Lung cancer remains the number one cancer killer, leading to about 150,000 deaths per year in the United States and accounting for approximately 25% of all cancer deaths in the nation. Early detection has improved survival in other malignancies such as breast, colon, and cervical cancers, but optimizing and encouraging the uptake of a screening program for lung cancer have been an uphill battle that began decades ago.
Overcoming Obstacles
Although a traditional chest x-ray may reveal an abnormal mass in the lungs, smaller lesions often go undetected, losing the opportunity for early detection and cure. The advent of low-dose computed tomography (CT), however, has reshaped the landscape of lung cancer screening.
Convincing the medical establishment of the clinical value of lung cancer screening was yet another hurdle. Value vs cost and the often-cited problem of false-positive screening results leading to unnecessary surgery were among the main arguments of detractors. Finally, in 2011, the long-awaited primary results of the National Lung Screening Trial (NLST) were released and published in The New England Journal of Medicine, demonstrating a 20% lower risk of dying of lung cancer than those who undergo x-ray screening.1
Claudia I. Henschke, PhD, MD
In 2013, the next obstacle was overcome, when the U.S. Preventive Services Task Force gave a B grade to low-dose CT screening, recommending the early detection procedure for a specified high-risk population. The rollout of low-dose CT programs, however, has been slow, according to some researchers at the vanguard of the lung cancer screening initiative, such as Claudia I. Henschke, PhD, MD. Dr. Henschke heads the International Early Lung Cancer Action Project (I-ELCAP) at the Icahn School of Medicine at Mount Sinai in New York. She further clarified the results of the NLST in a recent interview with The ASCO Post.
“The NLST demonstrated a 20% mortality reduction in those screened with low-dose CT. The confusion, however, arises between a mortality reduction, which is an endpoint of a clinical trial, and the long-term cure rates that you detect under screening. When you carefully examine the 20% mortality reduction after three rounds of low-dose CT screening, the results are absolutely compatible with the 80% long-term survival rates that we show with our I-ELCAP data,” she noted.2
“To be clear, to infer that a 20% mortality reduction means that only one screened person out of five who is diagnosed with lung cancer has a benefit is absolutely wrong. Again, the endpoint of the NLST does not give the true survival rate, which is 80% or better given the stage at diagnosis. This has been a key misunderstanding responsible for underestimating the true benefits of screening,” Dr. Henschke said.
Low-Dose CT Is Effective and Safe
James L. Mulshine, MD
Another longtime advocate of early detection is James L. Mulshine, MD, a lung cancer expert at Rush University, Chicago, and Chair of the International Association for the Study of Lung Cancer Early Detection and Screening Committee. “Recent published studies demonstrate that the concern about overdiagnosis in CT screening wasn’t the boogeyman it was made out to be. If you do the workup that’s used by the NELSON study and I-ELCAP, in which volumetrics are employed to determine when surgical intervention is appropriate, the false-positive rate falls below 10%.3 Moreover, low-dose CT in lung cancer is as good or better than any other screening method we’ve employed in health care,” said Dr. Mulshine.
He continued, “The central message that needs to resonate throughout the medical community and the lay public is that CT screening for lung cancer is a cost-effective and value-based tool to detect early-stage treatable lung cancer. It also provides an opportunity for professionals to provide smoking-cessation counseling and other general health benefits to those high-risk individuals that should be screened. It’s a win-win situation for public health outcomes.”
Minimally Invasive Video-Assisted Thoracoscopic Surgery
Traditionally, lung cancer surgery was performed by a thoracotomy incision, which requires cutting through major muscles of the chest wall and using a rib spreader to gain access to the lungs. Because the ribs have limited flexibility, rib fracture is common. There is wide consensus that thoracotomy is one of the more painful surgical procedures that patients can undergo.
However, the advent of video-assisted thoracoscopic surgery has transformed lung cancer care, providing a minimally invasive procedure that effectively treats early-stage lung cancer and also offers patients far less pain after surgery. Moreover, video-assisted thoracoscopic surgery is associated with a significantly shorter recovery time than thoracotomy. And patients who undergo video-assisted lobectomy better tolerate additional therapies such as chemotherapy.
Raja M. Flores, MD
Thoracic surgeon Raja M. Flores, MD, Chief of Thoracic Surgery at the Icahn School of Medicine at Mount Sinai in New York, explained the procedure to The ASCO Post. “Any patient with a localized cancer in the lung that has not spread outside of the chest is a candidate for curative surgery. In a [video-assisted thoracoscopic lobectomy], the patient is positioned on the bed in a way that allows unobstructed movement of the thoracoscope. We use three small incisions that allow us to insert the thoracoscope and remove the lobe with the lesion.”
