11. Quality indicators – Prostate Cancer

Kattan 2003

≤0,5 cc, organbegrenzt, keine gering differenzierten Elemente.

Kattan-Nomogramm (PSA, Prostata-Volumen, cT, GS).

409

20% mit bestätigtem insignifikantem PCa; ROC 0,64-0,79.

Fizazi K. et al, 2011

RCT

Multizentrisch

N=1904

Pat. mit  kastrationsresistenem PCa und Knochenmetastasen ohne vorausgegangene Bisphosphonattherapie

950 Pat mit

Denosumab

120mg s.c. +i.v. Placebo

Med. Follow up : 12,2Mo

951 Pat. mit Zoledronsäure i.v.4mg + s.c. Placebo

Med. Follow up :

11,2 Mo

Zeit bis zum Auftreten des 1. Skeletal Related Events (SRE)

Rate an Progression

Gesamtüberleben

Nebenwirkungen

Lebensqualität

Anteil Patienten mit SRE

Denosumab: 36% (n=341)

Zoledronsäure: 41% (n=386)

1. Zeit bis zum Auftreten des 1. skeletal Related Events (Monate)

Denosumab-Gruppe: 20,7 [95%KI 18,8-24,9%]

 Zoledronsäure-Gruppe: 17,1 [95%KI 15-19,4]

Cave: bei Betrachtung des absoluten Unterschieds überlappen die Konfidenzintervalle!

Nichtunterlegenheit Denosumab: HR 0,82 [95%KI 0,71-0,92] p=0,0002

Überlegenheit Denosumab: s.o. p=0,008

2. Rate an Progression

Denosumab + Zoledronsäure im Median 8,4 Mo n.s.

3. Gesamtüberleben
Denosumab im Median 19,4 Mo

Zoledronsäure im Median 19,8 Mo n.s.

4. Nebenwirkungen

Viele NW n.s., hier nur aufgeführt die mit Unterschieden

a. Grade 3 o. 4 adverse events nach CTCAE (Common Terminology Criteria for Adverse Events )

Denosumab Gruppe: 72%

Zoledronsäure Gruppe 66% p< 0,01

b. Hypokalzämie

Denosumab Gruppe: 13%

Zoledronsäure Gruppe:  6% p< 0,0001

c. Kiefernekrose

Denosumab Gruppe: 2% (n=22)

Zoledronsäure Gruppe:  1% (n=8) p = 0,09

d. Auftreten eines weiteren Malignoms

Denosumab Gruppe: 2% (n=18)

Zoledronsäure Gruppe:  1% (n=10) p = 0,13

5. Lebensqualität: nicht erfasst.

Randomisierung ok.

in Gruppe mit Zoledronsäure: 4% mehr Patienten>65J , 3,7Mo länger von ED bis Randomisierung., 2,5 Mo länger von ED Knochenmet. bis Randomisierung.

Studie ist von AMGEN gesponsert. (AMGEN sammelte die Daten und machte die Auswertung)

Studie als Non-inferioeritätsstudie angelegt, sekundär auch Auswertung auf Superiorität

1+

Wegelin O. Comparing Three Different Techniques for Magnetic Resonance Imaging-targeted Prostate Biopsies: A Systematic Review of In-bore versus Magnetic Resonance Imaging-transrectal Ultrasound fusion versus Cognitive Registration. Is There a Preferred Technique?
Eur Urol 2016.

primary diagnostic studies reporting on PCa detection rates among pat.s at risk of PCa using MRI-TB, or FUS-TB, or COG-TB

n = 43 articles relevant for review question
n = 25 studies reporting on
both MRI-GB (any technique) and TRUS-GB results
separately within same population

inclusion of publications up to Oct.2014

A comprehensive search of literature (PubMed, Embase, and CENTRAL databases; range of last 10y) was performed. The search terms used were ‘‘Prostate OR Prostatic Neoplasm’’ AND ‘‘Biopsy’’ AND ‘‘Magnetic Resonance Imaging OR Image-Guided Biopsy’’

Published primary diagnostic studies reporting on PCa
detection rates among patients at risk of PCa using MRI-TB, or FUS-TB, or COG-TB were included.

Heterogenität:
The 43 included studies demonstrate significant variation in cohort size, ranging from 16 to 1003 (median, 106) patients.
The mean PSA value ranged from 5.1 ng/ml to 15.3 ng/ml and the mean age ranged from 61.8 yr to 70.0 yr. The populations varied with respect to biopsy history. For all subsequent analysis, we used clinical homogenous data on detection rates among patients with no or negative prior biopsies.

Considerable heterogeneity was found with respect to the applied definition of csPCa. Furthermore, several studies did not present a definition of csPCa, and
consequently did not report data on the detection of csPCa.

PCa-suspekte MRI-Befunde in 73% der Pat.; Studien (n=6) mit Bx-naiven in 68%, mit vorheriger neg.Bx (n=7 Studien) in 79%

Werte für Studien mit Bx-naiv sowie prev.neg.bx gepoolt:
MRI-GB and TRUS-GB did not significantly differ in overall PCa detection, rel. sensitivity of 0.98 (95% CI: 0.90-1.07)
- SE for MRI-GB: 0.81 ( 0.76-0.85)
- SE for TRUS-GB: 0.83 (0.77–0.88)
--> MRI-GB missed 19% of all cancers, while TRUS-GB missed 17%.

