Computerized Tomography (CT) Updates and Challenges in Diagnosis of Bone Metastases During Prostate Cancer

Author(s): Jinguo Zhang, Guanzhong Zhai, Bin Yang, Zhenhe Liu*

Journal Name: Current Medical Imaging
Formerly: Current Medical Imaging Reviews

Volume 16 , Issue 5 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Prostate cancer is one of the most common cancers in men. This cancer is often associated with indolent tumors with little or no lethal potential. Some of the patients with aggressive prostate cancer have increased morbidity and early deaths. A major complication in advanced prostate cancer is bone metastasis that mainly results in pain, pathological fractures, and compression of spinal nerves. These complications in turn cause severe pain radiating to the extremities and possibly sensory as well as motor disturbances. Further, in patients with a high risk of metastases, treatment is limited to palliative therapies. Therefore, accurate methods for the detection of bone metastases are essential. Technical advances such as single-photon emission computed tomography/ computed tomography (SPECT/CT) have emerged after the introduction of bone scans. These advanced methods allow tomographic image acquisition and help in attenuation correction with anatomical co-localization. The use of positron emission tomography/CT (PET/CT) scanners is also on the rise. These PET scanners are mainly utilized with 18F-sodium-fluoride (NaF), in order to visualize the skeleton and possible changes. Moreover, NaF PET/CT is associated with higher tracer uptake, increased target-to-background ratio and has a higher spatial resolution. However, these newer technologies have not been adopted in clinical guidelines due to lack of definite evidence in support of their use in bone metastases cases. The present review article is focused on current perspectives and challenges of computerized tomography (CT) applications in cases of bone metastases during prostate cancer.

Keywords: Prostatic Neoplasms, tomography, neoplasm metastases, diagnosis, bone neoplasms, CT.

Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136(5): E359-86.
[] [PMID: 25220842]
DE Nunzio C, Presicce F, Giacinti S, Bassanelli M, Tubaro A. Castration-resistance prostate cancer: what is in the pipeline? Minerva Urol Nefrol 2018; 70(1): 22-41.
[PMID: 28707844]
Ballon-Landa E, Parsons JK. Nutrition, physical activity, and lifestyle factors in prostate cancer prevention. Curr Opin Urol 2018; 28(1): 55-61.
[] [PMID: 29049045]
Litwin MS, Tan HJ. The diagnosis and treatment of prostate cancer: a review. JAMA 2017; 317(24): 2532-42.
Vargas HA, Schor-Bardach R, Long N, et al. Prostate cancer bone metastases on staging prostate MRI: prevalence and clinical features associated with their diagnosis. Abdom Radiol (NY) 2017; 42(1): 271-7.
[] [PMID: 27480976]
Daniels CP, Millar JL, Spelman T, Sengupta S, Evans SM. Predictors and rate of adjuvant radiation therapy following radical prostatectomy: A report from the Prostate Cancer Registry. J Med Imaging Radiat Oncol 2016; 60(2): 247-54.
[] [PMID: 26548940]
Mayor de Castro J, Caño Velasco J, Aragón Chamizo J, Andrés Boville G, Herranz Amo F, Hernández FC. Locally advanced prostate cancer. Definition, diagnosis and treatment. Arch Esp Urol 2018; 71(3): 231-8.
[PMID: 29633943]
Rosino-Sánchez A. [Preventive management of bone disease in advanced prostate cancer]. Arch Esp Urol 2018; 71(3): 258-66.
[PMID: 29633946]
Patel P, Mathew MS, Trilisky I, Oto A. Multiparametric MR imaging of the prostate after treatment of prostate cancer. Radiographics 2018; 38(2): 437-49.
[] [PMID: 29373089]
Logothetis C, Morris MJ, Den R, Coleman RE. Current perspectives on bone metastases in castrate-resistant prostate cancer. Cancer Metastasis Rev 2018; 37(1): 189-96.
[] [PMID: 29380085]
Park SH, Keller ET, Shiozawa Y. Bone marrow microenvironment as a regulator and Therapeutic target for prostate cancer bone metastasis. Calcif Tissue Int 2018; 102(2): 152-62.
[] [PMID: 29094177]
Castoldi E, Cappella A, Gibelli D, Sforza C, Cattaneo C. the difficult task of diagnosing prostate cancer metastases on dry bone. J Forensic Sci 2018; 63(3): 672-82.
[] [PMID: 28833112]
Bubendorf L, Schöpfer A, Wagner U, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol 2000; 31(5): 578-83.
[] [PMID: 10836297]
Nørgaard M, Jensen AO, Jacobsen JB, Cetin K, Fryzek JP, Sørensen HT. Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007). J Urol 2010; 184(1): 162-7.
[] [PMID: 20483155]
Zacho HD, Barsi T, Mortensen JC, et al. Prospective multicenter study of bone scintigraphy in consecutive patients with newly diagnosed prostate cancer. Clin Nucl Med 2014; 39(1): 26-31.
[] [PMID: 24217537]
Zacho HD, Mørch CD, Barsi T, Mortensen JC, Bertelsen H, Petersen LJ. Unexplained bone pain is an independent risk factor for bone metastases in newly diagnosed prostate cancer: a prospective study. Urology 2017; 99: 148-54.
[] [PMID: 27645522]
Briganti A, Passoni N, Ferrari M, et al. When to perform bone scan in patients with newly diagnosed prostate cancer: external validation of the currently available guidelines and proposal of a novel risk stratification tool. Eur Urol 2010; 57(4): 551-8.
[] [PMID: 20034730]
Bernhardsson M, Sandberg O, Ressner M, Koziorowski J, Malmquist J, Aspenberg P. Shining dead bone-cause for cautious interpretation of [18F]NaF PET scans. Acta Orthop 2018; 89(1): 124-7.
[] [PMID: 28914114]
Maggu J, Singh P, Majumdar A. Multi-echo reconstruction from partial K-space scans via adaptively learnt basis. Magn Reson Imaging 2018; 45: 105-12.
[] [PMID: 28964843]
Zacho HD, Barsi T, Mortensen JC, Bertelsen H, Petersen LJ. Validation of contemporary guidelines for bone scintigraphy in prostate cancer staging: A prospective study in patients undergoing radical prostatectomy. Scand J Urol 2016; 50(1): 29-32.
[] [PMID: 26323170]
Schnipper LE, Smith TJ, Raghavan D, et al. American Society of Clinical Oncology identifies five key opportunities to improve care and reduce costs: the top five list for oncology. J Clin Oncol 2012; 30(14): 1715-24.
[] [PMID: 22493340]
Mohler JL, Armstrong AJ, Bahnson RR, et al. Prostate Cancer, Version 1.2016. J Natl Compr Canc Netw 2016; 14(1): 19-30.
[] [PMID: 26733552]
Van den Wyngaert T, Strobel K, Kampen WU, et al. EANM Bone & Joint Committee and the Oncology Committee. The EANM practice guidelines for bone scintigraphy. Eur J Nucl Med Mol Imaging 2016; 43(9): 1723-38.
[] [PMID: 27262701]
Donohoe KJ, Brown ML, Collier BD. Society of nuclear medicine procedure guideline for bone scintigraphy. Bone Scintigr 2003; 205: 209.
Lee JW, Lee SW, Chang SH, Lee SM. Clinical role of bone scintigraphy in low-to-intermediate Framingham risk patients with atypical chest pain. Nucl Med Commun 2018; 39(5): 411-6.
