AUTHOR=Mao Ke-Fan , Sun Jing , Sun Chen , Sun Bo-Bo , Wu Zhi-Gang , Cai Jian , Zhou Chao-Feng 

TITLE=Pre−treatment cytokines plus TPSA predict biochemical progression−free survival in prostate cancer metastasis and discriminate metastatic status: a retrospective study

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1686570

DOI=10.3389/fimmu.2025.1686570

ISSN=1664-3224

ABSTRACT=IntroductionProstate 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 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.MethodsWe 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. Prognostic models were evaluated using ROC curves/AUC analysis. 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.IntroductionWe find that smoking, TPSA, and IL-8 emerged as independent metastasis risk factors. 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 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.DiscussionThese results underscore the immunological relevance of specific cytokines in PCa progression and their potential as complementary biomarkers to PSA for improving risk stratification.