MRI-GB detected significantly more csPCa than TRUS-GB, rel. sensitivity of 1.16 (1.02-1.32)
- SE for MRI-GB: 0.90 (0.85-0.94)
- SE for TRUS-GB: 0.79 (0.68-0.87)
--> MRI-GB missed 10% significant cancers whilst TRUS-GB missed 21%

no significant advantage of usage of any one technique of MRI-GB (cognitive / fusion / in-bore) for the detection of csPCa

1. a priori Design - nein
2. Selektion und Extraktion durch 2 unabh. Bearbeiter - ja
3. Literaturrecherche min 2 Datenbanken + 1 Zusatz - ja
4. graue Literatur eingeschl. - nein
5. Vollständige Liste ein- und ausgeschl. Studien - nein
6. Details der eingeschlossenen Studien - ja
7. Qualität der eingeschlossenen Studien bewertet - ja
8. In Conclusion Hinweise auf methodische Qualität - ja
9. Heterogenität erhoben?- ?
10. Publication bias (funnel plot) - nein
11. CoI / funding für Review UND für alle Studien berichtet - nein

AMSTAR-Score 5-6/11

2+


Aussagen zu MRI-tbx vs. Sbx

keine Metaanalyse für Bx-naive Subgruppe (Daten könnten ggf. extrahiert werden)

Gayet M. The value of magnetic resonance imaging and ultrasonography (MRI/US)-fusion biopsy platforms in prostate cancer detection: a systematic review. BJU Int 2016;117(3):392-400.

systematic review of prospective non-randomised controlled trials or in-patient control studies
Suchzeitraum: 01/2004-02/2015 (Begründung: Zulassung von fusion-Plattformen 2004)
Population: Bx-naive und Pat. mit vorheriger negativer Bx mit Verdacht auf PCa
Vergleichsgruppen: standard Bx (überwiegend 10-12 Stanzen) or another way of MRI-guided TB
Endpunkte: (clinically significant) prostate CDRs per patient
body of evidence: 11 eingeschl. Studien, 2602 eingeschl. Pat. (min 20, max 1003)

Ergebnisse: CDRs für alle PCa zwischen 35,7-79,5% bei fusion Bx vs. 28,5-56,6% bei Standard-Bx. CDRs für klinisch signifikante PCa zwischen 17,2-47,9% bei fusion Bx vs. 12,2-38% bei Standard-Bx.

Sicherheit: nicht erhoben / berichtet

author's conclusion: No clear advantage of MRI/US fusion-guided TBs was seen for cancer detection rates (CDRs) of all prostate cancers. However, MRI/US fusion-guided TBs tended to give higher CDRs for clinically significant prostate cancers in our analysis.
Important limitations of the present systematic review include: the limited number of included studies, lack of a general definition of ‘clinically significant’ prostate cancer, the heterogeneous study population, and a reference test with low sensitivity and specificity.
Although MRI/US-fusion TB has proved its value in men with prior negative biopsies, general use of this technique in diagnosing prostate cancer should only be performed after critical consideration. Before bringing MRI/US fusion-guided TB in to general practice, there is a need for more prospective studies on prostate cancer diagnosis.

1 Protokoll/Suchstrategie/ Fragestellung vorhanden - nein
2 Selektion und Extraktion durch 2 unabh. Bearbeiter - ja
3 Literaturrecherche min 2 Datenbanken + 1 Zusatz - (ja)
4 Bericht über Ausschlüsse - ja
5 Vollständige Liste der ein- und ausgeschlossenen Studien - nein
6 Details der eingeschlossenen Studien - ja
7 Qualität der eingeschlossenen Studien bewertet - ja
8 In Conclusion Hinweise auf methodische Qualität - ja
9 Heterogenität erhoben?- ja
10 Publication bias berichtet (funnel plot/verbal) - nein
11 CoI/funding für Review UND für alle Studien berichtet - nein

--> AMSTAR-Score: 7/11

2+

Wu J. Is magnetic resonance/ultrasound fusion prostate biopsy better than systematic prostate biopsy? An updated meta- and trial sequential analysis. Oncotarget 2015;6(41):43571-80.

