Primary analysis of a phase II study of metastasis-directed ablative therapy to PSMA ( 18 F-DCFPyL) PET-MR/CT defined oligorecurrent prostate cancer.

5553 Background: Despite maximal local therapies (MLT) (radical prostatectomy followed by radiotherapy [RT]), 20-30% of men will progress to incurable prostate cancer (PCa). Most recurrences in this scenario are characterized by rise in PSA with negative bone scan (BS) and computed tomography (CT). We conducted a phase II trial for men with rising PSA after MLT using 18 F-DCFPyL (PSMA) PET-MR/CT followed by metastasis-directed therapy (MDT) to PET positive foci. We report the results of our primary analysis. Methods: Patients with rising PSA (0.4-3.0 ng/mL) after MLT, negative BS/CT and no prior salvage ADT were eligible. All patients underwent PSMA PET-MR and PET-CT. Those with limited disease burden amenable to MDT underwent either stereotactic ablative RT (SABR) or surgery (lymph node dissection). No ADT was used. The primary endpoint was biochemical response rate (complete [undetectable PSA] or partial [PSA decline ≥50% from baseline]) following MDT. A Simon’s two-stage study design was employed. Estimated time of delay in salvage ADT was calculated using the Kaplan-Meier method. Toxicity was prospectively recorded (CTCAE v4.0). Results: After a median of 63 months (range 3-180) post MLT, 72 patients underwent PSMA PET-MR/CT with median PSA 0.98 ng/mL (range 0.4-3.1). Sixteen patients had negative and 56 had positive PET-MR/CT scans, of which 37 (51%) were amenable to MDT. The median number of treated lesions was 2 (range 1-5). Of the treated patients, 30 (81%) had miT0N1M0 disease, 2 (5.5%) had miT0N1M1a, 2 (5.5%) had miT0N0M1a and 3 (8%) had miT0N0M1b. Twenty-seven patients underwent SABR (median 30 Gy in 3 fractions) and 10 had surgery. At a median of 11 months (range 1-29) post MDT, 8 patients (22%) had complete (CR) and 14 (38%) had partial (PR) responses. Among the 8 CRs, 5 had surgery and 3 had SABR; of the 14 PRs, 2 had surgery and 12 had SABR. The estimated median delay in salvage ADT for the entire cohort, PR and CR subgroups was 13 months (IQR 8-20), 16 months (IQR 13-20) and 30 months (IQR not reached), respectively. Two grade 2+ toxicities were observed, both in surgical patients: deep venous thrombosis and ureteric injury requiring stent placement. Conclusions: 18 F-DCFPyL PET-MR/CT has high detection rates (78%) in men with rising PSA after MLT. We observed a favorable therapeutic index with MDT (60% response rate) for patients with metachronous PSMA-unveiled oligometastatic PCa following MLT. Phase III studies using validated intermediate clinical endpoints are needed before integration into routine practice. Clinical trial information: NCT03160794 .