PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml: Two case reports and a literature review

Localization of prostate cancer recurrence, particularly in the bones, is a major challenge with standard of care imaging in patients with biochemical recurrence following curatively intended treatment. Gallium-68-labeled prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on 68Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (<2 ng/ml) and PSA doubling time >6 months. The bone metastases were verified by supplementary imaging with 18F‐sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, 68Ga-PSMA PET/CT is promising for the restaging of patients with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics. Introduction Localization of prostate cancer recurrence is a major challenge in patients with biochemical recurrence following curatively intended treatment. The currently applied imaging modalities such as bone scintigraphy and abdominal pelvic computed tomography (CT) are too insensitive, particularly at low serum prostate‐specific antigen (PSA) values (1). These two modalities only reliably show the site of relapse in patients with very high PSA levels (>10 ng/ml) (2). This is of particular importance as salvage radiotherapy in these patients is most effective at serum PSA values <0.5 ng/ml (3,4). Established positron emission tomography (PET) tracers such as 11Cor 18F-choline or 11C-acetate are able to directly detect tumor tissue, which is also true at the bone level, where these tracers show tumor tissue, as opposed to reactive bone as with bone scans and 18F‐sodium fluoride (NaF) PET/CT. This result may convey higher sensitivity for both osteoblastic and osteolytic bone lesions at low PSA levels (5). However, the majority of large series have included patients with a PSA level >2 ng/ml (6,7). Most studies that included patients with low PSA levels have shown infrequent bone metastases, and little information is provided concerning tumor characteristics in individual patients (8-11). Generally, choline PET is only indicated in biochemical failure if the PSA level is >2 ng/ml or the PSA level is rising rapidly (12). Gallium‐68‐labelled prostate‐specific membrane antigen (68Ga-PSMA) PET/CT has recently been introduced as a promising method for prostate cancer imaging, both for staging and restaging (13-17). In contrast to existing PET tracers, 68Ga-PSMA PET has revealed pathological sites of uptake, even with low PSA levels, in several retrospective series (13-17). In 2015, the present authors initiated two prospective trials with 68Ga-PSMA PET/CT in prostate cancer, including a study of PSMA-11 (DKFZ-PSMA-11, also known as PSMA-HBED-CC) PET/CT in recurrent prostate cancer in 68Ga-PSMA PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml: Two case reports and a literature review LARS J. PETERSEN1,2, JULIE B. NIELSEN1,2, KATJA DETTMANN3, RUNE V. FISKER1,4, UWE HABERKORN5,6, LOUISE STENHOLT7 and HELLE D. ZACHO1,2 1Department of Nuclear Medicine, Clinical Cancer Research Center, Aalborg University Hospital; 2Department of Clinical Medicine, Aalborg University, DK-9000 Aalborg; 3Department of Urology, Regional Hospital West Jutland, DK‐7500 Holstebro; 4Department of Radiology, Clinical Cancer Research Center, Aalborg University Hospital, DK-9000 Aalborg, Denmark; 5Department of Nuclear Medicine, University Hospital of Heidelberg; 6Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Centre, D-69120 Heidelberg, Germany; 7The Medical Library, Aalborg University Hospital, DK-9000 Aalborg, Denmark Received March 14, 2017; Accepted May 23, 2017 DOI: 10.3892/mco.2017.1280 Correspondence to: Professor Lars J. Petersen, Department of Nuclear Medicine, Clinical Cancer Research Center, Aalborg University Hospital, Hobrovej 18-22, DK-9000 Aalborg, Denmark E-mail: [email protected] Abbreviations: CT, computed tomography; 68Ga, Gallium-68; MRI, magnetic resonance imaging; NaF, 18F-sodium fluoride; PET, positron emission tomography; PSMA, prostate specific membrane antigen; PSA, prostate specific antigen; PSAdt, PSA doubling time; STARD, the standards for reporting of diagnostic accuracy