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An Expert’s Perspective: Non-Small-Cell Lung Cancer

Medically Reviewed by Neha Pathak, MD on November 30, 2020

By Joshua Sabari, MD, assistant professor of medicine, thoracic medical oncology, and phase I drug development, NYU Langone Health Perlmutter Cancer Center, as told to Stephanie Watson

Lung cancer used to be a disease that primarily affected smokers. After the surgeon general came out in the 1960s stating that smoking caused cancer, smoking rates declined significantly. In the late 1990s and early 2000s, we saw a significant drop-off in the death rate for lung cancer. We think that it was mostly due to people quitting smoking.

Now I'm diagnosing more and more people who are younger and were never smokers. In fact, a lot of them have never smoked. Many of these people have gene mutations that drive the development of their lung cancer.

One of the key questions is, why are we seeing this increase in lung cancer in never-smokers? We don’t know, but we suspect it may be related to pollution or radon exposure. Most of the areas where we’re seeing these increases are heavily populated industrial areas.

Diagnosing Lung Cancer Early

Classically, we think of lung cancer symptoms such as shortness of breath, cough, and weight loss. But often, those signs and symptoms are not there until the cancer has spread. By the time most people have symptoms, they already have stage IV disease. That’s why screening is so important, especially in people who are heavy smokers. You want to identify the tumor before it spreads so you can do something about it.

For smokers, we clearly have evidence that doing a low-dose CT scan of the chest will reduce the risk of dying from lung cancer. Unfortunately, most people are still diagnosed with stage IV disease. At that stage, the disease is treatable, but not curable. The goal of treatment is to relieve symptoms and hopefully extend the person's life. Thanks to the implementation of lung cancer screening, I'm seeing an increase in the number of people diagnosed with earlier-stage disease with a high cure rate.

But we still have a long way to go. Probably less than 10% of those who are eligible for CT screening actually get the test. I think part of the reason is a lack of awareness. I also think there’s a stigma related to lung cancer. Breast cancer and colon cancer screenings are high because these diseases aren't seen as being caused by something you did. What I tell people is, "The only thing you need to get lung cancer are lungs." We need to erase this idea that lung cancer only happens in smokers.

Learning More About Your Cancer

Every time I meet a new patient, it’s critical to define the stage of their disease. I want to make sure that I have imaging of the person's whole body -- an MRI of their brain, as well as a PET scan of their chest, abdomen, and pelvis to try to understand where the cancer started and where it has spread. After that, the next step is to obtain a tissue biopsy to define the histology, as well as perform molecular testing that can help guide further management and treatment options.

Biomarker testing is critical in people with lung cancer. I need to know if there are any gene alterations, such as EGFR, KRAS, or ALK. These mutations will affect which treatment I choose.

If there are no genetic alterations, the next thing I look at is PDL1 expression (programmed death ligand-1). The way I like to think about PDL1 is as a disguise on the cancer cells. If someone's PDL1 expression is high, their cancer is very well-disguised and their immune system can't recognize and attack it. Cancers with high PDL1 expression respond well to certain immunotherapies. People with low PDL1 expression need a combination of immunotherapy and chemotherapy.

What Treatments Are Right for You?

If somebody has an early-stage cancer, I’m going to refer them to a surgeon. Surgery is a mainstay for early-stage cancers. In stage IV cancer, there’s really no role for surgical therapy, because the cat’s already out of the bag. The cancer has spread.

Five or 10 years ago, we had only one treatment for late-stage cancer -- chemotherapy -- and its success was limited. Chemotherapy kills cancer cells, but unfortunately it can also kill normal cells. So it causes side effects such as fatigue, nausea, vomiting, and weakening of the immune system.

Now we have better treatments for stage IV cancers. There’s targeted therapy, which targets certain proteins or gene mutations that help the cancer cells grow. It’s very important that I understand upfront if someone has a mutation that I can act upon, because it changes their survival time and it changes the therapies that are available to them. There are now seven different genetic alterations for which there are approved therapies. Five years ago, there were only two targeted therapies approved.

There's also immunotherapy, which helps the immune system better recognize and attack the cancer. There has been a lot of excitement over the last 4 to 5 years, with multiple approvals of different immunotherapy drugs. There are cytokines and cancer vaccines that rev up the immune system response. And recently, there has been a lot of work using adoptive T-cell therapies. We're harnessing our own immune cells to try to get them to better recognize the cancer.

Who Can Benefit From a Clinical Trial?

Right now, clinical trials are mostly an option when standard treatments stop working. I think we need to change that. We need to think about what will give someone with lung cancer the best chance of a response, the longest-lasting response, and the best quality of life.

At every stage and with every treatment decision that I make with a patient, I’m always looking at what clinical trials are available. If I see a clinical trial that I think has a better chance of working than the standard therapy that's available, I’m going to recommend it.

How Has Lung Cancer Survival Improved?

The average survival for someone with stage IV lung cancer used to be about a year to 16 months. Now, with the use of targeted drugs, the overall survival can be greater than 3 years for certain people. Treatment with immunotherapy has resulted in people who are alive and thriving at 5 years. We don’t have 10-year data yet, but people are starting to talk about the "C" word -- cure -- for people with stage IV disease who have responded well to immunotherapy.

People with lung cancer are definitely living longer and doing better. I hope in my lifetime that we have the ability to cure stage IV disease.

WebMD Feature

Sources

Joshua Sabari, MD, assistant professor of medicine, thoracic medical oncology, and phase I drug development, NYU Langone Health Perlmutter Cancer Center, New York City.

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