Tumor Prostate-Specific Antigen Density Can Predict Tumor Aggressiveness and Heterogeneity in Prostate Cancer

Prostate cancer is a highly heterogeneous disease, this study assessed the association between tumor prostate-specific antigen density (TPSAD) and tumor heterogeneity in prostate cancer.

A retrospective study was performed from January 2022 to December 2024 to analyze the correlation between TPSAD and subsequent clinical features in patients with nonmetastatic prostate cancer. The tumor volume was delineated by two radiologists on multi-parametric prostate MRI images using three-dimensional (3D) Slicer software; the TPSAD was calculated by dividing the serum PSA density by the tumor volume. The clinical features between patients with low TPSAD and high TPSAD were analyzed. Immunohistochemistry (IHC) was performed to analyze RB1, TP53, PTEN, and neuroendocrine differentiation (NED) markers in tumor species, to evaluate the heterogeneity of prostate cancer.

A total of 172 patients were enrolled in the study; the median tumor volume was 5.47 cm³, and the median TPSAD was 3.50 ng/mL/cm³. Differential analysis showed that patients with low TPSADs had a higher tumor volume (18.82 vs. 2.10 cm³), were in a higher ISUP group, and presented with a higher T stage compared with patients with high TPSADs (p < 0.001). Univariate and multivariate logistic regression analyses indicated that the TPSAD was an independent protective factor for ISUP 5 pathological type (aOR = 0.846, 95% CI: 0.746-0.959; p = 0.009), and low TPSAD indicated a shorter biochemical recurrence-free survival in patients received radical prostatectomy (25.5 months vs. not reached, p = 0.007). The IHC indicated that patients with a low TPSADs had reduced PSA expression and a higher positive KI67 index in tumor tissues compared with patients with a high TPSADs. Further molecular detection found higher incidences of PTEN loss and NED in patients with low TPSADs (all p < 0.05).

TPSAD represents a good predictor of prostate cancer heterogeneity. A low TPSAD indicates prostate cancer with high aggressiveness and poor prognosis, which is associated with low PSA expression and high heterogeneity in the tumor.