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Simple Summary  The role of PET/CT with two novel tracers was investigated in prostate cancer patients with both a biochemical failure after surgery and a presumed local failure at multiparametric MR. Overall, both PET tracers detected only about 50% of local failures. Therefore, multiparametric MR remains the exam of choice to investigate the prostatic fossa in patients who fail surgery.    Abstract  Background: We aimed assess the detection rate (DR) of positron emission tomography/computed tomography with two novel tracers in patients referred for salvage radiotherapy (sRT) with a presumed local recurrence at multiparametric magnetic resonance (mpMR) after radical prostatectomy (RP). Methods: The present prospective study was conducted at a single institution between August 2017 and June 2020. Eligibility criteria were undetectable PSA after RP; subsequent biochemical recurrence (two consecutive PSA rises to 0.2 ng/mL or greater); a presumed local failure at mpMR; no distant metastases at  18 F-fluorocholine PET/CT (CH/PET); no previous history of androgen deprivation therapy. Patients were offered both  64 CuCl 2  PET/CT (CU/PET) and  64 Cu-PSMA PET/CT (PSMA/PET) before sRT. After image co-registration, PET findings were compared to mpMR ones in terms of DR and independent predictors of DR investigated at logistic regression. Results: A total of 62 patients with 72 nodules at mpMR were accrued. Compared to mpMR (DR = 100%, 95%CI: 94.9–100%), DRs were 47.2% (95%CI: 36.1–58.6%) and 54.4% (95%CI: 42.7–65.7%) for CU/PET and PSMA/PET, respectively ( p  < 0.001 for both). Both experimental PET/CT performed particularly poorly at PSA levels consistent with early sRT. Conclusions: The two novel radiotracers are inferior to mpMR in restaging the prostatic fossa for sRT planning purposes, particularly in the context of early salvage radiotherapy.

A Prospective Study Assessing the Post-Prostatectomy Detection Rate of a Presumed Local Failure at mpMR with Either 64CuCl2 or 64CuPSMA PET/CT