Tumors can spread from one lung to the other and beyond. How are possible cancer metastases diagnosed in early stages?
In 2002, 53-year-old David Sturges made an appointment with a cardiologist to screen for heart disease, which ran in his family. He underwent electron beam computed tomography (CT) to check calcification in the arteries, an indicator of the disease.
Although significant calcium buildup was not detected, he saw something else in the results.
“It was literally a note that said, ‘We noticed this mass ... on the lower lobe of the right lung,’” Sturges, now 75, recalls. “If it’s being followed (by a physician), good, keep following it. If not, we suggest the patient go in for further follow-
up,’ which I did.”
Sturges’ biopsy was performed in February 2002 and showed that he had stage 1a non-small cell lung cancer. He underwent a lobectomy to remove the lower lobe of his right lung and continued with follow-up exams and scans, per his oncologist’s instructions, for a year after diagnosis, when another suspicious nodule was detected.
Some eight months later, his then-surgeon recommended the tumor be removed.
Unfortunately, the night before surgery, Sturges had a heart attack, and the procedure was not performed. He ended up seeing another oncologist, this time at UCLA, who did not recommend surgery.
Monitoring continued until late 2016, when imaging showed that the tumor had grown. Surgery was once again on the table and was finally performed in August 2017 at Mayo Clinic in Rochester, Minnesota.
The follow-up schedule that Sturges’ oncologists suggested, which included CT scans and blood tests, allowed them to monitor not only tumor growth, but also cancer recurrence.
There are two main types of lung cancer: non-small cell lung cancer (NSCLC), which constitutes some 85% of cases, and small cell lung cancer (SCLC), which accounts for the other 15%.
According to Dr. Malcolm DeCamp, chair of the Division of Cardiothoracic Surgery at the University of Wisconsin School of Medicine and Public Health in Madison, SCLC usually grows and spreads more quickly and is often treated with chemotherapy and radiation because tumors are too large or widespread for surgical removal.
“Non-small cell lung cancers are broken down into stages 1, 2, 3 and 4,” DeCamp says. “If it’s under 5 centimeters without lymph nodes involved, it’s stage 1 and treated primarily with surgery, assuming the patient is fit enough. Stage 2 disease is typically treated with surgery plus chemotherapy, as lymph nodes within the lung near the tumor are now involved. Stage 3 disease is locally advanced and requires chemotherapy plus radiation or plus surgery, or maybe all three. Then stage 4 is metastatic disease that has spread outside the chest. This stage is rarely, if ever, cured and treated primarily with chemotherapy, (targeted therapy or immunotherapy) to extend survival.”
Catching a tumor in the early stages, when it can be removed, is optimal since it is potentially curable. Because Sturges’ cancer was diagnosed at stage 1a, he only underwent surgery and needed no further intervention, although afterward he learned that a different treatment plan may have been more beneficial.
“It was probably two or three years after my initial surgery when (doctors) said they were finding that adjuvant therapy in combination with surgery probably gave a better outcome for people in my situation,” he says.
As with many other cancers, the fear of recurrence can linger long after treatment is over. But how likely is lung cancer to come back, and how can doctors monitor it?
Dr. Xiuning Le, assistant professor of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston, explains that the disease typically does not return for most patients with stage 1 non-small cell lung cancer. The five-year survival rate for patients with stage 2 disease is 40% to 60%, which decreases to 15% to 35% in patients with stage 3 disease.
According to the American Cancer Society, most doctors recommend that patients who no longer show evidence of disease come in for follow-up, which may include CT scans and blood tests, every three months during the first two years, every six months for the next three years, and at least once annually after five years.
Dr. Dennis Wigle, clinician scientist and chair of thoracic surgery at Mayo Clinic in Rochester, puts it this way: “With the higher stages and potentially higher recurrence rates, we want to look more frequently right after someone’s finished ... treatment so that we can detect recurrences as early as possible.”
Screening with low-dose CT scans is also done to detect new cancers, not recurrences, which are more common in current and ex-smokers (for about five to 10 years, then the risk decreases). But new cancers are more curable than recurrences, which are rarely curable.
SCLC is altogether different.
“Small cell lung cancer has a reputation of early metastasis and early recurrence,” Le says. “It often spreads to the brain.”
The five-year survival rate is 29% if the cancer is localized, 18% if it has spread in the chest and 3% if it has spread beyond the chest.
“We don’t have a good way to predict where the cancer is going to recur,”
Le says. “It can recur at the same location, spread to the other side of the lung or spread to other organs like the liver, adrenal glands and colon. Most thoracic oncologists do a CT scan that includes the lungs but also the upper part of the abdomen because these are the high-risk locations for metastasis.”
Additionally, Le notes that oncologists say they don’t know exactly why NSCLC is more likely to spread to certain organs than others, but some experts hypothesize that it is because these locations are rich in blood circulation.
