Biomarkers Prostate
Prostate MRI
Update: April 2025
|
Biomarker |
Acquisition Modality |
Acquisition requirements |
Target/rationale |
Potential application(s) |
References |
Level of evidence [1!] |
Issues |
|
Apparent Diffusion Coefficient (ADC) |
DWI |
DWI acquisition with at least two b-values, ideally between 50-100 sec/mm² and 800-1000 sec/mm². The maximum b-value should not exceed 1,000 sec/mm² to minimise diffusion kurtosis effect [2!]. |
Areas of restricted free water motion indicate highly cellular regions (i.e., cancer), as opposed to non-restricted normal gland (large cytoplasm, low cellularity). |
Discrimination between pathological and non-pathological tissue, non-invasive assessment of cancer grade, prediction of staging and upgrade during active surveillance, evaluation of tumour response to treatment. |
[3-15!]
|
Moderate |
ADC values depend on DWI protocols (e.g., b-values, signal averages, TE, diffusion models) and scanner characteristics (e.g., manufacturer, 1.5T vs. 3T), resulting in variability of absolute values and thresholds used to distinguish normal from pathological tissue. |
|
Intravoxel incoherent motion (IVIM) |
DWI |
DWI acquisition with multiple b-values. |
A biexponential function modelling enables the separation of molecular water diffusion (true diffusion) from microvascular perfusion (pseudo-diffusion) within a voxel. |
Enhanced discrimination between pathological and non-pathological tissue, non-invasive assessment of cancer grade. |
[16-21!] |
Low |
Lack of protocol standardisation (e.g., b-values) and reproducibility, variable cut-off values, oversimplification of biological complexity (limited to only two compartments), long acquisition times, high demands on hardware and software for both acquisition and post-processing, absence of demonstrated benefits over ADC alone. |
|
Diffusion Kurtosis Imaging (DKI) |
DWI |
DWI acquisition with multiple (at least three) non-zero b-values. |
Assessment of the non-Gaussian behaviour of water molecule diffusion in biological tissues, reflecting microstructural heterogeneity and providing additional insights into tissue complexity. |
Enhanced discrimination between pathological and non-pathological tissue, with potential for increased specificity, non-invasive assessment of cancer grade. |
[18, 22-26!] |
Low |
Lack of protocol standardisation (e.g., b-values) and reproducibility, variable cut-off values, long acquisition times, high demands on hardware and software for both acquisition and post-processing, absence of demonstrated benefits over ADC alone. |
|
Restriction Spectrum Imaging (RSI) |
DWI |
DWI acquisition with multiple gradient directions and b-values ("multi-shell"). |
Assessment of water diffusion in two compartments: the extracellular space (geometric tortuosity from cell packing) and the intracellular compartment. Computation of the RSI cellularity index (RSI-CI). |
Enhanced discrimination between pathological and non-pathological tissue, with potential for increased specificity, non-invasive assessment of cancer grade, prediction of upgrade during active surveillance. |
[27-31!] |
Low |
Lack of protocol standardisation (e.g. b-values), high demands on hardware and software for both acquisition and post-processing, vendor-dependent, absence of demonstrated benefits over ADC alone. |
|
Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumours (VERDICT) |
DWI |
DWI acquisition with multiple b-values. |
Assessment of water diffusion in three compartments (intracellular, intravascular and extracellular-extravascular), to estimate the intracellular volume fraction (FIC). |
Enhanced discrimination between pathological and non-pathological tissue, with potential for increased specificity; enhanced biological specificity with the assessment of differences in microstructure (cellular, vascular and extracellular-extravascular fractions). |
[6, 32-34!] |
Low |
Lack of protocol standardisation (e.g. b-values), need for custom pulse-sequences and scanner-specific calibration (e.g. using phantom), dedicated software analysis, long acquisition time. |
