Serum [-2]proPSA as a Candidate Phenotypic Correlate of Molecular Alterations and Prognostic Marker in Metastatic Castration-Resistant Prostate Cancer.
- 1Unit of Medical Oncology and Biomolecular Therapy and CREATE Center for Research and Innovation Medicine Department of Medical and Surgical Sciences Policlinico Riuniti University of Foggia Foggia Italy unifg.it.
- 2Department of Translational Medical Sciences University of Naples "Federico II" Naples 80131 Italy unina.it.
Abstract
Background
Serum biomarkers that complement molecular profiling and provide prognostic information are of interest in metastatic castration-resistant prostate cancer (mCRPC).Methods
We performed a single-centre retrospective exploratory analysis of 31 patients with mCRPC receiving systemic therapy. Baseline serum total PSA, free PSA, [-2]proPSA (p2PSA) and prostate health index (PHI) were evaluated together with tumour somatic molecular alterations and overall survival (OS). Baseline p2PSA was analysed both continuously after log2 transformation and using an exploratory 300 pg/mL threshold. On-treatment p2PSA change was reanalysed as a time-dependent covariate because follow-up sampling occurred at variable times.Results
Median age was 75.1 years (range 60.2-83.2). Median follow-up was 38.3 months (95% CI 22.5-42.8). Each doubling of baseline p2PSA was associated with shorter OS (HR 1.51, 95% CI 1.16-1.96; p = 0.0019). Patients with p2PSA > 300 pg/mL (n = 8; 6 deaths) had shorter OS than those with p2PSA ≤ 300 pg/mL (n = 23; 8 deaths; HR 4.61, 95% CI 1.46-14.56; log-rank p = 0.0043). Total PSA, free PSA and PHI were also associated with OS, and adding p2PSA to total PSA did not significantly improve model fit (likelihood-ratio p = 0.156). Baseline p2PSA was higher in patients with a pathogenic/likely pathogenic somatic alteration detected (n = 9) than in those with no pathogenic alteration detected (n = 22; Mann-Whitney p = 0.0348; Cliff's delta 0.49), but this association attenuated after exclusion of extreme values. On-treatment p2PSA change was not associated with OS after time-dependent modelling (failure to achieve ≥ 50% decline: HR 1.44, 95% CI 0.42-4.90; p = 0.557).Conclusions
In this small hypothesis-generating mCRPC cohort, higher baseline p2PSA was associated with poorer OS and with the presence of pathogenic/likely pathogenic somatic tumour alterations. These findings support prospective validation of p2PSA as an exploratory prognostic marker and candidate phenotypic correlate, rather than a surrogate for tumour genomics.
Related
- Prevalence of homologous recombination repair genes alterations in metastatic castration-resistant prostate cancer, a multicentric study
- Peripheral blood mRNA-based prognostic model for progression to metastatic castration-resistant prostate cancer and identification of SLC6A8 as a glycolysis-promoting biomarker
- Prognostic Value of Baseline High-Uptake PSMA Tumor Volume Fraction in Metastatic Castration-Resistant Prostate Cancer Patients Treated with [177Lu]Lu-PSMA Radioligand Therapy
- A Literature-Derived Muscle Wasting-Related Prognostic Signature Identifies ZBTB7C as a Candidate Associated with Tumor-Related Skeletal Muscle Alterations in Esophageal Cancer
- Real‐World Overall Survival With Abiraterone Acetate and Enzalutamide in Patients With Chemotherapy‐Naïve Metastatic Castration‐Resistant Prostate Cancer From the Flatiron Electronic Health Records Database
BibTeX
@article{conteduca2026serum,
title = {{Serum [-2]proPSA as a Candidate Phenotypic Correlate of Molecular Alterations and Prognostic Marker in Metastatic Castration-Resistant Prostate Cancer.}},
author = {Vincenza Conteduca and Marianna Garofoli and Giuseppina Bruno and Matteo Landriscina and Mariano Fiorenza and Carmela Polito and Rosa Sirica and Daniela Terracciano},
journal = {Prostate cancer},
year = {2026},
month = oct,
doi = {10.1155/proc/4207108},
url = {https://europepmc.org/article/MED/42959566},
note = {CC BY},
}
RIS
TY - JOUR
TI - Serum [-2]proPSA as a Candidate Phenotypic Correlate of Molecular Alterations and Prognostic Marker in Metastatic Castration-Resistant Prostate Cancer.
AU - Vincenza Conteduca
AU - Marianna Garofoli
AU - Giuseppina Bruno
AU - Matteo Landriscina
AU - Mariano Fiorenza
AU - Carmela Polito
AU - Rosa Sirica
AU - Daniela Terracciano
PY - 2026
DA - 2026/10/28
JO - Prostate cancer
DO - 10.1155/proc/4207108
UR - https://europepmc.org/article/MED/42959566
AB - Background Serum biomarkers that complement molecular profiling and provide prognostic information are of interest in metastatic castration-resistant prostate cancer (mCRPC).Methods We performed a single-centre retrospective exploratory analysis of 31 patients with mCRPC receiving systemic therapy. Baseline serum total PSA, free PSA, [-2]proPSA (p2PSA) and prostate health index (PHI) were evaluated together with tumour somatic molecular alterations and overall survival (OS). Baseline p2PSA was analysed both continuously after log2 transformation and using an exploratory 300 pg/mL threshold. On-treatment p2PSA change was reanalysed as a time-dependent covariate because follow-up sampling occurred at variable times.Results Median age was 75.1 years (range 60.2-83.2). Median follow-up was 38.3 months (95% CI 22.5-42.8). Each doubling of baseline p2PSA was associated with shorter OS (HR 1.51, 95% CI 1.16-1.96; p = 0.0019). Patients with p2PSA > 300 pg/mL (n = 8; 6 deaths) had shorter OS than those with p2PSA ≤ 300 pg/mL (n = 23; 8 deaths; HR 4.61, 95% CI 1.46-14.56; log-rank p = 0.0043). Total PSA, free PSA and PHI were also associated with OS, and adding p2PSA to total PSA did not significantly improve model fit (likelihood-ratio p = 0.156). Baseline p2PSA was higher in patients with a pathogenic/likely pathogenic somatic alteration detected (n = 9) than in those with no pathogenic alteration detected (n = 22; Mann-Whitney p = 0.0348; Cliff's delta 0.49), but this association attenuated after exclusion of extreme values. On-treatment p2PSA change was not associated with OS after time-dependent modelling (failure to achieve ≥ 50% decline: HR 1.44, 95% CI 0.42-4.90; p = 0.557).Conclusions In this small hypothesis-generating mCRPC cohort, higher baseline p2PSA was associated with poorer OS and with the presence of pathogenic/likely pathogenic somatic tumour alterations. These findings support prospective validation of p2PSA as an exploratory prognostic marker and candidate phenotypic correlate, rather than a surrogate for tumour genomics.
SN - 2090-3111
SN - 2090-312X
ER -