Study of PSMA PET/CT Imaging to Help Select Men With Low-Risk Prostate Cancer for Active Surveillance

Prostate cancer is the most common malignancy in men and demonstrates heterogeneous clinical behavior. While many low-risk patients have indolent disease, a subset harbors clinically significant prostate cancer (csPCa) requiring early intervention. Active Surveillance (AS) is widely used to avoid overtreatment; however, current selection criteria-PSA, DRE, biopsy Gleason score, number of positive cores, PSA density, and mpMRI-lack sufficient predictive accuracy. Studies indicate that up to 30% of patients classified as low-risk by biopsy are found to have higher-grade disease at radical prostatectomy. The Istanbul PSMA PET/CT Criteria (IPPC) were developed by a multidisciplinary expert panel in Turkey to classify intraprostatic lesions on delayed (120-minute) Ga-68 PSMA PET/CT imaging into three risk categories:

• IPPC 1 No or homogeneous low uptake - safe for monitoring.
• IPPC 2: Indeterminate uptake - AS with close follow-up.
• IPPC 3: Focal, lentiform, high SUVmax ≥12 uptake in peripheral zone - definitive treatment recommended.

This study will evaluate the diagnostic performance of IPPC compared to standard mpMRI and biopsy findings, using radical prostatectomy pathology or long-term clinical follow-up as the reference standard.

Inclusion criteria

• mpMRI performed within 3 months prior to enrollment
• Systematic or MRI-targeted prostate biopsy performed
• Biopsy-confirmed ISUP Grade 1 low-risk PCa
• Prostate biopsy report specifying tumor localization and number of positive cores
• Meets AS criteria: ISUP 1, PSA ≤10 ng/mL, PSAd >0.15 ng/mL², clinical stage cT1c-T2a, ≤3 positive cores
• Life expectancy ≥10 years
• No prior PSMA PET imaging
• No evidence of extra-prostatic disease on mpMRI
• Signed informed consent for study procedures

Exclusion criteria

• High-risk or unfavorable intermediate-risk PCa, or adverse histologies (neuroendocrine, ductal adenocarcinoma, basal cell carcinoma, TP53 or BRCA1/2 mutations if available)
• Prior prostate cancer treatment or prostate surgery
• MRI evidence of extracapsular extension, seminal vesicle invasion, or nodal metastasis
• History of pelvic radiotherapy
• Life expectancy <10 years
• Severe renal impairment
• Inability to comply with follow-up schedule