Predictive and prognostic value of baseline serum biomarkers for neuroendocrine differentiation in metastasized castrate-resistant prostate cancer patients treated with [Lu-177]-PSMA-617

Ziel/Aim To evaluate the predictive and prognostic value of neuroendocrine differentiation (NED) serum biomarkers chromogranin A (CgA) and neuron specific enolase (NSE) for treatment response after 2 cycles of Lu-177 PSMA (RLT) and overall survival (OS) in metastasized castration-resistant prostate cancer (mCRPC).

Methodik/Methods 28 consecutive mCRPC patients (69 ± 9y) undergoing RLT and minimum follow-up of 6 months after last RLT were included. Baseline PSAi, CgAi, NSEi, LDHi and APi prior to 1^st RLT were analyzed. PSA and PSMA-PET/CT (PET) based response assessment was performed at 4 and 6 weeks after the 2^nd RLT respectively. Statistical tests (Mann Whitney U test, Kaplan Meier curve and cox regression analyses) were performed using SPSS.

Ergebnisse/Results Patients were followed up (mean±SD) for 11.6 ± 5.2 months after median 4 (range 2-7) RLT cycles. Median OS was 17 (95% CI 13.7-20.3) months. Baseline CgA/NSE values (n,%) were elevated in (19,68)/(17,61) of patients. 12 (45%) had PSA-based partial response (PR; >50% PSA decrease), 9 (33%) stable disease (SD) and 6 (22%; >25% PSA increase) progression of disease (PD). On PET (n = 15) PR/SD/PD were observed in 33/27/40 % of patients. Elevated CgAi and NSEi did not predict PSA response. In univariate and multivariate analyses only elevated NSEi was found to be positive prognostic factor (p = 0.03) and elevated APi tends to be a negative prognostic factor (p = 0.05) for OS. PSA- and PET-based response after 2 RLT cycles did not correlate with prognosis.

Schlussfolgerungen/Conclusions mCRPC patients referred for RLT frequently harbor NED. Although initially elevated CgA and NSE as a marker for NED does not predict response after 2 cycles of RLT, NSEi appears to have a positive prognostic value. As enolase is involved in inflammatory processes, further research on RLT triggered changes in tumor microenvironment of CRPC metastases is needed. Patients with elevated neuroendocrine biomarkers should therefore not be excluded from an RLT.

Publication History

Article published online:
08 April 2021