Living with Early-Stage Lung Cancer
Resources, expertise, and survivor support to help in the months & years after diagnosis

“What would you do if someone in your family got cancer?” We put that question to some of the most renowned cancer doctors in the country. National Cancer Institute Chief of Surgery Dr. Steven Rosenberg recommends seeking out multiple professional opinions to confirm a diagnosis and figure out the options.

Patients should not feel guilty about doing this — as many doctors will recommend and even encourage it.

As we highlight in several areas of SurvivorNet, highly respected doctors sometimes disagree on the right course of treatment, and advances in genetics and immunotherapy are creating new options.

Also, in some instances the specific course of treatment is not clear cut. That’s even more reason why understanding the potential approaches to your disease is crucial.

“What the task becomes is having the courage to live in the face of uncertainty, realizing that you cannot necessarily control the uncertainty in life … the suffering that occurs, challenges both good and bad,” Dr. Breitbart said.

“You may not be able to control those but you have control over how you choose to respond.”

Those struggling with feelings of loss of control that cancer can bring can seek help in many different ways — from traditional therapy to support groups for people living with cancer to making lifestyle adjustments to help cope with stress.

Non-small cell lung cancer

There are three general subtypes of NSCLC: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma.

Adenocarcinoma, which accounts for about 40% of all NSCLC cases, is the single most common subtype of lung cancer. It is typically found along the outer perimeter of the lungs and tends to progress at a slower rate compared to other lung cancer types.

Squamous cell carcinoma typically manifests in the central portion of the lungs. Due to this central localization, symptoms are often exhibited earlier rather than later compared to other types of NSCLC.

Large cell carcinoma is the rarest main classification and accounts for about only 15% of cases.

Other less common subtypes of NSCLC include the following: carcinoid tumor, salivary gland carcinoma, pleomorphic, and carcinomas that remain unclassified.

Not everybody can get to a designated comprehensive cancer center, but the data is clear that these centers are extremely helpful, especially when your disease is complex.

There are plenty of excellent physicians who are not at comprehensive cancer centers. That being said, when you are looking into care, you should be asking, “Am I getting doctors with different specialties like medical oncology, radiation oncology, surgery, pathology and radiology?”

The really important thing is that you’ve got the right people and that they know the latest science.

That can happen away from a major cancer center, or it can happen at one. In order to get the best guidance, you will need to sift through the options in your area — and consider if you need to travel to a larger medical center.

Staging can also be used to predict how cancer may progress and respond to various therapies.

“The stage is really the essence of how you determine what the correct treatment options are,” said Dr. Joseph Friedberg, chief of thoracic surgery at Temple University Health System.

Stage 1 and 2 lung cancer is considered “early-stage” disease, while stages 3 and 4 indicate that cancer has spread further into the body — and the treatment approaches will vary.

The lung cancer staging process begins once a lung cancer diagnosis is confirmed. Beyond an initial computed tomography (CT or CAT) scan, your doctor will likely order a brain magnetic resonance imaging (MRI) scan to see if there is any evidence of disease in the brain, a common area of metastasis, and a positron emission tomography (PET) scan to see whether the lung cancer has metastasized to your bones, adrenal glands, and/or liver.

TNM Classification of Tumors
The American Joint Committee on Cancer (AJCC) TNM classification system is the lung cancer staging system utilized in NSCLC. The stage of cancer is dependent on a combination of these three factors listed below.

• Tumor (T) refers to the size/shape and extent of the primary tumor’s growth, as well as its specific location. This category can be assigned a letter or number, which correlates directly to the primary tumor’s size/size and location.
• Nodes (N) refers to the involvement of lymph nodes. This category helps to determine whether the cancer has advanced to the lymphatic system.
• Metastasis (M) refers to the spread of cancer to any other organ(s).

If you want to learn more about lung cancer staging, make sure to check out SurvivorNet’s break-down of the process.

The following are the most common mutations that have FDA-approved targeted treatment options already:

• EGFR
• ALK
• ROS1
• BRAF
• KRAS
• MET
• HER2
• RET
• NTRK

There are various types of EGFR mutations. Think of mutations like typos in DNA; there can be missing or added words (deletions or insertions), or the DNA can be misspelled at certain points (point mutations).

