Integrating health status and survival data: the palliative effect of lung volume reduction surgery

Abstract

Rationale: In studies that address health-related quality of life (QoL) and survival, subjects who die are usually censored from QoL assessments. This practice tends to inflate the apparent benefits of interventions with a high risk of mortality. Assessing a composite QoL-death outcome is a potential solution to this problem.

Objectives: To determine the effect of lung volume reduction surgery (LVRS) on a composite endpoint consisting of the occurrence of death or a clinically meaningful decline in QoL defined as an increase of at least eight points in the St. George's Respiratory Questionnaire total score from the National Emphysema Treatment Trial.

Methods: In patients with chronic obstructive pulmonary disease and emphysema randomized to receive medical treatment (n = 610) or LVRS (n = 608), we analyzed the survival to the composite endpoint, the hazard functions and constructed prediction models of the slope of QoL decline.

Measurements and main results: The time to the composite endpoint was longer in the LVRS group (2 years) than the medical treatment group (1 year) (P < 0.0001). It was even longer in the subsets of patients undergoing LVRS without a high risk for perioperative death and with upper-lobe-predominant emphysema. The hazard for the composite event significantly favored the LVRS group, although it was most significant in patients with predominantly upper-lobe emphysema. The beneficial impact of LVRS on QoL decline was most significant during the 2 years after LVRS.

Conclusions: LVRS has a significant effect on the composite QoL-survival endpoint tested, indicating its meaningful palliative role, particularly in patients with upper-lobe-predominant emphysema.

Figure 1.

Probability of reaching the composite event (CE) or mortality for the lung volume reduction surgery (LVRS) or medical treatment groups. Failure functions, shown as the proportion of patients developing the event over time, in the following samples of patients: (A) All patients in the study. (B) Patients without high risk of perioperative mortality. (C) Patients without high risk for perioperative mortality, upper-lobe–predominant emphysema, and high exercise capacity. (D) Patients without high risk for perioperative mortality, upper-lobe–predominant emphysema, and low exercise capacity. (E) Patients without high risk for perioperative mortality, non–upper-lobe predominant emphysema, and high exercise capacity. (F) Patients without high risk for perioperative mortality, non–upper-lobe predominant emphysema, and low exercise capacity. Solid lines relate to the composite event, which is the occurrence of death or the occurrence of at least an eight-point increase in the total score on St. George's Respiratory Questionnaire, whichever happened first. Gray solid lines represent the medical treatment group, and black solid lines represent the LVRS group. Dotted lines represent the previously reported results of survival analysis for the same sets of patients (n = 9) and are included for comparison. The P value in the upper left corner of each panel refers to the value found when Wilcoxon tests were used to compare the failure functions for the composite event in the medical treatment group with those in the LVRS group. The number at risk refers to the number at risk for the composite event. The failure functions are described for death alone and for the composite event.

Figure 2.

Hazard ratio (HR) of lung volume reduction surgery (LVRS) to medical treatment for decline of at least a nine-point increase in the total St. George's Respiratory Questionnaire (SGRQ) score or composite event. Discrete hazard ratios are shown for the following samples of patients: (A) All patients in the study. (B) Patients without a high risk of perioperative mortality. (C) Patients without high risk for perioperative mortality, and with upper-lobe–predominant emphysema, and high exercise capacity. (D) Patients without high risk for perioperative mortality, upper-lobe–predominant emphysema, and low exercise capacity. (E) Patients without high risk for perioperative mortality, non–upper-lobe predominant emphysema, and high exercise capacity. (F) Patients without a high risk for perioperative mortality, non–upper-lobe predominant emphysema, and low exercise capacity. Black lines indicate HRs for the composite event, which is the occurrence of death or the occurrence of an at least eight-point or higher increase in the total score on the SGRQ, whichever happened first. Gray lines indicate HRs for an at least eight-point increase in the total SGRQ score only. An HR of greater than one favors the medical treatment group for the specific endpoint, and an HR of less than one favors the LVRS group for the specific endpoint. *Statistical significance (P < 0.05).

Figure 3.

Predicted progression of total scores measured in St. George's Respiratory Questionnaire (SGRQ) for the following samples of patients: (A) All patients in the study. (B) Patients without a high risk of perioperative mortality. (C) Patients without high risk for perioperative mortality, and with upper-lobe–predominant emphysema and high exercise capacity. (D) Patients without a high risk for perioperative mortality, upper-lobe–predominant emphysema, and low exercise capacity. (E) Patients without a high risk for perioperative mortality, non–upper-lobe predominant emphysema, and high exercise capacity. (F) Patients without a high risk for perioperative mortality, non–upper-lobe predominant emphysema, and low exercise capacity. Black lines indicate predicted total SGRQ scores for the lung volume reduction surgery (LVRS) treatment group. Gray lines indicate predicted total SGRQ scores for the medical group.