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Background: To evaluate how prostate-specific antigen (PSA) levels decrease after removal of isolated prostate cancer (PCa) nodal metastases in relation to their diameter/volume ("PSA-density of PCa-metastases") and maximum standardized uptake value (SUV max )., Methods: A total of 83 consecutive patients with solitary nodal recurrence after radical prostatectomy who underwent prostate-specific membrane antigen-radioguided salvage surgery were retrospectively analyzed. Using multivariable linear regression models, the PSA-decrease after removal of each PCa-metastases (=PSA-contribution of each PCa-metastases) was correlated with the long axis diameter/estimated volume and the SUV max of each removed metastasis. Sizes were measured by imaging and histopathologic examination., Results: A total of 83 patients were included with a median (interquartile range [IQR]) PSA-decrease of 0.56 [0.22, 1.31] ng/mL after salvage surgery. The median [IQR] long axis diameters in imaging and histopathological examination were 8.0 [6.0, 11.0] mm and 8.4 [5.5, 11.1] mm, respectively. The median [IQR] estimated volumes were 0.13 [0.05, 0.32] cc (imaging) and 0.05 [0.02, 0.17] cc (pathology). In multivariable linear regression analyses, the estimated PSA-contribution ([95% confidence interval [CI]) of each millimeter of long axis diameter was 0.09 [0.03, 0.14] ng/mL (imaging) or 0.08 [0.03, 0.12] ng/mL (histology). The minimum diameter for biochemical recurrence (PSA ≥ 0.2 ng/mL) was >2.2 mm (imaging) or >2.5 mm (histology). The estimated PSA-contribution [95% CI] of each cc cancer volume was 1.23 [0.51, 1.94] ng/mL (imaging) or 1.46 [0.40, 2.52] ng/mL (histology). SUV max as surrogate parameter for tissue composition was associated with increased PSA-contribution of PCa-metastases (+0.03-0.05 ng/mL per unit increase)., Conclusions: The diameter/volume and SUV max of metastatic tissue correlate with its contribution to PSA levels. Therefore, very small metastases may produce too little PSA for biochemical recurrence., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)