When cancer spreads to the lungs, surgery can help patients live longer. Many are offered major “open” procedures involving large incisions. However, a new study in the Journal of Surgical Oncology warns that these surgeries may be too risky for frail patients, who have less strength and ability to recover. Instead, minimally invasive (MI) surgical techniques may be a safer choice for them.

“If you reduce the extent and invasiveness of the surgery, you are more likely to get patients who are otherwise frail through the operation safely,” said Brooks Udelsman, MD, MHS, FACS, the study’s principal investigator and Assistant Professor in the Keck School of Medicine of the University of Southern California.

The researchers found that frailty, aside from age or chronic illnesses from prior literature, is a powerful predictor of poor outcomes from secondary lung cancer surgery, such as complication, longer hospital stays, or extended nursing care.

“When we do an operation, we rely on the patient to have some reserve so that they can recover from the trauma of that operation and get back to their baseline functional status,” Brooks said. “If your baseline functional status is already reduced, then you have less tolerance for perturbations.”

The research team reviewed nearly 9,000 cases of pulmonary metastasectomy—lung surgery to remove tumors that have spread from other parts of the body—from 2017 to 2019. The study drew on the Nationwide Readmissions Database, which provides nationwide hospital data. Just over 3 percent of patients were classified as frail under the Johns Hopkins Adjusted Clinical Groups indicator, which measures a person’s physical function, independence, and overall reserve.

To handle the scale and complexity of the datasets, Udelsman collaborated with statistician Li Ding, MD, MPH, co-author of the study and member of the Biostatistics Epidemiology and Research Design (BERD) team at the Southern California Clinical and Translational Science Institute (SC CTSI).

Doctors often use comorbidity scores to estimate surgical risk. Comorbidity scores measure the number and severity of a patient’s chronic diseases such as heart disease or diabetes. But these don’t indicate the strength or resilience of a patient.

Frail patients who received open surgery (thoracotomy) were twice as likely to suffer complications and stayed in the hospital about 2.6 times longer than non-frail patients. Even smaller open procedures, called sublobar resections, didn’t ease the risk.

Frail patients who received MI operations, such as video-assisted or robot-assisted surgeries, still had higher odds of complications and longer hospital stays. However, complication rates fell sharply when surgeons combined MI with sublobar resections, which are less extensive operations removing only a segment or wedge of the lung. Hospital stays were shorter, and outcomes were closer to those of non-frail patients.

The researchers found that frailty magnifies risk, but an appropriate surgical approach—less invasive and less extensive—can bring outcomes closer to those of non-frail patients.

Udelsman’s collaboration with SC CTSI and medical students was crucial to the success of this research project, he said.

Udelsman credits Ding for the study’s rigorous design, careful statistical analysis, and a collaborative workflow, which ensured its methodological rigor and validity. She also provided medical students with critical training. Several trainees (including first author and medical student Hannah Sidhu) learned biostatistics, study design and hands-on data analysis, gaining skills that will serve them as future clinician-researchers.

Ding was involved from the earliest stages of this study, which she strongly recommends as a model.

“We always want to get involved as early as possible so we can have the best study design to start with,” she added. “We can look at different analysis plans at the very beginning and have better discussions about approaches.”

This study also highlights the essential role of interdisciplinary teamwork and the appropriate statistical infrastructure in conducting large-scale health services research.

“SC CTSI is critical infrastructure,” Udelsman said. “If you had a wet lab with cellular biology and working in a cell hood and doing cultures, or working on mice, you need the animal techs. You need the proper equipment and infrastructure. The CTSI is similar in that it's the infrastructure for health services and large data-set analysis. This work can’t be done without statisticians and people who know how to analyze that data.”