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Prostate Cancer: Diagnosis and evaluation: Difference between revisions

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==== <span style="color:#ff0000">Primary</span> ====
==== <span style="color:#ff0000">Primary</span> ====
* '''<span style="color:#ff0000">Transrectal ultrasound (TRUS)</span>'''
 
** '''<span style="color:#ff0000">Compared to DRE, TRUS does not improve the ability to stage prostate cancer</span>'''
===== '''<span style="color:#ff0000">Transrectal ultrasound (TRUS)</span>''' =====
** '''<span style="color:#ff0000">In general, TRUS under-stages rather than over-stages prostate cancer</span>'''
* '''<span style="color:#ff0000">Compared to DRE, TRUS does not improve the ability to stage prostate cancer</span>'''
* '''<span style="color:#ff0000">Multi-parametric MRI (mpMRI)</span>'''
* '''<span style="color:#ff0000">In general, TRUS under-stages rather than over-stages prostate cancer</span>'''
** MRI acquires imaging data by detecting varying signal intensities from tissues based on the proton content of that tissue
 
** '''mpMRI is the combination of multiple MRI sequences usually consisting of T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) imaging and magnetic resonance spectroscopic imaging.'''
===== '''<span style="color:#ff0000">Multi-parametric MRI (mpMRI)</span>''' =====
** '''<span style="color:#ff0000">Imaging sequences</span>'''
* MRI acquires imaging data by detecting varying signal intensities from tissues based on the proton content of that tissue
*** '''The primary diagnostic parameters are T2WI and DWI'''
* '''mpMRI is the combination of multiple MRI sequences usually consisting of T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) imaging and magnetic resonance spectroscopic imaging.'''
*** '''<span style="color:#ff0000">T1WI</span>'''
* '''<span style="color:#ff0000">Imaging sequences</span>'''
**** Captures the movement of protons in the z-axis
** '''The primary diagnostic parameters are T2WI and DWI'''
**** '''Often used to look at normal anatomical details.'''
** '''<span style="color:#ff0000">T1WI</span>'''
**** '''<span style="color:#ff0000">Optimal sequence to identify areas of hemorrhage within the prostate</span>'''
*** Captures the movement of protons in the z-axis
***** '''<span style="color:#ff0000">Blood has high signal intensity on T1</span>, against a homogenous low signal background.'''
*** '''Often used to look at normal anatomical details.'''
**** '''<span style="color:#ff0000">Prostate cancer has low signal intensity on T1'''
*** '''<span style="color:#ff0000">Optimal sequence to identify areas of hemorrhage within the prostate</span>'''
*** '''<span style="color:#ff0000">T2WI</span>'''
**** '''<span style="color:#ff0000">Blood has high signal intensity on T1</span>, against a homogenous low signal background.'''
**** Captures the movement of protons in the xy-axis (transverse)
*** '''<span style="color:#ff0000">Prostate cancer has low signal intensity on T1'''
**** Primary means of visualization of zonal and anatomical features of the prostate.
** '''<span style="color:#ff0000">T2WI</span>'''
**** '''<span style="color:#ff0000">Optimal sequence to measure lesions in the transition zone</span>'''
*** Captures the movement of protons in the xy-axis (transverse)
**** '''Due to its high water content, the peripheral zone normally displays high signal intensity. By contrast, <span style="color:#ff0000">prostate cancer has low signal intensity on T2</span> allowing for identification of suspicious lesions'''
*** Primary means of visualization of zonal and anatomical features of the prostate.
***** As 70% of all prostate cancers occur within the peripheral zone, the tissue characteristics allow for T2WI to detect a significant number of tumors in this zone
*** '''<span style="color:#ff0000">Optimal sequence to measure lesions in the transition zone</span>'''
***** '''Various conditions such as prostatitis, hemorrhage, atrophy, scars and post-treatment changes have low signal intensity on T2 and can mimic cancer on T2WI.'''
