Screening programs and improved technology are boosting early detection, but the disease remains the top cause of cancer deaths in the country.
The Ministry of Health and Welfare (MOHW) announced in July that a national government-funded screening program had discovered 531 cases of positive results for lung cancer among nearly 50,000 people in its first year of operation. The new program offers free low-dose computed tomography (LDCT) scans in an effort to increase early detection of lung cancer.
An LDCT is a special type of X-ray that takes multiple pictures while the patient lies on a table that slides in and out of the machine. Encouragingly, about 85% of the discovered cases from the screenings were Stage 0 or 1 of the disease, when surgical intervention is most likely to be curative.
Lung cancer has long been one of the deadliest malignancies because there are often no symptoms until it has metastasized to distant organs. The overall five-year survival rate (for all stages of the disease) is just 18.6%, according to the American Lung Association. However, that figure jumps to 56% when the disease is still localized in the lungs.
“Lung cancer early detection and late detection outcomes are extremely different,” says Dr. Wang Ming-jiuh, a former vice president of the National Taiwan University Hospital (NTUH). Wang is now the deputy mayor of Taoyuan, where he is leading a program across 20 of the city’s hospitals aiming to screen 25,000 at-risk people per year.
As measured by several indicators, Taiwan has made significant strides in curbing lung cancer mortalities since the mid-2000s. For instance, MOHW data shows that the mortality rate of lung cancer in Taiwan was 21.8 deaths per 100,000 people in 2022, down 16.2% from 26 deaths per 100,000 people in 2011.
A key reason behind these improvements has been Taiwan’s growing ability to detect the disease at its early stages, according to a study published by Taiwanese researchers in the September 2022 edition of the Journal of Thoracic Oncology. Researchers analyzed the data of more than 17,000 patients diagnosed with lung cancer from 2006 to 2019 in the NTUH database. They found that the five-year survival rate improved substantially from 22.1% in 2006-2011 to 54.9% in 2015-2020.
“The prominent improvement in survival was primarily driven by the stage shift from advanced to localized, potentially curable disease,” the researchers said in the report. They also noted that mortality rates declined much faster after an LDCT lung cancer screening trial in 2015, “indicating that the LDCT has been of great importance.”
While decreasing tobacco use in Taiwan is likely also a reason for the improved outcomes, the high incidence of lung cancer among Taiwanese never-smokers remains a major obstacle in the battle against the disease. The Journal of Thoracic Oncology study notes that lung cancer in never-smokers – especially women – is more prevalent in East Asia than in other regions of the world.
In Taiwan, the never-smoker demographic accounts for a higher proportion of lung cancer cases than smokers. MOHW data from 2019 shows that the smoking prevalence in Taiwan’s lung cancer patients is only 33.7%. Among women, it’s just 5.9%.
Scientists have proposed different explanations for this troubling phenomenon, including exposure to carcinogens in cooking fumes in spaces with inadequate ventilation, as well as regular inhalation of polluted air. However, there are limited peer-reviewed studies of these theories.
One study published by Taiwanese researchers in Scientific Reports in April 2020 found that certain cooking methods involving the use of oil are associated with the risk of lung cancer, but that long-term use of a fume extractor in cooking can reduce the risk of the disease by about 50%.
Particle pollution from outdoor air is a more well-researched cause of lung cancer, and Taiwan has long struggled to battle air pollution. In 2014, Taiwanese legislators and the Taiwan Healthy Air Action Alliance noted that Taiwan’s air quality was the worst among the Four Asian Tigers (Hong Kong, South Korea, Singapore, and Taiwan). The biggest sources of air pollution in Taiwan are cross-border pollution coming from China, scooters, religious rituals, and industrial emissions.
In a call to action to address the rising incidence of lung cancer, the Changhua Medical Alliance for Public Affairs in 2015 attributed around 70% of central Taiwan’s air pollution to the coal-burning Taichung Power Plant and Formosa Plastics Group’s Sixth Naphtha Cracking Plant, both of which emit large amounts of sulfur oxides, known to be connected to lung diseases and cancer. Since then, the government has worked with industry on numerous initiatives to improve air quality.
One encouraging development in the battle against lung cancer is the advent of artificial intelligence-enhanced diagnostic screening. Compared to X-ray imaging, computed tomography can detect smaller lung tumors or nodules and provide better anatomical details. However, interpreting LDCT images is a burden for physicians, as they need to review an average of nearly 400 images. Prolonged image interpretation can lead to fatigue and potential oversights.
