Baseline characteristics of patients
A total of 335 patients with MPE were histologically comfirmed NSCLC. Ninety-one patients were excluded for some reasons, including 45 patients incomplete data, 18 patients lost to follow-up and 28 patient no treatment. Finally, 244 patients were enrolled in this study (Fig 1).
Characteristics of the patients are outlined in Table 1. Their median age was 60 years (31-79 years). Among all patients, 132 (54.1%) were females and 201 (82.4%) were diagnosed with adenocarcinoma. For first line anticancer treatment, 194 (79.5%) patients received traditional systemic chemotherapy and 50 (20.5%) patients underwent targeted therapy. Median PFS and OS were 6.1 months and 12.7 months, respectively (Fig 2). Univariate analyses for OS and PFS are shown in Table 1.
Serum CEA was elevated in 155 of the 244 patients analyzed (63.5%), serum CYFRA21-1 in 137 of 244 patients (56.1%), serum CA-125 in 145 of 244 patients(59.4%), and serum NSE in 135 of 244 patients (55.3%). PF CEA was elevated in 176 of the 244 patients analyzed (72.1%), PF CYFRA21-1 in 175 of 244 patients (71.7%), PF CA-125 in 177 of 244 patients (72.5%), and PF NSE in 138 of 244 patients (55.3%). Serum and pleural fluid (SPF) CEA was elevated in 138 of the 244 patients analyzed (56.6%), SPF CYFRA21-1 in 135 of 244 patients (55.3%), SPF CA-125 in 134 of 244 patients (54.9%), and SPF NSE in 114 of 244 patients (46.7%).
In our population, 44 patients (18.0%) presented the 4 serum tumor markers elevated, 62 patients (25.4%) 3 serum tumor markers elevated, 88 patients (36.1%) 2 serum tumor markers elevated and 35 patients (14.3%) 1 serum tumor markers elevated.
Levels of tumor markers in serum and PF
Table 3 describes the levels of serum and PF tumor markers. Serum levels of CEA, CYFRA21-1, CA-125 and NSE were 79.15 ± 186.36 ng/mL, 9.63 ± 29.36 ng/mL, 156.98 ± 251.65 U/mL and 19.71 ± 34.99 ng/mL, respectively. PF levels of CEA, CYFRA21-1, CA-125 and NSE were 280.96 ± 358.16 ng/mL, 136.85 ± 175.19 ng/mL, 1103.26 ± 1340.92 U/mL and 38.15 ± 75.10 ng/mL, respectively, and were significantly higher than those in serum (all P < 0.001 ).
CEA analysis
High levels of serum CEA was adversely prognostic factors for PFS and OS. The PFS was 6.6 months versus 5.0 months in patients with normal and elevated level of serum CEA (P = 0.003) and the OS was 15.0 months versus 12.0 months in patients with normal and high levels of tumor marker (P = 0.030). We analyzed the prognostic value of combination of serum and pleural fluid CEA. High levels of SPF CEA were related to worse PFS and OS. The PFS was 6.6 months versus 5.0 months in patients with normal and elevated level of SPF CEA (P = 0.003) and the OS was 15.3 months versus 10.6 months in patients with normal and high levels of tumor marker (P = 0.001) (Fig 3).
CYFRA21-1 analysis
We found that abnormal levels of serum CYFRA21-1 and SPF CYFRA21-1 were negative prognostic factors. The PFS was 6.5 months versus 5.3 months in patients with normal and elevated level of serum CYFRA21-1 (P < 0.001) and the OS was 16.1 months versus 11.7 months in patients with normal and high levels of tumor marker (P = 0.004). The PFS was 6.5 months versus 5.3 months in patients with normal and elevated level of SPF CYFRA21-1 (P = 0.001) and the OS was 15.8 months versus 11.1 months in patients with normal and high levels of tumor marker (P = 0.001) (Fig 4).
CA-125 analysis
Serum CA-125 and SPF CA-125 were negative prognostic factors for OS. The OS was 15.0 months versus 12.0 months in patients with normal and elevated level of serum CA-125 (P = 0.043) and 12.7 months versus 12.0 months in patients with normal and high levels of SPF CA-125 (P = 0.023) (Fig 5).
NSE analysis
High levels of SPF NSE was a negative prognostic factor for PFS. The PFS was 6.4 months versus 5.5 months in patients with normal and elevated level of SPF NSE (P = 0.019) (Fig 6).
Serum CEA, CYFRA21-1, CA-125 and NSEcombination
We analyzed the prognostic value of combination of serum tumor markers. For patients with 4 tumor markers elevated PFS was 4.0 months versus 5.5 months in patients with 3 tumor markers, 6.4 months in patients with 2 tumor markers, 7.0 months in patients with 1 tumor marker and 6.8 months in patients with all the tumor markers negative (P = 0.001). We found the same results for OS in patients with a combination of serum tumor markers (P = 0.018) (Fig 7).
Significant variables from univariate analysis were evaluated by multivariate analysis. High levels of SPF CYFRA21-1 (HR 1.581, 95% CI 1.138-2.199; P = 0.006) was a independent predictive variable for shorter OS. High levels of SPF CEA (HR 1.426, 95% CI 1.007-2.018; P = 0.045) and SPF CYFRA21-1 (HR 1.597, 95% CI 1.181-2.158; P = 0.002) were independent predictive variables for shorter PFS. Results are shown in Table 2.