*** '''Due to its high water content, the peripheral zone normally displays high signal intensity. By contrast, <span style="color:#ff0000">prostate cancer has low signal intensity on T2</span> allowing for identification of suspicious lesions'''
****** Post-biopsy hemorrhage can interfere with tumor detection, since areas of hemorrhage appear similar to tumor on T2WI. For this reason, it is recommended to wait an interval of at least 6-8 weeks after prostate biopsy for resolution of hemorrhage or hematoma before performing prostate MRI.
**** As 70% of all prostate cancers occur within the peripheral zone, the tissue characteristics allow for T2WI to detect a significant number of tumors in this zone
**** '''Low signal intensity tumors on T2WI of the central gland are more difficult to distinguish from the similarly hypointense stromal hyperplasia, ie benign prostatic hyperplasia'''
**** '''Various conditions such as prostatitis, hemorrhage, atrophy, scars and post-treatment changes have low signal intensity on T2 and can mimic cancer on T2WI.'''
**** Central zone also displays intermediate signal intensity while seminal vesicles display high signal intensity
***** Post-biopsy hemorrhage can interfere with tumor detection, since areas of hemorrhage appear similar to tumor on T2WI. For this reason, it is recommended to wait an interval of at least 6-8 weeks after prostate biopsy for resolution of hemorrhage or hematoma before performing prostate MRI.
*** '''<span style="color:#ff0000">Diffusion weighted imaging (DWI)</span>'''
*** '''Low signal intensity tumors on T2WI of the central gland are more difficult to distinguish from the similarly hypointense stromal hyperplasia, ie benign prostatic hyperplasia'''
**** Measures the diffusion of water protons within tissue
*** Central zone also displays intermediate signal intensity while seminal vesicles display high signal intensity
**** The images are acquired by sequentially applying multiple magnetic field gradients, known as b-values, to calculate apparent diffusion coefficient values and construct ADC maps. The higher the b-value, the stronger the diffusion effects
** '''<span style="color:#ff0000">Diffusion weighted imaging (DWI)</span>'''
**** '''ADC values are calculated by the software and displayed as a parametric map reflecting the degree of diffusion of water molecules through different tissues.'''
*** Measures the diffusion of water protons within tissue
***** Protons are mobile in normal water-rich glandular tissue but have restricted movement in densely packed water-poor tissue such as that found in tumors.
*** The images are acquired by sequentially applying multiple magnetic field gradients, known as b-values, to calculate apparent diffusion coefficient values and construct ADC maps. The higher the b-value, the stronger the diffusion effects
***** '''Normal glandular prostate tissue''' allows unrestricted free water movement and '''displays isointense regions on ADC maps''', which results in '''prostate cancer appearing as a decreased signal, ie restricted diffusion, on the ADC map and as high signal intensity focus on high b-value images.'''
*** '''ADC values are calculated by the software and displayed as a parametric map reflecting the degree of diffusion of water molecules through different tissues.'''
**** '''<span style="color:#ff0000">Tumors with the higher restriction (low ADC values) tend to be higher grade</span>'''
**** Protons are mobile in normal water-rich glandular tissue but have restricted movement in densely packed water-poor tissue such as that found in tumors.
**** '''<span style="color:#ff0000">Optimal sequence to evaluate suspicious lesions in the peripheral zone</span>'''
**** '''Normal glandular prostate tissue''' allows unrestricted free water movement and '''displays isointense regions on ADC maps''', which results in '''prostate cancer appearing as a decreased signal, ie restricted diffusion, on the ADC map and as high signal intensity focus on high b-value images.'''
*** '''<span style="color:#ff0000">Dynamic contrast enhancement (DCE)</span>'''
*** '''<span style="color:#ff0000">Tumors with the higher restriction (low ADC values) tend to be higher grade</span>'''
**** '''DCE imaging uses a series of T1WI obtained shortly after injection of an intravenous gadolinium based contrast agent to''' '''<span style="color:#ff0000">measure the vascularity of prostate tissue</span>'''.