Your test results might show an EGFR 19 deletion or an EGFR L858R point mutation, which are the most common types we know of. This information helps doctors pinpoint where the mistake is in the DNA. EGFR 19 deletions and EGFR L858R point mutations are usually treated the same way.

In lung cancer testing for EGFR mutations, there are some rare types that need different treatment than the more common ones. A significant example in lung cancer is EGFR exon 20 insertions. This type of EGFR mutation doesn’t respond to the usual treatment for EGFR-positive lung cancer, which is called tyrosine kinase inhibitors (TKIs).

Is EGFR-mutated lung cancer common?

The rate of EGFR-mutated lung cancer can vary depending on the population, but it typically comprises around 15% of North American and European patients. It can be almost 50% in Asian populations.

This mutation is more common in the following lung cancer patients:

• Those with the adenocarcinoma subtype of non-small cell lung cancer
• Those with minimal to no smoking history
• Women
• Young adults
• People of Asian or East Asian heritage

This means that many lung cancer patients won’t have to deal with the harmful effects of chemotherapy, like side effects and toxicity, because they’ll receive treatments that are finely tuned to their individual needs.

“I could not be more excited about targeted therapy. We’re discovering more and more targets and more known targets are becoming actionable,” Dr. Jared Weiss, a medical oncologist specializing in lung and head and neck cancer at UNC Lineberger Comprehensive Cancer Center, tells SurvivorNet.

In addition, Dr. Weiss says, he tests PD-L1 and performs what is called “liquid biopsy,” which is a blood test that looks for dead cancer cells circulating in your bloodstream. This is a newer technology but is also very important to do in tandem, according to Dr. Weiss.

“One, it’s another shot on goal for getting an answer, right? If the tissue is inadequate, if there isn’t enough left, if there’s some quality problem with it, this is a second way to get at it. And number two, it’s faster. The good testing (NGS tumor-based testing) can take three or four weeks.  And no one wants to wait three or four weeks. If the blood gets you an answer, it can get you an answer within days to a week.”

Different molecular tests will be employed depending on the stage and type of lung cancer, as well as response to prior therapies.

When discussing lung cancer there are two main types, small cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is where a majority of molecular testing is performed. In early and locally advanced NSCLC, a workup is performed with history and physical exam, lab tests, imaging, and biopsy.

Additional molecular testing performed on the biopsy typically includes PD-L1 testing and genetic testing for common mutations known to cause lung cancer such as EGFR, KRAS, and ALK.

In metastatic (advanced) disease, next generation sequencing is also performed — and it looks a multitude of potential DNA mutations that could be targeted by systemic therapy. Sometimes multiple molecular tests can be run in patients with metastatic disease to test for development of new mutations when the disease has progressed or stopped responding to the current systemic therapy. In this case, liquid biopsy can be used to reduce morbidity of repeat tissue biopsy.

“It’s absolutely clear that every stage four patient with non-squamous, non-small cell lung cancer should have comprehensive and sensitive molecular testing done early, and with  PD-L1,” Dr. Weiss explains.

PD-L1 refers to an expression of a protein on cancer’s surface that it may be using to avoid detection by the immune system.

NGS has become the standard of care in lung cancer treatment. You may be a candidate for NGS testing if you have been diagnosed with:

• Advanced stage adenocarcinoma of the lung
• Advanced stage squamous cell cancer of the lung
• Advanced stage adenosquamous cancer of the lung
• In early stage lung cancer, you should discuss if NGS testing could be right for you, too.

A tissue biopsy is the preferred method but when molecular profiling is performed repeatedly, a tissue biopsy can become inconvenient. Liquid biopsy addresses some of the shortcomings of repeated tissue biopsy and is quickly shaping the future of cancer therapy.

“Liquid biopsy can be analyzed to look for changes in the genetic material, mutations, and sometimes we combine tissue and liquid biopsies to get the most comprehensive information about how your cancer changes over time,” says Dr. Valsamo Anagnostou, a thoracic oncologist, and leader of the Johns Hopkins Molecular Tumor Board at The Sidney Kimmel Comprehensive Cancer Center.

How Does Liquid Biopsy Work?

“Molecular profiling of blood also known as liquid biopsies leverages the fact that tumors routinely shed free DNA in the bloodstream. That happens when the cancer cells die and release their contents,” says Dr. Anagnostou.