|
T2 mapping |
T2-WI |
Multiecho T2WI sequences (T2 mapping). |
Quantification of T2 relaxation time |
Differentiation between benign and malignant tissues, assessment of treatment response. |
[35-43!] |
Low |
Lack of protocol standardisation (e.g. TE) and reproducibility across protocols, need for scanner-specific and calibration (e.g. using phantom), dedicated post-processing analysis, long acquisition time, poor discrimination of relaxivity across tissues. |
|
Luminal Water Imaging |
T2-WI |
Multiecho T2-WI sequences |
Modelling of two compartments: 1) the luminal space; 2) the stromal and epithelial space. It allows the estimation of the Luminal Water Fraction (LWF). |
Enhanced differentiation between benign and malignant tissues, with the potential for greater specificity, estimation of tumour grade; enhanced biological specificity with the assessment of differences in microstructure (luminal space vs cellular and stromal space). |
[44-51!] |
Low |
Lack of protocol standardisation (e.g. TE values), need for custom pulse-sequences and scanner-specific and calibration (e.g. using phantom), dedicated post-processing analysis, long acquisition time. |
|
Hybrid Multidimensional MRI (HM-MRI) |
DWI/T2-WI |
Multi-echo, multi-b value DWI sequences |
Characterisation of tissue microstructure by assessing the volume fractions of lumen, stroma, and epithelium through changes in ADC and T2 values as functions of echo time and b-value, respectively. |
Enhanced differentiation between benign and malignant tissue; enhanced biological specificity with the assessment of differences in microstructure (lumen, stroma and epithelium). |
[52-55!] |
Low |
Lack of protocol standardisation, need for custom pulse-sequences, dedicated post-processing analysis, long acquisition time. |
|
MRI Fingerprinting (MRF) |
T1/T2-WI |
Inversion recovery based steady-state free precession (SSFP) MR sequence |
Explores multiple tissue properties simultaneously by creating a unique "fingerprint" for each tissue type based on its characteristic signal evolution. |
Reduced scan times, Simultaneous multiparametric mapping with potentially enhanced differentiation between benign and malignant tissue. |
Low |
Lack of protocol standardisation, dependency on dictionary accuracy, computational demand. |
|
|
Quantitative DCE |
DCE |
DCE sequences, T1 mapping |
Information about tissue vascularity and perfusion. The application of pharmacokinetic models allows the extraction of quantitative perfusion biomarkers, such as kTrans (used as a proxy for vascular permeability and perfusion). |
Enhanced differentiation between benign and malignant tissue. |
Low |
Lack of protocol standardisation, values are potentially affected by many factors (e.g. haemodynamic effects, contrast medium concentration and injection rate) and post-processing technique (e.g. pharmacokinetic model, arterial input function). |
|
|
Radiomics |
T2, DWI, DCE |
\ |
High-throughput image analysis to extract quantitative features (morphological, statistical and textural). |
Enhanced differentiation between benign and malignant tissue, assessment of tumour heterogeneity linked to tumour grade and prognostic features, enhanced staging. |
Low |
Lack of reproducibility, highly dependent on acquisition protocols, segmentation/feature extraction methods, lack of external validation of proposed models, lack of biological interpretability. |
- Martí-Bonmatí L (2021) Evidence levels in radiology: the insights into imaging approach. Insights Imaging 12:. https://doi.org/10.1186/S13244-021-00995-7
- Turkbey B, Rosenkrantz AB, Haider MA, et al (2019) Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Reporting and Data System Version 2. Eur Urol 76:340–351. https://doi.org/10.1016/J.EURURO.2019.02.033
- Langer DL, Van Der Kwast TH, Evans AJ, et al (2009) Prostate cancer detection with multi-parametric MRI: logistic regression analysis of quantitative T2, diffusion-weighted imaging, and dynamic contrast-enhanced MRI. J Magn Reson Imaging 30:327–334. https://doi.org/10.1002/JMRI.21824
