An Introduction to Squamous Cell Lung Cancer

Juhi Kunde, Director of Patient Gateways and Science Marketing
Dr. Paik smiling with the blog title

Lung squamous cell carcinoma (LSCC), also called squamous cell lung cancer, is one of the major subtypes of non-small cell lung cancer (NSCLC). Fifty years ago, LSCC was the most common lung cancer diagnosis. LSCC was considered the classic smoker’s lung cancer, as most patients with LSCC had a history of smoking cigarettes. Today, the incidence of LSCC depends on where you live. In areas with decreasing smoking rates, we’ve also seen a reduction in the number of LSCC diagnoses. Overall, while lung adenocarcinoma is now the most common type of NSCLC in the US, approximately 15-30% of lung cancer patients in the US are diagnosed with LSCC.  

LUNGevity Foundation spoke with Paul K. Paik, MD, medical oncologist and researcher at Memorial Sloan Kettering Cancer Center and a member of LUNGevity’s Scientific Advisory Board, to understand what LSCC is and where we stand with treatment options for this disease.  

LUNGevity Foundation: Why is this type of lung cancer called squamous cell?  

Dr. Paik: LSCC cells have iconic features when seen under a microscope that distinguish them from lung adenocarcinoma cells. Squamous cells are flat cells that look like skin cells under a microscope. These cells are found in the tissues that form the surface of the skin, the digestive tract, and the passages of the respiratory system, including the lungs. These cells can develop key genomic changes that cause them to grow unchecked, forming a tumor.  

LF: LSCC was originally diagnosed based on their appearance under the microscope — is that still the case?  

DP: Yes. Pathologists would study tissue samples under a microscope to identify the histology, or physical characteristics of the cells. This allowed them to know what type of NSCLC a patient had. This process continues today. Now they also use panels of stains and dyes to color tissue samples and determine if the cancer is LSCC. Two proteins, p40 and p63, are important for the diagnosis of squamous cell lung cancer. 

LF: What is the prognosis for patients with LSCC?  

DP: It depends on the stage of the disease.  

Early-stage LSCC is potentially curable through surgery or radiation therapy.  

Metastatic LSCC is a treatable disease but not a curable one. Over the past 15-20 years, we’ve seen overall improvements in the prognosis for patients with all types of NSCLC. Immunotherapy has been an exciting addition to the treatment portfolio for many types of cancer, including NSCLC. There are a handful of LSCC patients who are still on immunotherapy and living for more than five years with the disease.  

LF: Patients often hear the term 'mixed histology.' Can you explain this? 

DP: We’ve known about mixed histologies for a long time. It’s exactly what it sounds like. It’s when you look in a microscope and see cells in a tissue sample with two different sets of histologies, or characteristics. Most commonly in lung cancer, we see a mix of LSCC and lung adenocarcinoma. 

There are two ways this can arise. One way is a called a collision tumor. Two separate tumors — one lung adenocarcinoma and one LSCC — have grown and collided into each other. It’s also possible that although the histology appears mixed under the microscope, further testing shows that the cells are related biologically. This can sometimes happen after treatment, as the tumor develops ways to avoid the drug and continue growing. 

LF: What are the treatment options for LSCC? 

DP: This also depends on the stage of the disease.  

For patients with early-stage LSCC, the treatments are identical to how we treat lung adenocarcinoma. We use surgery and radiation.  

Treatment options for patients with metastatic LSCC differ considerably. The current standard of care is to try immunotherapy by itself or chemotherapy with immunotherapy. After that, we’re left with standard chemotherapy treatments. I wish we had more treatments to offer patients.  

LF: Are targeted therapies an option?  

DP: We have seen an explosion in targeted therapies to treat lung adenocarcinoma, but that hasn’t translated to patients with LSCC. Only about 5% of patients with LSCC will be eligible (i.e., have the appropriate genomic alteration) for an existing targeted therapy. Although most LSCC patients won’t be eligible, we still recommend biomarker testing so that those patients who are eligible can consider targeted therapy.  

LF: Are new clinical trials in the works? 

DP: There are some clinical trials but not enough. We have been trying to better understand the biology of LSCC because we’ve learned that what worked for lung adenocarcinoma is unlikely to work for LSCC. 

About 10 years ago, we were very optimistic in our approach to developing targeted therapies for LSCC, but it didn’t work out the way we expected. Now we are trying other approaches to gain a deeper understanding of the biology of LSCC to develop effective treatments. We are treading carefully and setting a high bar for starting a clinical trial. This means fewer trials, but it also means better results for patients.  

LF: Do the demographics of LSCC patients matter? 

DP: I think they do, and I think that patients and their families will agree with this. There are biological differences and patient characteristic differences between lung adenocarcinoma and LSCC. The typical patient with LSCC is in their 70s or 80s, often with a history of tobacco exposure. These patients are older, more frail, and can have other health issues, such as heart disease or lung disease, which aren’t as frequent in patients with lung adenocarcinoma. When we treat patients with LSCC we have to be mindful of quality-of-life and functional issues and really understand what we are trying to achieve for them. 

LF: How can patient advocacy organizations, like LUNGevity, make an impact for families dealing with a LSCC diagnosis? 

DP: For anyone dealing with lung cancer, an LSCC diagnosis is an even darker space because it is not as successfully treated as lung adenocarcinoma. LUNGevity is a light in the dark for these patients and their loved ones by offering crucial support and information. It’s so important to help guide patients through this and to help them figure out what they need. Sometimes, it’s just about being there with them during a truly difficult time.   

LF: Why did you choose to study LSCC and work in this field?  

DP: On a professional level, when I joined Memorial Sloan Kettering Cancer Center, we didn’t have anyone focused on LSCC. We were at the cusp of the explosion of targeted therapies for lung adenocarcinoma, so I wanted to translate those findings to LSCC.   

On a personal level, as physicians, we love all our patients but can have a fondness for different populations. I gravitate toward elderly patients — I appreciate their history, wisdom, vulnerabilities, and the specialized care they require.  

We see patients every two or three weeks, so we get to know them and their families as much as possible. Some of the relationships can get deep. They understand that we are trying to take care of them as best we can. The remarkable thing is that even in the middle of cancer treatment, patients can still be shining lights, caring just as much for me and my team as we care about them.  

It’s a wonderful testimony to the human experience. 

LF: Is there anything you’d like to add?  

DP: I just really want to emphasize that the research goes on. We’ve had some setbacks, but we aren’t giving up. There are still researchers doggedly trying to get answers for how to treat this disease. We are trying to break through the ceiling. The encouraging thing is that we have seen the ceiling crumble for patients with lung adenocarcinoma, so we have set that as a realistic, attainable goal to achieve for patients with LSCC.