Cancer cells require a blood supply to grow and gather nutrients. Cancer cells can travel in the bloodstream in an attempt to spread and can also die for a variety of reasons including cancer therapies, a person’s immune system attacking them, or even the cancer cells themselves mutating and changing to the point where they cannot sustain life.

When cancer cells die, pieces of them are released into the bloodstream, namely ctDNA.

According to Dr. Anagnostou, “These very small pieces of DNA can be ‘biopsied’ using a liquid biopsy compared to traditional tissue biopsy.” DNA is the genetic code that the cell uses as a blueprint to function. Cancer DNA is unique from the DNA of our normal cells because of specific mutations or changes in its code.

Many cancers such as colon, lung, breast, and prostate cancer all have unique mutations or alterations that can occur in the DNA, which provide valuable information including targetable mutations. Once identified, these mutations can be treated with specific medications that target these changes in the cancer DNA.

Am I a Good Candidate for Liquid Biopsy?

Typically, when diagnosed with cancer, an initial tissue biopsy and molecular testing results are used to inform treatment options and evaluate if you are a candidate for more targeted cancer therapies. Following the initial diagnosis of cancer, through treatment, and in the time following treatment, various DNA mutations can arise which can be tested. And according to Dr. Anagnostou, “That provides new information in a dynamic manner that allows for identification of new mutations that may be emerging during therapy, matching your tumor and you as an individual and a patient with the appropriate and more effective targeted therapy.”

Currently, liquid biopsy is most often performed when you have metastatic cancer and current therapies are not working. Metastatic cancer is when the disease has spread from the original site to other parts of the body. The decision for repeat biopsy and whether you need a tissue biopsy or liquid biopsy is a decision that you should discuss with your healthcare team.

Although liquid biopsy is most often used in combination with tissue biopsy to inform ongoing cancer therapies for a known diagnosis of cancer, new advances are making it possible to “capture minimal residual disease for individuals with early-stage cancer, or even be used for early cancer detection and an interception,” explained Dr. Anagnostou.

Essentially, the way cancer is typically diagnosed is when patients have symptoms, or a large enough volume of disease is seen on imaging or during evaluation by a healthcare provider.

Because liquid biopsy is testing small pieces of cancer (ctDNA) or circulating tumor cells (CTCs) in the blood there is the possibility to detect cancer at its earliest stages or at first signs of recurrence which can potentially improve outcomes. Early detection and diagnosis of cancer with liquid biopsy is an ongoing field of investigation and more data is needed to better understand how to use a liquid biopsy in this manner.

Limitations of Liquid Biopsy and False Negatives

Currently, liquid biopsy is not a standard method for early diagnosis or detection of cancer.

Liquid biopsy looks for very small pieces of tumor DNA and circulating cells in the blood which can be difficult to detect, as opposed to tissue biopsy which often takes a piece of a known tumor or mass.

Because liquid biopsies are testing for the evidence or traces of a tumor with these small pieces of DNA and circulating cells in the blood and not testing a tumor itself, there is a higher chance the liquid biopsy misses the diagnosis and has a false negative result.

What Liquid Biopsy is Available and What Can I Expect?

Several types of liquid biopsies have been approved by the U.S. Food and Drug Administration (FDA), including:

• Labcorp Plasma Focus is used for non-small cell lung cancer (NSCLC), colorectal, breast, esophageal, gastric, gastroesophageal junction carcinomas and melanoma through ctDNA. Results can come back in 7-10 days.
• Cobas EGFR Mutation Test v2 is used in non-small cell lung cancer (NSCLC) and detects a mutation in the EGFR gene through ctDNA which can help determine targeted treatment.
• Guardant 360 CDx is used in non-small cell lung cancer (NSCLC) and can help detect specific mutations in ctDNA to help guide treatment.
• FoundationOne Liquid CDx uses ctDNA to detect mutations in prostate, NSCLC, ovarian, and breast cancer to better tailor therapy.
  When undergoing a liquid biopsy, a healthcare provider will take a sample of your blood, much like a complete blood count, which will be sent to an additional laboratory for testing. This is much less invasive and time-intensive than other biopsy procedures.