- Yu AC, Badve C, Ponsky LE, et al (2017) Development of a Combined MR Fingerprinting and Diffusion Examination for Prostate Cancer. Radiology 283:729–738. https://doi.org/10.1148/RADIOL.2017161599
- Panda A, Obmann VC, Lo WC, et al (2019) MR Fingerprinting and ADC Mapping for Characterization of Lesions in the Transition Zone of the Prostate Gland. Radiology 292:685–694. https://doi.org/10.1148/RADIOL.2019181705
- Singh S, Rogers H, Kanber B, et al (2022) Avoiding Unnecessary Biopsy after Multiparametric Prostate MRI with VERDICT Analysis: The INNOVATE Study. Radiology 305:623–630. https://doi.org/10.1148/RADIOL.212536
- Giganti F, Coppola A, Ambrosi A, et al (2016) Apparent diffusion coefficient in the evaluation of side-specific extracapsular extension in prostate cancer: Development and external validation of a nomogram of clinical use. Urol Oncol 34:291.e9-291.e17. https://doi.org/10.1016/J.UROLONC.2016.02.015
- Tavakoli AA, Hielscher T, Badura P, et al (2023) Contribution of Dynamic Contrast-enhanced and Diffusion MRI to PI-RADS for Detecting Clinically Significant Prostate Cancer. Radiology 306:186–199. https://doi.org/10.1148/RADIOL.212692
- Goh V (2023) Tumor Physiology and Clinically Significant Prostate Cancer Detection. Radiology 306:200–201. https://doi.org/10.1148/RADIOL.221798
- Hötker AM, Mazaheri Y, Aras Ö, et al (2016) Assessment of Prostate Cancer Aggressiveness by Use of the Combination of Quantitative DWI and Dynamic Contrast-Enhanced MRI. AJR Am J Roentgenol 206:756–763. https://doi.org/10.2214/AJR.15.14912
- Fennessy FM, Maier SE (2023) Quantitative diffusion MRI in prostate cancer: Image quality, what we can measure and how it improves clinical assessment. Eur J Radiol 167. https://doi.org/10.1016/J.EJRAD.2023.111066
- Hötker AM, Mazaheri Y, Zheng J, et al (2015) Prostate Cancer: assessing the effects of androgen-deprivation therapy using quantitative diffusion-weighted and dynamic contrast-enhanced MRI. Eur Radiol 25:2665–2672. https://doi.org/10.1007/S00330-015-3688-1
- Dinis Fernandes C, van Houdt PJ, Heijmink SWTPJ, et al (2019) Quantitative 3T multiparametric MRI of benign and malignant prostatic tissue in patients with and without local recurrent prostate cancer after external-beam radiation therapy. J Magn Reson Imaging 50:269–278. https://doi.org/10.1002/JMRI.26581
- Boss MA, Snyder BS, Kim E, et al (2022) Repeatability and Reproducibility Assessment of the Apparent Diffusion Coefficient in the Prostate: A Trial of the ECOG-ACRIN Research Group (ACRIN 6701). J Magn Reson Imaging 56:668–679. https://doi.org/10.1002/JMRI.28093
- Shukla-Dave A, Obuchowski NA, Chenevert TL, et al (2019) Quantitative imaging biomarkers alliance (QIBA) recommendations for improved precision of DWI and DCE-MRI derived biomarkers in multicenter oncology trials. J Magn Reson Imaging 49:e101–e121. https://doi.org/10.1002/JMRI.26518
- Cui Y, Li C, Liu Y, et al (2020) Differentiation of prostate cancer and benign prostatic hyperplasia: comparisons of the histogram analysis of intravoxel incoherent motion and monoexponential model with in-bore MR-guided biopsy as pathological reference. Abdom Radiol (NY) 45:3265–3277. https://doi.org/10.1007/S00261-019-02227-5
- Valerio M, Zini C, Fierro D, et al (2016) 3T multiparametric MRI of the prostate: Does intravoxel incoherent motion diffusion imaging have a role in the detection and stratification of prostate cancer in the peripheral zone? Eur J Radiol 85:790–794. https://doi.org/10.1016/J.EJRAD.2016.01.006
- Shan Y, Chen X, Liu K, et al (2019) Prostate cancer aggressive prediction: preponderant diagnostic performances of intravoxel incoherent motion (IVIM) imaging and diffusion kurtosis imaging (DKI) beyond ADC at 3.0 T scanner with gleason score at final pathology. Abdom Radiol (NY) 44:3441–3452. https://doi.org/10.1007/S00261-019-02075-3