Metaanalyse mit 16 paired cohort studies (in-patient control)
Suchzeitraum: bis Mai 2015
Population: Pat. mit Verdacht auf PCa; keine Unterscheidung, ob Bx-naiv oder nicht
Interventionen: MRI-TRUS fusion Bx
Vergleichsgruppen: standard biopsy (überwiegend (10-)12 core Bx)
Endpunkte: Detektion von PCa
body of evidence: 16 eingeschl. Studien, 3105 eingeschl. Pat. (30-1003, jedoch überwiegend kleine Studien)

Heterogenität: moderat (I^2 = 28%)

Ergebnisse/Effektivität: es wurden signifikant mehr PCa detektiert mit MRI-US fusion: risk ratio 1,06 (95% KI 1.01-1,12; p=0,03)
Subgruppenanalysen: bei moderatem/hohem Verdacht im MRI lag das risk ratio bei 1,46 (95% KI 1.28-1,67; p<0,001; I^2 = 0). bessere Ergebnisse auch bezogen auf klin. signif. PCa: RR 1,19 (95% KI 1.10-1,29; p<0,01; I^2 = 0)

Sicherheit: nicht berichtet
Qualität der Evidenz für einzelne Outcomes: s. I^2-Werte; geringer Publikationsbias

author's conclusion: We found that, although more evidence is needed, MR/US fusion prostate biopsy alone detected more prostate cancers than systematic biopsy and was better than systematic biopsy in detecting clinically significant prostate cancers. For those men with moderate/high suspicion in mp-MRI, MR/US fusion biopsy showed a great advantage.

1 Protokoll/Suchstrategie/ Fragestellung vorhanden - nein
2 Selektion und Extraktion durch 2 unabh. Bearbeiter - ja
3 Literaturrecherche min 2 Datenbanken + 1 Zusatz - ?(3 DB)
4 Bericht über Ausschlüsse - ja
5 Vollständige Liste der ein- und ausgeschlossenen Studien - nein
6 Details der eingeschlossenen Studien - ja
7 Qualität der eingeschlossenen Studien bewertet - ja
8 In Conclusion Hinweise auf methodische Qualität - nein
9 Heterogenität erhoben?- ja
10 Publication bias berichtet (funnel plot/verbal) - ja
11 CoI/funding für Review UND für alle Studien berichtet - nein

--> AMSTAR-Score: 6-7/11

2+

Valerio M. Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review. Eur Urol 2015;68(1):8-19.

Systematic review mit v.a. paired cohort studies (in-patient control)
Suchzeitraum: bis Dez. 2013

body of evidence: 15 eingeschl. Studien (davon 14 paired cohort design) (+ Bericht über 7 weitere nicht-publ.), 2293 eingeschl. Pat. (13-582)
Population: Pat. in 3 Studien Bx-naiv, in 3 Studien vorherige negative TRUS-Bx, in 8 Studien gemischt
Interventionen: MRI-TRUS fusion Bx
Vergleichsgruppen: current standard of TRUS biopsy (10-12 Stanzen) (no adequate reference test in any of the studies)
Endpunkte: Detektionsrate klin. signif. PCa (jeweils definiert in Studien, z.T. unterschiedlich)

Ergebnisse
Effektivität: The median detection of clinically significant disease was 23,6% (range 4,8-52%) for standard biopsy and 33,3% (13,2-50%) for MRI-TRUS fusion. Across all studies in which both rates were reported, fusion Bx allowed the detection of greater numbers of clinically significant cancers compared to standard Bx. The absolute difference in detection rates was a median of 6,8% (0,9-41,4%) always in favour of fusion Bx. Considering absolute differences, fusion Bx detected a median of 9,1% (5-16,2%) additional clinically significant cancers that were missed by standard Bx alone.
Detektion PCa insgesamt (signifikant / insignifikant): ähnliche Werte (allerdings in 4 Studien höhere Detektionsraten mit Standard-TRUS)
Efficiency: The median difference in number of cores needed to detect one man with clinically significant cancer was 32,1 cores in favour of the targeted approach.

Sicherheit: AEs nur in 2 Studien berichtet, davon in 1 nicht vorgekommen, in der anderen nicht zu unterscheiden, welches Verfahren zu AE geführt hat.
Heterogenität der eingeschl. Populationen vorhanden (wird als positiv diskutiert: Erhöhung der externen Validität)
Qualität der Evidenz für einzelne Outcomes: most studies had low RoB and low applicability concerns with respect to pat. selection. In four studies the index test domain demonstrated a high RoB and applicability concern.
Limitations: 1) the definition of clinically significant disease varied between studies.2)  it was not possible to determine the overall accuracy of a MRI-TRUS image fusion approach because an accurate reference test was not used.

author's conclusion: mpMRI-US fusion targeted Bx detect more clinically significant cancers using fewer cores compared with standard Bx. [findings need to be confirmed by large multicentre validating studies]

1 Protokoll/Suchstrategie/ Fragestellung vorhanden - ja
2 Selektion und Extraktion durch 2 unabh. Bearbeiter - ja
3 Literaturrecherche min 2 Datenbanken + 1 Zusatz - ja
4 Bericht über Ausschlüsse - ja
5 Vollständige Liste der ein- und ausgeschlossenen Studien - nein
6 Details der eingeschlossenen Studien - ja
7 Qualität der eingeschlossenen Studien bewertet - ja
8 In Conclusion Hinweise auf methodische Qualität - ja
9 Heterogenität erhoben?- nein
10 Publication bias berichtet (funnel plot/verbal) - nein
11 CoI/funding für Review UND für alle Studien berichtet - nein

--> AMSTAR-Score: 7/11

2+

Schoots IG. Magnetic resonance imaging-targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis. Eur Urol 2015;68(3):438-50.