“With AI-assisted interpretation, physicians are aided in analyzing complex lung nodule characteristics and their locations,” says Kuo Naichen, an industry analyst at the semi-governmental Market Intelligence & Consulting Institute (MIC).
After a physician confirms the accuracy of the results, a standard format report that meets government requirements can be generated with just one click, reducing the total report completion time from 15 to two minutes.
The accuracy of AI-enhanced screening is generally very high. Citing data from Taiwanese healthcare technology companies, Kuo says that the AI system can detect pulmonary nodules above 6mm with an average accuracy of over 90%, providing results within just 20 seconds. For smaller nodules, the AI accuracy rate is 85%.
Several Taiwanese companies have developed products for AI screening. TaiHao Medical, founded in 2013, offers AI software to analyze and report chest CT images, with a focus on identifying pulmonary nodules, particularly the ground-glass opacity (GGO) lesions common in Asian individuals. aetherAI, established in 2015, provides solutions for digital pathology transformation, AI-powered diagnostic support systems, and biopharma enterprise services. The company’s collaboration with Cathay General Hospital developed the AI-LDCT Detection System for lung nodules.
Another benefit of using AI in lung cancer screening is the potential to reduce false positives – situations when radiographic images indicate signs of a disease, but a physician’s examination determines that no such condition exists. The potential harm of overdiagnosis includes additional costs, patient anxiety, and the possibility of further consequences from overtreatment.
In the United States, around 23% of the LDCT scans in the National Lung Screening Trial launched in 2002 have resulted in false positives, according to the U.S. National Cancer Institute (NCI).
“We anticipate that AI can substantially reduce the false-positive rate of low-dose CT screening while minimally affecting test sensitivity, thereby reducing diagnostic uncertainty,” Dr. Paul Pinsky, chief of the NCI’s Early Detection Research Branch, wrote in a December 2022 blog post. “But for AI research to be an effective tool for lung cancer screening, we need current high-quality image databases.”
In 2020, Taiwanese and UK researchers published a study of 103 patients that provided crucial new insights into the reasons why non-smoking women in East Asia have a higher incidence of lung cancer than counterparts elsewhere in the world.
The study, published in the peer-reviewed scientific journal Cancer Cell, noted that Taiwanese patients have been shown to have a demographically distinct cancer genome mainly driven by two EGFR (a protein expressed on the surface of cells) mutations: Del19 and L858R. The latter protein is associated with shorter survival outcomes, greater propensity to develop fluid and cancer cells between the chest wall, and a higher risk of cancer spreading.
The study investigated these proteins in patients with early-stage-lung adenocarcinoma – a type of cancer that starts in glands – through proteomic stratification, a process that can help identify potential biomarkers or therapeutic targets for different diseases. Through the proteomic stratification, patients were divided into five distinct subtypes, revealing a novel “late-like” class.
The patients in the “late-like” class were only at Stage 1B of the disease, when it has yet to spread outside the lungs. Nevertheless, “the protein profile was very similar to patients at the late stage,” says Dr. Chen Yi-Ju, a chemist at Academia Sinica in Taipei and one of the leaders of the study. As a result, their outcomes “could be similar to those at the late stage,” she notes. “This kind of molecular profile is useful – it allows clinicians to identify those who are at high risk at an early stage [of the disease] to receive closer monitoring and possible adjuvant therapy.”
Additionally, when the researchers compared tumor tissues to matching normal tissues, they discovered a significant link between mutations in APOBEC (a group of RNA-binding proteins) and the development of cancer. In 74% of the female never-smokers younger than 60, researchers found strong APOBEC mutational patterns. These mutational patterns were associated with the activity of DNA repair and replication processes.
The researchers also found a correlation between high APOBEC signature and good response to immunotherapy, “making it a potential marker candidate for early-stage diagnosis and immunotherapy treatment,” Dr. Chen says.
For his part, Taoyuan Deputy Mayor Wang lauds the progress Dr. Chen and her colleagues have made in their lung cancer research. However, he hopes to see more cities in Taiwan implement free LDCT screening programs in the future, since patients in Taiwan are unlikely to reap the benefits of lung cancer immunotherapy progress due to the cost of the procedure.
“It may make sense for the United States, which has a huge pharmaceutical sector and a very different healthcare system than Taiwan, but Taiwan has limited healthcare resources and funding, especially when we consider how costly some lung cancer treatment can be,” he says.
Some immunotherapy treatments for lung cancer can cost up to US$100,000 per year. In Taiwan’s single-payer system, where National Health Insurance (NHI) covers most medical expenses, footing these types of bills is difficult.
“NHI won’t pay for it,” Wang says. “Our medical expenditure will be better spent on early detection.”