Alex Bryant, MD,
School of Medicine,
University of California, San Diego

SAN DIEGO — While increased use of stereotactic body radiation might have played a key role in doubling survival rates for early-stage non-small cell lung cancer (NSCLC) among veterans between 2001 and 2010 compared to conventional radiation, a new study confirms that isn’t always the best way to assure longer survival.

The 2016 study presented at that year’s American Society for Radiation Oncology (ASTRO) annual meeting credited increased use of stereotactic body radiation therapy (SBRT) instead of conventional radiation therapy with largely driving the improved outcomes seen at the VA.1

Now a new study published online by The Annals of Thoracic Surgery suggested that patients with early stage NSCLC live longer when they receive a lobectomy—the most common type of operation for the disease—rather than a less-extensive operation or any type of radiation treatment.2

“Our data suggest that the more aggressively we treat early lung cancer, the better the outcome,” explained first author Alex Bryant, MD, of the School of Medicine at the University of California, San Diego. “This study is one of the best-powered and detailed analyses to date and suggests that lobectomy is still the preferred treatment of this disease for most patients.”

Lead researcher James D. Murphy, MD, of UCSD and colleagues tapped into the VA Informatics and Computing Infrastructure (VINCI) to identify patients who were diagnosed with early stage NSCLC between 2006 and 2015 and were treated with either surgery or radiation.

Included were 4,069 patients, 73% (2,986) of whom underwent lobectomy to remove the entire lobe of the lung; 16% (634) who received a sublobar resection, with wedge and segmental resections, and 11% (449) who received SBRT, which delivers very high doses of radiation over a week or two, precisely targeting the tumor.

VINCI is an “extremely rich source of health information,” according to the researchers, because it includes patient-specific data related to preoperative pulmonary function, smoking history and tumor staging. The study was unique, Bryant said, because that information is generally unavailable to be analyzed.

Results indicated that the five-year incidence of cancer death was lowest in the lobectomy group at 23%, compared with the sublobar group at 32%, and SBRT patients at 45%. SBRT also was associated with a 45% increased risk of cancer death compared with lobectomy.

Specifically, the multivariable analysis considering long-term survival found higher cancer-specific mortality for SBRT compared with lobectomy (subdistribution hazard ratio 1.45, 95% confidence interval: 1.09 to 1.94, p = 0.01), although no significant survival difference was documented between SBRT and sublobar resection (subdistribution hazard ratio 1.25, 95% confidence interval: 0.93 to 1.68, p = 0.15).

On the other hand, unadjusted analysis found higher immediate postprocedural mortality in both surgery groups compared with the SBRT group. The 30-day mortality was 1.9% for lobectomy, 1.7% for sublobar resection, and 0.5% for SBRT, which were blamed on overall surgery risks.

Surpassing SBRT

Over time and with longer follow-up, however, the surgery groups surpassed SBRT, with long-term survival favoring surgery, especially lobectomy, over radiation. In fact, the five-year overall survival rate for lobectomy patients was 70%, followed by the sublobar resection group at 56%, and SBRT at 44%, researchers reported.

“Our data suggest that the higher operative risks of surgery are more than offset by improved survival in the months and years after treatment, particularly for lobectomy,” Bryant pointed out.
Perhaps because of the previous research, SBRT increased dramatically over the study period; making up only 2% of VA treatments in 2006 but rising to 19% by 2015.

SBRT is the best option for patients unable to undergo lobectomy, but the more extensive surgery remains the standard treatment for early lung cancer patients who can tolerate it, Bryant emphasized. He noted that, while sublobar resections remain an option, concerns continue about higher incidences of tumor recurrences.

“Among a large cohort of early stage lung cancer patients, we found that lobectomy had improved survival compared with SBRT, although we found no survival difference between sublobar resection and SBRT,” study authors concluded. “Despite these findings, the potential for unmeasured confounding remains and prospective randomized trials are needed to better compare these treatment modalities.”

“The public should be aware that lung cancer—even when caught at a very early stage—is a serious diagnosis and deserves aggressive treatment,” Bryant added.

The earlier study of SBRT used the VA’s Central Cancer registry to identify 14,177 patients with stage I NSCLC. Half the patients had stage IA NSCLC, and 41.5% had squamous cell carcinoma.1

Even then, the majority of the early stage patients had surgery, but 3,132 received only radiation as their initial treatment—an approach typically used to treat patients with inoperable lung cancer. Among the patients with known fractionation, 468 had SBRT, while 1,203 had conventional radiation therapy.

A breakout of survival rates by treatment type revealed significant differences. Patients who received SBRT had a four-year survival rate of 37%, compared with 18.8% among those receiving conventional radiation therapy (CRT). Disease-specific survival rates also varied sharply, at 53.2% among those receiving SBRT vs. 28.3% for patients receiving CRT.

Multivariate analysis showed that SBRT was associated with a 28% reduction in the risk of death compared to CRT.

Lung/bronchus cancer is among the three most-frequently diagnosed cancers among VA patients, making up 18% of 46,170 invasive cancers in 2010. About 21% of lung/bronchus were diagnosed with Stage I disease, according to a report published last year in Military Medicine.3

VA, meanwhile, is trying to make sure that an increasing percentage of lung cancer cases are discovered early. Sponsored by the Bristol-Myers Squibb Foundation, a project launched by the healthcare system seeks to develop the VA-PALS Implementation Network (VA-Partnership to increase Access to Lung Screening). The goal is creating more early-detection programs for lung cancer, noting that the malignancy has an 80% cure rate when diagnosed early.

Plans for the project included launching lung-screening services at the Phoenix VA Health Care System by last month and extending the services to nine additional VAMCs, starting this year.

“The VA-PALS lung screening initiative demonstrates our priority to work together with outside organizations to provide more efficient care aimed at addressing serious health concerns,” explained VA Secretary David J. Shulkin, MD.

1Boyer M, Williams C, Kelley MJ, Salama JK. Survival with Stereotactic Body Radiation Therapy (SBRT) and Conventional Radiation Therapy (CRT) in Stage I NSCLC Patients in the Veterans Health Administration. ASTRO. September 25, 2016.

2Bryant AK, Mundt RC, Sandhu AP, Urbanic JJ, Sharabi AB, Gupta S, Daly ME, Murphy JD. Stereotactic Body Radiation Therapy Versus Surgery for Early Lung Cancer Among US Veterans. Ann Thorac Surg. 2017 Nov 21. pii:S0003-4975(17)31099-8. doi: 10.1016/athoracsur.2017.07.048. [Epub ahead of print] PubMed PMID: 29198624.

3Zullig LL, Sims KJ, McNeil R, Williams CD, Jackson GL, Provenzale D, Kelley MJ. Cancer Incidence Among Patients of the U.S. Veterans Affairs Health Care System: 2010 Update. Mil Med. 2017 Jul;182(7):e1883-e1891. doi: 10.7205/MILMED-D-16-00371. PubMed PMID: 28810986; PubMed Central PMCID: PMC5650119.