Metaanalyse von ausschl. Studien mit beiden Interventionen / Methoden beim selben Pat. (in-patient-control studies)
Suchzeitraum: bis Mai 2014

Population: Pat. mit positivem MRI (keine Einschränkungen bzgl. Alter)
Interventionen: MRI-targeted biopsy und TRUS-Bx (8-12 Stanzen), jeweils im selben Pat.

Vergleichsgruppen: jeweils der selbe Pat. mit MRI-TBx und (davon unabh.) TRUS-Bx (überwiegend 10-12 Stanzen)
Endpunkte: detection of PCa (significant, insignificant - hier jedoch unterschiedl. Definitionen in den Studien) by MRI-TBx vs. TRUS-Bx
body of evidence: 16 eingeschl. Studien, 1926 eingeschl. Pat.
(Studien: 7x MRI-visual / 10x -fusion / 1x -in-bore)

Heterogenität untersucht bzgl. patient recruitment (initial Bx / prev.neg. / mixed); navigational system (MRI-visual / -fusion / -in-bore), jeweils bezogen aufeinander. Heterogenität (I^2 >40%) in den meisten Analysen vorhanden

Ergebnisse:
keine signifikanten Unterschiede zwischen MRI-TBx und TRUS-Bx bzgl. overall PCa-Detektion (Sensitivität: 0,85; 95%-KI: 0,80-0,89 bzw. 0,81 und 0,70-0,88)
MRI-TBx and TRUS-Bx did not significantly differ in overall prostate cancer detection, with a relative sensitivity of 1.05 (95% CI 0.94–1.19)
MRI-TBx and TRUS-Bx missed the diagnosis of prostate cancer in 15% and 19% of cases, respectively, with a concordance between the tests of 65% (54–74%).

relevante Subgruppenanalysen: relative Sensitivität von MRI-fusion/TRUS =1,09, d.h. höhere Detektion durch MRI-fusion, jedoch hohe Heterogenität (I^2 89)
bzgl. signifikantem PCa: relative Sensitivität MRI-fusion /TRUS=1,29
Subgruppe Pat. mit vorhergehender negativer Biopsie: relative Sensitivität 1,54 (vs. 1,10 bei initialer Biopsie)

author's conclusion:
In men with clinical suspicion of prostate cancer and a suspicious lesion seen on multiparametric MRI, MRI-TBx and TRUS-Bx did not differ in overall detection of prostate cancer. However, MRI-TBx had a higher rate of detection of potentially significant prostate cancer and a lower rate of detection of insignificant prostate cancer compared to the standard TRUS-Bx. Subgroup analysis showed that MRI-TBx improved the detection of significant prostate cancer in men with a previous negative biopsy, rather than in men with an initial biopsy.
However, we found significant heterogeneity, which limits the strengths of the conclusions that can be made. Furthermore, as a consequence of underlying methodological flaws of MRI-TBx, the comparison to standard systematic biopsy needs to be regarded with caution.

1 Protokoll/Suchstrategie/ Fragestellung vorhanden - nein
2 Selektion und Extraktion durch 2 unabh. Bearbeiter - ja
3 Literaturrecherche min 2 Datenbanken + 1 Zusatz - ja
4 Bericht über Ausschlüsse - ?
(We excluded unpublished data or abstracts because information that is needed to correctly assess the study
quality and interpret the results was not available in abstracts.)
5 Vollständige Liste der ein- und ausgeschlossenen Studien - nein
6 Details der eingeschlossenen Studien - ja
7 Qualität der eingeschlossenen Studien bewertet - ja
8 In Conclusion Hinweise auf methodische Qualität - ja
9 Heterogenität erhoben?- ja
10 Publication bias berichtet (funnel plot/verbal) - ja
11 CoI/funding für Review UND für alle Studien berichtet - nein

--> AMSTAR-Score: 7/11

2+

Link

https://pubmed.ncbi.nlm.nih.gov/31022301/

https://pubmed.ncbi.nlm.nih.gov/31326219/

AMSTAR 2 rating

moderate

Design

systematic review and meta-analysis

Sources

CENTRAL, MEDLINE, Embase, eight other databases and one trials register

(up to 31 July 2018)

Selection criteria

Inclusion criteria:

-      cross-sectional study, if it investigated:

-      the diagnostic accuracy of one or more of the index tests (MRI, MRI pathway (including MRI-targeted biopsy) or systematic biopsy) verified by the reference standard (template-guided biopsy), with each index test and reference standard performed in the same men or compared as in a randomised trial of test accuracy; or

-      agreement evidence between the MRI pathway and systematic biopsy, with each test performed in the same men

-      had to report on both MRI-positive and MRI-negative men

Exclusion criteria:

-      when they could not extract a complete two-by-two table on a per-participant basis for the primary target condition, even after contacting the study authors

