Prostate Indeterminate Lesions on Magnetic Resonance Imaging-Biopsy Versus Surveillance: A Literature Review.

The indeterminate multiparametric prostate magnetic resonance image (mpMRI) lesion is one which cannot be classified as "positive" or "negative" for suspected cancer. Currently, there is no consensus on how to manage patients with indeterminate mpMRIs where areas cannot be classified as positives or negatives (Prostate Imaging Reporting and Data System [PI-RADS] 3 or Likert 3). To define the concept of indeterminate lesion and describe the management strategies that may be adopted for these patients. A literature search of the PubMed database was performed including the search terms "prostate indeterminate lesions", "PI-RADS 3", "Likert 3", "magnetic resonance imaging", and "prostate cancer". There is no universally accepted definition of what constitutes an indeterminate lesion on mpMRI. This is partly due to the experience of the reporting radiologist and their willingness to call a lesion indeterminate, knowing that this may have consequences for biopsy decisions. This is also partly due to the significant variation in mpMRI acquisition parameters used between different sites. Strategies for managing the indeterminate lesion include: (1) biopsy, where there is a highly variable prevalence of prostate cancer (PCa), reflecting the differences in clinically significant PCa definitions, mpMRI protocols and interobserver variability in characterization of indeterminate lesions and (2) surveillance, where early results suggest that this strategy may be of value for some selected patients with prostate-specific antigen (PSA) monitoring and/or interval mpMRI. The use of prebiopsy MRI, in conjunction with traditional clinical parameters and secondary biomarkers-nomograms, may allow a more accurate selection of patients who can avoid biopsy. A strategy of close surveillance based on PSA monitoring and interval mpMRI is a feasible management option for motivated patients with indeterminate mpMRI. This surveillance strategy could result in fewer men needing to undergo biopsy, and although early results are promising, long-term results for such a strategy are awaited. In some patients who have an MRI scan of their prostate, the scan may identify an area which may or may not contain cancer. This area is typically called the "indeterminate" lesion. In this report, we attempted to define the concept of indeterminate lesion on multiparametric magnetic resonance (mpMRI) and described the strategies that may be performed for these patients. The use of mpMRI in conjunction with traditional clinical parameters may allow more accurate risk stratification and assessment of the need for prostate biopsy.

Gómez Rivas J ，Giganti F ，Álvarez-Maestro M ，Freire MJ ，Kasivisvanathan V ，Martinez-Piñeiro L ，Emberton M ... -  《European Urology Focus》

Multiparametric Magnetic Resonance Imaging Second Opinion May Reduce the Number of Unnecessary Prostate Biopsies: Time to Improve Radiologists' Training Program?

To understand the multiparametric magnetic resonance imaging (mpMRI) interreader agreement between radiologists of peripheral and academic centers and the possibility to avoid prostate biopsies according to magnetic resonance imaging second opinion. This prospective observational study enrolled 266 patients submitted to mpMRI at nonacademic centers for cancer detection or at active surveillance begin. Images obtained were reviewed by 2 unblinded radiologists with 8 and 5 years' experience on mpMRI, respectively. We recorded Prostate Imaging Reporting and Data System (PI-RADS) v2 categories and management strategy changes after mpMRI rereadings. Interreader agreement was assessed by the Cohen kappa. For mpMRI second opinion, positive predictive value and negative predictive value were calculated. In the original readings, no lesions (ie, PI-RADS < 2) were observed in 17 cases (6.5%). Reported index lesion (IL) PI-RADS category was 2 in 23 (8.5%), 3 in 85 (32%), 4 in 98 (37%), and 5 in 13 (5%) men, respectively. It is noteworthy that in 30 examinations (11%), an IL was recognized by radiologists, but a suspicious score was not assigned. According to first reading of mpMRI, initial clinical strategy included performing a targeted (226; 85%) or a systematic biopsy (8; 3%), scheduling the patient to an active surveillance program without repeat biopsy (10; 4%), or monitoring prostate-specific antigen without prostate sampling (22; 8%). The mpMRI rereads did not change IL PI-RADS category in 91 cases (38.5%), although in 20 (8.5%) and 125 (53%) IL PI-RADS was upgraded or downgraded, respectively (κ = 0.23). The clinical management changed in 113 patients (48%) (κ = 0.2). Overall, 102 targeted biopsies (51%) were avoided and 72 men (34.5%) were not submitted to biopsy after mpMRI second opinion. Positive predictive value and negative predictive value of the mpMRI rereading were 58% and 91%, respectively. Major limitations of the study are limited-time follow-up and the lack of a standard of reference for some men, who were not submitted to biopsy according to mpMRI second opinion. There is an important level of discordance between mpMRI reports. According to imaging second opinion, roughly half of targeted biopsies could be avoidable and 34.5% of men could skipped prostate sampling. Prospective randomized trials are needed to confirm our findings.

Luzzago S ，Petralia G ，Musi G ，Catellani M ，Alessi S ，Di Trapani E ，Mistretta FA ，Serino A ，Conti A ，Pricolo P ，Nazzani S ，Mirone V ，Matei DV ，Montanari E ，de Cobelli O ... -  《-》

The Use of Multiparametric Magnetic Resonance Imaging for Follow-up of Patients Included in Active Surveillance Protocol. Can PSA Density Discriminate Patients at Different Risk of Reclassification?