- Zhang YD, Wang Q, Wu CJ, et al (2015) The histogram analysis of diffusion-weighted intravoxel incoherent motion (IVIM) imaging for differentiating the gleason grade of prostate cancer. Eur Radiol 25:994–1004. https://doi.org/10.1007/S00330-014-3511-4
- Tavakoli AA, Kuder TA, Tichy D, et al (2021) Measured Multipoint Ultra-High b-Value Diffusion MRI in the Assessment of MRI-Detected Prostate Lesions. Invest Radiol 56:94–102. https://doi.org/10.1097/RLI.0000000000000712
- Pang Y, Turkbey B, Bernardo M, et al (2013) Intravoxel incoherent motion MR imaging for prostate cancer: an evaluation of perfusion fraction and diffusion coefficient derived from different b-value combinations. Magn Reson Med 69:553–562. https://doi.org/10.1002/MRM.24277
- Liu Y, Wang X, Cui Y, et al (2020) Comparative Study of Monoexponential, Intravoxel Incoherent Motion, Kurtosis, and IVIM-Kurtosis Models for the Diagnosis and Aggressiveness Assessment of Prostate Cancer. Front Oncol 10:. https://doi.org/10.3389/FONC.2020.01763
- Si Y, Liu R bo (2018) Diagnostic Performance of Monoexponential DWI Versus Diffusion Kurtosis Imaging in Prostate Cancer: A Systematic Review and Meta-Analysis. AJR Am J Roentgenol 211:358–368. https://doi.org/10.2214/AJR.17.18934
- Hectors SJ, Semaan S, Song C, et al (2018) Advanced Diffusion-weighted Imaging Modeling for Prostate Cancer Characterization: Correlation with Quantitative Histopathologic Tumor Tissue Composition-A Hypothesis-generating Study. Radiology 286:918–928. https://doi.org/10.1148/RADIOL.2017170904
- Tamada T, Prabhu V, Li J, et al (2017) Prostate Cancer: Diffusion-weighted MR Imaging for Detection and Assessment of Aggressiveness-Comparison between Conventional and Kurtosis Models. Radiology 284:100–108. https://doi.org/10.1148/RADIOL.2017162321
- Wang X, Tu N, Qin T, et al (2018) Diffusion Kurtosis Imaging Combined With DWI at 3-T MRI for Detection and Assessment of Aggressiveness of Prostate Cancer. AJR Am J Roentgenol 211:797–804. https://doi.org/10.2214/AJR.17.19249
- Zhong AY, Digma LA, Hussain T, et al (2022) Automated Patient-level Prostate Cancer Detection with Quantitative Diffusion Magnetic Resonance Imaging. Eur Urol Open Sci 47:20–28. https://doi.org/10.1016/J.EUROS.2022.11.009
- Brunsing RL, Schenker-Ahmed NM, White NS, et al (2016) Restriction Spectrum Imaging: An evolving imaging biomarker in prostate magnetic resonance imaging. J Magn Reson Imaging 45:323. https://doi.org/10.1002/JMRI.25419
- Eng SE, Basasie B, Lam A, et al (2022) Prospective comparison of restriction spectrum imaging and non-invasive biomarkers to predict upgrading on active surveillance prostate biopsy. Prostate Cancer and Prostatic Diseases 2022 27:1 27:65–72. https://doi.org/10.1038/s41391-022-00591-w
- Besasie BD, Sunnapwar AG, Gao F, et al (2021) Restriction Spectrum Imaging-Magnetic Resonance Imaging to Improve Prostate Cancer Imaging in Men on Active Surveillance. J Urol 206:44–51. https://doi.org/10.1097/JU.0000000000001692
- Felker ER, Raman SS, Shakeri S, et al (2019) Utility of restriction spectrum imaging among men undergoing first-time biopsy for suspected prostate cancer. American Journal of Roentgenology 213:365–370. https://doi.org/10.2214/AJR.18.20836/ASSET/IMAGES/LARGE/08_18_20836_03H_CMYK.JPEG
- Palombo M, Valindria V, Singh S, et al (2023) Joint estimation of relaxation and diffusion tissue parameters for prostate cancer with relaxation-VERDICT MRI. Scientific Reports 2023 13:1 13:1–13. https://doi.org/10.1038/s41598-023-30182-1
- Panagiotaki E, Chan RW, Dikaios N, et al (2015) Microstructural characterization of normal and malignant human prostate tissue with vascular, extracellular, and restricted diffusion for cytometry in tumours magnetic resonance imaging. Invest Radiol 50:218–227. https://doi.org/10.1097/RLI.0000000000000115
- Johnston EW, Bonet-Carne E, Ferizi U, et al (2019) VERDICT MRI for Prostate Cancer: Intracellular Volume Fraction versus Apparent Diffusion Coefficient. Radiology 291:391–397. https://doi.org/10.1148/RADIOL.2019181749