Outcome(s)

accuracy (pooled estimates of sensitivity and specificity): MRI, MRI-targeted biopsy, MRI pathway, systematic biopsy versus reference standard (template-guided biopsy)

agreement (number of target conditions identified - concordance and discordance - proportion of detected cases (total number of cancers) as the number of concordant positive results plus the number of discordant positive results of both tests, detection rate, pooled estimates of detection ratios): MRI pathway versus systematic biopsy

pooled proportions of prostate cancer not detected by systematic biopsy but only by the MRI pathway (added value MRI pathway) and pooled proportions of prostate cancer not detected by the MRI pathway but only by systematic biopsy (added value systematic biopsy)

negative predictive values (NPV) and positive predictive values (PPV)

Quality of evidence

methodological quality: Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool; Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance for studies of diagnostic accuracy

-      a considerable number of studies (test accuracy) had a high or unclear risk of bias in the participant selection (n = 9/18) and reference standard domains (n = 12/18)

-      no risk of bias was present in the index test (n = 1/18) and flow and timing domains (n = 3/18)

-      three out of 18 studies had applicability concerns because either they had selected an explicitly high-risk population or had used an alternative MRI-scale or MRI-positivity threshold (other than the default 5-point scale with an MRI-positivity threshold of 3/5 or more) (s. also Table 1 and Figure 4-6 within the publication)

-      a considerable number of studies (agreement) (n = 13/25) had a high or unclear risk of bias in the participant selection domain (s. Figure 7 within the publication)

-      the index test domain, a considerable number of studies (n = 15/25) had a high or unclear risk of bias in the performance of systematic biopsy but almost no risk of bias was present in the performance of the MRI pathway (n = 1/18)

-      few studies had a high or unclear risk of bias in the flow and timing domain (n = 8/25)

-      applicability concerns were present in 15 out of 25 studies, mainly because they used an alternative method to perform one of the index tests

-      the quality of evidence for the main findings of this review was rated as low

Results

43 articles were eligible for inclusion (mainly from Western countries, of men aged 61 to 73 years)

-      18 studies in the diagnostic test accuracy analysis (n=15 on MRI, n=8 on MRI, MRI-targeted biopsy and the MRI pathway in the same men, n=4 on systematic biopsy)

• including 6871 men (5075 were biopsy naïve and 1796 had a history of at least one prior negative biopsy)
• 13 prospective studies
• 5 retrospective studies

-      25 studies in the agreement analysis

• including 6944 men (5353 were biopsy naïve and 1591 had a history of at least one prior negative biopsy)
• 18 prospective studies
• 7 retrospective studies

Population: men with a clinical suspicion of prostate cancer (based on PSA or digital rectal exam (DRE) outcome) in the biopsy-naïve or prior-negative biopsy setting (or a mix of both) - excluded were men with a previous diagnosis of prostate cancer

Table 1 Detecting ISUP grade 2 or higher prostate cancer by MRI, MRI-targeted biopsy, MRI-pathway and systematic biopsy (n=13,770)

CI=confidence interval, ISUP: International Society of Urological Pathology, MRI=magnetic resonance imaging, P=participants, SB=systematic biopsy

*using a baseline prevalence of 30%

#for example: “In a population of 1000 men at risk for prostate cancer, where 300 men actually have clinically significant prostate cancer, MRI will correctly identify 273 men as having clinically significant prostate cancer but miss the remaining 27 men; for the 700 men that do not have clinically significant prostate cancer, MRI will correctly identify 259 as not having prostate cancer but will misclassify 441 men as having clinically significant prostate cancer.”

number needed to biopsy (NNB)

for systematic biopsy in addition to MRI-targeted biopsy:

-      in biopsy-naïve men with a positive MRI:

• grade ≥2 PCa detection: 20 (95 % CI 12-36)
• grade ≥3 PCa: 27 (95% CI 16-45)

-      in biopsy-naïve men with a negative MRI:

• grade ≥2 PCa detection: 13 (95% CI 9-18)
• grade ≥3 PCa: 33 (95% CI 18-63)

-      in men with a prior negative biopsy and a positive MRI:

• grade ≥2 PCa: 37 (95% CI 18-83)
• grade ≥3 PCa: 83 (95% CI 31-250)

-      in men with a prior negative biopsy and MRI-negative:

• grade ≥2 PCa: 19 (95% CI 11-32)
• grade ≥3 PCa: 31 (95% CI 16-63)

Table 2 Detecting ISUP grade 1 prostate cancer by MRI, MRI-targeted biopsy, MRI-pathway and systematic biopsy (n=10,051)

Comments

Articles included in this study:

eighteen studies (test accuracy - index tests versus reference standard (template-guided biopsy):

-      15 studies on MRI (Abd-Alazeez 2014; Ahmed 2017; Dal Moro 2019; Distler 2017; Grey 2015; Hansen 2016a; Hansen 2018; Hansen 2017; Kesch 2017; Lawrence 2014; Mortezavi 2018; Muthuveloe 2016; Pepe 2013; Thompson 2016; Tsivian 2017);

-      eight studies on MRI, MRI-targeted biopsy and the MRI pathway in the same men (Dal Moro 2019; Distler 2017; Hansen 2016a; Hansen 2017; Kesch 2017; Lawrence 2014; Mortezavi 2018; Pepe 2013);