*** '''<span style="color:#ff0000">Optimal sequence to evaluate suspicious lesions in the peripheral zone</span>'''
***** Tumors have increased vascularity due to neo-angiogenesis and, therefore, take up the contrast agent more rapidly than normal tissue. Moreover, this contrast washes out of tumor regions quickly leading to a steep wash-in-wash-out enhancement curve.
** '''<span style="color:#ff0000">Dynamic contrast enhancement (DCE)</span>'''
**** While DCE imaging has a high sensitivity, there remains a variability in the evaluation methods questioning it’s value; preferentially detects larger and higher-grade cancer foci
*** '''DCE imaging uses a series of T1WI obtained shortly after injection of an intravenous gadolinium based contrast agent to''' '''<span style="color:#ff0000">measure the vascularity of prostate tissue</span>'''.
*** '''<span style="color:#ff0000">Magnetic resonance spectroscopic imaging (MRSI)</span>'''
**** Tumors have increased vascularity due to neo-angiogenesis and, therefore, take up the contrast agent more rapidly than normal tissue. Moreover, this contrast washes out of tumor regions quickly leading to a steep wash-in-wash-out enhancement curve.
**** '''Uses the relative concentration of cellular metabolites in the prostate, specifically citrate and choline, to detect prostate cancer.'''
*** While DCE imaging has a high sensitivity, there remains a variability in the evaluation methods questioning it’s value; preferentially detects larger and higher-grade cancer foci
***** '''Citrate is a marker of normal prostatic tissue, whereas high levels of choline can be found in cancerous cells owing to increased cell turnover, which, in turn, leads to an increased choline-to-citrate ratio in patients with prostate cancer'''
** '''<span style="color:#ff0000">Magnetic resonance spectroscopic imaging (MRSI)</span>'''
**** '''<span style="color:#ff0000">When combined with T2WI, MRSI has been found to have the highest sensitivity of all MRI sequences (92%) in detecting prostate cancer.</span>'''
*** '''Uses the relative concentration of cellular metabolites in the prostate, specifically citrate and choline, to detect prostate cancer.'''
**** While MRSI is a promising imaging sequence, it requires an extra 10 to 15 minutes of examination time. Also, for this phase an endorectal coil (see below) is mandatory at 1.5T and optional at 3T. For these reasons, MRSI is less commonly performed than other mpMRI sequences in prostate MRI studies.
**** '''Citrate is a marker of normal prostatic tissue, whereas high levels of choline can be found in cancerous cells owing to increased cell turnover, which, in turn, leads to an increased choline-to-citrate ratio in patients with prostate cancer'''
*** '''Biparametric MRI'''
*** '''<span style="color:#ff0000">When combined with T2WI, MRSI has been found to have the highest sensitivity of all MRI sequences (92%) in detecting prostate cancer.</span>'''
**** A limitation of mpMRI for implementation as an adjunct tool for prostate cancer screening is the time required to complete the study, including the placement of an endorectal coil and the use of gadolinium based contrast agents requiring intravenous access. To overcome these limitations, it has been suggested that a '''limited mpMRI study incorporating only non-contrast T2WI and DWI series be performed.'''
*** While MRSI is a promising imaging sequence, it requires an extra 10 to 15 minutes of examination time. Also, for this phase an endorectal coil (see below) is mandatory at 1.5T and optional at 3T. For these reasons, MRSI is less commonly performed than other mpMRI sequences in prostate MRI studies.
**** This biparametric MRI requires less than half the in-bore magnet time to perform compared with the complete mpMRI, can be performed without an endorectal coil, and obviates the need for intravenous access and contrast administration.
** '''Biparametric MRI'''
** '''<span style="color:#ff0000">Magnet strength</span>'''
*** A limitation of mpMRI for implementation as an adjunct tool for prostate cancer screening is the time required to complete the study, including the placement of an endorectal coil and the use of gadolinium based contrast agents requiring intravenous access. To overcome these limitations, it has been suggested that a '''limited mpMRI study incorporating only non-contrast T2WI and DWI series be performed.'''
