What Are We Missing? False-Negative Cancers at Multiparametric MR Imaging of the Prostate.

Purpose To characterize clinically important prostate cancers missed at multiparametric (MP) magnetic resonance (MR) imaging. Materials and Methods The local institutional review board approved this HIPAA-compliant retrospective single-center study, which included 100 consecutive patients who had undergone MP MR imaging and subsequent radical prostatectomy. A genitourinary pathologist blinded to MP MR findings outlined prostate cancers on whole-mount pathology slices. Two readers correlated mapped lesions with reports of prospectively read MP MR images. Readers were blinded to histopathology results during prospective reading. At histopathologic examination, 80 clinically unimportant lesions (<5 mm; Gleason score, 3+3) were excluded. The same two readers, who were not blinded to histopathologic findings, retrospectively reviewed cancers missed at MP MR imaging and assigned a Prostate Imaging Reporting and Data System (PI-RADS) version 2 score to better understand false-negative lesion characteristics. Descriptive statistics were used to define patient characteristics, including age, prostate-specific antigen (PSA) level, PSA density, race, digital rectal examination results, and biopsy results before MR imaging. Student t test was used to determine any demographic differences between patients with false-negative MP MR imaging findings and those with correct prospective identification of all lesions. Results Of the 162 lesions, 136 (84%) were correctly identified with MP MR imaging. Size of eight lesions was underestimated. Among the 26 (16%) lesions missed at MP MR imaging, Gleason score was 3+4 in 17 (65%), 4+3 in one (4%), 4+4 in seven (27%), and 4+5 in one (4%). Retrospective PI-RADS version 2 scores were assigned (PI-RADS 1, n = 8; PI-RADS 2, n = 7; PI-RADS 3, n = 6; and PI-RADS 4, n = 5). On a per-patient basis, MP MR imaging depicted clinically important prostate cancer in 99 of 100 patients. At least one clinically important tumor was missed in 26 (26%) patients, and lesion size was underestimated in eight (8%). Conclusion Clinically important lesions can be missed or their size can be underestimated at MP MR imaging. Of missed lesions, 58% were not seen or were characterized as benign findings at second-look analysis. Recognition of the limitations of MP MR imaging is important, and new approaches to reduce this false-negative rate are needed. © RSNA, 2017 Online supplemental material is available for this article.

Validation of PI-RADS Version 2 in Transition Zone Lesions for the Detection of Prostate Cancer.

Purpose To determine the association between Prostate Imaging Reporting and Data System (PI-RADS) version 2 scores and prostate cancer (PCa) in a cohort of patients undergoing biopsy of transition zone (TZ) lesions. Materials and Methods A total of 634 TZ lesions in 457 patients were identified from a prospectively maintained database of consecutive patients undergoing prostate magnetic resonance imaging. Prostate lesions were retrospectively categorized with the PI-RADS version 2 system by two readers in consensus who were blinded to histopathologic findings. The proportion of cancer detection for all PCa and for clinically important PCa (Gleason score ≥3+4) for each PI-RADS version 2 category was determined. The performance of PI-RADS version 2 in cancer detection was evaluated. Results For PI-RADS category 2 lesions, the overall proportion of cancers was 4% (one of 25), without any clinically important cancer. For PI-RADS category 3, 4, and 5 lesions, the overall proportion of cancers was 22.2% (78 of 352), 39.1% (43 of 110), and 87.8% (129 of 147), respectively, and the proportion of clinically important cancers was 11.1% (39 of 352), 29.1% (32 of 110), and 77.6% (114 of 147), respectively. Higher PI-RADS version 2 scores were associated with increasing likelihood of the presence of clinically important PCa (P < .001). Differences were found in the percentage of cancers in the PI-RADS category between PI-RADS 3 and those upgraded to PI-RADS 4 based on diffusion-weighted imaging for clinically important cancers (proportion for clinically important cancers for PI-RADS 3 and PI-RADS 3+1 were 11.1% [39 of 352] and 30.8% [28 of 91], respectively; P < .001). Conclusion Higher PI-RADS version 2 scores are associated with a higher proportion of clinically important cancers in the TZ. PI-RADS category 2 lesions rarely yield PCa, and their presence does not justify targeted biopsy.

Computer-aided diagnosis prior to conventional interpretation of prostate mpMRI: an international multi-reader study.

