Pre‑treatment Cytokines Plus TPSA Predict Biochemical Progression‑Free Survival in Prostate Cancer Metastasis and Discriminate Metastatic Status: A Retrospective Study

Kefan Mao¹Jing Sun²Chen Sun¹Bo-Bo Sun¹Zhi-Gang Wu¹Jian Cai¹Chao-Feng Zhou^1*

• ¹The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
• ²Wenzhou Medical University, Wenzhou, China

Prostate cancer (PCa) ranks as the second most common malignancy in men worldwide. While serum prostate‑specific antigen (PSA) is routinely monitored, its low specificity frequently leads to overdiagnosis. Cytokines within the tumor microenvironment (TME) demonstrate strong tumor‑progression associations, but their combined predictive utility with PSA for metastasis and chemotherapy response remains undetermined. This study investigates the combined predictive value of PSA and cytokines for PCa metastasis and treatment outcomes. This study aimed to quantify cross‑sectional differences in pre‑treatment cytokine levels based on metastatic status, assess their prognostic value for biochemical progression‑free survival in metastatic patients, and characterize cytokine profiles from baseline to biochemical recurrence.We retrospectively analyzed 328 PCa patients (175 metastatic, 153 non‑metastatic), collecting data on age, smoking history, Gleason score, total PSA (TPSA), and cytokines. Metastasis‑associated factors were identified by Spearman correlation and logistic regression. Predictive models were evaluated using ROC curves/AUC analysis. Prognostic models were evaluated using ROC curves/AUC analysis. Multi index combination was used to find the best prediction efficiency group. Multi index combination was used to find the best prognostic group.Survival analysis employed Kaplan‑Meier methodology, while Cox regression assessed post‑chemotherapy PSA rebound predictors. We find that smoking, TPSA, and IL‑8 emerged as independent metastasis risk factors. Predictive Prognostic indices PRE1 (smoking, TPSA, IL‑8) and PRE2 (all significant factors) achieved AUCs of 0.788 and 0.787 respectively, with PRE1 demonstrating superior calibration. The AUC of TPSA+IL‑6+IL‑8+IL‑10 four factor combination was 0.753, and the prediction efficiency was the best, and this combination yielded high prognostic performance, and the proportion of metastasis group was significantly higher than that of non‑metastasis group. Univariate Cox analysis associated age, TPSA, IL‑6, IL‑8, and TNF‑α with PSA rebound, though multivariate analysis identified no independent predictors. These results underscore the immunological relevance of specific cytokines in PCa progression and their potential as complementary biomarkers to PSA for improving risk stratification.