*** '''mpMRI can be performed at field strengths of 1.5T or 3T with or without an endorectal coil.'''
*** This biparametric MRI requires less than half the in-bore magnet time to perform compared with the complete mpMRI, can be performed without an endorectal coil, and obviates the need for intravenous access and contrast administration.
**** 3T magnets reduce image acquisition time and improve spatial resolution
* '''<span style="color:#ff0000">Magnet strength</span>'''
**** Greater magnet strength does not necessarily mean greater cancer detection rates.
** '''mpMRI can be performed at field strengths of 1.5T or 3T with or without an endorectal coil.'''
** '''<span style="color:#ff0000">Endorectal coil</span>'''
*** 3T magnets reduce image acquisition time and improve spatial resolution
*** '''Standard clinical field strengths of 1.5T do not provide sufficient signal-to-noise ratio for clinical diagnosis of prostate cancer. To compensate for this deficiency, the use of surface and/or endorectal coil arrays has been proposed <span style="color:#ff0000">to increase the SNR</span>'''
*** Greater magnet strength does not necessarily mean greater cancer detection rates.
*** An ERC can lead to deformation of the gland which may affect the image registration for targeted biopsy or radiation planning, although concerns regarding alterations in prostate volume have largely been dispelled.
* '''<span style="color:#ff0000">Endorectal coil</span>'''
*** The absolute benefit of an ERC may be offset by patient discomfort, additional time required for proper placement and verification, and associated cost
** '''Standard clinical field strengths of 1.5T do not provide sufficient signal-to-noise ratio for clinical diagnosis of prostate cancer. To compensate for this deficiency, the use of surface and/or endorectal coil arrays has been proposed <span style="color:#ff0000">to increase the SNR</span>'''
*** '''There is consensus regarding the use of a surface body coil and an endorectal coil at 1.5T but controversy remains regarding the need for an endorectal coil at 3T.'''
** An ERC can lead to deformation of the gland which may affect the image registration for targeted biopsy or radiation planning, although concerns regarding alterations in prostate volume have largely been dispelled.
**** '''<span style="color:#ff0000">The highest signal-to-noise ratio (SNR) is achieved at 3T with an endorectal coil</span> but acceptable results can be achieved at 3T without an endorectal coil.'''
** The absolute benefit of an ERC may be offset by patient discomfort, additional time required for proper placement and verification, and associated cost
** '''<span style="color:#ff0000">Prostate imaging and reporting archiving data system'''
** '''There is consensus regarding the use of a surface body coil and an endorectal coil at 1.5T but controversy remains regarding the need for an endorectal coil at 3T.'''
*** '''The PI-RADS score provided guidance for interpretation of different sequences and prostate zones'''
*** '''<span style="color:#ff0000">The highest signal-to-noise ratio (SNR) is achieved at 3T with an endorectal coil</span> but acceptable results can be achieved at 3T without an endorectal coil.'''
****'''<span style="color:#ff0000">Positive predictive values ISUP grade group ≥2 based on PI-RADS score:</span>[https://pubmed.ncbi.nlm.nih.gov/35393568/]'''
* '''<span style="color:#ff0000">Prostate imaging and reporting archiving data system'''
*****'''<span style="color:#ff0000">PI-RADS 3: 12–15%</span>'''
** '''The PI-RADS score provided guidance for interpretation of different sequences and prostate zones'''
*****'''<span style="color:#ff0000">PI-RADS 4: 39–48%</span>'''
***'''<span style="color:#ff0000">Positive predictive values ISUP grade group ≥2 based on PI-RADS score:</span>[https://pubmed.ncbi.nlm.nih.gov/35393568/]'''
*****'''<span style="color:#ff0000">PI-RADS 5: 72%</span>'''
****'''<span style="color:#ff0000">PI-RADS 3: 12–15%</span>'''
*** Lesions in the peripheral zone appear round or irregular, and are focally hypointense, whereas transition zone lesions are non-circumscribed and moderately hypointense, and may exhibit a characteristic ‘‘erased charcoal’’ sign.
