Eric H Kim1, Barry A Siegel2, Eugene J Teoh3, Gerald L Andriole4. 1. Division of Urologic Surgery, Department of Surgery and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO,. Electronic address: ehkim@wustl.edu. 2. Division of Nuclear Medicine, Mallinckrodt Institute of Radiology and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO. 3. Blue Earth Diagnostics Ltd, the Oxford Science Park, Robert Robinson Avenue, Oxford OX4 4GA, UK. 4. Division of Urologic Surgery, Department of Surgery and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO.
Abstract
INTRODUCTION: Despite improvements in overall survival, biochemical recurrence of prostate cancer, characterized by rising prostate-specific antigen (PSA) levels after curative intent primary therapy, remains common. With the advent of highly sensitive molecular imaging, men with limited metastatic disease burden, or oligometastatic prostate cancer, are increasingly being identified. The LOCATE trial (NCT02680041) assessed the impact of positron emission tomography (PET) with 18F-fluciclovine on management of men with prostate cancer recurrence after curative intent primary therapy and negative/equivocal conventional imaging. Here, we use LOCATE data to characterize the sites of disease recurrence and explore the potential for 18F-fluciclovine-PET/CT to evaluate oligometastatic disease. METHODS: Eligible men (≥18 years; prior curative intent treatment of prostate cancer; recurrence based on rising PSA; negative/equivocal conventional imaging) underwent 18F-fluciclovine-PET/CT according to standard protocols. The primary outcome measure of the LOCATE trial was a revised management plan post-scan. We performed a secondary analysis of the LOCATE imaging data to characterize anatomical sites of disease recurrence and to explore the potential for 18F-fluciclovine-PET/CT to evaluate oligometastatic disease. Imaging results were stratified by baseline PSA levels and prior treatment(s) and the Fisher exact test used to analyze differences between groups. Oligometastatic disease was defined as 1-5 extraprostatic lesions (≤3 lesions in any single organ system) plus negative prostate/bed imaging (as a surrogate for primary tumor control). RESULTS: Of 213 enrolled patients, 164 (77%) had undergone prostatectomy as their initial treatment; their median PSA was 0.57ng/ml. For the 49 patients with an intact prostate, the median PSA was 5.5ng/ml. The overall 18F-fluciclovine-PET/CT detection rate was 57%. Detection rates were 84% in men with intact prostates and 49% in those who had undergone prostatectomy, with the difference being attributable to prostate/bed findings (71% vs. 18%, respectively). The detection rate in lymph nodes was 29% and in bone was 11%. In total, 53/213 (25%) had oligometastatic disease. Twenty (38%) oligometastatic patients had PSA ≤1.0 ng/ml. Forty-two (79%) experienced a change to their management plan following the scan, commonly to target a lesion identified by 18F-fluciclovine-PET/CT. The majority of management changes (74%) involved a new treatment modality; however, 10 patients (24%) experienced a modification of the existing plan for radiotherapy to incorporate a boost to an area guided by the 18F-fluciclovine-PET/CT results. CONCLUSION: Even at low PSA levels, 18F-fluciclovine-PET/CT identified a diverse pattern of recurrence missed with conventional imaging. One-quarter of men had oligometastatic disease, raising the potential for 18F-fluciclovine-PET/CT to guide targeted treatment of oligometastases.
INTRODUCTION: Despite improvements in overall survival, biochemical recurrence of prostate cancer, characterized by rising prostate-specific antigen (PSA) levels after curative intent primary therapy, remains common. With the advent of highly sensitive molecular imaging, men with limited metastatic disease burden, or oligometastatic prostate cancer, are increasingly being identified. The LOCATE trial (NCT02680041) assessed the impact of positron emission tomography (PET) with 18F-fluciclovine on management of men with prostate cancer recurrence after curative intent primary therapy and negative/equivocal conventional imaging. Here, we use LOCATE data to characterize the sites of disease recurrence and explore the potential for 18F-fluciclovine-PET/CT to evaluate oligometastatic disease. METHODS: Eligible men (≥18 years; prior curative intent treatment of prostate cancer; recurrence based on rising PSA; negative/equivocal conventional imaging) underwent 18F-fluciclovine-PET/CT according to standard protocols. The primary outcome measure of the LOCATE trial was a revised management plan post-scan. We performed a secondary analysis of the LOCATE imaging data to characterize anatomical sites of disease recurrence and to explore the potential for 18F-fluciclovine-PET/CT to evaluate oligometastatic disease. Imaging results were stratified by baseline PSA levels and prior treatment(s) and the Fisher exact test used to analyze differences between groups. Oligometastatic disease was defined as 1-5 extraprostatic lesions (≤3 lesions in any single organ system) plus negative prostate/bed imaging (as a surrogate for primary tumor control). RESULTS: Of 213 enrolled patients, 164 (77%) had undergone prostatectomy as their initial treatment; their median PSA was 0.57ng/ml. For the 49 patients with an intact prostate, the median PSA was 5.5ng/ml. The overall 18F-fluciclovine-PET/CT detection rate was 57%. Detection rates were 84% in men with intact prostates and 49% in those who had undergone prostatectomy, with the difference being attributable to prostate/bed findings (71% vs. 18%, respectively). The detection rate in lymph nodes was 29% and in bone was 11%. In total, 53/213 (25%) had oligometastatic disease. Twenty (38%) oligometastatic patients had PSA ≤1.0 ng/ml. Forty-two (79%) experienced a change to their management plan following the scan, commonly to target a lesion identified by 18F-fluciclovine-PET/CT. The majority of management changes (74%) involved a new treatment modality; however, 10 patients (24%) experienced a modification of the existing plan for radiotherapy to incorporate a boost to an area guided by the 18F-fluciclovine-PET/CT results. CONCLUSION: Even at low PSA levels, 18F-fluciclovine-PET/CT identified a diverse pattern of recurrence missed with conventional imaging. One-quarter of men had oligometastatic disease, raising the potential for 18F-fluciclovine-PET/CT to guide targeted treatment of oligometastases.
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