Staging of Prostatic Carcinoma - The evolving use of SPECT-CT and Positron Emission Tomography (PET)

Transcription

1 Staging of Prostatic Carcinoma - The evolving use of SPECT-CT and Positron Emission Tomography (PET) Poster No.: C-2477 Congress: ECR 2015 Type: Educational Exhibit Authors: B. Rawal, N. Vasdev, R. P. Patel, A. Patel; Stevenage/UK Keywords: Metastases, Cancer, Staging, SPECT-CT, PET, Nuclear medicine conventional, Nuclear medicine, Genital / Reproductive system male DOI: /ecr2015/C-2477 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 ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR 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 ECR 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 and any other multimedia files are not available in the pdf version of presentations. Page 1 of 23

2 Learning objectives To recognise the uses and limitations of bone scintigraphy, SPECT-CT and choline PET in the staging of prostatic carcinoma. To learn about further advances in nuclear medicine techniques such as PET with 68Ga-labelled Prostate-specific Membrane Antigen (PSMA). Background In the UK, prostate carcinoma is the most common cancer in men with over 400,000 cases diagnosed each year. The symptoms of prostate carcinoma include lower urinary tract symptoms and the sequelae of metastasis in advanced disease. The majority of cases are diagnosed in primary care by digital rectal examination (DRE) and measurement of prostate specific antigen (PSA) in symptomatic individuals. The routine measurement of PSA as a screening tool is controversial and not currently adopted in the UK due to non-specificity of a positive finding and conflicting evidence. Patients with symptoms and/or significantly raised PSA levels are assessed by urologists and depending on the individual centre, patients would proceed directly to either transrectal ultrasound (TRUS) guided prostate biopsy or pre-biopsy multiparametric prostate MRI, followed by biopsy as guided by clinical assessment and MRI findings. According to the American Joint Committee on Cancer (AJCC), the TNM system for prostate carcinoma is based on 5 key pieces of information: Extent of primary tumour (T stage) Local lymph node involvement (N stage) Absence of presence of distant metastasis (M stage) PSA level at time of diagnosis Gleason score based on prostate biopsy Based on current practice, the T and N stage is determined by multiparametric prostate MRI. The M stage is determined by assessment for osteoblastic metastases using bone scintigraphy with Technetium m (commonly Tc m-methylene diphosphonate). Computed tomography is also selectively used to assess for distant metastasis. In recent years there have been advances in several nuclear medicine techniques specifically in the diagnosis of prostate carcinoma, such as SPECT-CT for assessment of distant metastases and choline PET for both primary tumour evaluation and metastatic Page 2 of 23

3 spread. We will discuss the limitations and strengths of such evolving nuclear medicine techniques and their implications within the diagnostic pathway for prostate carcinoma. Findings and procedure details Detection of osteoblastic metastases 99m Bone scintigraphy with Technetium Diphosphonate has for decades been the firstline investigation, offering a widely available low cost whole body examination. (Fig 1-3) Page 3 of 23

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5 Fig. 2: Bone scintigram demonstrating multiple osteoblastic metastases throughout the bony skeleton. References: - Stevenage/UK The sensitivity and specificity is however limited and in response to this, SPECT-CT (single-photon emission computerized tomography) has rapidly evolved over recent years offering both greater sensitivity and specificity for osteoblastic metastases and better anatomical detail. (see Fig 4 and 5) Page 5 of 23

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7 Fig. 4: Bone scintigraphy demonstrates uptake within the L4/5 vertebrae. References: - Stevenage/UK Fig. 5: SPECT-CT demonstrating avid uptake within the L4/L5 vertebral bodies. References: - Stevenage/UK A study compared the detection of bone metastases by bone scintigraphy and SPECT (as well as 18F-Fluoride PET) in patients with high-risk prostate carcinoma. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all far greater with SPECT than planar bone scintigraphy. A more recent meta-analysis of the available literature compared choline-pet/ct, MRI, SPECT, and bone scintigraphy. On a per-lesion basis, the pooled sensitivities of choline PET/CT, SPECT and bone scintigraphy were 84%, 90% and 59% respectively. The pooled specificities were 93% for choline PET/CT, 85% for SPECT and 75% for BS. On a per-patient basis however MRI was better than both choline-pet/ct and SPECT. Page 7 of 23

