Aggressive Nature of Extensive-Stage Small Cell Lung Cancer

Kathryn Gold, MD: You’ve both touched already on how aggressive this is, so talk about how that factors into your initial work-up and treatment. Historically, how has this patient population been treated? What were their treatment options in the past?

Taofeek K. Owonikoko, MD, PhD: We know that small cell lung cancer is aggressive and fast growing, and for that reason, we always want to get the patient on treatment as soon as possible. Whether it is limited stage or extensive stage, there’s really not enough time to waste in working the patient up. This has been the bane of the field, that we tend to establish diagnosis based on whatever sample we can get, whether a cytology sample or fine needle aspiration biopsies, and that we don’t end up with a significant amount of tissue. This is not a time where we go back and say we want to get genomic information or any of that form of pathologic authorization. Just a basic diagnosis of small cell has been sufficient for us to move forward with treatment.

Going back in time, small cell used to be looked at as a very poor prognostic situation for patients, where a lot of patients didn’t get any treatment at all. We looked at the SEER [Surveillance, Epidemiology, and End Results program] database recently, going back about 3 decades, and we still see that, even in the United States, close to 30% to 40% of patients don’t get treatment for their diagnosis of small cell—in part because of the historical experience of nothing worked, so why put a patient through something that’s not going to help them? I think if we look back to today, which has been influenced by the last 2 decades with the use of platinum-based doublet chemotherapy, we know that this approach has had meaningful impact on patients’ quality of life in terms of reducing symptoms. For patients who do respond—about 50% to 60% of patients will respond to platinum-based doublet chemotherapy— it does have an impact on survival as well.

We’ve all come to accept platinum-based doublet chemotherapy as the platform on which we build whatever strategy we want to treat the patient. For those with limited stage, the addition of radiation and chemotherapy together using platinum doublet has been shown to be safe, and that resulted in a better outcome than radiation alone or chemotherapy alone. More recently, the addition of immunotherapy to that platform is helping to advance and improve the outcome for patients with extensive-stage disease.

In terms of reviewing treatment options with patients and the urgency of getting on with the treatment, I think we have to let them know we have very limited options, but what we have is most likely going to work for the majority of the patients to start with. In the frontline setting, 60% to 70% of patients will respond to the treatment. Where we are failing is when the disease stops responding and relapses. We do not have very effective salvage therapy, and that is what eventually, unfortunately, leads to the demise of the patient.

In setting the goals, it’s usually a matter of being very open and candid with the patients, that if we don’t do anything, we know what’s going to happen. The median survival for untreated patients is only about 3 to 4 months, and that has not changed over the last 3 decades. That’s why there’s been an improvement in supportive care; if we don’t treat small cell at all, patients don’t live much longer from the time of diagnosis. If you do treat, that is where the discussion comes for the patient in terms of what is important to them. These are well-established treatment options; we know their adverse effect profile, and we know how to manage them, whether with dose reduction or growth factor support. Once we’ve told the patient what to expect, then it becomes a matter of them balancing that against what their own expectations are. A lot of patients, when they come in, they’ve already heard so much about small cell that they come in with the idea that there’s really nothing you can do to help them. It’s more a matter of helping them see the potential benefit of going on with the treatment.

I think that when compared to non–small cell lung cancer, especially where we’re talking of the early stages of the disease, we tend to talk more about a cure. When the patient goes to surgery, they get adjuvant treatment, even for locally advanced where they get chemoradiation and then get consolidation with immunotherapy, where we put cure front and center. Unfortunately, that has not been the case with small cell lung cancer, especially the extensive-stage disease. The reason for that is even when a patient responds, we know that the relapse rate is very high—almost 80%—and when that happens, the outcome is not as great. You have to situate that reality against the goals for the patient, and that is where you have a joint discussion to ask what is most important: Quality of life, quantity of life, or both? Then, we try to marry those 2 to craft the most tolerable intervention that we can offer the patient to help improve the outcome.

Kathryn Gold, MD What advice do you have for our community physician colleagues when they’re facing a patient recently diagnosed with extensive-stage small cell?

Konstantinos Leventakos, MD, PhD: I think that Taofeek explained very well why it is so urgent to treat the patient. First, we have to make sure that all physicians believe that the treatment is important in small cell because we have such good outcomes. It’s very sad when we hear about cases of someone who was diagnosed, and because of the description of the bad prognosis, they didn’t do anything. The second thing: We see in our practice that even very sick patients, while symptomatic, may respond; this number that Taofeek discussed, 60% to 80%, can get better. In oncology, we have this paradigm of not treating patients with bad performance status. I can tell you that with small cell lung cancer, we may all feel a little more bold to treat patients who are symptomatic due to their disease, even though they have small cell lung cancer, because we know that the response rate is very good.

I don’t know why the symptomatic small cell lung cancer, in my experience, is usually the Friday afternoon patient. It’s always that the urgent thing will happen on Friday afternoon, especially before a long weekend, but this is a case in which we do not wait for treatment. We admit the patient and institute the treatment appropriately because it is urgent. As we discussed before, the doubling time of this disease is very strong, so in cases with liver disease, you may see liver function enzymes rising so high that if you leave treatment for Monday or for the next week, you would not have an appropriately healthy liver to treat. I have seen a couple of cases, and my previous experience is that my patients became so thrombocytopenic while waiting for treatment, which caused a big battle for them. For us, we teach our fellows that this is an oncologic emergency and that we should start treatment right away. The 2 things we know are that treatment improves survival and symptoms, since we are talking about targeted treatment here, and how urgent it is.

Transcript Edited for Clarity