Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales

Abstract

Background: Although the prognosis of most patients presenting with malignant pleural mesothelioma (MPM) is poor, a small proportion survives long term. We investigated factors associated with survival in a large patient series.

Methods: All patients registered with the NSW Dust Diseases Board (2002-2009) were included in an analysis of prognostic factors using Kaplan-Meier and Cox regression analysis. On the basis of these analyses, we developed a risk score (Prognostic Index (PI)).

Results: We identified 910 patients: 90% male; histology (epithelioid 60%; biphasic 13%; sarcomatoid 17%); stage (Tx-I-II 48%; III-IV 52%); and calretinin expression (91%).

Treatment: chemotherapy(CT) 44%, and extrapleural-pneumonectomy (EPP) 6%. Median overall survival (OS) was 10.0 months. Longer OS was associated with: age <70 (13.5 vs 8.5 months; P<0.001); female gender (12.0 vs 9.9 months; P<0.001); epithelioid subtype (13.3 vs 6.2 months; P<0.001); ECOG status 0 (27.4 vs 9.7 months; P=0.015), calretinin expression (10.9 vs 5.5 months; P<0.001); neutrophil-lymphocyte ratio (NLR) <5 (11.9 vs 7.5 months; P<0.001); platelet count <400 (11.5 vs 7.2 months; P<0.001); and normal haemoglobin (16.4 vs 8.8 months; P<0.001). On time-dependent analysis, patients receiving pemetrexed-based chemotherapy (HR=0.83; P=0.048) or EPP (HR=0.41; P<0.001) had improved survival. Age, gender, histology, calretinin and haematological factors remained significant on multivariate analysis. In all, 24% of patients survived >20 months: 16% of these receiving EPP, and 66% CT. The PI offered improved prognostic discrimination over one of the existing prognostic models (EORTC).

Conclusions: We identified calretinin expression, age, gender, histological subtype, platelet count and haemoglobin level as independent prognostic factors. Patients undergoing EPP or pemetrexed-based chemotherapy demonstrated better survival, but 84% and 34% of long survivors, respectively, did not receive radical surgery or chemotherapy.

Figure 1

CONSORT diagram of patient recruitment.

Figure 2

Four-month landmark analysis: effect of EPP surgery within 4 months on survival after 4 months. Analyses included up to 721 patients alive at 4 months. *Unknown group (N=78) excluded from analysis as zero patients in this category underwent surgery.

Figure 3

Extended Kaplan–Meier survival curves, stratified by time-varying EPP surgery status in good prognosis group (i.e., EORTC=low risk, N=305). Hazard ratios and P-values are from a Cox regression model with a time-varying covariate.

Figure 4

Probability of 20-month survival following a MPM diagnosis using risk scores based on a patient's demographic, diagnosticand tumour characteristics.

Figure 5

(A) Kaplan–Meier curves demonstrating survival according to prognostic indices (PI Score—0–5 vs 6+) and EORTC score (Low risk—0–2 vs High risk—3+). (B) Survival by PI cross-classification.