****'''<span style="color:#ff0000">PI-RADS 4: 39–48%</span>'''
** '''<span style="color:#ff0000">MRI in Prostate Cancer</span>'''
****'''<span style="color:#ff0000">PI-RADS 5: 72%</span>'''
*** '''<span style="color:#ff00ff">Cochrane Systematic Review and Meta-analysis (2019)</span>'''
** Lesions in the peripheral zone appear round or irregular, and are focally hypointense, whereas transition zone lesions are non-circumscribed and moderately hypointense, and may exhibit a characteristic ‘‘erased charcoal’’ sign.
****'''MRI compared with template‐guided biopsy'''
* '''<span style="color:#ff0000">MRI in Prostate Cancer</span>'''
*****'''Detection of grade 2 or higher prostate cancer'''
** '''<span style="color:#ff00ff">Cochrane Systematic Review and Meta-analysis (2019)</span>'''
******'''Sensitivity: 0.91 (95% CI 0.83 to 0.95)'''
***'''MRI compared with template‐guided biopsy'''
******'''Specificity: 0.37 (95% CI 0.29 to 0.46)'''
****'''Detection of grade 2 or higher prostate cancer'''
*****'''Detection of grade 3 or higher prostate cancer'''
*****'''Sensitivity: 0.91 (95% CI 0.83 to 0.95)'''
******'''Sensitivity: 0.95 (95% CI 0.87 to 0.99)'''
*****'''Specificity: 0.37 (95% CI 0.29 to 0.46)'''
******'''Specificity: 0.35 (95% CI 0.26 to 0.46)'''
****'''Detection of grade 3 or higher prostate cancer'''
****[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483565/ Drost, Frank‐Jan H., et al.] "Prostate MRI, with or without MRI‐targeted biopsy, and systematic biopsy for detecting prostate cancer." ''Cochrane Database of Systematic Reviews'' 4 (2019).
*****'''Sensitivity: 0.95 (95% CI 0.87 to 0.99)'''
***'''<span style="color:#ff00ff">PROMIS (2017)</span>'''
*****'''Specificity: 0.35 (95% CI 0.26 to 0.46)'''
**** '''<span style="color:#ff0000">Objective:</span> compare the <span style="color:#ff0000">accuracy of mpMRI</span> with TRUS biopsy to determine the utility of mpMRI as a triage test <span style="color:#ff0000">to decide which men with an elevated PSA may be able to avoid biopsy</span>'''
***[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483565/ Drost, Frank‐Jan H., et al.] "Prostate MRI, with or without MRI‐targeted biopsy, and systematic biopsy for detecting prostate cancer." ''Cochrane Database of Systematic Reviews'' 4 (2019).
**** '''<span style="color:#ff0000">Population: 576 men with a clinical suspicion of prostate cancer (PSA ≤15 ng/mL)</span>'''
**'''<span style="color:#ff00ff">PROMIS (2017)</span>'''
**** '''<span style="color:#ff0000">Intervention: mpMRI followed by standard TRUS biopsy with template prostate mapping biopsy as gold standard reference</span>'''
*** '''<span style="color:#ff0000">Objective:</span> compare the <span style="color:#ff0000">accuracy of mpMRI</span> with TRUS biopsy to determine the utility of mpMRI as a triage test <span style="color:#ff0000">to decide which men with an elevated PSA may be able to avoid biopsy</span>'''
**** '''<span style="color:#ff0000">Results:</span>'''
*** '''<span style="color:#ff0000">Population: 576 men with a clinical suspicion of prostate cancer (PSA ≤15 ng/mL)</span>'''
***** '''<span style="color:#ff0000">mpMRI displayed a moderate sensitivity</span>''' and negative predictive value for predicting Gleason ≥3+4 disease (88% and 76%, respectively), '''<span style="color:#ff0000">but poor specificity</span>''' and positive predictive value (45% and 65%, respectively).
