Assessment of Skeletal Metastases in Prostate Cancer: 68Ga-PSMA PET vs 99mTc-MDP WBBS - A Case Series

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1 Assessment of Skeletal Metastases in Prostate Cancer: 68Ga-PSMA PET vs 99mTc-MDP WBBS - A Case Series Poster No.: R-0094 Congress: 2016 ASM Type: Scientific Exhibit Authors: O. Bennett, Y.-T. T. Huang; Brisbane/AU Keywords: Genital / Reproductive system male, Oncology, Nuclear medicine, PET-CT, Nuclear medicine conventional, SPECT-CT, Diagnostic procedure, Staging, Cancer, Neoplasia DOI: /ranzcr2016/R-0094 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply RANZCR's endorsement, sponsorship or recommendation of the third party, information, product or service. RANZCR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold RANZCR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies,.ppt slideshows,.doc documents and any other multimedia files are not available in the pdf version of presentations. Page 1 of 17

2 Purpose To compare 99m 99m Technetium-hydroxymethylenediphosphonate ( 68 Tc-HDP) whole body 68 bone scan (WBBS) and Gallium ( Ga)-prostate-specific membrane antigen ligand positron emission tomography/computed tomography (PSMA-PET/CT) for the assessment of skeletal metastases in prostate cancer. Background Prostate cancer is the second most commonly diagnosed cancer in Australian males, after non-melanoma skin cancers, and the second highest cause of cancer death after lung cancer. For men, there is a 1 in 9 chance of being diagnosed with prostate cancer before age 75, and a 1 in 6 chance of being diagnosed before age 85 [1]. Prostate cancer can follow a variable course depending on whether it is low-risk or highrisk, defined by histologic Gleason score. Treatment pathways are based on tumour grade and stage, and can range from surveillance thorough to radical prostatectomy or radical radiotherapy, with or without neoadjuvant and/or adjuvant therapy [2-3]. Unfortunately, treatment failure can occur due to local recurrence or progression of metastases not initially detected and included in the treatment field. This can be identified through rising serum prostate specific antigen (PSA) levels, with biochemical recurrence defined as a PSA > 0.2 ng/l post-radical prostatectomy, or PSA > 2 ng/l above the PSA nadir post radical radiotherapy [3]. The presence of skeletal metastases at both staging and in recurrence of prostate cancer has a profound impact upon patient prognosis and available treatment options. The current European Association of Urology Guidelines, recommend WBBS to 99m determine the presence of skeletal metastases [2]. Tc-HDP selectively concentrates in areas of high osteoblastic activity within bone by adsorbing onto its mineral (i.e. crystalline hydroxyapatite) component. As the skeletal metastases of prostate cancer are predominantly sclerotic (i.e. osteoblastic) WBBS has excellent utility in their detection. However, WBBS is non-specific and increased uptake can be seen in a number of other conditions where there is increased osteoblastic activity such as fractures, infection, arthritis, and Paget disease. Recently, PSMA-PET/CT has emerged as an additional imaging modality in the assessment of prostate cancer and its associated metastases, including skeletal Page 2 of 17

3 metastases. Preliminary studies are proving it to be highly sensitive and specific [4-6], and its clinical use is rapidly increasing. Prostate-specific membrane antigen (PSMA) is a cell membrane protein that is overexpressed by prostate cancer cells with further increased expression in prostate cancer metastases and higher grade prostate malignancies [7, 8, 9]. Despite its name however, cell membrane PSMA is expressed physiologically by a number of tissues including salivary glands, lacrimal glands, proximal small bowel, and kidney; in nonprostate diseases (e.g. Paget disease) [10]; and in the neovasculature of various nonprostate malignancies [7, 11, 12], although usually at lower concentrations. PSMAnegative prostate cancers have also been reported, although they appear to be rare [8]. 68 Cell membrane PSMA is the target molecule for Ga-PSMA ligand, which binds to it with high avidity and specificity [7, 13]. This combined with the superior spatial resolution of PET appears to contribute to its superior sensitivity. Furthermore, PSMA-PET/CT is comprehensive, providing information regarding the primary tumour, nodal and distant metastases, as well as skeletal metastases in a single study. Methods and materials A retrospective analysis was performed on patients with histologically proven prostate cancer imaged with both WBBS and PSMA-PET/CT within 120 days of each other between July 2014 and July All WBBS had whole-body planar and torso singlephoton emission computed tomography (SPECT) acquisitions, and the PET/CT was performed with non-contrast-enhanced low-dose CT for attenuation correction and improved lesion localisation and characterisation. The WBBS and PSMA-PET/CT scans were interpreted independently by a dual-qualified radiologist/nuclear medicine specialist blinded to the results of the comparative examination. Subject's clinical, biochemical and prior imaging data were accessible at time of scan interpretation and were documented into the study database. Images for this section: Page 3 of 17

