Background and purpose The metabolic phenotype of negative prostate-specific membrane antigen (PSMA) and positive [18F]F-fluorodeoxyglucose ([18F]F-FDG) uptake is an established indicator of unfavorable prognosis in advanced-stage prostate cancer. It is also associated with resistance to PSMA-targeted therapies. However, its prognostic significance in the preoperative setting for treatment-naive patients scheduled for therapy with curative intent remains to be elucidated. This study aimed to investigate whether metabolic heterogeneity assessed by dual-tracer [68 Ga]Ga-PSMA-11 and [18F]F-FDG PET/CT could predict biochemical recurrence after radical. Methods This retrospective cohort study included 104 treatment-naive prostate cancer patients who underwent both [68 Ga]Ga-PSMA-11 and [18F]F-FDG PET/CT before radical prostatectomy. Based on tracer uptake in the primary tumor, patients were stratified into three metabolic subgroups: PSMA-positive/FDG-positive (n = 65), PSMA-positive/FDG-negative (n = 30), and PSMA-negative/FDG-positive (n = 9). The primary endpoint was biochemical progression-free survival (bPFS). Univariate and multivariate Cox regression analyses were performed to identify independent predictors of bPFS. Results Of the 104 patients, 65 had positive uptake for both [68 Ga]Ga-PSMA-11 and [18F]F-FDG, 30 patients had positive uptake for [68 Ga]Ga-PSMA-11 and negative for [18F]F-FDG, and 9 patients had negative uptake for [68 Ga]Ga-PSMA-11 and positive for [18F]F-FDG. Metabolic subgrouping was identified as an independent predictor of biochemical recurrence following radical prostatectomy (P = 0.044). The [68 Ga]Ga-PSMA-11 negative/[18F]F-FDG positive group had the lowest 3-year bPFS rate (1/9, 11.11%), followed by the [68 Ga]Ga-PSMA-11 positive/[18F]F-FDG positive group (19/65, 29.23%), and the [68 Ga]Ga-PSMA-11 positive/[18F]F-FDG negative group (17/30, 56.67%), with significant differences (P = 0.009). Conclusions The preoperative PSMA-negative/FDG-positive phenotype is a significant and independent predictor of early biochemical recurrence following radical prostatectomy in treatment-naive prostate cancer. These findings suggest that dual-tracer PET/CT may serve as a valuable preoperative risk stratification tool to identify patients with aggressive disease who might be suitable for neoadjuvant or intensified adjuvant therapeutic strategies.

Dual-tracer PET/CT identifies an aggressive PSMA-negative/FDG-positive phenotype predicting early failure of radical prostatectomy in treatment-naive prostate cancer

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发表日期：

2025年11月10日

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Ruohua Chen,
Yining Wang,
Qiaochu Chen,
Liang Dong,
Gang Huang,
Jianjun Liu

摘要

Background and purpose

The metabolic phenotype of negative prostate-specific membrane antigen (PSMA) and positive [¹⁸F]F-fluorodeoxyglucose ([¹⁸F]F-FDG) uptake is an established indicator of unfavorable prognosis in advanced-stage prostate cancer. It is also associated with resistance to PSMA-targeted therapies. However, its prognostic significance in the preoperative setting for treatment-naive patients scheduled for therapy with curative intent remains to be elucidated. This study aimed to investigate whether metabolic heterogeneity assessed by dual-tracer [⁶⁸ Ga]Ga-PSMA-11 and [¹⁸F]F-FDG PET/CT could predict biochemical recurrence after radical.

Methods

This retrospective cohort study included 104 treatment-naive prostate cancer patients who underwent both [⁶⁸ Ga]Ga-PSMA-11 and [¹⁸F]F-FDG PET/CT before radical prostatectomy. Based on tracer uptake in the primary tumor, patients were stratified into three metabolic subgroups: PSMA-positive/FDG-positive (n = 65), PSMA-positive/FDG-negative (n = 30), and PSMA-negative/FDG-positive (n = 9). The primary endpoint was biochemical progression-free survival (bPFS). Univariate and multivariate Cox regression analyses were performed to identify independent predictors of bPFS.

Results

Of the 104 patients, 65 had positive uptake for both [⁶⁸ Ga]Ga-PSMA-11 and [¹⁸F]F-FDG, 30 patients had positive uptake for [⁶⁸ Ga]Ga-PSMA-11 and negative for [¹⁸F]F-FDG, and 9 patients had negative uptake for [⁶⁸ Ga]Ga-PSMA-11 and positive for [¹⁸F]F-FDG. Metabolic subgrouping was identified as an independent predictor of biochemical recurrence following radical prostatectomy (P = 0.044). The [⁶⁸ Ga]Ga-PSMA-11 negative/[¹⁸F]F-FDG positive group had the lowest 3-year bPFS rate (1/9, 11.11%), followed by the [⁶⁸ Ga]Ga-PSMA-11 positive/[¹⁸F]F-FDG positive group (19/65, 29.23%), and the [⁶⁸ Ga]Ga-PSMA-11 positive/[¹⁸F]F-FDG negative group (17/30, 56.67%), with significant differences (P = 0.009).

Conclusions

The preoperative PSMA-negative/FDG-positive phenotype is a significant and independent predictor of early biochemical recurrence following radical prostatectomy in treatment-naive prostate cancer. These findings suggest that dual-tracer PET/CT may serve as a valuable preoperative risk stratification tool to identify patients with aggressive disease who might be suitable for neoadjuvant or intensified adjuvant therapeutic strategies.