Can Tc-99m-PSMA SPECT/CT Be Used as Accessible Alternative for Diagnosis of Biochemically Recurrent Prostate Cancer? A Prospective Study

<b>Objective:</b> To evaluate Tc-99m-PSMA SPECT/CT detection of biochemical recurrence (BCR) of prostate cancer across serum PSA levels in patients treated with radical prostatectomy or radiation therapy, to explore clinical/pathologic predictors of scan positivity and metastatic disease, and to assess its potential role as a pragmatic alternative when PSMA PET/CT is unavailable in resource-limited settings. <b>Materials and Methods</b>: In this prospective single-center study, we included 132 men with biochemical recurrence who underwent Tc-99m-PSMA SPECT/CT between January 2024 and December 2025 after predefined inclusion and exclusion criteria were applied, and they were further stratified by primary treatment (radical prostatectomy or radiation therapy). Patients were followed up for up to 6 months after imaging to verify observed findings (histopathology, confirmatory imaging and PSA response) and a logistic regression was applied to identify predictors of scan positivity and metastatic disease. <b>Results</b>: In men initially treated with radical prostatectomy, detection increased from 38.9% at PSA 0.2 to <2 ng/mL to 63.2% at 2 to <4 ng/mL, 71.4% at 4 to <7 ng/mL, and 90% at PSA ≥ 7 ng/mL (overall 69.1%). In the radiation therapy cohort, detection was 58.3% at PSA 2 to <4 ng/mL, rising to 85.7% at 4 to <7 ng/mL and 96% at PSA ≥ 7 ng/mL (overall 84.3%). In the multivariable analysis, PSA doubling (log2[PSA]) independently predicted scan positivity and metastatic disease in both cohorts, while seminal vesicle invasion independently predicted metastatic spread in the post-prostatectomy group. <b>Conclusions:</b> Tc-99m-PSMA SPECT/CT is a useful tool for detecting prostate cancer BCR, with performance strongly dependent on PSA and higher detection in patients with higher PSA levels. Increasing PSA independently predicted scan positivity and metastatic disease, while seminal vesicle invasion was independently associated with metastatic spread. In settings where PSMA PET/CT is unavailable, Tc-99m-PSMA SPECT/CT may represent a practical alternative, particularly for patients with elevated PSA.