[] [PMID: 29538096]
Kaur H, Muhleman M, Balon HR. Hypertrophic osteoarthropathy on bone scintigraphy. J Nucl Med Technol 2018; 46(2): 147-8.
[] [PMID: 29127245]
Suh CH, Shinagare AB, Westenfield AM, Ramaiya NH, Van den Abbeele AD, Kim KW. Yield of bone scintigraphy for the detection of metastatic disease in treatment-naive prostate cancer: a systematic review and meta-analysis. Clin Radiol 2018; 73(2): 158-67.
[] [PMID: 28958581]
Wong KK, Piert M. Dynamic bone imaging with 99mTc-labeled diphosphonates and 18F-NaF: mechanisms and applications. J Nucl Med 2013; 54(4): 590-9.
[] [PMID: 23482667]
Segall G, Delbeke D, Stabin MG, et al. SNM. SNM practice guideline for sodium 18F-fluoride PET/CT bone scans 1.0. J Nucl Med 2010; 51(11): 1813-20.
[] [PMID: 21051652]
Kasalak Ö, Glaudemans AWJM, Overbosch J, Jutte PC, Kwee TC. Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma? Skeletal Radiol 2018; 47(3): 363-7.
[] [PMID: 29124298]
Blake GM, Puri T, Siddique M, Frost ML, Moore AEB, Fogelman I. Site specific measurements of bone formation using [18F] sodium fluoride PET/CT. Quant Imaging Med Surg 2018; 8(1): 47-59.
[] [PMID: 29541623]
Ruggiero A, Lanni V, Librizzi A, et al. Diagnostic accuracy of 18F-FDG PET/CT in the staging and assessment of response to chemotherapy in children with ewing sarcoma. J Pediatr Hematol Oncol 2018; 40(4): 277-84.
[] [PMID: 29620679]
Hillner BE, Siegel BA, Hanna L, Duan F, Shields AF, Coleman RE. Impact of 18F-fluoride PET in patients with known prostate cancer: initial results from the National Oncologic PET Registry. J Nucl Med 2014; 55(4): 574-81.
[] [PMID: 24578240]
Li R, Ravizzini GC, Gorin MA, et al. The use of PET/CT in prostate cancer. Prostate Cancer Prostatic Dis 2018; 21(1): 4-21.
[] [PMID: 29230009]
Giovacchini G, Giovannini E, Riondato M, Ciarmiello A. PET/CT With 68Ga-PSMA in prostate cancer: radiopharmaceutical background and clinical implications. Curr Radiopharm 2018; 11(1): 4-13.
[] [PMID: 29090673]
Castellucci P, Ceci F, Fanti S. Imaging of prostate cancer using 11C-Choline PET/computed tomography. Urol Clin North Am 2018; 45(3): 481-7.
[] [PMID: 30031467]
Hofman MS, Hicks RJ, Maurer T, Eiber M. Prostate-specific membrane antigen PET: clinical utility in prostate cancer, normal patterns, pearls, and pitfalls. Radiographics 2018; 38(1): 200-17.
[] [PMID: 29320333]
Cook GJ, Houston S, Rubens R, Maisey MN, Fogelman I. Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions. J Clin Oncol 1998; 16(10): 3375-9.
[] [PMID: 9779715]
Damle NA, Bal C, Bandopadhyaya GP, et al. The role of 18F-fluoride PET-CT in the detection of bone metastases in patients with breast, lung and prostate carcinoma: a comparison with FDG PET/CT and 99mTc-MDP bone scan. Jpn J Radiol 2013; 31(4): 262-9.
[] [PMID: 23377765]
Iagaru A, Mittra E, Dick DW, Gambhir SS. Prospective evaluation of (99m)Tc MDP scintigraphy, (18)F NaF PET/CT, and (18)F FDG PET/CT for detection of skeletal metastases. Mol Imaging Biol 2012; 14(2): 252-9.
[] [PMID: 21479710]
Evangelista L, Bertoldo F, Boccardo F, et al. Diagnostic imaging to detect and evaluate response to therapy in bone metastases from prostate cancer: current modalities and new horizons. Eur J Nucl Med Mol Imaging 2016; 43(8): 1546-62.
[] [PMID: 26956538]
Wondergem M, van der Zant FM, van der Ploeg T, Knol RJ. A literature review of 18F-fluoride PET/CT and 18F-choline or 11C-choline PET/CT for detection of bone metastases in patients with prostate cancer. Nucl Med Commun 2013; 34(10): 935-45.
[] [PMID: 23903557]
Pyka T, Okamoto S, Dahlbender M, et al. Comparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43(12): 2114-21.
[] [PMID: 27290607]
Lengana T, Lawal IO, Boshomane TG, et al. 68Ga-PSMA PET/CT replacing bone scan in the initial staging of skeletal metastasis in prostate cancer: a fait accompli? Clin Genitourin Cancer 2018; S1558-7673(18) 30526
Petersen LJ, Strandberg J, Stenholt L, Johansen MB, Zacho HD. Reporting and handling of indeterminate bone scan results in the staging of prostate cancer: a systematic review. Diagnostics (Basel) 2018; 8(1) E9
[] [PMID: 29337860]
Cuccurullo V, Di Stasio GD, Mansi L. Nuclear medicine in prostate cancer: a new era for radiotracers. World J Nucl Med 2018; 17(2): 70-8.
[PMID: 29719480]
Cook GJ, Goh V. Functional and hybrid imaging of bone metastases. J Bone Miner Res 2018; 33(6): 961-72.
[] [PMID: 29665140]
Palmedo H, Marx C, Ebert A, et al. Whole-body SPECT/CT for bone scintigraphy: diagnostic value and effect on patient management in oncological patients. Eur J Nucl Med Mol Imaging 2014; 41(1): 59-67.
[] [PMID: 23974666]
Withofs N, Grayet B, Tancredi T, et al. 18F-fluoride PET/CT for assessing bone involvement in prostate and breast cancers. Nucl Med Commun 2011; 32(3): 168-76.