*** '''<span style="color:#ff0000">Intervention: mpMRI followed by standard TRUS biopsy with template prostate mapping biopsy as gold standard reference</span>'''
**** [https://pubmed.ncbi.nlm.nih.gov/28110982/ Ahmed, Hashim U., et al.] "Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study." The Lancet 389.10071 (2017): 815-822.
*** '''<span style="color:#ff0000">Results:</span>'''
*** '''<span style="color:#ff00ff">PRECISION (2018)</span>'''
**** '''<span style="color:#ff0000">mpMRI displayed a moderate sensitivity</span>''' and negative predictive value for predicting Gleason ≥3+4 disease (88% and 76%, respectively), '''<span style="color:#ff0000">but poor specificity</span>''' and positive predictive value (45% and 65%, respectively).
**** Objective: can MRI be used to increase detection of clinically significant prostate cancer and decrease detection of clinically insignificant prostate cancer
*** [https://pubmed.ncbi.nlm.nih.gov/28110982/ Ahmed, Hashim U., et al.] "Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study." The Lancet 389.10071 (2017): 815-822.
**** '''Design: Non-inferiority trial'''
** '''<span style="color:#ff00ff">PRECISION (2018)</span>'''
**** '''<span style="color:#ff0000">Population: 500 men with clinical suspicion of prostate cancer based on elevated PSA or abnormal DRE</span>'''
*** Objective: can MRI be used to increase detection of clinically significant prostate cancer and decrease detection of clinically insignificant prostate cancer
**** '''<span style="color:#ff0000">Randomized to MRI +/- targeted biopsy vs. standard TRUS–guided biopsy</span>'''
*** '''Design: Non-inferiority trial'''
***** '''Men in the MRI group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy'''
*** '''<span style="color:#ff0000">Population: 500 men with clinical suspicion of prostate cancer based on elevated PSA or abnormal DRE</span>'''
**** '''Outcomes'''
*** '''<span style="color:#ff0000">Randomized to MRI +/- targeted biopsy vs. standard TRUS–guided biopsy</span>'''
***** '''Primary: proportion of men who received a diagnosis of clinically significant cancer'''
**** '''Men in the MRI group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy'''
***** Secondary: proportion of men who received a diagnosis of clinically insignificant cancer
*** '''Outcomes'''
**** '''<span style="color:#ff0000">Results:</span>'''
**** '''Primary: proportion of men who received a diagnosis of clinically significant cancer'''
***** '''<span style="color:#ff0000">MRI-targeted biopsy was non-inferior and superior to detecting clinically significant cancer</span>''' (absolute risk difference 12%, 38% MRI vs. 26% standard TRUS)
**** Secondary: proportion of men who received a diagnosis of clinically insignificant cancer
***** '''<span style="color:#ff0000">MRI-targeted biopsy was associated with fever patients being diagnosed with clinically insignificant cancer</span>''' (absolute risk difference -13%)
*** '''<span style="color:#ff0000">Results:</span>'''
**** Authors’ conclusion: Using MP-MRI to triage men might allow 27% of patients avoid a primary biopsy and diagnosis of 5% fewer clinically insignificant cancers. If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of clinically significant cancer might be detected compared with the standard pathway of TRUS-biopsy for all. MP-MRI, used as a triage test before first prostate biopsy, could reduce unnecessary biopsies by a quarter. MP-MRI can also reduce over-diagnosis of clinically insignificant prostate cancer and improve detection of clinically significant cancer.
**** '''<span style="color:#ff0000">MRI-targeted biopsy was non-inferior and superior to detecting clinically significant cancer</span>''' (absolute risk difference 12%, 38% MRI vs. 26% standard TRUS)
**** [https://pubmed.ncbi.nlm.nih.gov/29552975/ Kasivisvanathan, Veeru, et al.] "MRI-targeted or standard biopsy for prostate-cancer diagnosis." New England Journal of Medicine 378.19 (2018): 1767-1777.
