Serial PSMA PET for Therapy Monitoring in Clinically Significant Prostate Cancer

This prospective, multicenter study aims to evaluate the clinical utility of serial PSMA PET for therapy monitoring in patients with newly diagnosed clinically significant prostate cancer.

Clinically significant prostate cancer is defined as Gleason score ≥7.Patients will undergo baseline PSMA PET/CT prior to any treatment. A second PSMA PET/CT will be performed either at PSA recurrence (PSA rise ≥2 ng/mL above nadir after radiotherapy or biochemical progression per PCWG3 criteria) or at a fixed time window of 12-24 months after treatment completion for those without biochemical recurrence.

Primary Outcome:

1\. Absolute and relative change in SUVmax from baseline to follow-up PSMA PET, correlated with treatment response categories (complete response, partial response, stable disease, progressive disease) defined by a composite reference standard (PSA kinetics, conventional imaging, clinical outcomes).

\[Time Frame: Baseline and follow-up (up to 24 months)\]

Secondary Outcomes:

1. Absolute and relative change in the number of PSMA-avid lesions (primary tumor, nodal, bone metastases) as a supportive exploratory endpoint. 2. Proportion of patients with treatment strategy change following serial PSMA PET. 3. Agreement between PSMA PET response (≥30% decrease in SUVmax) and PSA50 response (≥50% PSA decline) using Cohen's kappa. 4. Agreement between PSMA PET response and PSA90 response (≥90% PSA decline). 5. Prognostic value of baseline and follow-up PSMA PET parameters for progression-free survival (PFS). 6. Prognostic value of baseline and follow-up PSMA PET parameters for time to castration resistance (ADT-treated patients only). 7. Subgroup analyses by treatment type (radiotherapy, ADT, chemotherapy), baseline disease burden (oligometastatic vs. polymetastatic), and Gleason grade group (≤7 vs. ≥8). 8. Inter-reader agreement for PSMA-avid lesion counts. \[Time Frame: Up to 2 years, except inter-reader agreement at baseline\]

Need:

Current treatment response evaluation relies on PSA changes and conventional imaging, which lack sensitivity and accuracy for early assessment. PSMA PET has demonstrated superior sensitivity for detecting prostate cancer lesions, but its role in longitudinal therapy monitoring remains undefined, with no specific regulatory approval for this indication. Prospective data on serial PSMA PET to guide treatment decisions in patients with clinically significant prostate cancer (Gleason score ≥7) are urgently needed.

Inclusion Criteria:

1. Newly diagnosed, histologically confirmed clinically significant prostate cancer with Gleason score ≥7. 2. Planned curative-intent or systemic therapy. 3. Baseline PSMA PET performed prior to any treatment. 4. Age ≥18 years. 5. Written informed consent.

Exclusion Criteria:

1. Prior prostate cancer treatment before baseline PSMA PET. 2. Contraindication to PSMA PET imaging. 3. Other active malignancy within past two years (excluding non-melanoma skin cancer). 4. Unable to comply with follow-up schedule.