If a patient has a recurrence, Le takes a multidisciplinary approach.
“We start by evaluating the pattern of recurrence,” she says. “If the cancer comes back in one location, we may be able to offer local treatment, but if it comes back in multiple locations, there is still a role for aggressive treatment. In that case, we need to consult with medical oncology, surgery and radiation oncologists.”
After Sturges’ heart attack, his doctor recommended he have CT scans every three months and then yearly until late 2016, when the scan showed his tumor had grown. In August 2017, he underwent a wedge resection in the upper lobe of his right lung and has been disease-free ever since.
So how do physicians catch lung cancer in the beginning or in the early stage of a recurrence?
DeCamp says that people at high risk should be on the lookout for voice changes or a cough that doesn’t go away or worsens. However, by the time symptoms appear, the disease may already be advanced. So the best way of detecting early-stage tumors is with CT scans. This is primarily considered in individuals at high risk due to smoking history.
Wigle agrees and points to the National Lung Screening Trial, in which 53,454 patients who were current or former smokers were assigned to undergo regular CT scans or chest X-rays. Investigators found more lung cancers in the CT group, and those patients had better survival outcomes.
“Increasing the buy-in to screening, at least in the at-risk population, is the lowest-hanging fruit and is the easiest way to improve survival,” DeCamp says. “The next lowest-hanging fruit is preventing people from smoking and getting people who smoke to quit. Then it’s going to be getting a better understanding of that group that gets cancer despite not smoking.”
The U.S. Preventive Services Task Force recommends annual screening for adults aged 50 to 80 years who have a 20 pack-year smoking history.
Wigle says that much of his job entails determining the risk level for each patient’s lung mass.
“The frequency of having any kind of nodule is relatively high,” he says. “I always tell patients if we randomly did 100 scans in people at risk for lung cancer, 25 would have some kind of lung nodule that would require more investigation, but (fewer) than one of those would actually have a lung cancer.”
Currently, there is no approved screening test for nonsmokers, but some interesting plans are in the works.
“Dogs have an incredible sense of smell,” DeCamp says. “Some can actually smell ... cancer (if they are trained to do so). We’re trying to understand what those neural pathways are in the canine. Then we can create a device that a patient can breathe into that can detect some of the byproducts of cancer metabolism to use as a screening test.”
DeCamp also says that because the entire respiratory tract can be at risk for lung cancer, it may be possible to develop a test that looks for a particular structure of cells swabbed from the nose or mouth that will show whether an individual is predisposed to it.
And there are a number of companies looking for molecular markers present in the blood of patients with cancer that disappear when the tumor is removed. If found, such biomarkers could be used to screen for lung cancer and test for recurrence.
Wigle suggests that this type of blood test could be used in combination with standard screening. “It might even take over as the screening protocol, meaning you wouldn’t get a CT scan until you had a positive result on some kind of blood test.”
Sturges had smoked for about 17 years but had stopped 15 or 20 years before his diagnosis.
“There’s ... an attitude that there’s nothing you can do for those patients,” DeCamp says. “That’s wrong. There’s something to do for almost all of them. And then there’s the stigma. ‘Oh, they did it to themselves; they smoked, right?’ Well, a growing population of lung cancer patients have never smoked. So we need to change the face of lung cancer. Our society views a woman with breast cancer as a victim. But people don’t often look at lung cancer patients as victims.”
According to DeCamp, of the 200,000 people in the U.S. who develop lung cancer every year, about 15% (30,000 patients) do so without having any known cancer risk.
Two-thirds of those 30,000 are women, but it is not known why.
But is the number of nonsmokers with cancer growing, or is the number of smokers who are diagnosed with lung cancer decreasing?
“The epidemiology is changing over time,” Le says. “Smoking overall has declined in (the) U.S. ... in the last decade. We definitely see more nonsmoker lung cancer patients, but I don’t think this number is growing. They are proportionally more of the patients we see in the clinic.”
According to Wigle, lung cancers are the deadliest cancer in America and lead to more deaths annually than many other cancers combined. Nevertheless, research in the field suffers from low funding from the National Institutes of Health and other government agencies.
After undergoing two surgeries and witnessing the benefits of screening for himself, in 2009 Sturges and two others set up the Lung Cancer Foundation of America. This nonprofit organization raises money for research into innovative treatment modalities that may one day lead to a cure.
“I’ve been very active in terms of sounding the alarm on the need for research and money to support research,” Sturges says. “We started our foundation because we were concerned that we weren’t getting ... a fair share from the National Cancer Institute and others, not enough money, not enough focus. ... And we need the money for research, and hopefully we can find a cure or at least as many treatment options as other cancers, so we can live and go forward.”
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To learn more about David Sturges's story of getting diagnosed with stage 1A non-small lung cancer from a footnote of a CT scan and hear his thoughts on how lung cancer treatments have changed in the past 21 years, listen to this "Cancer Horizons" podcast episode.