Plasma progastrin-releasing peptide level shows different predictive profiles for treatment response by androgen receptor axis-targeted agents in patients with metastatic castration-resistant prostate cancer.

Autor: Yashi M; Department of Urology, Dokkyo Medical University, Tochigi, Japan., Nishihara D; Department of Urology, Dokkyo Medical University, Tochigi, Japan., Yokoyama M; Department of Urology, Dokkyo Medical University, Tochigi, Japan., Fuchizawa H; Department of Urology, Dokkyo Medical University, Tochigi, Japan., Okazaki A; Department of Urology, Dokkyo Medical University, Tochigi, Japan., Takei K; Department of Urology, Dokkyo Medical University, Tochigi, Japan., Suzuki I; Department of Urology, Dokkyo Medical University, Tochigi, Japan., Sakamoto K; Department of Urology, Dokkyo Medical University, Tochigi, Japan., Kijima T; Department of Urology, Dokkyo Medical University, Tochigi, Japan., Kobayashi M; Department of Urology, Utsunomiya Memorial Hospital, Tochigi, Japan., Kamai T; Department of Urology, Dokkyo Medical University, Tochigi, Japan.
Jazyk: angličtina
Zdroj: Cancer reports (Hoboken, N.J.) [Cancer Rep (Hoboken)] 2023 Mar; Vol. 6 (3), pp. e1762. Date of Electronic Publication: 2022 Dec 05.
DOI: 10.1002/cnr2.1762
Abstrakt: Background: The neuroendocrine (NE) pathway cannot be ignored as a mechanism for castration-resistant prostate cancer (CRPC) progression. The neuromediator, gastrin-releasing peptide (GRP) may be involved in the aberrant activation of the normal androgen receptor (AR) and increased AR variants. This study focused on plasma levels of progastrin-releasing peptide (ProGRP) and examined the treatment outcomes with androgen receptor axis-targeted (ARAT) agents.
Methods: One hundred patients with metastatic CRPC were enrolled. Enzalutamide (ENZ) or abiraterone acetate/prednisone (AA/P) were administered to 50 patients each in a nonrandomized manner as a first-line or later choice. Plasma ProGRP levels were determined using a chemiluminescent enzyme immunoassay, and data were collected prospectively. The study endpoints were prostate-specific antigen (PSA) response and survival estimates.
Results: In the ENZ series, ProGRP levels correlated with the maximum PSA change from baseline (high ProGRP: -34.5% vs. low ProGRP: -85.7% p = .033). PSA progression-free survival (PFS), radiographic/symptomatic (r/s) PFS, and overall survival (OS) in patients with high ProGRP were significantly worse than those in patients with low ProGRP (median PSA-PFS: 3.3 vs. 10.0 months, p = .001, r/s PFS: 5.0 vs. 15.0 months, p < 0.001, and OS 17.5 vs. 49.0 months, p < .001, respectively). In addition, ProGRP showed an independent predictive value for all survival estimates in multivariate analyses. In the AA/P series, ProGRP levels did not correlate with the PSA change or predict PSA-PFS and r/s PFS, but they maintained a significant difference in OS (19.0 vs. 48.0 months, p = .003).
Conclusions: Plasma ProGRP provides a consistent predictive value for OS in metastatic CRPC patients who underwent therapy with ARAT agents. Meanwhile, ProGRP showed different predictive profiles for PSA- and r/s PFS between ENZ and AA/P. These findings clinically suggest a mechanism for CRPC progression involving the NE pathway via the GRP. The underlying mechanism of different predictive profiles by the ARAT agent should be explored in future research.
(© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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