[F]DCFPyL PET/CT versus [F]fluoromethylcholine PET/CT in Biochemical Recurrence of Prostate Cancer (PYTHON): a prospective, open label, cross-over, comparative study.

Purpose: Primary objective was to compare the per-patient detection rates (DR) of [F]DCFPyL versus [F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM).

Methods: This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [F]DCFPyL (investigational medicinal product) or [F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [F]DCFPyL and [F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs.

Results: A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [F]DCFPyL- and/or [F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [F]DCFPyL- compared to [F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [F]DCFPyL- and [F]fluoromethylcholine -PET/CT, respectively). [F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed.

Conclusions: The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [F]DCFPyL compared to [F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [F]DCFPyL was safe and well tolerated.