When undergoing a liquid biopsy, a healthcare provider will take a sample of your blood, much like a complete blood count, which will be sent to an additional laboratory for testing. This is much less invasive and time-intensive than other biopsy procedures.

Stage 1 lung cancer means that your cancer is only in your lungs and has not started to spread to your lymph nodes or beyond your lungs to other organs throughout your body.

When you are diagnosed with lung cancer your medical team will conduct a series of tests to determine what stage the cancer is and how to best treat your lung cancer. The process of conducting additional tests and imaging studies is called lung cancer staging and is the backbone of what informs treatment decisions.

For individuals with stage 1 cancer who can’t have surgery because of underlying health conditions, the current standard of care is stereotactic body radiation therapy (SBRT), which directs extremely high doses of radiation to the tumor and minimizes the dose to nearby structures, reducing the risk of damage to healthy organs.

This type of treatment is becoming much more common and is being used more frequently even in patients who are healthy enough for surgery but who choose to have SBRT as a non-invasive option after an informed discussion with their treating teams.

Although surgery remains the current gold standard for treating stage 1 lung cancer, there are currently trials comparing these two approaches (surgery and SBRT) head-to-head to determine which is best for patients.

For now, surgery remains the best option, but if you or a loved one is not able to have surgery, SBRT is an excellent alternative with tumor control rates approaching those seen with surgical resection in some studies.

Stage 2 lung cancer is considered a localized disease and is primarily treated with surgery.

Dr. Geoffrey Oxnard tells Survivornet: “Surgery to remove a lobe of the lung (a lobectomy) and the affected lymph node(s) is the first-line treatment for stage 2 lung cancer. ”

In some patients who achieve a negative margin resection (no tumor left after surgery) and who have no lymph nodes involved with cancer, surgery is curative and no additional therapy or treatment is needed. This group of patients will be monitored for cancer recurrence by their oncologists but do not require additional treatment with chemotherapy, targeted agents, or immunotherapy.

When are additional treatments needed?

In some cases, chemotherapy may be recommended after surgery to lower the risk of cancer coming back or spreading. Chemotherapy given in this manner is called adjuvant and when treating lung cancer is typically a platinum agent like cisplatin.

Chemotherapy is often recommended in patients with high-risk features such as tumors greater than 4 cm, poorly differentiated, tumors that invade the visceral pleura tumors, or have vascular invasion. There are other factors your clinical team will also consider when deciding on whether chemotherapy is right for you.

In addition to chemotherapy, some patients may also be considered for other therapies — including the targeted agent osimertinib and the immunotherapy drug called atezolizumab.

Patients that underwent surgery but have residual disease left behind may also be candidate for not only chemotherapy but also radiation.

These drugs are very different from chemotherapy and are often much better tolerated. However, to receive these drugs the tumor must test positive for certain biomarkers that allow these drugs to be effective.

The treatment for stage 3 lung cancer depends on if you have stage 3A or a more advanced stage 3 cancer like stage 3B or stage 3C.

The decision to proceed with surgery for stage 3A lung cancer is not always black and white, and it’s an area where doctors can disagree. In stage 3A, where the cancer has spread to the lymph nodes on the same side of the chest where the cancer started, surgery can play a role depending on where the cancer is, how close it is to other structures, and how many lymph nodes are affected.

Chemotherapy or radiation may also be an option before surgery to shrink the tumor and destroy any errant cancer cells.

In other scenarios, some people with stage 3A cancer will be treated with radiation therapy and chemotherapy followed by immunotherapy without surgery.

If the cancer is EGFR+ targeted therapies may be added post-surgery as well. Immunotherapy drug pembrolizumab (Keytruda) may be used alone as your first treatment when your lung cancer has not spread outside your chest (stage 3) and you cannot have surgery or chemotherapy with radiation.

With stage 3B lung cancer or stage 3C, your cancer has spread to the lymph nodes on the opposite side of your chest or has invaded another area such as the veins feeding your heart.

For patients with stage 3B and 3C lung cancer, radiation therapy with chemotherapy followed by immunotherapy is the standard of care.

Most patients with stage 3 lung cancer will have radiation therapy with chemotherapy followed by immunotherapy to treat their disease. Surgery is only used for very select patients with stage 3A disease.

In stage 4 lung cancer, the disease has spread to other regions of the body, which is called metastasis.