-      four studies: on systematic biopsy (Ahmed 2017; Nafie 2014; Nafie 2017; Ploussard 2014)

twenty-five studies (agreement between the MRI pathway and systematic biopsy in detecting prostate cancer): Alberts 2017; Boesen 2017a; Boesen 2018; Castellucci 2017; Chang 2017; Chen 2015; Cool 2016; Costa 2013; Delongchamps 2013; Filson 2016; Garcia Bennett 2017; Grönberg 2018; Jambor 2015; Jambor 2017; Kim 2017; Lee 2016; Lee 2017; Okcelik 2016; Panebianco 2015; Peltier 2015; Pokorny 2014; Rouvière 2019a; Say 2016; Tonttilla 2016; Van der Leest 2018)

_____________________________________________

Abd-Alazeez 2014 {published and unpublished data}. Abd-Alazeez, M, Arya HU, Charman SC, Anastasiadis E, Freeman A, Emberton M, et al. The accuracy of multiparametric MRI in men with negative biopsy and elevated PSA level-Canit rule out clinically significant prostate cancer?. Urologic Oncology 2014;32(1):45.e17-45.e22.

Ahmed 2017 {published and unpublished data}. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 2017;389(10071):815-22.

Alberts 2017 {published data only}. Alberts AR, Schoots IG, Bokhorst LP, Drost FH, Van Leenders GJ, Krestin GP, et al. Characteristics of prostate cancer found at fiSh screening in the European Randomized Study of Screening for Prostate Cancer Rotterdam: can we selectively detect high-grade prostate cancer with upfront multivariable risk stratification and magnetic resonance imaging?. European Urology 19 June 2017 [Epub ahead of print];S0302-2838(17):30514-6.

Boesen 2017a {published data only (unpublished sought but not used)}. Boesen L, Nørgaard N, Løgager V, Balslev I, Thomsen HS. A prospective comparison of selective multiparametric magnetic resonance imaging fusion-targeted and systematic transrectal ultrasound-guided biopsies for detecting prostate cancer in men undergoing repeated biopsies. Urologia Internationalis 2017;99(4):384-91.

Boesen 2018 {published and unpublished data}. Boesen L, Nørgaard N, Løgager V, Balslev I, Bisbjerg R, Thestrup K-C, Winther, et al. Assessment of the diagnostic accuracy of biparametric magnetic resonance imaging for prostate cancer in biopsy-naïve men the Biparametric MRI for Detection of Prostate Cancer (BIDOC) Study. JAMA Network Open 2018;1(2):e180219.

Castellucci 2017 {published and unpublished data}. Castellucci R, Linares Quevedo AI, Sánchez GómezFJ, Díez Rodríguez J, Cogorno L, Cogollos Acuña I, et al. Prospective nonrandomized study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy to magnetic resonance imaging with subsequent MRIguided biopsy in biopsy-naïve patients. Minerva Urologica e Nefrologica 2017;69(6):589-95.

Chang 2017 {published and unpublished data}. Chang CH, Chiu HC, Lin WC, Ho TL, Chang H, Chang YH, et al. The influence of serum prostate-specific antigen on the accuracy of magnetic resonance imaging targeted biopsy versus saturation biopsy in patients with previous negative biopsy. BioMed Research International 2017;2017:7617148.

Chen 2015 {published data only}. Chen J, Yi XL, Jiang LX, Wang R, Zhao JG, Li YH, et al. 3-tesla magnetic resonance imaging improves the prostate cancer detection rate in transrectral ultrasound‑guided biopsy. Experimental and Therapeutic Medicine 2015;9(1):207-12.

Cool 2016 {published data only}. Cool DW, Romagnoli C, Izawa JI, Chin J, Gardi L, Tessier D, et al. Comparison of prostate MRI-3D transrectal ultrasound fusion biopsy for first-time and repeat biopsy patients with previous atypical small acinar proliferation. Canadian Urological Association Journal 2016;10(9-10):342-8.

Costa 2013 {published data only}. Costa DN, Bloch BN, Yao DF, Sanda MG, Ngo L, Genega EM, et al. Diagnosis of relevant prostate cancer using supplementary cores from magnetic resonance imaging-prompted areas following multiple failed biopsies. Magnetic Resonance Imaging 2013;31(6):947-52.

Dal Moro 2019 {published and unpublished data}. Dal Moro F, Zecchini G, Morlacco A, Gardiman MP, Lacognata CS, Lauro A, et al. Does 1.5 T mpMRI play a definite role in detection of clinically significant prostate cancer? Findings from a prospective study comparing blind 24-core saturation and targeted biopsies with a novel data remodeling model. Aging Clinical and Experimental Research 2019;31(1):115-23.

Delongchamps 2013 {published data only}. Delongchamps NB, Peyromaure M, Schull A, Beuvon F, Bouazza N, Flam T, et al. Prebiopsy magnetic resonance imaging and prostate cancer detection: comparison of random and targeted biopsies. The Journal of Urology 2013;189(2):493-9.