The objective of this study was to test Prostate Imaging Reporting and Data System (PI-RADS) classification on multiparametric magnetic resonance imaging (mpMRI) and MRI-derived prostate-specific antigen density (PSAD) in predicting the risk of reclassification in men in active surveillance (AS), who underwent confirmatory or per-protocol follow-up biopsy. Three hundred eighty-nine patients in AS underwent mpMRI before confirmatory or follow-up biopsy. Patients with negative (-) mpMRI underwent systematic random biopsy. Patients with positive (+) mpMRI underwent targeted fusion prostate biopsies + systematic random biopsies. Different PSAD cutoff values were tested (< 0.10, 0.10-0.20, ≥ 0.20). Multivariable analyses assessed the risk of reclassification, defined as clinically significant prostate cancer of grade group 2 or more, during follow-up according to PSAD, after adjusting for covariates. One hundred twenty-seven (32.6%) patients had mpMRI(-); 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. The rate of reclassification to grade group 2 PCa was 16%, 22%, 31%, and 39% for mpMRI(-) and PI-RADS 3, 4, and 5, respectively, in case of PSAD < 0.10 ng/mL2; 16%, 25%, 36%, and 44%, in case of PSAD 0.10 to 0.19 ng/mL2; and 25%, 42%, 55%, and 67% in case of PSAD ≥ 0.20 ng/mL2. PSAD ≥ 0.20 ng/mL2 (odds ratio [OR], 2.45; P = .007), PI-RADS 3 (OR, 2.47; P = .013), PI-RADS 4 (OR, 2.94; P < .001), and PI-RADS 5 (OR, 3.41; P = .004) were associated with a higher risk of reclassification. PSAD ≥ 0.20 ng/mL2 may improve predictive accuracy of mpMRI results for reclassification of patients in AS, whereas PSAD < 0.10 ng/mL2 may help selection of patients at lower risk of harboring clinically significant prostate cancer. However, the risk of reclassification is not negligible at any PSAD cutoff value, also in the case of mpMRI(-).

Roscigno M ，Stabile A ，Lughezzani G ，Pepe P ，Galosi AB ，Naselli A ，Naspro R ，Nicolai M ，La Croce G ，Aljoulani M ，Perugini G ，Guazzoni G ，Montorsi F ，Balzarini L ，Sironi S ，Da Pozzo LF ... -  《-》

What Is the Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in Excluding Prostate Cancer at Biopsy? A Systematic Review and Meta-analysis from the European Association of Urology Prostate Cancer Guidelines Panel.

It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy. To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa. The Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer. A total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range [IQR], 36.4-57.7%) for overall cancer and 32.9% (IQR, 28.1-37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0-92.4%) for overall cancer and 88.1% (IQR, 85.7-92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer (r=-0.64, p<0.0001) and csPCa (r=-0.75, p=0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval [95% CI], 77-99%) to 67% (95% CI, 56-79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%. The NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative. This systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer.

Moldovan PC ，Van den Broeck T ，Sylvester R ，Marconi L ，Bellmunt J ，van den Bergh RCN ，Bolla M ，Briers E ，Cumberbatch MG ，Fossati N ，Gross T ，Henry AM ，Joniau S ，van der Kwast TH ，Matveev VB ，van der Poel HG ，De Santis M ，Schoots IG ，Wiegel T ，Yuan CY ，Cornford P ，Mottet N ，Lam TB ，Rouvière O ... -  《-》

Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real-time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure.

To examine the value of additional transrectal ultrasonography (TRUS)-guided random biopsy (RB) in patients with negative magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB) and to identify possible reasons for TB failure. We conducted a subgroup analysis of 61 men with prostate cancer (PCa) detected by 10-core RB but with a negative TB, from a cohort of 408 men with suspicious multiparametric magnetic resonance imaging (mpMRI) between January 2012 and January 2015. A consensus re-reading of mpMRI results (using Prostate Imaging Reporting and Data System [PI-RADS] versions 1 and 2) for each suspicious lesion was performed, with the image reader blinded to the biopsy results, followed by an unblinded anatomical correlation of the lesion on mpMRI to the biopsy result. The potential reasons for TB failure were estimated for each lesion. We defined clinically significant PCa according to the Epstein criteria and stratified patients into risk groups according to the European Association of Urology guidelines. Our analysis showed that RB detected significant PCa in 64% of patients (39/61) and intermediate-/high-risk PCa in 57% of patients (35/61). The initial mpMRI reading identified 90 suspicious lesions in the cohort. Blinded consensus re-reading of the mpMRI led to PI-RADS score downgrading of 45 lesions (50%) and upgrading of 13 lesions (14%); thus, negative TB could be explained by falsely high initial PI-RADS scores for 32 lesions (34%) and sampling of the target lesion by RB in the corresponding anatomical site for 36 out of 90 lesions (40%) in 35 of 61 patients (57%). Sampling of the target lesion by RB was most likely for lesions with PI-RADS scores of 4/5 and Gleason scores (GS) of ≥7. A total of 70 PCa lesions (67% with GS 6) in 44 patients (72%) were sampled from prostatic sites with no abnormalities on mpMRI. In cases of TB failure, RB still detected a high rate of significant PCa. The main reason for a negative TB was a TB error, compensated for by positive sampling of the target lesion by the additional RB, and the second reason for TB failure was a falsely high initial PI-RADS score. The challenges that arise for both MRI diagnostics and prostate lesion sampling are evident in our data and support the integration of RB into the TB workflow.

Cash H ，Günzel K ，Maxeiner A ，Stephan C ，Fischer T ，Durmus T ，Miller K ，Asbach P ，Haas M ，Kempkensteffen C ... -  《-》