Clinical Investigation
Comparative Effectiveness of 5 Treatment Strategies for Early-Stage Non-Small Cell Lung Cancer in the Elderly

https://doi.org/10.1016/j.ijrobp.2012.07.2354Get rights and content

Purpose

The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation.

Methods and Materials

Treatment strategy and covariates were determined in 10,923 patients aged ≥66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specific survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options.

Results

The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses.

Conclusions

In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select populations. Evaluation of these therapies in randomized trials is urgently needed.

Introduction

Although advanced non-small cell lung cancer is associated with poor prognosis, early-stage presentations are potentially curable, with 5-year rates of overall survival (OS) approaching 50% (1). In the United States, 2 public health developments will increase the burden of early lung cancer and strain limited health care dollars. First, the overall incidence of NSCLC among adults over 65 is expected to rise dramatically from a level of 163,000 in 2010 to 271,000 by 2030 because of the demographic changes associated with population aging (2). Second, recent evidence showing a mortality benefit from computed tomography screening may lead to a rise in newly diagnosed early-stage (T1a-T2a N0) lung cancers as screening disseminates into routine care (3).

Patients with NSCLC are frequently older and experience a high burden of comorbid illness. Surgical resection for early-stage disease affords a high likelihood of cure but is often precluded by comorbid illness that renders patients medically inoperable. New minimally invasive methods for thoracic surgery and a novel radiation therapy modality, stereotactic ablative radiation therapy (SABR), promise to improve outcomes in elderly patients who previously would not have been candidates for curative surgical therapy. However, no phase 3 randomized data are available to guide integration of these newer therapies into treatment selection for the elderly.

Given the urgency of this health policy question and the lack of randomized data to guide therapy, we used the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort to identify patients older than 65 treated for early-stage NSCLC between 2001 and 2007, during which time all major contemporary treatment strategies were in use. We sought to determine the comparative effectiveness of lobectomy, sublobar resection, conventional radiation, SABR, and observation with respect to OS and lung cancer-specific survival (LCSS).

Section snippets

Data source

The Surveillance, Epidemiology, and End Results (SEER)-Medicare database captures clinical, pathologic, and insurance claims data for incident cancers diagnosed in Medicare beneficiaries who reside within 1 of 16 geographic catchment areas that account for 26% of the United States population. The case ascertainment rate for the SEER data is approximately 98% (4). In this study, demographic and tumor characteristics for incident malignancies diagnosed from January 1, 2001, to December 31, 2007,

Baseline characteristics and unadjusted outcomes

Among the 10,923 patients, the median age was 75 years, 54.1% were female, and 29% had moderate to severe comorbidity. The treatment strategy was as follows: 6531 lobectomy (58.9%), 1277 sublobar resection (11.7%), 1613 conventional radiation (14.8%), 1378 supportive care (12.6%), and 124 SABR (1.1%). Nodal sampling to establish pathologic node-negative status was accomplished in 94% of the lobectomy patients, 42% of the sublobar resection patients, and fewer than 10% of the nonsurgical

Discussion

The median age of patients with NSCLC is 70 years (10), and the most prevalent risk factor is chronic smoking, which is associated with many systemic medical conditions including chronic obstructive pulmonary disease and coronary artery disease. This combination of advanced age and comorbid illness poses therapeutic challenges and increases the morbidity and mortality risks of treatment. In the absence of randomized data, clinical decision making for the rising number of elderly patients can be

Acknowledgment

The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database.

References (20)

There are more references available in the full text version of this article.

Cited by (233)

  • Advances in Imaging to Aid Segmentectomy for Lung Cancer

    2022, Surgical Oncology Clinics of North America
View all citing articles on Scopus

Supported by grants from the Cancer Prevention & Research Institute of Texas [Grant RP101207] and the Department of Health and Human Services National Cancer Institute [Grants CA16672, T32CA77050] to Dr Smith.

A portion of this study was funded by a research grant from Varian Medical Systems (SR2011-00034954RG 01). This entity had no role in the study design, data analysis, or data interpretation. Dr Welsh reports a compensated consultory role to Reflexion Medical.

View full text