**** '''<span style="color:#ff0000">MRI-targeted biopsy was associated with fever patients being diagnosed with clinically insignificant cancer</span>''' (absolute risk difference -13%)
*** '''<span style="color:#ff00ff">MRI-FIRST (2019)</span>'''
*** Authors’ conclusion: Using MP-MRI to triage men might allow 27% of patients avoid a primary biopsy and diagnosis of 5% fewer clinically insignificant cancers. If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of clinically significant cancer might be detected compared with the standard pathway of TRUS-biopsy for all. MP-MRI, used as a triage test before first prostate biopsy, could reduce unnecessary biopsies by a quarter. MP-MRI can also reduce over-diagnosis of clinically insignificant prostate cancer and improve detection of clinically significant cancer.
**** Objective: determine whether MRI prior to biopsy increases detection of clinically significant prostate cancer
*** [https://pubmed.ncbi.nlm.nih.gov/29552975/ Kasivisvanathan, Veeru, et al.] "MRI-targeted or standard biopsy for prostate-cancer diagnosis." New England Journal of Medicine 378.19 (2018): 1767-1777.
**** '''Population: 275 patients with clinical suspicion of prostate cancer'''
** '''<span style="color:#ff00ff">MRI-FIRST (2019)</span>'''
**** '''Intervention: MRI followed by standard systematic biopsy then targeted biopsy of up to 2 lesions on MRI. Patients with negative multiparametric MRI (Likert score ≤2) had systematic biopsy only.'''
*** Objective: determine whether MRI prior to biopsy increases detection of clinically significant prostate cancer
**** '''Primary outcome: detection of clinically significant prostate cancer'''
*** '''Population: 275 patients with clinical suspicion of prostate cancer'''
**** '''Results:'''
*** '''Intervention: MRI followed by standard systematic biopsy then targeted biopsy of up to 2 lesions on MRI. Patients with negative multiparametric MRI (Likert score ≤2) had systematic biopsy only.'''
***** '''No difference in detection of clinically significant prostate cancer''' (30% systematic biopsy vs. 32% targeted biopsy)
*** '''Primary outcome: detection of clinically significant prostate cancer'''
***** Clinically significant prostate cancer would have been missed in 5% of patients had systematic biopsy not been done, and in 8% of patients had targeted biopsy not been done
*** '''Results:'''
**** '''Obtaining a multiparametric MRI before biopsy in biopsy-naive patients can improve the detection of clinically significant prostate cancer compared to systematic biopsy alone but does not seem to avoid the need for systematic biopsy'''
**** '''No difference in detection of clinically significant prostate cancer''' (30% systematic biopsy vs. 32% targeted biopsy)
**** [https://pubmed.ncbi.nlm.nih.gov/30470502/ Rouvière, Olivier, et al.] "Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study." The Lancet Oncology 20.1 (2019): 100-109.
**** Clinically significant prostate cancer would have been missed in 5% of patients had systematic biopsy not been done, and in 8% of patients had targeted biopsy not been done
***'''MRI may identify more clinically significant disease, avoid clinically insignificant disease, and help tailor treatment; however, up to 20% of negative MRI have clinically significant prostate cancer'''
*** '''Obtaining a multiparametric MRI before biopsy in biopsy-naive patients can improve the detection of clinically significant prostate cancer compared to systematic biopsy alone but does not seem to avoid the need for systematic biopsy'''
****'''<span style="color:#ff00ff">STHLM3 - MRI-targeted vs. standard biopsy in prostate cancer screening</span>'''
*** [https://pubmed.ncbi.nlm.nih.gov/30470502/ Rouvière, Olivier, et al.] "Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study." The Lancet Oncology 20.1 (2019): 100-109.
