Associations between progastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) and survival in patients with limited-stage small cell lung cancer (LS SCLC) receiving twice-daily chemoradiotherapy (BID CRT)

There are no established biomarkers for predicting outcomes of chemoradiotherapy (CRT) in limited-stage small cell lung cancer (SCLC). Progastrin-releasing peptide (ProGRP) is a more sensitive and specific biomarker of SCLC than neuron-specific enolase (NSE). We investigated whether ProGRP was associated with treatment outcomes in a randomized phase II trial of LS SCLC (n = 170). Patients received platinum-etoposide chemotherapy and were randomized to receive twice-daily (BID) thoracic radiotherapy (TRT) of either 45 Gy or 60 Gy. Patients commencing TRT with baseline measurements of ProGRP and NSE were eligible for this study. We analyzed 89 patients. Median age was 65 years, 56.2 % were female, 89.9 % had performance status 0-1, and 85.4 % had stage III disease. At baseline, 79.8 % had elevated ProGRP and 58.4 % elevated NSE. After CRT, 23.6 % had elevated ProGRP and 5.6 % elevated NSE. Patients with elevated ProGRP at baseline had shorter PFS (median 12.2 months vs. not reached [NR], p = 0.006) and OS (median 29.3 months vs. NR, p = 0.001) than patient. Similarly, elevated ProGRP after CRT was associated with shorter PFS (median 11.1 months vs. NR, p = 0.006) and OS (median 30.6 months vs. NR, p = 0.002). Patients with elevated baseline ProGRP but normalized ProGRP after CRT had longer PFS (median 49.3 months vs. 7.8 months, p = 0.003) and OS (median NR vs. 30.5, p < 0.001) than patients with persistently elevated ProGRP. All associations remained significant in multivariable analyses. NSE was not associated with PFS or OS. ProGRP levels at baseline and after CRT were associated with PFS and OS in patients with LS SCLC.