- Simpkin CJ, Morgan VA, Giles SL, et al (2013) Relationship between T2 relaxation and apparent diffusion coefficient in malignant and non-malignant prostate regions and the effect of peripheral zone fractional volume. Br J Radiol 86:. https://doi.org/10.1259/BJR.20120469
- Chatterjee A, Devaraj A, Mathew M, et al (2019) Performance of T2 Maps in the Detection of Prostate Cancer. Acad Radiol 26:15–21. https://doi.org/10.1016/J.ACRA.2018.04.005
- Hoang Dinh A, Souchon R, Melodelima C, et al (2015) Characterization of prostate cancer using T2 mapping at 3T: a multi-scanner study. Diagn Interv Imaging 96:365–372. https://doi.org/10.1016/J.DIII.2014.11.016
- Dregely I, Margolis DAJ, Sung K, et al (2016) Rapid quantitative T2 mapping of the prostate using three-dimensional dual echo steady state MRI at 3T. Magn Reson Med 76:1720–1729. https://doi.org/10.1002/MRM.26053
- Sathiadoss P, Schieda N, Haroon M, et al (2022) Utility of Quantitative T2-Mapping Compared to Conventional and Advanced Diffusion Weighted Imaging Techniques for Multiparametric Prostate MRI in Men with Hip Prosthesis. J Magn Reson Imaging 55:265–274. https://doi.org/10.1002/JMRI.27803
- Chatterjee A, Turchan WT, Fan X, et al (2022) Can Pre-treatment Quantitative Multi-parametric MRI Predict the Outcome of Radiotherapy in Patients with Prostate Cancer? Acad Radiol 29:977–985. https://doi.org/10.1016/J.ACRA.2021.09.012
- Dinis Fernandes C, van Houdt PJ, Heijmink SWTPJ, et al (2019) Quantitative 3T multiparametric MRI of benign and malignant prostatic tissue in patients with and without local recurrent prostate cancer after external-beam radiation therapy. J Magn Reson Imaging 50:269–278. https://doi.org/10.1002/JMRI.26581
- Kershaw LE, Logue JP, Hutchinson CE, et al (2008) Late tissue effects following radiotherapy and neoadjuvant hormone therapy of the prostate measured with quantitative magnetic resonance imaging. Radiother Oncol 88:127–134. https://doi.org/10.1016/J.RADONC.2008.02.018
- Chatterjee A, Nolan P, Sun C, et al (2020) Effect of Echo Times on Prostate Cancer Detection on T2-Weighted Images. Acad Radiol 27:1555–1563. https://doi.org/10.1016/J.ACRA.2019.12.014
- Sabouri S, Chang SD, Savdie R, et al (2017) Luminal Water Imaging: A New MR Imaging T2 Mapping Technique for Prostate Cancer Diagnosis. Radiology 284:451–459. https://doi.org/10.1148/RADIOL.2017161687
- Sabouri S, Fazli L, Chang SD, et al (2017) MR measurement of luminal water in prostate gland: Quantitative correlation between MRI and histology. J Magn Reson Imaging 46:861–869. https://doi.org/10.1002/JMRI.25624
- Chan RW, Lau AZ, Detzler G, et al (2019) Evaluating the accuracy of multicomponent T2 parameters for luminal water imaging of the prostate with acceleration using inner-volume 3D GRASE. Magn Reson Med 81:466–476. https://doi.org/10.1002/MRM.27372
- Sabouri S, Chang SD, Goldenberg SL, et al (2019) Comparing diagnostic accuracy of luminal water imaging with diffusion-weighted and dynamic contrast-enhanced MRI in prostate cancer: A quantitative MRI study. NMR Biomed 32:. https://doi.org/10.1002/NBM.4048
- Carlin D, Orton MR, Collins D, deSouza NM (2019) Probing structure of normal and malignant prostate tissue before and after radiation therapy with luminal water fraction and diffusion-weighted MRI. J Magn Reson Imaging 50:619–627. https://doi.org/10.1002/JMRI.26597
- Devine W, Giganti F, Johnston EW, et al (2019) Simplified Luminal Water Imaging for the Detection of Prostate Cancer From Multiecho T2 MR Images. J Magn Reson Imaging 50:910–917. https://doi.org/10.1002/JMRI.26608
- Hectors SJ, Said D, Gnerre J, et al (2020) Luminal Water Imaging: Comparison With Diffusion-Weighted Imaging (DWI) and PI-RADS for Characterization of Prostate Cancer Aggressiveness. J Magn Reson Imaging 52:271–279. https://doi.org/10.1002/JMRI.27050
- Retter A, Gong F, Syer T, et al (2021) Emerging methods for prostate cancer imaging: evaluating cancer structure and metabolic alterations more clearly. Mol Oncol 15:2565–2579. https://doi.org/10.1002/1878-0261.13071
