Differences in Treatment Facilities, Histology Account for Survival Disparities in NSCLC

A retrospective analysis of survival data from patients with metastatic non–small cell lung cancer showed that patients who received treatment at academic centers had better survival rates than those treated at community-based centers, and this disparity was more pronounced when patients were stratified by histology.

A retrospective analysis of survival data from patients with metastatic non—small cell lung cancer (NSCLC) showed that patients who received treatment at academic centers (ACs) had better survival rates than those treated at community-based centers (CCs), and this disparity was more pronounced when patients were stratified by histology.1

“There has been an improvement in the treatment of advanced lung cancers over the last 20 years and it is happening at both the community and the academic level,” explained Jeffrey Crawford, MD, the study’s senior author, George Barth Geller Professor of Medicine, and the codirector of the Solid Tumor Therapeutics Program at the Duke Cancer Institute in Durham, North Carolina. “Notably, it is happening in the adenocarcinoma population and not the squamous population. That was the most important observation because that had not been recognized before.”

Survival advantage between the 2 settings was analyzed from data collected from the National Cancer Database (NCDB) between 1998 and 2010 in patients with advanced NSCLC. The primary outcome was 2-year survival, or the proportion of patients surviving at least 24 months past the time of diagnosis.

An increase in the 2-year survival rate was observed in both groups between 1998 and 2010; however, patients treated in ACs had better survival rates and the survival disparity increased over time.

The 2-year survival rate in 1998 was 11.5% versus 9.2% in ACs and CCs, respectively. By 2010, the rates were 17.4% and 13.1%, accounting for a 2% increase in the survival disparity between the 2 groups over time.

“New innovations in treatment that we see at the clinical trial level are playing out at the overall population level,” Crawford said. “These studies were initially done at academic centers and therefore [they may have been better equipped] to adopt those changes sooner,” he explained.

A greater increase in survival rates was also dependent on histologic factors with adenocarcinoma outpacing squamous cell carcinoma by 0.59% per year in the 2-year survival rate. For all patients, histology-dependent survival in 1998 was comparable between patients with adenocarcinoma (10.2%) and squamous cell carcinoma (9.9%). However, there was a statistically significant disparity by 2010 with 17.3% of patients with adenocarcinoma surviving at 2 years versus 10.1% with squamous cell carcinoma.

Survival in patients with adenocarcinoma also varied by treatment facility with a 2-year survival rate of 12.3% versus 9.1% in ACs and CCs, respectively, in 1998. By 2010, both groups saw an increase in survival, 20.5% versus 15.5%, respectively, accounting for a 1.8% increase in the survival-rate disparity.

Study investigators say several factors may account for the disparity between the 2 settings including more availability of lung cancer—specific pathologists and molecular testing.

“Perhaps [pathologists at academic centers] are more tuned in on separating squamous from nonsquamous cancer. These are questions we cannot really answer from the database,” said Crawford.

The increasing importance of histology in treating NSCLC started around the early 2000s, Crawford said, and this could explain why there was a disparity observed in the designated study period. Treatment approaches became separated by squamous and nonsquamous histology because of 2 factors: the squamous population has a high risk of bleeding when bevacizumab (Avastin) is added to chemotherapy regimens and is therefore not used in this population, and the data for pemetrexed showed it was beneficial in nonsquamous but not in squamous cancers.

He went on to explain that targeted therapies for patients that have genetic aberrations inEGFR,ALK, and other genes were being introduced and mainly benefited patients in the adenocarcinoma population.

“Over the time period, there was really no difference in outcome for [patients with squamous cell carcinoma]. It is unfortunate, but it serves as a good control since we have not seen an advance over this time period and there was not a real change,” Crawford said.

Past studies have suggested that treatment choices and outcomes in NSCLC vary between academic and nonacademic settings. According to a study by Samson et al, patients at academic centers were more likely to receive neoadjuvant chemotherapy (49.6% vs 40.6%;P<.001) while those in nonacademic centers were more likely to receive radiotherapy (54.7% vs 49.4%;P<.001).2

But even when accounting for confounders including performance status, distance traveled to receive treatment, time between diagnosis and care, and treatment plans that did not include chemotherapy, there was no advantage observed that would disproportionately favor ACs.

“The adoption of new regimens and new information has to do with disparities in care. We have to figure out how to [reduce] these disparities in the academic and community centers. I think that is the call going forward,” said Crawford.

He went on to explain that advances in the last 5 to 10 years, especially in immunotherapy and targeted therapies, necessitate another look at the data to see if these disparities have persisted.

This work was led by Sendhilnathan Ramalingam, MD, a hematology/oncology fellow at Duke. Ramalingam is currently analyzing more recent data from the NCDB, which includes the era of targeted therapy and immune therapy. The group is hoping these results will be ready for submission to the American Society of Clinical Oncology in 2019.


  1. Ramalingam S, Dinan MA, Crawford J. Survival comparison in patients with stage IV lung cancer on academic centers in the United States.J Thorac Oncol. 2018;13(12):1842-1850. doi: 10.1016/j.jtho.2018.09.007.
  2. Samson P, Patel A, Crabtree TD, et al. Multidisciplinary treatment for stage IIIA non—small cell lung cancer: does institution matter?Ann Thorac Surg. 2018;100(5):1773-1779. doi: 10.1016/j.athoracsur.2015.04.144.