about how aggressive they wish to be with their care. The 2-year survival rates for stage four non-small-cell lung cancer are about 20%. And 5-year survival rates are generally less than 5%. Though this is an evolving field now with the molecularly targeted therapies and immunotherapies, we are seeing more longer term survivors, though cure remains elusive. In general, treatment by stages, is that for stage I patients, surgery is generally recommended. A few of these people with larger stage IB tumors maybe eligible for adjuvant chemotherapy. But most of these patients, adjuvant chemotherapy has not been shown to be beneficial. For people with stage II disease, surgery with adjuvant chemotherapy afterwards is the standard of care. To the majority of people with stage III disease, the treatment is chemoradiation in a definitive manner, perhaps with consolidation, either chemotherapy or immunotherapy. Surgery can be used for some small subset of people with stage three IIIA disease who the surgeon thinks they can get a good surgical margin on. For people at stage IV disease, when good performance status, we have a number of options now with chemotherapy, immunotherapy, or targeted therapy. And with that, we are seeing some longer term survivors. Though, the overall 5-year survival rate remains quite low. For people with poor performance status in stage IV disease, generally the best treatment is palliative care, unless they happen to have a particular driver mutation, in which potential for response and improvement in their function is higher. Overall, the 5-year survival rate for people with non small cell lung cancer including all stages is only about 18%. And this is relatively low, because the majority of people present with stage III or IV disease. For small cell lung cancer, this is a different disease and is treated somewhat differently. Small cell is one of the few diseases left where we don't generally use the TNM classification for staging. Though, it can be utilized and does correlate with prognosis, we generally utilize limited versus extensive stage. Limited stage is when the disease is confined to one hemithorax, with a mass in the lung and lymph nodes. And the goal here is cure. This is similar to stage III, non small cell lung cancer, where concurrent chemotherapy and early thoracic radiation therapy is the standard of care. With high response rates, 80 to 90% of people will have good shrinkage and improvement in their symptoms. We do use prophylactic cranial irradiation, because it does improve survival, knowing that without radiation, about 60% of people will develop brain metastases at some point in their disease. And here, the 5-year survival rate, or the cure rate at this point, would be about 20 to 25%. So we are curing some people, though clearly not as high as we would like to see. For people with extensive stage small cell lung cancer, the goal is palliation. This is essentially stage IV small cell lung cancer. General treatment is combination chemotherapy, which does improve and prolong survival. There are also high response rates, so most people do feel better with treatment and have significant improvement in their symptoms. However, it is not a long lasting duration of response. Thoracic radiation can be used after chemotherapy and may improve survival by decreasing intrathoracic complications. For management of the brain, we can either do close MRI surveillance for brain metastases, and then treat them sooner, when they're still in an asymptomatic stage, or one can do prophylactic cranial radiation, or PCI. Though, now, we are favoring MRI surveillance as a strategy. The 5-year survival here is very low, and 5-year survivors are rare. Overall for small cell lung cancer, the 5-year survival rate is approximately 5%, because the majority of people, about 70%, present with extensive stage disease. For now, we'll talk about how we do surveillance for people who have been treated for definitive therapy, meaning potentially curative therapy with either non small cell or small cell lung cancer. There is actually very little data to drive what we do in this situation, as there are very few studies of surveillance and what the benefits are. For the first 2 or 3 years, recurrence is the biggest risk. And then beyond that, the biggest risk becomes the development of a second primary cancer. Vast majority of these people are smokers, and whatever caused them to get their first cancer, tobacco carcinogens, can cause them to get a second cancer. So the second primary rate is quite high, and screening scans can improve survival. So for early stage non small cell lung cancer, we recommend that people undergo clinical evaluations and CT scans of the chest every 6 to 12 months for a couple of years. We can do that more frequently in people at stage III disease who have a residual abnormality where the risk of recurrence is higher. After two years, then doing low-dose screening CT scans of the chest is good annual follow up. All patients should be encouraged to stop smoking, because people who stop smoking do do better and have lower second primary rates. PET scans and MRIs of the brain do not have a role in the follow up of people with non small cell lung cancer. For people at limited stage small cell lung cancer treated with curative intent, again, clinical evaluation and CT scan done a little more frequently every 3 to 4 months for a couple of years and then every 6 months until to the fifth year. And beyond that, you've pretty much are cured if small cell hasn't recurred. And at that point, you can go into a screening low dose CT scan on an annual basis. All new lung nodules that develop in people who've had small cell should be treated as a second primary. And surgical evaluation should be considered for these individuals. Smoking cessation, again, is necessary in order to try and improve outcomes. And PET scan is not indicated in the surveillance of people with small cell or non-small cell lung cancer. So taking care of people with lung cancer is a multidisciplinary prospect. That includes input from many people on many different teams, as you see listed here. The newest addition to this list is the molecular diagnostics labs that give us vital information about how best to manage, particularly our advance non-small cell lung cancer patients. Integration of palliative care early in the course of the disease can improve overall survival and outcomes. So we'll come back to our lecture question talking about which of the scenarios is treatment given with palliative intent. For a, c and d, all stage II or III disease, the treatment is given with curative intent, regardless of the potential age of the patient. Though, we do recommend that patients be fit in order to undergo these therapies. Even though she was the youngest person on the list, the 42-year-old with an EGFR-mutant non-small lung cancer stage IV is being treated with palliative intent with erlotinib. Though, it has a very high response rate, the disease will eventually recur. And we are not expecting the woman to be cured. So our take home points for this lecture, that early-stage non-small cell is curable with surgery. Adjuvant chemotherapy improves the survival of people with pathologic stage II and III disease. Stage III non-small cell and limited stage small cell are both potentially curable with chemotherapy and radiation. And for the people with stage IV non small cell or extensive stage small cell the goal is to palliate symptoms and improve survival. However, cure is elusive and chemotherapy, targeted therapy, or immunotherapy does prolong survival and improve the quality-of-life. Thank you