- Wang S, Peng Y, Medved M, et al (2014) Hybrid multidimensional T(2) and diffusion-weighted MRI for prostate cancer detection. J Magn Reson Imaging 39:781–788. https://doi.org/10.1002/JMRI.24212
- Chatterjee A, Mercado C, Bourne RM, et al (2022) Validation of Prostate Tissue Composition by Using Hybrid Multidimensional MRI: Correlation with Histologic Findings. Radiology 302:368–377. https://doi.org/10.1148/RADIOL.2021204459
- Chatterjee A, Watson G, Myint E, et al (2015) Changes in Epithelium, Stroma, and Lumen Space Correlate More Strongly with Gleason Pattern and Are Stronger Predictors of Prostate ADC Changes than Cellularity Metrics. Radiology 277:751–762. https://doi.org/10.1148/RADIOL.2015142414
- Lee GH, Chatterjee A, Karademir I, et al (2022) Comparing Radiologist Performance in Diagnosing Clinically Significant Prostate Cancer with Multiparametric versus Hybrid Multidimensional MRI. Radiology 305:399–407. https://doi.org/10.1148/RADIOL.211895
Imaging guidelines in newly diagnosed prostate cancer
|
Guideline |
Categories |
Imaging recommendation |
|
EAU |
Low-risk* |
- No imaging |
|
Intermediate-risk*; predominantly GI 4 |
- Multiparametric MRI for local staging 1! - CT-abdomen/pelvis - Bone scan 2, 3, 4, 5! |
|
|
High-risk* |
- Multiparametric MRI for local staging - CT-abdomen/pelvis - Bone scan2, 3, 4, 5! |
|
|
General / any risk |
- No CT / TRUS for local staging - No Choline-PET for detection of LN-metastases - No final recommendation on Ga/F-PSMA PET - No final recommendation on WB-MRI |
|
|
NCCN (Version : 2.2017) |
If life expectancy >5y or asymptomatic AND: - T1 and PSA >20ng/ml - T2 and PSA >10ng/ml - Gleason 9 - T3 or T4 |
- Bone scan2, 3, 4, 5! |
|
Symptomatic AND: - T3; T4; - T1-T2 and nomogram >10% risk of LN-metastases Cagiannos I., et al 7! |
- CT/MRI |
|
|
AUA/ASTRO SUO 2017 |
Very low and Low risk* |
- No CT-abdomen/pelvis or Bone scan |
|
Unfavourable Intermediate/ High-Risk* |
- CT/MRI - Bone scan |
|
|
IKNL |
- PSA >20ng/ml - cT3 - Gleason 8 - Symptomatic |
- Bone scan or choline PET6! |
|
General / any risk |
- Multiparametric MRI for primary diagnosis (if available) 1!
- No CT for staging |
* Low-risk: PSA < 10 ng/mL; GS < 7 (ISUP grade 1); cT1-2a
Intermediate-risk: PSA 10-20 ng/mL; GS 7 (ISUP grade 2/3) or cT2b
High-risk: PSA > 20 ng/mL; or GS > 7 (ISUP grade 4/5); or locally advanced
x Very Low Risk: PSA <10 ng/ml AND Grade Group 1 AND clinical stage T1-T2a AND <34% of biopsy cores positive AND no core with >50% involved, AND PSA density <0.15 ng/ml/cc
Low Risk: PSA <10 ng/ml AND Grade Group 1 AND clinical stage T1-T2a
Intermediate Risk: PSA 10-<20 ng/ml OR Grade Group 2-3 OR clinical stage T2b-c
Favorable: Grade Group 1 (with PSA 10-<20) OR Grade Group 2 (with PSA<10)
Unfavorable: Grade Group 2 (with either PSA 10-<20 or clinical stage T2b-c) OR Grade Group 3 (with PSA < 20)
High Risk: PSA >20 ng/ml OR Grade Group 4-5 OR clinical stage >T3 OR locally advanced
- Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, Collaco-Moraes Y, Ward K, Hindley RG, Freeman A, Kirkham AP, Oldroyd R, Parker C, Emberton M; PROMIS study group. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017 Feb 25;389(10071):815-822.
- 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: 551–8.
- 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. 2014; 43: 1503–13.
- Zacho HD, Manresa JAB, Aleksyniene R, et al. Three-minute SPECT/CT is sufficient for the assessment of bone metastasis as add-on to planar bone scintigraphy: prospective head-to-head comparison to 11-min SPECT/CT. EJNMMI Res 2017; 7: 1.
- 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: 59–67.
- Beheshti M, Imamovic L, Broinger G, et al. 18F choline PET/CT in the preoperative staging of prostate cancer in patients with intermediate or high risk of extracapsular disease: a prospective study of 130 patients. Radiology 2010; 254: 925–33.62.
- Cagiannos I, Karaciwicz P, Eastham JA, et al. A Preoperative Nomogram Identifying Decreased Risk of Positive Pelvic Lymph Nodes in Patients With Prostate Cancer. J Urol 2003; 170: 1798–803.
