Imaging Efficacy of [18F]CTT1057 PET/CT in Patients with Biochemically Recurrent Prostate Cancer: Results from GuidePath-A Phase 3, Prospective Multicenter Study

Abstract

Improved diagnostic accuracy in patients with prostate cancer at first biochemical recurrence (BCR) with low prostate-specific antigen (PSA) levels is needed. This prospective study (GuidePath; NCT04838613) aimed to evaluate the imaging performance of the prostate-specific membrane antigen (PSMA)-targeted PET radiotracer [¹⁸F]CTT1057 to detect PSMA-positive lesions in patients diagnosed predominantly at first BCR. Methods: Eligible patients had a PSA of 0.2 ng/mL or greater after radical prostatectomy or an increase in PSA level of at least 2 ng/mL above nadir after radiation therapy. Patients received 370 MBq of [¹⁸F]CTT1057 and 150 MBq of [⁶⁸Ga]Ga-PSMA-11 and underwent PET/CT 90 min (±30 min) and 50-100 after injection, respectively. [¹⁸F]CTT1057 images were assessed by 3 independent readers blinded to all clinical information. Coprimary endpoints were region-level correct localization rate (CLR) and patient-level positive predictive value (PPV) of [¹⁸F]CTT1057 to detect PSMA-positive lesions and were compared with a hierarchical composite truth standard (CTS). The CTS comprised 3 levels of standard-of-truth procedures (in order of priority): histopathology (CTS level 1); imaging, including at least 1 contrast-enhanced CT scan and 1 [⁶⁸Ga]Ga-PSMA-11 PET/CT scan (CTS level 2); and a decrease in PSA level of 50% or greater 3 mo after radiation therapy (CTS level 3). For study success, the lower-bound 95% CI had to surpass 50% for region-level CLR and 20% for patient-level PPV for at least 2 of the 3 [¹⁸F]CTT1057 PET/CT readers. Results: Of 202 patients screened, 161 were evaluable for efficacy. Among these, 93.2% were experiencing their first BCR, 96.3% had received radical prostatectomy as initial definitive therapy, and baseline median PSA level was 0.4 ng/mL (interquartile range, 0.3-0.8 ng/mL). The imaging standard of truth was used for 159-160 patients (99%) across the 3 readers. Both coprimary endpoints were met. Region-level CLR ranged from 65.2% to 75.0% (lower-bound 95% CI, 53.4%-62.1%), and patient-level PPV ranged from 64.6% to 76.5% (lower-bound 95% CI, 51.8%-62.5%). Conclusion: [¹⁸F]CTT1057 met the predefined thresholds for region-level CLR and patient-level PPV in a clinically relevant patient cohort predominantly at first BCR with low PSA levels. [¹⁸F]CTT1057 is an accurate PSMA-targeted PET radiotracer for BCR detection.

Keywords: PET; [18F]CTT1057; biochemical recurrence; clinical trial; prostate-specific membrane antigen.

Graphical abstract

FIGURE 1.

[¹⁸F]CTT1057 and [⁶⁸Ga]Ga-PSMA-11 PET/CT scan images (axial slices) showing true-positive prostate bed lesion. True-positive [¹⁸F]CTT1057 and [⁶⁸Ga]Ga-PSMA-11 prostate bed lesion (blue arrows) in 71-y-old patient with BCR (pT2c; Gleason score, 7 [4 + 3]) diagnosed 56 mo after initial RP (PSA level at time of PET scans, 0.49 ng/mL). HU = Hounsfield unit.

FIGURE 2.

[¹⁸F]CTT1057 and [⁶⁸Ga]Ga-PSMA-11 PET/CT scan images (axial slices) showing true-positive lesions in pelvic lymph node metastases. True-positive [¹⁸F]CTT1057 and [⁶⁸Ga]Ga-PSMA-11 perirectal lymph node (A, green arrow) and left external iliac lymph node (B, red arrows) lesions in 71-y-old patient with BCR (pT3a; Gleason score, 7 [3 + 4]) diagnosed 67 mo after initial RP (PSA level at time of PET scans, 0.25 ng/mL). HU = Hounsfield unit.

FIGURE 3.

Overall region-level CLR (A) and patient-level PPV (B) of [¹⁸F]CTT1057 PET/CT (efficacy analysis set). Data for each reader presented as mean percentage, with 95% CI in parentheses.