Clinical pathological changes in prostate cancer patients after hormonal therapy: A single-center pilot study.
This study highlights potential biomarkers in prostate cancer but emphasizes the need for larger, multicenter studies to validate these findings before clinical application.
Where it sits
this study against the rest of the goserelin corpusSummary and findings
This study evaluated plasma coagulation parameters, inflammatory cytokines, and molecular markers in prostate cancer patients undergoing hormonal therapy. The study involved 32 patients and measured changes before and after six months of treatment. Hormonal therapy partially reversed certain alterations toward values observed in benign prostatic hyperplasia and healthy controls.
Abstract
<h4>Background</h4>Prostate cancer (PCa) remains a leading malignancy with variable prognosis, and while PSA is widely used for disease monitoring, it frequently lacks sufficient specificity. This study investigated plasma coagulation parameters, inflammatory cytokines, and molecular markers as complementary biomarkers in PCa patients undergoing hormonal therapy.<h4>Methods</h4>In a prospective single-center pilot study, patients with newly diagnosed PCa were evaluated alongside patients with benign prostatic hyperplasia (BPH) and healthy men as controls. Coagulation parameters (PT, INR, APTT, fibrinogen, D-dimer), inflammatory cytokines (IFN-γ, IL-1β, TGF-β), and gene expression of p53 and NF-κB were measured before and after six months of hormonal therapy. Statistical analyses included non-parametric tests, ROC curve analysis, Firth penalized logistic regression adjusted for age, tumor grade, and PSA, and internal validation via 5-fold cross-validation and 1000-iteration bootstrapping.<h4>Results</h4>PCa patients exhibited a hypercoagulable state, with elevated IL-1β, p53, and NF-κB, alongside reduced IFN-γ and TGF-β, compared with BPH and healthy controls. Hormonal therapy partially reversed these alterations toward values observed in the BPH and healthy control groups. ROC analysis demonstrated high discriminatory potential for IL-1β and NF-κB (AUC = 1.000) in the full dataset; however, this likely reflects near-perfect group separation in a small cohort (n = 32 PCa). Internal validation via 5-fold cross-validation and 1000-iteration bootstrapping yielded a corrected mean AUC of 0.725 (95% CI: 0.58-0.87), which is the primary performance estimate reported.<h4>Conclusion</h4>Coagulation disturbances, cytokine imbalance, and alterations in molecular markers are closely associated with PCa biology and short-term therapeutic response. These findings are hypothesis-generating, and long-term clinical endpoints, including biochemical recurrence and survival, require evaluation in adequately powered, multicenter longitudinal studies before these biomarkers can be considered for clinical integration.
Background
This paper addresses the need for more specific biomarkers in prostate cancer (PCa) monitoring, as PSA often lacks specificity. Previous studies have indicated potential roles for coagulation parameters and inflammatory cytokines in cancer biology. This study aims to explore these markers in PCa patients undergoing hormonal therapy, contributing to the understanding of their therapeutic response.
Methods
This was a prospective single-center pilot study involving 32 patients with newly diagnosed PCa, alongside patients with benign prostatic hyperplasia (BPH) and healthy controls. Coagulation parameters, inflammatory cytokines, and gene expression were measured before and after six months of hormonal therapy. Statistical analyses included non-parametric tests, ROC curve analysis, and Firth penalized logistic regression adjusted for confounding factors.
Results
PCa patients exhibited a hypercoagulable state with elevated IL-1β, p53, and NF-κB, and reduced IFN-γ and TGF-β compared to controls. Hormonal therapy partially reversed these changes. The ROC analysis indicated an AUC of 1.000 for IL-1β and NF-κB, but the corrected mean AUC was 0.725 (95% CI: 0.58-0.87) after internal validation.
Interpretation
The findings suggest that coagulation disturbances and cytokine imbalances are associated with PCa biology and short-term responses to hormonal therapy. However, the effect sizes, while statistically significant, may not be clinically meaningful given the small sample size. The study's limitations, including its single-center design and lack of long-term clinical endpoints, restrict the conclusions that can be drawn.
Key findings
- AUC for IL-1β and NF-κB was 1.000 in the full dataset.
- Corrected mean AUC via internal validation was 0.725 (95% CI: 0.58-0.87).
- PCa patients exhibited elevated IL-1β, p53, and NF-κB.
- PCa patients showed reduced IFN-γ and TGF-β compared to controls.
Limitations
- small n=32
- single-center design
- short follow-up of six months
- no long-term clinical endpoints evaluated