Imaging guidelines at biochemical recurrence of prostate cancer
|
Guideline |
Categories |
Imaging recommendation |
|
EAU |
After prostatectomy: |
|
|
- PSA <1ng/ml |
- No imaging |
|
|
- PSA >1ng/ml |
- Choline or PSMA-ligand PET8! |
|
|
After radiotherapy: |
- Multiparametric MRI - Choline-PET9, 10, 11! - Ga-PSMA PET no standard tool, yet should be considered if available12, 13, 14, 15, 16, 17, 18! |
|
|
General / any risk: - Only if PSA >10ng/ml - PSAdt <6mnth - PSA velocity>0,5ng/ml/mo |
- CT-abdomen/pelvis19, 20! - Bone scan19, 20! - No final recommendation on WB-MRI21, 22! |
|
|
NCCN (Version : 2.2017) |
After prostatectomy: |
- Bone scan |
|
After Radiotherapy |
- X-ray chest |
|
|
IKNL |
- PSA >5ng/ml - PSA >1ng/ml and PSAdt <3mo - Gleason 8 |
- Choline PET - Bone scan only if PSA >20ng/ml |
|
General / any risk |
- No CT for staging |
- Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2017; 71: 618–29.
- Umbehr MH, Muntener 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 2013; 64: 106–17.
- Evangelista L, Zattoni F, Guttilla A, et al. Choline PET or PET/CT and biochemical relapse of prostate cancer: A systematic review and meta-analysis. Clin. Nucl. Med. 2013; 38: 305–14.
- Treglia G, Ceriani L, Sadeghi R, Giovacchini G, Giovanella L. Relationship between prostate-specific antigen kinetics and detection rate of radiolabelled choline PET/CT in restaging prostate cancer patients: A meta-analysis. Clin Chem Lab Med 2014; 52: 725–33.
- Afshar-Oromieh A, Malcher A, Eder 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 2013; 40: 486–95.
- Perera M, Papa N, Christidis D, et al. Sensitivity, Specificity, and Predictors of Positive 68Ga–Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis. Eur. Urol. 2016; 70: 926–37.
- Afshar-Oromieh A, Hetzheim H, Kratochwil C, et al. The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions. J Nucl Med 2015; 56: 1697–705.
- Eiber M, Maurer T, Souvatzoglou M, et al. Evaluation of hybrid 68Ga-PSMA-ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med 2015; 56: 668–74.
- Ceci F, Uprimny C, Nilica B, et al. 68Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging 2015; 42: 1284–94.
- Montorsi F, Gandaglia G, Fossati N, et al. Robot-assisted Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer. Eur Urol 2017; 72: 432–8.
- Maurer T, Weirich G, Schottelius M, et al. Prostate-specific Membrane Antigen-radioguided Surgery for Metastatic Lymph Nodes in Prostate Cancer. Eur Urol 2015; 68: 530–4.
- Kane CJ, Amling CL, Johnstone PAS, et al. Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy. Urology 2003; 61: 607–11.
- Lindenberg ML, Turkbey B, Mena E, Choyke PL. Imaging locally advanced, recurrent, and metastatic prostate cancer: A review. JAMA Oncol. 2017; 3: 1415–22.
- Eschmann SM, Pfannenberg AC, Rieger A, et al. Comparison of 11C-choline-PET/CT and whole body-MRI for staging of prostate cancer. NuklearMedizin. 2007; 46: 161–8.
- Zacho HD, Nielsen JB, Afshar-Oromieh A, Haberkorn U, deSouza N, De Paepe K, Dettmann K, Langkilde NC, Haarmark C, Fisker RV, Arp DT, Carl J, Jensen JB, Petersen LJ. Prospective comparison of (68)Ga-PSMA PET/CT, (18)F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2018; 45:1884-1897.
- Evangelista L, Zattoni F, Guttilla A, et al. Choline PET or PET/CT and biochemical relapse of prostate cancer: A systematic review and meta-analysis. Clin. Nucl. Med. 2013; 38: 305–14.
