Secondary cancers outside the chest emerge late for many lung cancer survivors, MSKCC study finds

Many lung cancer survivors may face health issues long after their initial treatment ends, according to a study published today in JAMA Network Open. Research out of Memorial Sloan-Kettering Cancer Center (MSKCC) in New York shows that some survivors may be at increased risk of developing non-lung secondary cancer — that is, entirely new and unrelated cancer arising in other organs — often years after treatment. The pattern suggests that follow-up care may need to look beyond the lungs, especially for certain higher-risk patients.

Lung cancer care has improved steadily over the past decade, and that progress means more people are now living for years after curative treatment. But even when a person is disease-free, the risk of new problems does not disappear. Survivors of the most common type of lung cancer, known as non-small cell lung cancer (NSCLC), face an estimated 1% to 2% annual risk of a second primary lung cancer, which is a new, distinct tumor arising in the lung. About 10% to 38% of NSCLC survivors experience disease recurrence (when the original lung cancer comes back, either inside the chest or elsewhere in the body).

Routine chest CT scans help detect recurring or new tumors in the lungs, but cancers that form in other parts of the body may go unnoticed for longer. However, the timing and frequency of non-lung secondary cancers (i.e., new, biologically unrelated cancers that develop outside the lungs and are not metastases from the original lung cancer) have not been well defined.

To better understand these risks, a team of researchers, led by Matthew T. McMillan, M.D., at the Department of Radiation Oncology at MSKCC, evaluated 496 survivors with Stage 1 to 3 NSCLC. All had completed curative-intent surgery or radiotherapy and had been free of disease for at least 12 months before entering the center’s survivorship clinic between January and May 2019. The researchers tracked recurrence, second primary lung cancers, new cancers outside the chest and deaths.

After a median follow-up of almost six years, 13.5% of survivors experienced recurrence. Another 23.4% developed a new cancer, including 15.5% who developed a second primary lung cancer and 7.9% who developed a secondary cancer in another organ system. These outside-the-chest cancers tended to appear late in survivorship, with a median time to diagnosis of just over four years. At five years, the cumulative incidence was 5.6% for secondary cancers outside the chest, compared with 16.8% for new cancers in the chest.

A few aspects of the data stood out as particularly important for clinical practice, according to the authors. About one in five people who developed a secondary cancer outside the chest already had metastatic disease at the time it was found, and their outcomes were generally poor, with a median survival of approximately 20 months. Most of these cancers came to light only after symptoms started, and nearly one-third were discovered incidentally on imaging done for other reasons. None were caught through population screening, even for cancers that have established programs. They also found that almost 13% of survivors had cancer outside the chest even though their lungs looked normal, showing that chest-only follow-up can overlook serious problems.

Another striking finding was that inherited cancer syndromes or pathogenic germline variants were strongly linked to these later secondary cancers. In statistical models, survivors with a hereditary predisposition had a markedly higher risk, while smoking intensity did not independently increase the likelihood of developing a new cancer outside the chest.

“Prospective, multicenter studies are warranted to validate our findings and to test whether risk-aligned pathways may improve the timeliness of diagnosis, treatment candidacy, and long-term outcomes,” McMillian and his colleagues wrote in their conclusion. They suggest routinely documenting family history, using brief hereditary-risk assessments with referral when indicated and responding quickly to new symptoms. Rather than expanding whole-body imaging, they emphasize a more tailored approach that focuses attention where risk is most likely.