Mortality of lung cancer as a second primary malignancy: A population-based cohort study

Abstract

Lung cancer as a second primary malignancy (lung-2) is increasingly common, but its prognosis is poorly understood. This study aims to examine the overall and cancer-specific survival of patients diagnosed with lung-2 compared to lung-1. Primary lung cancer patients diagnosed from 1988 to 2014 in the Surveillance, Epidemiology, and End Results (SEER) program were included. Lung-2 was identified in patients with a previous diagnosis of nonlung primary malignancy in SEER. Hazard ratios (HRs) of overall and lung cancer-specific mortality were estimated among patients with lung-2 compared to lung-1, adjusting for age and calendar period at diagnosis, sex, race, socioeconomic status, tumor stage, histology, tumor grade, and treatment. A total of 679 541 and 85 758 patients were identified as lung-1 and lung-2, respectively. Compared to lung-1, patients with lung-2 were more likely to be diagnosed at localized stage, with smaller primary tumor, and treated with surgery. Lung-2 patients were at lower risk of lung cancer-specific mortality in the first 5 years (HR, 0.77; 95% CI, 0.76-0.78 at <1 year; HR, 0.87; 95% CI, 0.86-0.89 from 1 to <5 years) but at higher risk thereafter (HR, 1.32; 95% CI, 1.27-1.37 from 5 to 10 years), independent of tumor characteristics and cancer treatment. Similar pattern was found for overall mortality, although the survival benefit was restricted to the first year after diagnosis. Patients diagnosed with lung-2 face a favorable lung cancer-specific survival within the early period after diagnosis. A conservative approach to manage lung-2 solely based on malignancy history is not supported.

Keywords: cohort study; lung cancer; mortality; prognosis; second primary.

Conflict of interest statement

The authors have declared no conflict of interest.

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1

Cumulative mortality rates by causes of death among patients with first and second primary lung cancers from cancer diagnosis to 10 years afterwards: a population‐based cohort study in US, 1988‐2014

Figure 2

Hazards ratios (HRs) of overall and lung cancer‐specific mortality among patients with second primary lung cancer from cancer diagnosis to 10 years afterwards, compared to patients with first primary lung cancer: a population‐based cohort study in US, 1988‐2014. HRs were estimated from flexible parametric survival models, allowing the effect of second primary lung cancer to vary over time. A spline with 5 df (four intermediate knots and two knots at each boundary, placed at quintiles of distribution of events) was used for the baseline rate, while 3 df was used for the time‐varying effect. HRs in model A were adjusted for age and calendar period at diagnosis, sex, race, cohabitation status, and percentile of high‐school education and cost of living in county of residence. HRs in model B were additionally adjusted for tumor stage, histology, tumor grade, and treatment modalities