8 FDG 18F-fluorodeoxyglucose (FDG) PET FDG PET is limited in the primary evaluation of prostate carcinoma due to: 1) low FDG uptake by cellular tissue of prostate carcinoma 2) uptake masked by tracer activity within the urinary bladder. FDG-PET cannot reliably differentiate between benign prostatic hyperplasia (BPH), prostate cancer and scar tissue vs. local recurrence. Furthermore, FDG-PET is not accurate for nodal and bone involvement in prostate cancer. Choline PET Choline has been identified as an integral part of cell membrane phospholipids. In prostate cancer cells choline metabolism and turnover is upregulated compared with normal prostate cells Given the limitations of FDG-PET, C-choline, F-fluorocholine and have emerged as the frontrunners in prostate cancer imaging. 11 C-acetate PET In the UK, the Royal College of Radiologists has supported the use of choline PET in cases where there are: a) Equivocal findings on conventional imaging, such as indeterminate nodal or bony metastases (where exclusion or confirmation of metastatic disease would directly influence patient management.) b) Suspected recurrence of prostate carcinoma with rising PSA but equivocal findings on conventional imaging. The illustrated cases below demonstrate where choline PET has been useful in detecting metastatic disease in both primary staging and recurrent disease (Fig 6-8). Page 8 of 23

9 Fig. 6: Patient with rising PSA following prostatectomy. CT demonstrates several small pelvic nodes and a small subcentimetre retrocaval node. Choline PET demonstrates avid uptake consistent with recurrent disease. References: - Stevenage/UK Page 9 of 23

10 Fig. 7: PET avid mediastinal nodal disease. References: - Stevenage/UK Page 10 of 23

11 Fig. 8: PET avid right external iliac node in a patient considered for radical prostatectomy. References: - Stevenage/UK In a recent meta-analysis, Umbehr et al highlights that evidence is however not yet strong enough for routine restaging using choline PET and appropriate patient selection is important. Proposed criteria include; PSA # 1 ng/ml, short PSA doubling time (< 3 months to maximum of 6 months) and initial tumour stage (# pt3b or pn1). The evidence for choline PET in primary tumour evaluation is less well established. Similar to FDG PET, choline PET cannot reliably differentiate prostate carcinoma from BPH and prostatitis. Additionally, choline PET has 1) suboptimal lymph node metastasis sensitivity, 2) a minimum detectable tumour size of 5 mm and 3) does not reliably detect extraprostatic extension of tumour. ACETATE PET Prostate cancer cells demonstrate increased lipid synthesis due to over-expression of fatty acid synthase. Acetate is incorporated into these lipid cells and when radio-labelled with 11 C can identify prostate cancer cells. Evidence of acetate PET is less well developed compared to choline PET. Similarly, there are difficulties in differentiating prostate carcinoma from BPH and prostatitis and limited sensitivity in the detection of nodal metastases. PET with 68Ga-labelled PSMA Prostate-specific membrane antigen is a cell surface protein with high expression in prostate carcinoma cells. There is now emerging pre-clinical and clinical data for the use of 68 Gallium-labelled PSMA ligand for detection of recurrent prostate carcinoma. Compared to choline 18F-choline PET/CT, a recent study found that 68Ga-PSMA PET/ CT demonstrated a higher detection rate for recurrent prostate carcinoma. In this study, all lesions detected by choline PET/CT were also detected by 68GA-PSMA PET/CT, however the latter provided higher SUV values and therefore better contrast with normal tissue, even at low PSA levels. Initial experience of 68GA-PSMA PET/MRI has also yielded some promising results compared to conventional PET/CT, however further work is required and currently underway. Page 11 of 23

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14 Fig. 1: Bone scintigram demonstrating multiple osteoblastic metastases throughout the bony skeleton. Page 14 of 23

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16 Fig. 2: Bone scintigram demonstrating multiple osteoblastic metastases throughout the bony skeleton. Fig. 3: RPO image demonstrating multiple vertebral metastases within the thoracic spine. Page 16 of 23

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18 Fig. 4: Bone scintigraphy demonstrates uptake within the L4/5 vertebrae. Fig. 5: SPECT-CT demonstrating avid uptake within the L4/L5 vertebral bodies. Page 18 of 23

