Prostate-specific membrane antigen PET–CT for diagnosis in patients with suspected prostate cancer: a post-hoc analysis of the randomised, controlled, phase 3 RAPID trial

Background Prostate-specific membrane antigen (PSMA) PET–CT is a promising imaging modality for diagnosing clinically significant primary prostate cancer (csPCa). Its clinical value has been shown, particularly in patients with high-risk disease and in those with biochemical recurrence; however, evidence for its use in diagnostic-naive patients with suspected prostate cancer before biopsy remains limited. Therefore, in this study, we evaluated the diagnostic and prognostic value of PSMA PET–CT for the identification of csPCa. Methods We conducted a post-hoc analysis of the RAPID study, a randomised, controlled, single-centre, open-label phase 3 trial (NCT02659527) done at the Vienna General Hospital (Vienna, Austria), in adult men (≥18 years) with elevated prostate-specific antigen (PSA) concentrations (>4·0 ng/mL), increasing PSA levels under antibiotic treatment, or a free-to-total PSA ratio less than 22%, and no previous prostate cancer treatment, comparing the diagnostic efficacy of dual-tracer [ 18 F]fluoroethylcholine–[ 68 Ga]Ga-PSMA-11 PET–MRI with transrectal ultrasound-guided prostate biopsy. Patients were randomised to a standard biopsy group or an image-guided biopsy group, and the primary trial outcome has been reported previously. In this post-hoc secondary analysis, we focused on PSMA PET–CT data. All participants underwent an additional PSMA PET–CT after PET–MRI. The primary outcome of the post-hoc analysis was the diagnostic performance of PSMA PET–CT, and the secondary outcome was the prognostic performance of PSMA PET–CT in identifying an aggressive course of disease in patients with a follow-up duration of at least 2 years. Histopathological findings of biopsy and prostatectomy specimens were used as reference standards. Aggressive course of disease was defined as a composite endpoint, including metastatic disease at baseline, an increase of more than 0·2 ng/mL in PSA concentration after radical prostatectomy, or (chemo)hormonal therapy as primary treatment. PSMA PET–CT images were independently assessed by three experienced nuclear medicine physicians masked to the histopathological and PET–MRI findings. Diagnostic accuracy was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Findings 194 patients underwent PSMA PET–CT imaging in the RAPID trial and were included in this analysis. PSMA PET–CT identified prostate cancer in 84 (79%) of 106 histologically confirmed prostate cancers (The International Society of Urological Pathology [ISUP] grade group 1–5), with 79% (95% CI 71–86) sensitivity, 59% (49–69) specificity, 70% (61–78) PPV and 70% (59–80) NPV. In addition, PSMA PET–CT identified csPCa (ISUP grade group ≥2) in 70 (91%) of 77 histologically confirmed prostate cancers, with 91% (95% CI 82–96) sensitivity, 57% (48–66) specificity, 58% (49–67) PPV, and 91% (82–95) NPV. During a median follow-up period of 35 months (IQR 32–38), PSMA PET–CT identified prostate cancer with an aggressive course of disease in 23 (96%) of 24 men, among 176 patients eligible for follow-up analysis. Interpretation PSMA PET–CT had high sensitivity and a high NPV for the detection of csPCa and could help to reduce unnecessary biopsies in patients with negative PET findings. These results suggest a potential role for PSMA PET–CT in the initial diagnostic assessment of patients with elevated PSA and suspected prostate cancer. Funding Siemens Healthineers, Alliance Medical BSM, Medical University of Vienna, and Vienna General Hospital.