Second lung cancers occurring up to a decade after the first are on the rise, but their prognosis is similar – especially when detected early – which supports long-term surveillance in survivors, finds a large population-based study.

John M. Varlotto, MD, a radiation oncologist at the University of Massachusetts Medical Center, Worcester

Dr. John M. Varlotto

Although guidelines recommend continued annual low-dose CT scan surveillance extending beyond 4 years for this population based on expert consensus, long-term evidence of benefit is lacking.

Investigators led by John M. Varlotto, MD, a radiation oncologist at the University of Massachusetts Medical Center, Worcester, analyzed Surveillance, Epidemiology & End Results (SEER) data for more than 58,000 patients with first and sometimes second non–small cell lung cancers initially treated by surgical resection.

Study results reported in Lung Cancer showed that the age-adjusted incidence of second lung cancers occurring 4-10 years after the first lung cancer rose sharply during the 1985-2014 study period, driven by a large uptick in women patients.

Among all patients, second lung cancers had similar overall survival as first lung cancers, but poorer lung cancer–specific survival. However, among the subset of patients having early-stage resectable disease (tumors measuring less than 4 cm with negative nodes), both outcomes were statistically indistinguishable.

“Because our investigation noted that the overall survival of patients undergoing a second lung cancer operation was similar to those patients undergoing a first operation, and because there is a rising rate of second lung cancer in lung cancer survivors, we feel that continued surveillance beyond the 4-year interval as recommended by the American Association for Thoracic Surgery as well as the [National Comprehensive Cancer Network] guidelines would be beneficial to long-term survivors of early-stage lung cancer,” Dr. Varlotto and coinvestigators wrote.

“The recent results from recent lung cancer screening studies demonstrate that females may benefit preferentially from screening … and our study suggests that these preferential benefits of increased CT scan surveillance may extend to females who are long-term survivors of lung cancer as well,” they added.

Findings in context

Mara Antonoff, MD, an assistant professor of Thoracic and Cardiovascular Surgery at The University of Texas MD Anderson Cancer Center in Houston

Dr. Mara Antonoff

“As this is an observational study, it is challenging to understand what is driving the rise in prevalence of second lung cancers,” Mara Antonoff, MD, of The University of Texas MD Anderson Cancer Center in Houston commented in an interview.

“Overall, the findings are very important, as they suggest that we should continue to perform surveillance imaging for patients beyond recommended guidelines, which may allow us to achieve better survival outcomes for those individuals who develop a second lung cancer years after the first lung cancer,” she agreed.

“Just as lung cancer screening is important to identifying lung cancers at an earlier stage when they are more easily treatable and more likely to be cured, surveillance after an initial treatment for lung cancer would allow a diagnosis of second lung cancers at an earlier stage, so the patients can again achieve durable cure,” Dr. Antonoff concluded.

Study details

For the study, Dr. Varlotto and coinvestigators used data from SEER-13 and SEER-18 to identify patients with a lung cancer diagnosis during 1998-2013, and data from SEER-9, covering the years 1985-2014, to calculate rates of second cancers occurring 4-10 years after a first lung cancer.

Analyses were based on 58,758 patients with a surgically resected first primary lung cancer (55.9% with early-stage disease) and 384 patients with a surgically resected second primary lung cancer (77.6% with early-stage disease). Median follow-up was 76 months for the former and 46 months for the latter.

Results showed that in the 4-10 years after a first lung cancer diagnosis, the age-adjusted incidence of second lung cancers rose by study year but remained less than that of all other second cancers combined until the mid-2000s. Among women, incidence started rising sharply in 2001 and significantly exceeded that of all other second cancers starting in 2005.

In the entire population of study patients, propensity-adjusted analyses showed that second lung cancers were similar to first lung cancers on overall survival (P = .1726) but had worse lung cancer–specific survival (P = .0143). However, in the subset of patients with early-stage resectable disease, second and first lung cancers were similar on both overall survival (P = .3872) and lung cancer–specific survival (P = .1276).

Dr. Varlotto disclosed that he had no conflicts of interest. The study was funded by the Department of Radiation Oncology, University of Massachusetts. Dr. Antonoff disclosed that she had no relevant conflicts of interest.

SOURCE: Varlotto JM et al. Lung Cancer. 2020;147:115-122.