He continued: “It’s far easier on the patient, both during surgery and after surgery, than thoracotomy. And depending on the characteristic of the lesion, we don’t have to resect as much lung as we once used to when performing a lobectomy. Because of screening, we’re finding smaller and smaller cancers, so we don’t always need to do a lobectomy, and instead do a sublobar resection that includes either a wedge or a segmentectomy. We get very good survival results while sparing a lot more lung.”
Asked about the concern of false-positives and subsequent overtreatment, Dr. Flores replied, “It’s important to see a thoracic surgeon instead of a general surgeon. You don’t want someone with a quick surgical trigger finger. We know how to read scans. And if we determine there’s a 95% chance the lesion is malignant, we go in, but if it’s less than that, we’re not afraid to hold off and follow the patient. We did a study at Mount Sinai looking at our rate of false-positives, and we had it down to 2% to 3%. And that’s what everyone should aim for.”
Screening Protocol Important
Nasser K. Altorki, MB, BCh
To drill deeper into the issue of patient selection for surgery and screening, The ASCO Post spoke with Nasser K. Altorki, MB, BCh, Chief of Thoracic Surgery at Weill Cornell Medicine. “When we first began the [video-assisted thoracoscopic surgery], we were very careful in our patient selection in terms of the size of the tumor. We wanted to operate on smaller tumors in patients who did not get preoperative therapy and therefore would have less scarring in the lung area,” he said.
“In other words, we were looking for all the clinical issues that would make the surgery less challenging. But as we’ve gained more experience, we now do more than 95% of our procedures using [video-assisted thoracoscopic surgery] without any limitations. We expanded the indication to include larger tumors that were treated previously with chemotherapy or radiation or both. Then we further expanded the indication to include patients who’d had prior lung cancer surgery and thus had historically been excluded from [video-assisted thoracoscopic] surgery,” Dr. Altorki continued.
“I’m the principal investigator on a large trial that is randomizing patients with early-stage lung cancer to either have lobectomy or a sublobar resection,” he noted. “The trial is in highly selected centers of excellence, but nonetheless, about 80% of the procedures in both arms of the trial had minimally invasive surgery. That is much higher than the prevalence of minimally invasive surgery in an unselected nationwide group of surgeons.”
Asked about the slow rollout of low-dose CT lung cancer screening programs, Dr. Altorki responded, “Those who are still using false-positives and surgical risks as a rationale to diminish the value of low-dose CT screening are potentially preventing the use of a tool that reduces lung cancer mortality by at least 20%, as shown in the NLST, and by 35% in the Dutch-Belgian [NELSON] trial.” 4
He added: “The issue of false-positives is all determined by your diagnostic protocol. If you don’t have a protocol, everything you see on the scan is a nail, and you’re the big hammer. That said, we now have technology that lets us closely examine each nodule in its finest details, using volumetric analysis and even [artificial intelligence] down the road. Protocol-based management vastly reduces the magnitude of false-positive results, and minimally invasive surgery is an effective, low-risk strategy to treat lung cancer. We need to get that message out.”
Conclusions
For decades, most Americans at high risk for lung cancer didn’t have access to early highly effective detection tools, and consequently, a large percentage of those people presented with inoperable lung cancer. Due to the research efforts of determined physicians, scientists, and other investigators, lung cancer can be detected earlier, when the chance for cure is greater.
Multiple, rigorously designed large randomized trials have demonstrated conclusively that low-dose CT screening detects small lung nodules that can be surgically resected with minimally invasive surgery. Moreover, concerns about false-positives and surgical risks have also been addressed and resolved. The next step forward is to roll out low-dose CT screening programs. “[Early] lung cancer is curable. The answer is early detection and surgery,” said Dr. Flores.
DISCLOSURE: Drs. Henschke, Mulshine, and Flores reported no conflicts of interest. Dr. Altorki has stock and other ownership interests in Angiocrine Bioscience and has received institutional research funding from AstraZeneca.
REFERENCES
1. National Lung Screening Trial Research Team: Reduced lung cancer mortality with low-dose computed tomographic screening. N Engl J Med 365:395-409, 2011.
2. International Early Lung Cancer Action Program Investigators: Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 355:1763-1771, 2006.
3. Adamek M, Wachula E, Szablowska-Siwik S, et al: Risk factors assessment and risk prediction models in lung cancer screening candidates. Ann Transl Med 4:151, 2016.
4. De Koning H, Van Der Aalst C, Ten Haaf K, et al: Effects of volume CT lung cancer screening: Mortality results of the NELSON randomized-controlled population based trial. 2018 World Conference on Lung Cancer. Abstract PL02.05. Presented September 25, 2018.