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5 Fig. 1: A normal WBBS acquired as a whole-body sweep at 2 hours following 99mTcHDP injection and displayed in anterior and posterior projections. There is physiologic activity in normal bones as well as the urinary tract (kidneys and bladder). Incidental arthritis is present in the shoulders, sternoclavicular joints, knees and ankles. There is mild discovertebral degenerative changes in the spine. Fig. 2: A normal 68Gallium-PSMA PET/CT displaced as a maximal intensity projection (MIP). There is intense physiologic activity in the salivary glands, the renal tract (kidneys and bladder), moderate physiologic activity in the liver, spleen and duodenum as well as the posterior pituitary gland. Variable mild physiologic activity can be present within bowel and in reactive lymph nodes. Page 5 of 17

6 Results 41 patients were included in the analysis with a median of 40 days between WBBS and PSMA-PET/CT (mean 51, range 3 to 116 days). 34/41 (83%) patients had concordant findings on both scans, of which 29/34 (85%) were negative for skeletal metastases. 7/41 (17%) of cases were discordant. Of these seven cases, three were initial staging scans, two were investigating biochemical recurrence, one was assessing disease progression based on rising PSA in the absence of known metastases, and one was assessing progression of known skeletal metastases. In three of the discordant cases (43%), PSMA-PET/CT detected additional lesions not demonstrated on the WBBS, with a mean of 79 days between the two studies. In two cases (29%), the WBBS was falsely negative and subsequent identification of skeletal metastases altered the disease stage and thus available treatment options. One of the false negative WBBS occurred in a subject with a solitary, intensely PSMA-avid lytic vertebral metastasis, undetected by WBBS due to low osteoblastic activity in the lesion. There were two false-positive cases on WBBS, both due to benign osseous lesions. Images for this section: Page 6 of 17

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8 Fig. 4: Mr AH is a 77-year-old with clinical disease progression following prior radiation therapy for Gleason 3+4 prostate cancer. The WBBS shows multiple intensely osteoblastic lesions in the right hemi-pelvis including the ilium, ischium, and inferior sacrum. Small foci are also demonstrated in the right sternal margin and the distal left clavicle. SPECT did not reveal additional lesions. These osteoblastic foci correlated to sclerotic lesions on the concurrent low-dose CT. Fig. 5: The PSMA-PET/CT of Mr AH was performed only 14 days after the WBBS (left panel - MIP; right panels - PSMA-PET/CT fused coronal, sagittal and axial). It showed multiple additional intensely PSMA-avid skeletal lesions in the left hemi-pelvis and the posterior T12 vertebral body (red arrows). The right sternal lesion was also more clearly demonstrated on PSMA-PET/CT than on WBBS (white arrow). Other skeletal metastases detected on WBBS were well demonstrated on the PSMA-PET/CT. Page 8 of 17

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10 Fig. 6: Mr DN is a 64-year-old diagnosed with high-grade prostate cancer. At staging he underwent WBBS with SPECT/CT. No abnormal increased osteoblastic activity was demonstrated to suggest skeletal metastatic disease. WBBS revealed discovertebral degenerative changes throughout his spine with uptake within the disc spaces and in osteophytes, and moderate osteoarthritis in his shoulders and knees. Fig. 7: Mr DN had a PSMA-PET/CT approximately 3 months after the WBBS to exclude metastatic disease prior to radial prostatectomy. He received no interim treatment as the WBBS was negative for skeletal metastases and his PSA level was stable. The PSMAPET/CT revealed a large, moderately PSMA-avid mass in the left side of the prostate gland (far right panel - MIP, black arrow) and an intensely PSMA-avid focus in the right T12 vertebral body (far right panel - MIP, red arrow; left three panels - PSMA-PET/CT fusion (above) and PSMA-PET (below)). The uptake correlated with a well-circumscribed lytic focus on CT. No other PSMA-avid skeletal disease was demonstrated. Page 10 of 17