19 Fig. 6: Patient with rising PSA following prostatectomy. CT demonstrates several small pelvic nodes and a small subcentimetre retrocaval node. Choline PET demonstrates avid uptake consistent with recurrent disease. Page 19 of 23

20 Fig. 7: PET avid mediastinal nodal disease. Fig. 8: PET avid right external iliac node in a patient considered for radical prostatectomy. Page 20 of 23

21 Conclusion For the primary staging of prostate carcinoma, a combination of multiparametric MRI, bone scintigraphy and CT imaging allow accurate primary tumour evaluation and detection of both nodal and osseous metastases. In cases where conventional imaging reveals indeterminate findings and where patient management would be highly influenced, SPECT-CT and choline PET should be used as problem solving tools. However one must remember the need for appropriate patient selection and keep in mind the various limitations of choline PET, especially with regards to lymph node metastasis sensitivity. The evidence supporting choline PET and real-life clinical experience is still largely in the development phase. We look forward to various advances in PET imaging for prostate carcinoma including 68GA-PSMA PET/CT and 68GA-PSMA PET/MRI. Personal information Dr Amit Patel Consultant Radiologist Lister Hospital, Stevenage, UK. apatel11@nhs.net References 1) Mafeld S, Vasdev N, Patel A et al. Evolving use of PET imaging in urological malignancy. BJU Int Nov. Epub ahead of print. 2) The Royal College of Physicians and the Royal College of Radiologists. Evidencebased Indications for the use of PET-CT in the United Kingdom Page 21 of 23

22 3) Avril N, Dambha F, Murray I, Shamash J, Powles T, Sahdev A. The clinical advances of fluorine-2-d-deoxyglucose--positron emission tomography/computed tomography in urological cancers. Int J Urol Off J Jpn Urol Assoc Jun;17(6): ) Hofer C, Laubenbacher C, Block T, Breul J, Hartung R, Schwaiger M. Fluorine-18fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy. Eur Urol. 1999;36(1): ) Umbehr MH, Müntener M, Hany T, Sulser T, Bachmann LM. The role of 11C-choline and 18F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: a systematic review and meta-analysis. Eur Urol Jul;64(1): ) Picchio M, Briganti A, Fanti S, Heidenreich A, Krause BJ, Messa C, et al. The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer. Eur Urol Jan;59(1): ) Murphy RC, Kawashima A, Peller PJ. The utility of 11C-choline PET/CT for imaging prostate cancer: a pictorial guide. AJR Am J Roentgenol Jun;196(6): ) Schiavina R, Scattoni V, Castellucci P, Picchio M, Corti B, Briganti A, et al. 11Ccholine positron emission tomography/computerized tomography for preoperative lymphnode staging in intermediate-risk and high-risk prostate cancer: comparison with clinical staging nomograms. Eur Urol Aug;54(2): ) Brogsitter C, Zöphel K, Kotzerke J. 18F-Choline, 11C-choline and 11C-acetate PET/ CT: comparative analysis for imaging prostate cancer patients. Eur J Nucl Med Mol Imaging Jul;40 Suppl 1:S ) Martorana G, Schiavina R, Corti B, Farsad M, Salizzoni E, Brunocilla E, et al. 11C-choline positron emission tomography/computerized tomography for tumor localization of primary prostate cancer in comparison with 12-core biopsy. J Urol Sep;176(3): ; discussion ) Kato T, Tsukamoto E, Kuge Y, Takei T, Shiga T, Shinohara N, et al. Accumulation of [11C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer. Eur J Nucl Med Mol Imaging Nov;29(11): Page 22 of 23

23 12) Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging Apr;40(4): ) Afshar-Oromieh A, Haberkorn U, Eder M, Eisenhut M et al. [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECH. Eur J Nucl Med Mol Imaging Jun;39(6): ) Even-Sapir E, Metser U, Mishani E, Lievshitz G, Lerman H, Leibovitch I. The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT. J Nucl Med Feb;47(2): ) Shen G, Deng H, Hu S, Jia Z. Comparison of choline-pet/ct, MRI, SPECT, and bone scintigraphy in the diagnosis of bone metastases in patients with prostate cancer: a meta-analysis. Skeletal Radiol May 20 (epub ahead of print). Page 23 of 23