Dr Jason Porter Provides an Overview of the Current Treatment Landscape for Small Cell Lung Cancer

In this interview with The American Journal of Managed Care^® (AJMC^®), Jason Porter, MD, medical oncologist and hematologist, West Cancer Center and Research Institute, Memphis, Tennessee, defines small cell lung cancer and the risk factors associated with it. With smoking as a major risk factor, diagnosis for small cell lung cancer is rare compared with non–small cell lung cancer and varies widely by region in the United States.

Porter notes the challenge of developing biomarkers for small cell lung cancer making it difficult to develop targeted therapies for patients. Life expectancy is also an obstacle in finding patients to participate in research and clinical trials.

AJMC: What is small cell lung cancer? Can you just tell me a little bit about its pathophysiology and how it presents clinically?

Porter: Pretty much small cell lung cancer is exactly what it sounds like. We look at the cancer under a microscope. So, a patient has a biopsy, we look at it under the microscope, and it's pretty much a description of what we see, compared to non–small cell where the cells are bigger. These cells are just small. We usually call them small round blue cell or oat cell tumors. So, it's just small cells, literally, when we look under the microscope. But, unfortunately, the small cell histology, there's also some prognostic implications for that, which means that it's usually going to be a more aggressive disease with a poorer outcome.

AJMC: What are some of those risk factors for developing small cell lung cancer?

Porter: I would just go ahead and say 95% of patients who have small cell lung cancers are going to be smokers. Smoking is a huge risk factor. If I see a small cell lung cancer that's not a lung origin, I usually question a diagnosis. Most of the time, it's a smoker and it's a lung origin, but there are other small cell variants like from the prostate and from the gastrointestinal tract where we may see that the small cell was not necessarily related to smoking. But, usually smoking is a huge risk factor. There are some other environmental and occupational exposures too that we can associate with small cell lung cancer like exposure to certain gases. My dad was a welder and he had small cell lung cancer and this was one of the occupational risks that he had.

AJMC: How common is small cell lung cancer? What is its incidence and prevalence in the United States, and to go a step further, is it stemming primarily from smoking? Has the incidence and prevalence changed in the United States as a result of different trends in smoking or tobacco use in the United States?

Porter: Small cell lung cancer compared to non–small cell lung cancer is really rare, and it does vary by region of the United States for sure. When we look at the United States, in the south and the southeast there is a higher prevalence of smoking. My patient demographic in the south is different from what they see in the northeast and west coast. I will see probably about 20 to 25% of my patients with small cell lung cancer, where the national incidence is more like 15%. I use the 85/15 rule. I'll say 85% non–small cell and 15% small cell. It usually is about 87% and 13%. Just for simplicity, I'll say at 85/15, so about 15% of small cell lung cancer in the US. In certain regions, it's higher for sure, and we will see a trend towards lower incidence in other areas where smoking is now less common. The other thing we have to remember in those regions where smoking is less common, those patients will develop mutation-driven lung cancer or oncogene-driven lung cancers like EGFR mutant lung cancer. As a complication of EGFR mutation, some of those patients will have a kind of transition from their non-small cell to a small cell variant. They will still have some incidents of small cell lung cancer even when they're never smokers.

AJMC: How do these patients who are diagnosed with small cell lung cancer interact with the US health care system? Are these patients being hospitalized and that's how they learn of their diagnosis? What are some of the complications that are associated with small cell lung cancer?

Porter: Probably about 35 to 40% of patients with small cell lung cancer get diagnosed in the hospital. Unfortunately, it's a rapidly growing tumor. For that reason, patients may not have symptoms for the initial part of their disease process and then suddenly become very symptomatic. The symptomatic presentation may be with the actual disease itself causing metastases to the brain or to the vertebral column where they have neurologic deficit or devastation. Other presentations may be with peritoneal plastic syndromes, such as SIADH or the syndrome of inappropriate antidiuretic hormone. In this case, they come in with low sodium and they may have seizures at presentation or just altered mental status. There's Lambert-Eaton type syndromes where they just have weakness. Maybe there is an antibody that's developed against nerve endings or synapses, and then they just have weakness as a presentation. It can be a varied presentation. A lot of times these patients will have a small actual lung tumor with large lymph nodes in the mediastinum and chest and then metastatic disease to other places. They may not have a lot of call for shortness of breath, but because of the mediastinal lymph nodes they may have trouble breathing or even trouble swallowing. We see varied presentations and a disease can really go anywhere. Where it lands really determines how the patients present, and in places like the central nervous system they may present with hospitalization and neurologic devastation.

AJMC: In your experience, what have been some of the greatest challenges when it comes to researching and treating small cell lung cancer given its poor prognosis?

Porter: One of the problems is when we biopsy small cell lung cancer we get those small round blue cells that I was telling you about, but also there is a lot of tissue necrosis in the biopsy samples. In non-small cell lung cancer we've developed a lot of biomarkers, and we can target those biomarkers specifically. That depends on those biopsying, checking DNA, checking RNA, figuring out molecularly, and what's going on. When you have a necrotic biopsy sample you don't get good DNA, you don't get good RNA, and the proteins aren't easy to assess. Even cell surface proteins on those small blue cells are hard to assess so it is hard to develop in biomarkers and to subtype small cell. Because of that, it is hard to make targeted therapies against small cell lung cancer in the fashion that we've done in non-small cell. It is very challenging. The other thing is that these patients often don't live very long, and so follow-up may be limited. The follow-up and the ability to go on to second and third-line therapies may also be limited. If we want to develop a new second-line therapy, what percentage of those patients are going to be clinically able or stable enough to go on to a research trial? There is also the limitation of actual patients or subjects for a second line and beyond clinical trials.