Distler 2017 {published data only}. Distler FA, Radtke JP, Bonekamp D, Kesch C, Schlemmer HP, Wieczorek K, et al. The value of PSA density in combination with PI-RADS for the accuracy of prostate cancer prediction. The Journal of Urology 2017;198(3):575-82.

Filson 2016 {published data only}. Filson CP, Natarajan S, Margolis DJ, Huang J, Lieu P, Dorey FJ, et al. Prostate cancer detection with magnetic resonanceultrasound fusion biopsy: the role of systematic and targeted biopsies. Cancer 2016;122(6):884-92.

Garcia Bennett 2017 {published and unpublished data}. Garcia Bennett J, Vilanova JC, Guma Padro J, Parada D, Conejero A. Evaluation of MR imaging-targeted biopsies of the prostate in biopsy naïve patients. A single centre study. Diagnostic and Interventional Imaging 2017;98(10):677-84.

Grey 2015 {published and unpublished data}. Grey AD, Chana MS, Popert R, Wolfe K, Liyanage SH, Acher PL. Diagnostic accuracy of magnetic resonance imaging (MRI) prostate imaging reporting and data system (PI-RADS) scoring in a transperineal prostate biopsy setting. BJU International 2015;115(5):728-35.

Grönberg 2018 {published and unpublished data}. Grönberg H, Eklund M, Picker W, Aly M, Jäderling F, Adolfsson J, et al. Prostate cancer diagnostics using a combination of the Stockholm3 blood test and multiparametric magnetic resonance imaging. European Urology 2018;74(6):722-8.

Hansen 2016a {published and unpublished data}. Hansen N, Patruno G, Wadhwa K, Gaziev G, Miano R, Barrett T, et al. Magnetic resonance and ultrasound image fusion supported transperineal prostate biopsy using the Ginsburg protocol: technique, learning points, and biopsy results. Eurpean Urology 2016;70(2):332-40.

Hansen 2017 {published data only}. Hansen NL, Kesch C, Barrett T, Koo B, Radtke JP, Bonekamp D, et al. Multicentre evaluation of targeted and systematic biopsies using magnetic resonance and ultrasound image-fusion guided transperineal prostate biopsy in patients with a previous negative biopsy. BJU International 2017;120(5):631-8.

Hansen 2018 {published data only}. Hansen NL, Barrett T, Kesch C, Pepdjonovic L, Bonekamp D, O'SullivanR, et al. Multicentre evaluation of magnetic resonance imaging supported transperineal prostate biopsy in biopsy naïve men with suspicion of prostate cancer. BJU International 2018;122(1):40-9.

Jambor 2015 {published data only}. Jambor I, Kähkönen E, Taimen P, Merisaari H, Saunavaara J, Alanen K, et al. Prebiopsy multiparametric 3T prostate MRI in patients with elevated PSA, normal digital rectal examination, and no previous biopsy. Journal of Magnetic Resonance Imaging 2015;41(5):1394-404.

Jambor 2017 {published data only}. Jambor I, Boström PJ, Taimen P, Syvänen K, Kähkönen E, Kallajoki M, et al. Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial). Journal of Magnetic Resonance Imaging 2017;46(4):1089-95.

Kesch 2017 {published and unpublished data}. Kesch C, Radtke JP, Popeneciu IV, Gasch C, DieOenbacher SC, Klein T, et al. TOP: prospective evaluation of a volume based, computer assisted method for transperineal optimized prostate biopsy. Urologia Internationalis 2017;99(2):149-55.

Kim 2017 {published and unpublished data}. Kim EH, Weaver JK, Shetty AS, Vetter JM, Andriole GL, Strope SA. Magnetic resonance imaging provides added value to the prostate cancer prevention trial risk calculator for patients with estimated risk of high-grade prostate cancer less than or equal to 10%. Urology 2017;102:183-9.

Lawrence 2014 {published data only}. Lawrence EM, Tang SY, Barrett T, Koo B, Goldman DA, Warren AY, et al. Prostate cancer: performance characteristics of combined T2W and DW-MRI scoring in the setting of template transperineal re-biopsy using MR-TRUS fusion. European Radiology 2014;24(7):1497-505.

Lee 2016 {published and unpublished data}. Lee DH, Nam JK, Park SW, Lee SS, Han JY, Lee SD, et al. Visually estimated MRI targeted prostate biopsy could improve the detection of significant prostate cancer in patients with a PSA level. Yonsei Medical Journal 2016;57(3):565-71.

Lee 2017 {published and unpublished data}. Lee DH, Nam JK, Lee SS, Han JY, Lee JW, Chung MK, et al. Comparison of multiparametric and biparametric MRI in first round cognitive targeted prostate biopsy in patients with PSA levels under 10 ng/mL. Yonsei Medical Journal 2017;58(5):994-9.

Mortezavi 2018 {published data only}. Mortezavi A, Märzendorfer O, Donati OF, Rizzi G, Rupp NJ, WettsteinMS, et al. Diagnostic accuracy of multiparametric magnetic resonance imaging and fusion guided targeted biopsy evaluated by transperineal template saturation prostate biopsy for the detection and characterization of prostate cancer. Journal of Urology 2018;200(2):309-18.

