Prevalence and Medium-Term Outcomes of Patients with Biopsy-Proven Intermediate- to High-Risk Prostate Adenocarcinoma with Low Intraprostatic Uptake on [⁶⁸Ga]Ga-PSMA-11 PET/CT in the proPSMA Study

The current prevalence of low intraprostatic uptake for staging prostate-specific membrane antigen (PSMA) PET ranges between 4.4% and 17% in retrospective studies. We aimed to define the prevalence and describe the outcomes of patients with low intraprostatic uptake on PSMA PET/CT in the prospective proPSMA study. <b>Methods:</b> We identified patients with an SUV_max of 4 or less on PSMA PET/CT in the proPSMA study. Patients were followed up until 42 mo after randomization. The PRIMARY score was evaluated by 3 nuclear medicine physicians, with the result determined by consensus. Treatment failure was defined as new metastatic disease, biochemical recurrence, or initiation of salvage therapy. <b>Results:</b> Ten of 302 (3.3%; 95% CI, 1.6%-6.0%) patients had low intraprostatic uptake on PSMA PET/CT and normal findings on conventional imaging (CT and whole-body bone scanning). The median age was 66 y (interquartile range, 60.5-70.3 y). International Society of Urological Pathologists biopsy grade group was 3 in 5 patients and 5 in 5 patients, with no atypical histology identified. The median prostate-specific antigen level was 5.1 ng/nL (interquartile range, 2.3-8.3 ng/nL). The median follow-up interval was 30 mo (interquartile range, 24-39 mo). Multiparametric MRI was performed on 5 patients, with Prostate Imaging-Reporting and Data System score 5 in 2 patients, 4 in 1 patient, and 2 in 2 patients. The PRIMARY score was positive in 5 of 10 (50%) patients. Five (50%), 4 (30%), and 2 (20%) of 10 patients received radical prostatectomy, definitive radiotherapy, and androgen deprivation therapy alone, respectively. Of the 9 (90%) patients who received definitive treatment, 1 (11%) experienced treatment failure at 18 mo after radical prostatectomy and received metastasis-directed therapy. Biochemical recurrence was nonevaluable in the single patient who received androgen deprivation therapy alone. At the 42-mo follow-up after randomization, 4 of 9 (44%) patients who received definitive therapy remained on trial-none of whom had evidence of treatment failure. No other patients had new metastatic disease or initiation of salvage therapy during follow-up. <b>Conclusion:</b> In the proPSMA trial, there was a low prevalence (3.3%) of low intraprostatic uptake on PSMA PET/CT in patients with biopsy-confirmed prostate cancer, and treatment failure was infrequent.