¹⁸F-Fluciclovine PET/CT in patients with biochemical recurrence of prostate cancer: Impact on management and associations of clinical variables with scan findings

Objectives: The LOCATE trial (NCT02680041) is a study of ¹⁸F-fluciclovine positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer after curative-intent primary therapy. As key outcome measures, scan positivity rate and changes in management based on ¹⁸F-fluciclovine PET/CT were assessed. Herein, we report on these outcomes, focusing on the association between scan positivity and the following clinical variables: recurrence site, practice setting, prostate-specific antigen (PSA) level, and Gleason score.

Methods: Inclusion criteria included histologically confirmed adenocarcinoma of the prostate post curative-intent local treatment; suspicion of BCR of prostate cancer; negative or equivocal findings on standard-of-care imaging; and being considered for salvage therapy. Baseline PSA level, defined as the last measurement prior to PET, as well as Gleason score, was recorded. ¹⁸F-Fluciclovine PET/CT was performed according to standardized procedures in 15 participating US centers, including both private practice and academic settings. ¹⁸F-Fluciclovine PET/CT scans were performed with a mean dose of 10.0 mCi. ¹⁸F-Fluciclovine scans were classified as negative or positive, with site of disease specified for positive scans based on local reads by trained readers. Questionnaires completed by treating physicians documented changes in management after the PET study. The binomial confidence interval was estimated using the exact methods. The association of positivity and clinical variables were assessed using a nonparametric test for trend across ordered groups.

Results: A total of 213 evaluable patients were enrolled. The median time from initial diagnosis was 4.5 years, while the median time since BCR was nearly 6 months. The median Gleason score was 7 and the median pre-scan PSA level was 1.00 ng/mL. Of the 213 patients imaged, management changes were made in 124 (58%, 95% CI: 51-65%), with 58% observed in both private practice settings (47/81) and academic settings (77/132). In total, 122 patients had positive scans with management changes made for 88 (72%) as a result. Management changes were seen in 36 of 91 patients with a negative scan. Of positive scans, 52% demonstrated recurrence in the prostate/prostate bed and 66% had extraprostatic disease, including 50% with disease in lymph nodes (42% in pelvic nodes and 20% in retroperitoneal nodes), 4% in soft tissue/parenchyma and 19% with osseous disease. In total, 60% of scans performed in private practice were positive, while 55% of scans from academic settings were positive. No association was seen between staging Gleason scores and positive scans. The positive scan rate was associated with the PSA level, increasing from 31% (25/81) for PSA < 0.5ng/mL to 95% (18/19) for PSA > 10ng/mL (p<0.001).

Conclusions: ¹⁸F-Fluciclovine PET/CT has proved clinically valuable in detection of disease in patients with BCR of prostate cancer. Disease was detected in the prostate/bed, as well as in extraprostatic tissue, including pelvic and abdominal lymph nodes and, less commonly, in bone. Both positive and negative scans impacted patient management. No difference in the rate of management changes was seen between private practice and academic settings. No association was seen between positive scans and practice setting, nor between Gleason score at diagnosis and positive scans. There was a trend in PSA level and the rate of scan positivity. These findings may help guide the clinical application of ¹⁸F-fluciclovine PET/CT in its currently approved indication for imaging of men with BCR of prostate cancer.