Muthuveloe 2016 {published and unpublished data}. Muthuveloe D, Telford R, Viney R, Patel P. The detection and upgrade rates of prostate adenocarcinoma following transperineal template-guided prostate biopsy – a tertiary referral centre experience. Central European Journal of Urology 2016;69(1):42-7.

Nafie 2014 {published data only}. Nafie S, Mellon JK, Dormer JP, Khan MA. The role of transperineal template prostate biopsies in prostate cancer diagnosis in biopsy naïve men with PSA less than 20 ng mL-1. Prostate Cancer and Prostatic Diseases 2014;17(2):170-3.

Nafie 2017 {published data only}. Nafie S, Wanis M, Khan M. The eOicacy of transrectal ultrasound guided biopsy versus transperineal template biopsy of the prostate in diagnosing prostate cancer in men with previous negative transrectal ultrasound guided biopsy. Urology Journal 2017;14(2):3008-12.

Okcelik 2016 {published and unpublished data}. Okcelik S, Soydan H, Ates F, Berber U, Saygin H, Sonmez G, et al. Evaluation of PCA3 and multiparametric MRI's: collective benefits before deciding initial prostate biopsy for patients with PSA level between 3-10ng/mL. International Brazillian Journal of Urology 2016;42(3):449-55.

Panebianco 2015 {published and unpublished data}. Panebianco V, Barchetti F, Sciarra A, Ciardi A, Indino EL, Papalia R, et al. Multiparametric magnetic resonance imaging vs. standard care in men being evaluated for prostate cancer: a randomized study. Urologic Oncology 2015;33(1):17.e1-17.e7.

Peltier 2015 {published data only}. Peltier A, Aoun F, Lemort M, Kwizera F, Paesmans M, Van Velthoven R. MRI-targeted biopsies versus systematic transrectal ultrasound guided biopsies for the diagnosis of localized prostate cancer in biopsy naïve men. Biomed Research International 2015;2015:571708.

Pepe 2013 {published data only (unpublished sought but not used)}. Pepe P, Garufi A, Priolo G, Candiano G, Pietropaolo F, Pennisi M, et al. Prostate cancer detection at repeat biopsy: can pelvic phased array multiparametric MRI replace saturation biopsy?. Anticancer Research 2013;33(3):1195-200.

Ploussard 2014 {published data only}. Ploussard G, Nicolaiew N, Marchand C, Terry S, Vacherot F, Vordos D, et al. Prospective evaluation of an extended 21-core biopsy scheme as initial prostate cancer diagnostic strategy. European Urology 2014;65(1):154-61.

Pokorny 2014 {published and unpublished data}. Pokorny MR, De Rooij M, Duncan E, Schröder FH, Parkinson R, Barentsz JO, et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasoundguided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. European Urology 2014;66(1):22-9.

Rouvière 2019a {published data only}. Rouvière O, Puech P, Renard-Penna R, Claudon M, Roy C, Mège-Lechavallier F, et al. MRI-FIRST Investigators. Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naïve patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study. Lancet Oncology 2019;20(1):100-9.

Say 2016 {published data only}. SayRK. MRI-ultrasound fusion targeted biopsy in men with prior negative prostate biopsy for prostate cancer [PhD thesis]. Vol. 2078, New Haven, CT: Yale Medicine Thesis Digital Library, 2016. [elischolar.library.yale.edu/ymtdl/2078]

Thompson 2016 {published and unpublished data}. Thompson JE, Van Leeuwen PJ, Moses D, Shnier R, Brenner P, Delprado W, et al. The diagnostic performance of multiparametric magnetic resonance imaging to detect significant prostate cancer. Journal of Urology 2016;195(5):1428-35.

Tonttilla 2016 {published and unpublished data}. Tonttila PP, Lantto J, Pääkkö E, Piippo U, Kauppila S, Lammentausta E, et al. Prebiopsy multiparametric magnetic resonance imaging for prostate cancer diagnosis in biopsynaïve men with suspected prostate cancer based on elevated prostate-specific antigen values: results from a randomized prospective blinded controlled trial. European Urology 2016;69(3):419-25.

Tsivian 2017 {published and unpublished data}. Tsivian M, Gupta RT, Tsivian E, Qi P, Mendez MH, Abern MR, et al. Assessing clinically significant prostate cancer: diagnostic properties of multiparametric magnetic resonance imaging compared to three-dimensional transperineal template mapping histopathology. International Journal of Urology 2017;24(2):137-43.

Van der Leest 2018 {published data only}. Van der Leest MM, Cornel EB, Israël B, Hendriks RJ, Padhani AR, Hoogenboom M, et al. Head-to-head comparison of transrectal ultrasound-guided prostate biopsy versus multiparametric prostate resonance imaging with subsequent magnetic resonance-guided biopsy in biopsy-naïve men with elevated prostate-specific antigen: a large prospective multicentre clinical study. European Urology 23 November 2018 [Epub ahead of print];S0302-2838(18):30880-7. [DOI: 10.1016/j.eururo.2018.11.023]