*****'''Population: 1532 males aged 50-74 years with screening PSA > 3 ng/mL'''
**'''MRI may identify more clinically significant disease, avoid clinically insignificant disease, and help tailor treatment; however, up to 20% of negative MRI have clinically significant prostate cancer'''
*****'''Randomized to standard biopsy vs. MRI, with targeted and standard biopsy if the MRI results suggested prostate cancer'''
***'''<span style="color:#ff00ff">STHLM3 - MRI-targeted vs. standard biopsy in prostate cancer screening</span>'''
***** Primary outcome: proportion of males diagnosed with clinically significant cancer (Gleason score ≥7)
****'''Population: 1532 males aged 50-74 years with screening PSA > 3 ng/mL'''
***** Secondary outcome: proportion of males diagnosed with clinically insignificant cancers (Gleason score 6).
****'''Randomized to standard biopsy vs. MRI, with targeted and standard biopsy if the MRI results suggested prostate cancer'''
***** Results
**** Primary outcome: proportion of males diagnosed with clinically significant cancer (Gleason score ≥7)
****** MRI non-inferior to diagnose clinically significant disease (21% MRI vs. 18% standard biopsy)
**** Secondary outcome: proportion of males diagnosed with clinically insignificant cancers (Gleason score 6).
****** Significantly fewer clinically insignificant disease with MRI (4% MRI vs. 12% standard biopsy)
**** Results
***** [https://pubmed.ncbi.nlm.nih.gov/34237810/ Eklund, Martin, et al.] "MRI-targeted or standard biopsy in prostate cancer screening." ''New England Journal of Medicine'' (2021).
***** MRI non-inferior to diagnose clinically significant disease (21% MRI vs. 18% standard biopsy)
**** '''Use of MRI in prostate cancer diagnosis as per the 2017 Cancer Care Ontario Guidelines</span>'''
***** Significantly fewer clinically insignificant disease with MRI (4% MRI vs. 12% standard biopsy)
***** '''<span style="color:#ff0000">Biopsy-naïve: MRI should not be considered standard of care'''
**** [https://pubmed.ncbi.nlm.nih.gov/34237810/ Eklund, Martin, et al.] "MRI-targeted or standard biopsy in prostate cancer screening." ''New England Journal of Medicine'' (2021).
***** '''<span style="color:#ff0000">Prior negative biopsy: MRI followed by targeted biopsy may be considered</span>'''
*** '''Use of MRI in prostate cancer diagnosis as per the 2017 Cancer Care Ontario Guidelines</span>'''
*** '''MRI better at identifying anterior tumours'''
**** '''<span style="color:#ff0000">Biopsy-naïve: MRI should not be considered standard of care'''
*** '''MRI interobserver reproducibility remains a challenge.'''
**** '''<span style="color:#ff0000">Prior negative biopsy: MRI followed by targeted biopsy may be considered</span>'''
*** '''MRI has a learning curve related to reading and to performing fusion biopsies'''
** '''MRI better at identifying anterior tumours'''
*** '''Use of MRI for tumor staging remains controversial.'''
** '''MRI interobserver reproducibility remains a challenge.'''
**** Variable sensitivities (13-91%) and specificities (49-97%) have been reported for predicting extra-capsular extension.
** '''MRI has a learning curve related to reading and to performing fusion biopsies'''
* Modalities under investigation
** '''Use of MRI for tumor staging remains controversial.'''
** Positron Emission Tomography (PET)
*** Variable sensitivities (13-91%) and specificities (49-97%) have been reported for predicting extra-capsular extension.
*** One potential advantage of PSMA PET over mpMRI is that interpretation is not influenced by biopsy-related artifacts such as hemorrhage or inflammation
Modalities under investigation
** Multiparametric Ultrasonography
* Positron Emission Tomography (PET)
*** Contrast-enhanced (CE) TRUS produces a detailed image of microvascular distribution within the prostate using highly echogenic microbubble contrast agents that are minute enough to flow within capillaries.
** One potential advantage of PSMA PET over mpMRI is that interpretation is not influenced by biopsy-related artifacts such as hemorrhage or inflammation
* Multiparametric Ultrasonography
** Contrast-enhanced (CE) TRUS produces a detailed image of microvascular distribution within the prostate using highly echogenic microbubble contrast agents that are minute enough to flow within capillaries.


==== <span style="color:#ff0000">Metastasis</span> ====
==== <span style="color:#ff0000">Metastasis</span> ====
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