The Impact of Positron Emission Tomography with 18F-Fluciclovine on the Treatment of Biochemical Recurrence of Prostate Cancer: Results from the LOCATE Trial

Abstract

Purpose: The prospective, multicenter LOCATE (F Fluciclovine [FACBC] PET/CT in Patients with Rising PSA after Initial Prostate Cancer Treatment) trial assessed the impact of positron emission tomography/computerized tomography with F-fluciclovine on treatment plans in patients with biochemical recurrence of prostate cancer after primary therapy with curative intent.

Materials and methods: Men who had undergone curative intent treatment of histologically confirmed prostate cancer but who were suspected to have recurrence based on rising prostate specific antigen levels were enrolled prospectively. Each man had negative or equivocal findings on standard of care imaging. F-fluciclovine positron emission tomography/computerized tomography was performed according to standardized protocols. Treating physicians completed a questionnaire regarding the patient treatment plan before and after scanning, recording changes to the treatment modality (eg salvage radiotherapy to systemic androgen deprivation therapy) as major and changes in a modality (eg modified radiotherapy fields) as other.

Results: Between June 2016 and May 2017, 213 evaluable patients with a median age of 67 years and median prostate specific antigen 1.00 ng/ml were enrolled in study. F-fluciclovine avid lesions were detected in 122 of the 213 patients (57%). Overall 126 of the 213 patients (59%) had a change in management after the scan, which were major in 98 of 126 (78%) and in 88 (70%) were informed by positive positron emission tomography/computerized tomography findings. The most frequent major changes were from salvage or noncurative systemic therapy to watchful waiting (32 of 126 cases or 25%), from noncurative systemic therapy to salvage therapy (30 of 126 or 24%) and from salvage therapy to noncurative systemic therapy (11 of 126 or 9%).

Conclusions: F-fluciclovine positron emission tomography/computerized tomography detected 1 or more recurrence sites in the majority of men with biochemical recurrence, frequently resulting in major changes to management plans. Future studies will be planned to determine whether a management change leads to improved outcomes.

Figures

Figure 1.

LOCATE study design. AE, adverse event. Asterisk indicates that biopsy may be done after scan when clinically indicated.

Figure2.

Representative images of 77-year-old man with BCR after radical prostatectomy (Gleason 3 + 4 T2cN0Mx) in 2006.PSA was 1.38 ng/ml. In October 2016 abdominopelvic CT and bone scintigraphy were negative. 18F-fluciclovine PET/CT reveals positive, nonenlarged left common iliac node (A and C) and focus in right ilium without CT correlate, most consistent with bone metastasis (B and D). Prescan management plan was whole pelvis salvage radiotherapy. After PET/CT plan was revised to ADT and prostate bed salvage radiotherapy. Posttreatment PSA was 0.05 ng/ml in March 2017.

Figure 3.

18F-fluciclovine imaging detection rate by region (A) and PSA (B). Extraprostatic region consisted of lymph nodes, soft tissues/ parenchyma and bone. Lymph nodes consisted of pelvic and extrapelvic (retroperitoneal and other) nodes with overall 24% and 12% detection rate, respectively. Soft tissue/parenchyma positivity was identified in bowel and lung. Error bars indicate 95% CI.

Figure 4.

Intended treatment before (A) and after (B) 18F-fluciclovine PET/CT. Other than when indicated in men with no treatment plan change, adjuvant ADT was planned in1 of 2 whose intended plan was brachytherapy. Of patients with post-scan change in plan adjuvant ADT was planned in 3 of 7 scheduled for cryotherapy and in 1 of 3 scheduled for lymphadenectomy.

Figure 5.

Change in management decisions and associated 18F-fluciclovine PET/CT positivity. RT, radiotherapy.