[] [PMID: 21076343]
Mosavi F, Johansson S, Sandberg DT, Turesson I, Sörensen J, Ahlström H. Whole-body diffusion-weighted MRI compared with (18)F-NaF PET/CT for detection of bone metastases in patients with high-risk prostate carcinoma. AJR Am J Roentgenol 2012; 199(5): 1114-20.
[] [PMID: 23096187]
Langsteger W, Balogova S, Huchet V, et al. Fluorocholine (18F) and sodium fluoride (18F) PET/CT in the detection of prostate cancer: prospective comparison of diagnostic performance determined by masked reading. Q J Nucl Med Mol Imaging 2011; 55(4): 448-57.
[PMID: 21738117]
Jambor I, Kuisma A, Ramadan S, et al. Prospective evaluation of planar bone scintigraphy, SPECT, SPECT/CT, 18F-NaF PET/CT and whole body 1.5T MRI, including DWI, for the detection of bone metastases in high risk breast and prostate cancer patients: SKELETA clinical trial. Acta Oncol 2016; 55(1): 59-67.
[] [PMID: 25833330]
Oxford Centre for evidence-based medicine; OCEBM levels of evidence working group. The Oxford levels of evidence 2 Available at:.
Korevaar DA, Wang J, van Enst WA, et al. Reporting diagnostic accuracy studies: some improvements after 10 years of STARD. Radiology 2015; 274(3): 781-9.
[] [PMID: 25350641]
Naaktgeboren CA, de Groot JA, Rutjes AW, Bossuyt PM, Reitsma JB, Moons KG. Anticipating missing reference standard data when planning diagnostic accuracy studies. BMJ 2016; 352: 402-5.
[] [PMID: 26861453]
Reitsma JB, Rutjes AW, Khan KS, Coomarasamy A, Bossuyt PM. A review of solutions for diagnostic accuracy studies with an imperfect or missing reference standard. J Clin Epidemiol 2009; 62(8): 797-806.
[] [PMID: 19447581]
Bertens LC, Broekhuizen BD, Naaktgeboren CA, et al. Use of expert panels to define the reference standard in diagnostic research: a systematic review of published methods and reporting. PLoS Med 2013; 10(10) e1001531
[] [PMID: 24143138]
Sonpavde G, Pond GR, Armstrong AJ, et al. Radiographic progression by Prostate Cancer Working Group (PCWG)-2 criteria as an intermediate endpoint for drug development in metastatic castration-resistant prostate cancer. BJU Int 2014; 114(6b): E25-31.
[] [PMID: 24298897]
Ferda J, Ferdová E, Baxa J, Fínek J, Topolčan O. 18F-Fluorocholine PET/MRI in restaging of prostatic carcinoma in relation to psa level and detection of active disease. Anticancer Res 2018; 38(7): 4139-43.
[] [PMID: 29970541]
Morris MJ, Molina A, Small EJ, et al. Radiographic progression-free survival as a response biomarker in metastatic castration-resistant prostate cancer: COU-AA-302 results. J Clin Oncol 2015; 33(12): 1356-63.
[] [PMID: 25624432]
Nome R, Hernes E, Bogsrud TV, Bjøro T, Fosså SD. Changes in prostate-specific antigen, markers of bone metabolism and bone scans after treatment with radium-223. Scand J Urol 2015; 49(3): 211-7.
[] [PMID: 25515952]
Anand A, Morris MJ, Larson SM, et al. Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide. EJNMMI Res 2016; 6(1): 23.
[] [PMID: 26960325]
Armstrong AJ, Kaboteh R, Carducci MA, et al. Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC). Urol Oncol 2014; 32(8): 1308-16.
[] [PMID: 25240761]
Kaboteh R, Gjertsson P, Leek H, et al. Progression of bone metastases in patients with prostate cancer - automated detection of new lesions and calculation of bone scan index. EJNMMI Res 2013; 3(1): 64.
[] [PMID: 23947784]
Sadik M, Suurkula M, Höglund P, Järund A, Edenbrandt L. Quality of planar whole-body bone scan interpretations--a nationwide survey. Eur J Nucl Med Mol Imaging 2008; 35(8): 1464-72.
[] [PMID: 18373092]
Anand A, Morris MJ, Kaboteh R, et al. Analytic validation of the automated bone scan index as an imaging biomarker to standardize quantitative changes in bone scans of patients with metastatic prostate cancer. J Nucl Med 2016; 57(1): 41-5.
[] [PMID: 26315832]
Cook G Jr, Parker C, Chua S, Johnson B, Aksnes AK, Lewington VJ. 18F-fluoride PET: changes in uptake as a method to assess response in bone metastases from castrate-resistant prostate cancer patients treated with 223Ra-chloride (Alpharadin). EJNMMI Res 2011; 1(1): 4.
[] [PMID: 22214491]
Apolo AB, Lindenberg L, Shih JH, et al. Prospective study evaluating Na18F PET/CT in predicting clinical outcomes and survival in advanced prostate cancer. J Nucl Med 2016; 57(6): 886-92.
[] [PMID: 26795292]
Kairemo K, Joensuu T. Radium-223-dichloride in castration resistant metastatic prostate cancer-preliminary results of the response evaluation using F-18-Fluoride PET/CT. Diagnostics (Basel) 2015; 5(4): 413-27.
[] [PMID: 26854163]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [565 - 571]
Pages: 7
DOI: 10.2174/1573405614666181009144601
Price: $65

Article Metrics

PDF: 15
PRC: 1