Imaging guidelines at the castrate resistant stage of prostate cancer
|
Guideline |
CRPC (APC) |
Imaging recommendation |
comments |
|
EAU |
- PSA >2ng/ml |
- Bone scan 24, 25, 26, 27, 28, 29! - CT |
(If negative repeat when PSA >5ng/ml and after PSAdt) |
|
- mCRPC - monitoring of treatment |
- CT-chest - CT-abdomen/pelvis - Bone scan |
(Repeated every 6 months) |
|
|
NCCN(Version: 2.2017) |
Castration-naïve |
- Bone scan - X ray-chest - CT/MRI-abdomen/pelvis with and without contrast Consider:- Choline PET30, 31! |
|
|
Monitoring mCRPC |
- CT/MRI - Bone scan |
(Every 6-12 months) (Every 8-12 weeks) |
|
|
APCCC 2017 (Delphi method >75% agreement) |
Oligometastatic castration-naïve Pca |
-NoCT-abdomen/pelvis or Bone scan |
|
|
Staging and monitoring mCRPC when treating with Ra-223 |
- CT-Thorax/Abdomen - Bone scan |
||
|
APCC 2015 |
mCRPC |
- CT-chest - CT-abdomen/pelvis - Bone scan - No routine WB-MRI or PET/CT for staging |
(Before start of treatment) |
|
PCWG3 |
If locally persistent/recurrent |
- Multiparametric MRI |
|
|
All patients |
- CT-chest(<5 mm slices) - CT-abdomen/pelvis (<5 mm slices) - Bone scan - WB-MRI and PET/CT (all tracers) not recommended |
- Miyoshi Y, Yoneyama S, Kawahara T, et al. Prognostic value of the bone scan index using a computer-aided diagnosis system for bone scans in hormone-naive prostate cancer patients with bone metastases. BMC Cancer 2016; : 1–7.
- Poulsen MH, Rasmussen J, Edenbrandt L, et al. Bone Scan Index predicts outcome in patients with metastatic hormone-sensitive prostate cancer. BJU Int 2016; 117: 748–53.
- Reza M, Bjartell A, Ohlsson M, et al. Bone Scan Index as a prognostic imaging biomarker during androgen deprivation therapy. EJNMMI Res 2014; 4: 58.
- 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:
1308–16. - 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: 64.
- Ulmert D, Kaboteh R, Fox JJ, et al. A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the bone scan index. Eur Urol 2012; 62: 78–84.
- Ceci F, Castellucci P, Nanni C, Fanti S. PET/CT imaging for evaluating response to therapy in castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43: 2103–4.
- Schwarzenböck SM, Eiber M, Kundt G, et al. Prospective evaluation of [11C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory
prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43: 2105–13.
Imaging characteristics and evidence level
|
Imaging modality |
Newly diagnosis staging |
BCR |
CRPC |
||||
|
ROC characteristics |
Evidence level |
ROC characteristics |
Evidence level |
ROC characteristics |
Evidence level |
||
|
SIM |
CT |
Node: Sens + Spec ++ |
2a/B |
Limited value and not recommended unless a high PSA value |
3b/B |
NA |
2a/B |
|
Bone scintigraphy |
Bone: Sens +++ Spec +++ |
3a/B |
Limited value and not recommended unless PSA >10 ng/mL |
3b/B |
‘2+2 rule’ recommended by PCWG |
3b/B |
|
|
MIM |
18F-NaF |
Bone: Sens ++++ Spec +++ PPV+++ NPV ++++ |
2a/B |
NA |
NA |
NA |
NA |
|
18!F-Choline |
Bone: Sens +++ Spec ++++ Node: Sens ++ Spec ++++ PPV+++ NPV ++++ |
2a/B 1b/A |
Patient basis Sens +++ Spec +++ Influenced by PSA level at recurrence |
2a/B |
Bone & soft tissue: Sens++++ Spec ++++ PPV++++ NPV ++++ |
2b/B |
|
|
WB-MRI with DWI |
Bone: Sens++++ Spec++++ AUC ++++ |
2a/B |
Positive at low PSA levels |
2b/B |
Anatomic and functional criteria |
2b/B |
|
|
PSMA |
Bone: Sens +++ Spec ++++ Node: Sens++ Spec++++ PPV+++ NPV +++ |
2b/B |
Patient basis: Sens +++ Spec +++ Influenced by PSA level at recurrence |
2a/B |
Not reliable for AR axis targeting treatments |
NA |
|
“+” <50%;
“++” 50%-69%;
“+++” 70%-89%;
“++++” 90%
AR= androgen receptor;
BCR= biochemical relapse;
CRPC= castration-resistant prostate cancer;
DWI=diffusion weighted imaging;
NA=no adequate data in this population or similar ROC and evidence level to staging;
NPV=negative predictive value;
PPV=positive predictive value;
PCWG=prostate cancer working group;
PSA= prostate-specific antigen;
PSMA= prostate-specific membrane antigen;
ROC= receiver operating characteristic;
Sens= sensitivity;
Spec=specificity;
WB-MRI=whole body- magnetic resonance imaging