Stage 4 is the most advanced cancer stage. Lung cancer is commonly already in stage 4 when it is first diagnosed because it often does not present symptoms until it has spread.

The National Cancer Institute estimates that about 55% of lung or bronchus cancers are first diagnosed at this stage.

Late-stage disease that has metastasized and is widespread throughout the body is often considered incurable.

In this case, the goal of treatment is to control/shrink the tumor, reduce symptoms, continue a positive quality of life, and try to prevent further metastasis and subsequent complications.

Next Generation Sequencing is essential especially in this setting as targetable mutations such as EGFR, ROS1, ALK, as well as several others may help to slow the progression of the disease. It will also delay the need for more aggressive therapies such as chemotherapy.

Undoubtedly, stage 4 lung cancer treatment can be difficult. This is because, by the time you have developed metastasis, your tumor will have spread beyond the lung to other parts of the body through your blood or lymph nodes and can be difficult to control.

But it’s important to know that there are still many treatment options available and treatments are improving every year. These include surgery, chemotherapy, and radiation, as well as the newer targeted drugs and immunotherapy agents.

As Dr. Raja Flores, chair of the Department of Thoracic Surgery at Mount Sinai Hospital, explains: “you have to realize stage 4, again, does not mean death. You can have stage 4 [patients] who are alive eight, nine, and ten years later. There are people out there who are walking around who have had brain metastases, but it’s kept quiet.”

EGFR inhibitors can often manage the cancer for several months or even years, depending on the patient and the drug, but they do not cure the cancer. Eventually, the cancer may develop resistance to these treatments, known as “acquired resistance.”

When this occurs, it is recommended that your doctor repeats biomarker testing, either through tissue or liquid biopsy, to identify new biomarkers or mutations. This information helps your doctor determine the next suggested treatment.

Here are the available treatments for EGFR-positive lung cancer patients.

Tyrosine Kinase Inhibitors (TKIs)

• Afatinib (approved for stage 4 lung cancer)
• Dacomitinib (approved for stage 4 lung cancer)
• Erlotinib (approved for stage 4 lung cancer)
• Gefitinib (approved for stage 4 lung cancer)
• Osimertinib (approved for stage 1-4 lung cancer)

For lung cancer patients with an EGFR mutation, “TAGRISSO is the best drug in the metastatic setting,” Dr. Roy Herbst, told SurvivorNet.

Dr. Herbst is a nationally recognized lung cancer researcher who serves as deputy director and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital.

The use of Tagrisso plus chemotherapy improved progression-free survival (PFS) by nine months as compared to Tagrisso alone in patients with locally advanced or metastatic EGFR-mutated lung cancer. PFS means how long a patient goes after a treatment without the disease progressing or death.

At this time the current standard of care for metastatic EGFR-mutated lung cancer is typically taking Tagrisso alone.

If you have EGFR-mutated lung cancer and have questions regarding Tagrisso and combination chemotherapy, please don’t hesitate to talk about it with your healthcare team.

For patients undergoing lung cancer treatment with a tyrosine kinase inhibitor such as Osimertinib, there are several side effects that patients should be aware. The most common include diarrhea, rashes, stomatitis, nausea, dry skin, and low blood counts. If any of these side effects are severe, it can affect your continued treatment.

It’s important to be very detailed in the description of your condition when you contact your care team, says thoracic surgery nurse Melissa Culligan.

So, what can you do to manage it?

Doctors often recommend drinking more water, clear broth or  decaffeinated fluids to replace the fluids and electrolytes you lose — and to avoid certain foods that trigger or worsen diarrhea like milk, spicy, or fatty foods.

Other suggested recommendations include eating low-fiber foods, trying probiotics, and eating five to six small meals a day.

Dr. Ken Miller, Director of Outpatient Oncology at the University of Maryland, Greenebaum Cancer Center, has an additional four tips to help keep cancer survivors healthy. They include:

1. Exercise at least two hours a week — and walking counts.

2. Eat a low-fat diet.

3. Eat a colorful diet with lots of fruits and vegetables. The American Cancer Society recommends aiming for two to three cups of vibrant vegetables and fruits each day.

4. Maintain a healthy weight. Studies have shown that being obese can increase your risk for several types of cancer.