By Terence T. Sio, MD, MS, Professor of Radiation Oncology, Mayo Clinic Arizona
Sowmyanarayanan Thuppal, MD, PhD, et al. from Southern Illinois University, Division of Cardiothoracic Surgery and School of Medicine and Springfield Clinic, prospectively reported a single institutional clinical outcome and experience of 122 non-small cell lung cancer (NSCLC) patients undergoing surgery, versus 48 patients undergoing stereotactic body radiotherapy (SBRT). For patients who are diagnosed with early-stage NSCLC, although curative treatment options are widely available, there are fewer prospective data directly comparing the two most popular modalities, namely surgery or focused radiation using SBRT (also called SABR, stereotactic ablative radiotherapy). Historically, multiple phase III trials attempting to randomize operable patients between surgery and SBRT could not complete accrual. A recent phase II study from MD Anderson Cancer Center (Chang et al.) showed highly promising results combining immunotherapy and SBRT, and further studies are now pending.
In this study from Southern Illinois University, multiple aspects of prospective data were collected for patients who were diagnosed with early-stage NSCLC. Information on demographics, pulmonary function test results, and the National Surgical Quality Improvement Program (NSQIP) risk scores were gathered. A patient with a frailty index score of three or greater was considered frail. Health-related Quality-of-life (HRQOL) questionnaires, including the well validated EORTC (QLQ-C30 and LC13) and modified Medical Research Council (mMRC) dyspnea tools, were collected from the patients regularly.
From their results, we have a glimpse of the patient population in this study. Those who chose to undergo SBRT were likely more frail, had decreased FEV1%, with more morbidity or disability, and with a higher risk of death as predicted by NSQIP; however, we did not know if the surgery versus SBRT groups may have different primary tumor sizes (T1a, T1b, T1c, T2a, and T2b, by AJCC TNM staging, have different expected survival curves over time). The types of performed surgery (wedge, segmental/sublobar versus lobar resection, for example) were not reported in abstract form.
Looking at their functional data including NSQIP items, it may help us further interpret the results that were reported. In this cohort of 122 surgical versus 48 SBRT patients, there was likely a mix of both operable versus medically inoperable patients; the SBRT group only had a median FEV1 and DLCO of 60 and 55% respectively, in a group of patients with mean age of 72.2 years. The SBRT group may also have a statistically significantly higher rate of prior history of cancer (41% SBRT, versus 22% surgery); the rate of patients with past history of coronary artery bypass grafting (CABG) and angina almost tripled in the SBRT group (33.3-35.6 versus 12.0-12.8%). As a result, the two-year overall (OS) and recurrence-free (RFS) survivals may be biased against the SBRT group (for example, two-year RFS was 81.5% versus 64.8%), when we could not identify whether it was either a locoregional and/or distant recurrence, or if the patient’s death was caused by lung cancer and/or other non-NSCLC related comorbidities. With a prospectively followed cohort, the cause of death may be possible to identify. As a result, reporting NSCLC-specific survival, similar to prostate cancer-specific survival, may be feasible in their future analyses as follow-up matures.
The authors noticed certain QOL domains (physical functioning, fatigue and dyspnea) declined with the surgical cohort, and the role functioning domain was lower for SBRT patients. As limited by the abstract format reporting, no quantitative data were shown in the Results section. Overall, the median 90-day treatment-related Medicare/Medicaid costs appeared to be higher with surgical patients, however, if the patients did not have a major complication, treatment-related costs would be similar between SBRT and surgery. In the future, comparative quality-adjusted life year benefits may be able to be extracted from this interesting prospective cohort of early-stage NSCLC patients, as follow-ups lengthen in this dataset.
I applaud the tremendous effort the Southern Illinois University researchers have made in reporting this comparison study, and I offer congratulations to them for delivering an oral presentation at the 2023 Multidisciplinary Thoracic Cancers Symposium. The meticulous design of this study has laid a strong foundation for future research; while it is not surprising that more frail patients with increased NSQIP risks would choose a non-invasive, non-surgical modality being SBRT, being able to have this data validated, as compared to our real-life experiences, is refreshing. The cohort study design, especially involving quality-of-life and cost effectiveness measuring strategies, has laid a strong framework for potential multi-institutional clinical trials especially with operable early-stage NSCLC patients.