11 Fig. 8: In correlation with the initial WBBS, the lytic T12 lesion was present and unchanged in size (left panel - low-dose CT performed at time of staging WBBS, right panel - WBBS SPECT/CT fusion, red arrow). This lesion has no significant osteoblastic activity due to its lytic nature and therefore was falsely negative on the WBBS. While prostate cancer skeletal metastases are usually sclerotic, lytic lesions can occur although are rare. Page 11 of 17

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13 Fig. 9: Mr FC is a 69-year-old with rising PSA level, suggestive of disease progression, with no known metastatic disease. WBBS was performed and the planar images show a moderate focus of osteoblastic activity in the left 5th rib anterolaterally (red arrow). In addition, mild activity was noted in a lower left rib anteriorly (black arrow). Fig. 10: The MIP of the WBBS SPECT confirmed the left 5th rib lesion. It also revealed two mild foci in the left 8th and 9th ribs anteriorly near the costochondral junction, consistent with old rib fractures. No additional osteoblastic abnormality was evident. On the lowdose CT (not shown), there is corresponding irregular sclerosis of the left 5th rib at the site of uptake. This was interpreted as suspicious for a solitary skeletal metastasis. Page 13 of 17

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15 Fig. 11: As Mr FC was asymptomatic, no treatment was initiated. Approximately 3 months later, he was referred for a PSMA-PET/CT to further assess his disease status. No PSMA uptake was demonstrated in the left 5th rib lesion (right panel - MIP; top left panel - PSMAPET/CT fusion; bottom left panel - PSMA-PET). The CT appearance of the lesion had not changed since the WBBS. No other PSMA-avid skeletal abnormality was demonstrated. This lesion was confirmed to be a benign lesion based on subsequent serial imaging, and the WBBS was a false-positive. Fig. 3: Summary of discordant patients Page 15 of 17

16 Conclusion Skeletal metastatic disease is an important prognostic indicator in prostate cancer and significantly alters management both at staging and recurrence. The detection of sclerotic osseous metastases by imaging osteoblastic activity with WBBS is currently still considered the "gold-standard". However, PSMA-PET/CT as an emerging imaging technique for prostate cancer appears to be a comprehensive modality in the detection of osseous metastases as well as non-osseous disease. Early limited studies suggest PSMA-PET/CT is more sensitive and specific at detecting skeletal metastases than WBBS [6]. This small retrospective case series supports these findings, however, the cost and limited access to PSMA-PET/CT are considerable factors influencing its clinical utility. Personal information References Australian Institute of Health and Welfare Cancer in Australia: an overview, Cancer series no. 90. Cat. no. CAN 88. Canberra: AIHW. [Accessed 8 April 2016]. Available from: Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part I: screening, diagnosis, & local treatment with curative intent update Eur Urol. 2014;65: Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, & castration-resistant prostate cancer. Eur Urol. 2014;65: Afshar-Oromieh A, Zechmann CM, Malcher A, et al. Comparison of PET imaging with a Ga-labelled PSMA ligand & F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41: Eiber M, Maurer T, Souvatzoglou M, et al. Evaluation of hybrid Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56: Maurer T, Eiber M, Schwaiger M, et al. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016;13: Silver DA, Pellicer I, Fair WR, et al. Prostate-specific membrane antigen expression in normal & malignant human tissues. Clin Cancer Res. 1997;3: Page 16 of 17

17 8. 9. Mannweiler S, Amerdorfer P, Trajanoski S, et al. Heterogeneity of prostatespecific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res. 2009;15: Wright GL, Haley C, Beckett ML, et al. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol. 1995;1: Artigas C, Alexiou J, Garcia C. Paget bone disease demonstrated on 68GaPSMA ligand PET/CT. Eur J Nucl Med Mol Imaging. 2016;43: Chang SS. Overview of prostate-specific membrane antigen. Rev Urol. 2004;6:S13-S Chang SS, O'Keefe DS, Bacich DJ, et al. Identification of a novel tumourassociated neovasculature marker: prostate-specific membrane antigen (PSMA). Clin Cancer Res. 1999;5: Bostwick DG, Pacelli A, Blute M, et al. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia & adenocarcinoma: a study of 184 cases. Cancer. 1998;82: Page 17 of 17