Revisiting a longstanding clinical trial exclusion criterion: impact of prior cancer in early-stage lung cancer

Abstract

Background: Early-stage lung cancer represents a key focus of numerous multicenter clinical trials, but common exclusion criteria such as a prior cancer diagnosis may limit enrollment. We examined the prevalence and prognostic impact of a prior cancer diagnosis among patients with early-stage lung cancer.

Methods: We identified patients>65 years of age with early-stage lung cancer diagnosed 1996-2009 in the Surveillance, Epidemiology, and End Results-Medicare linked database. Prior cancers were characterized by type, stage, and timing with respect to the lung cancer diagnosis. All-cause and lung cancer specific-survival rates were compared between patients with and without prior cancer using Cox regression analyses and propensity scores.

Results: Among 42,910 patients with early-stage lung cancer, one-fifth (21%) had a prior cancer. The most common prior cancers were prostate (21%), breast (18%), gastrointestinal (17%), and other genitourinary (15%). Most prior cancers were localized, and 61% were diagnosed within 5 years of the lung cancer diagnosis. There was no difference in all-cause survival between patients with and without prior cancer (hazard ratio [HR] 1.01; P=0.52). Lung cancer specific survival was improved among patients with prior cancer (HR 0.79; P<0.001).

Conclusions: A prior cancer history may exclude a substantial proportion of patients with early-stage lung cancer from enrollment in clinical trials. Without adverse effect on clinical outcomes, inclusion of patients age >65 years with prior cancer in clinical trials should be considered to improve study accrual, completion rates, and generalizability.

Figure 1

Type (A), stage (B) and timing (C) of the most recent prior cancers. (Note: Cell sizes <11 are suppressed per the SEER-Medicare data use agreement; Denominators are not equal due to missing data).

Figure 2

All-cause (A) and lung cancer-specific (B) survival for patients with and without prior cancer.

Figure 3

All-cause survival according to timing (A), stage (B), and type (C) of prior cancer diagnosis (‘Other' denotes patients with no prior malignancy or a history of prior malignancy diagnosed outside the referenced time frame).