OBJECTIVES: To evaluate if computer-aided diagnosis (CAD) prior to prostate multi-parametric MRI (mpMRI) can improve sensitivity and agreement between radiologists. METHODS: Nine radiologists (three each high, intermediate, low experience) from eight institutions participated. A total of 163 patients with 3-T mpMRI from 4/2012 to 6/2015 were included: 110 cancer patients with prostatectomy after mpMRI, 53 patients with no lesions on mpMRI and negative TRUS-guided biopsy. Readers were blinded to all outcomes and detected lesions per PI-RADSv2 on mpMRI. After 5 weeks, readers re-evaluated patients using CAD to detect lesions. Prostatectomy specimens registered to MRI were ground truth with index lesions defined on pathology. Sensitivity, specificity and agreement were calculated per patient, lesion level and zone-peripheral (PZ) and transition (TZ). RESULTS: Index lesion sensitivity was 78.2% for mpMRI alone and 86.3% for CAD-assisted mpMRI (p = 0.013). Sensitivity was comparable for TZ lesions (78.7% vs 78.1%; p = 0.929); CAD improved PZ lesion sensitivity (84% vs 94%; p = 0.003). Improved sensitivity came from lesions scored PI-RADS < 3 as index lesion sensitivity was comparable at PI-RADS ≥ 3 (77.6% vs 78.1%; p = 0.859). Per patient specificity was 57.1% for CAD and 70.4% for mpMRI (p = 0.003). CAD improved agreement between all readers (56.9% vs 71.8%; p < 0.001). CONCLUSIONS: CAD-assisted mpMRI improved sensitivity and agreement, but decreased specificity, between radiologists of varying experience. KEY POINTS: • Computer-aided diagnosis (CAD) assists clinicians in detecting prostate cancer on MRI. • CAD assistance improves agreement between radiologists in detecting prostate cancer lesions. • However, this CAD system induces more false positives, particularly for less-experienced clinicians and in the transition zone. • CAD assists radiologists in detecting cancer missed on MRI, suggesting a path for improved diagnostic confidence.

Validation of the Dominant Sequence Paradigm and Role of Dynamic Contrast-enhanced Imaging in PI-RADS Version 2.

Purpose To validate the dominant pulse sequence paradigm and limited role of dynamic contrast material-enhanced magnetic resonance (MR) imaging in the Prostate Imaging Reporting and Data System (PI-RADS) version 2 for prostate multiparametric MR imaging by using data from a multireader study. Materials and Methods This HIPAA-compliant retrospective interpretation of prospectively acquired data was approved by the local ethics committee. Patients were treatment-naïve with endorectal coil 3-T multiparametric MR imaging. A total of 163 patients were evaluated, 110 with prostatectomy after multiparametric MR imaging and 53 with negative multiparametric MR imaging and systematic biopsy findings. Nine radiologists participated in this study and interpreted images in 58 patients, on average (range, 56-60 patients). Lesions were detected with PI-RADS version 2 and were compared with whole-mount prostatectomy findings. Probability of cancer detection for overall, T2-weighted, and diffusion-weighted (DW) imaging PI-RADS scores was calculated in the peripheral zone (PZ) and transition zone (TZ) by using generalized estimating equations. To determine dominant pulse sequence and benefit of dynamic contrast-enhanced (DCE) imaging, odds ratios (ORs) were calculated as the ratio of odds of cancer of two consecutive scores by logistic regression. Results A total of 654 lesions (420 in the PZ) were detected. The probability of cancer detection for PI-RADS category 2, 3, 4, and 5 lesions was 15.7%, 33.1%, 70.5%, and 90.7%, respectively. DW imaging outperformed T2-weighted imaging in the PZ (OR, 3.49 vs 2.45; P = .008). T2-weighted imaging performed better but did not clearly outperform DW imaging in the TZ (OR, 4.79 vs 3.77; P = .494). Lesions classified as PI-RADS category 3 at DW MR imaging and as positive at DCE imaging in the PZ showed a higher probability of cancer detection than did DCE-negative PI-RADS category 3 lesions (67.8% vs 40.0%, P = .02). The addition of DCE imaging to DW imaging in the PZ was beneficial (OR, 2.0; P = .027), with an increase in the probability of cancer detection of 15.7%, 16.0%, and 9.2% for PI-RADS category 2, 3, and 4 lesions, respectively. Conclusion DW imaging outperforms T2-weighted imaging in the PZ; T2-weighted imaging did not show a significant difference when compared with DW imaging in the TZ by PI-RADS version 2 criteria. The addition of DCE imaging to DW imaging scores in the PZ yields meaningful improvements in probability of cancer detection. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on July 27, 2017. Online supplemental material is available for this article.

Prospective Evaluation of PI-RADS™ Version 2 Using the International Society of Urological Pathology Prostate Cancer Grade Group System.

PURPOSE: The PI-RADS™ (Prostate Imaging Reporting and Data System), version 2 scoring system, introduced in 2015, is based on expert consensus. In the same time frame ISUP (International Society of Urological Pathology) introduced a new pathological scoring system for prostate cancer. Our goal was to prospectively evaluate the cancer detection rates for each PI-RADS, version 2 category and compare them to ISUP group scores in patients undergoing systematic biopsy and magnetic resonance imaging-transrectal ultrasound fusion guided biopsy. MATERIALS AND METHODS: A total of 339 treatment naïve patients prospectively underwent multiparametric magnetic resonance imaging evaluated with PI-RADS, version 2 with subsequent systematic and fusion guided biopsy from May 2015 to May 2016. ISUP scores were applied to pathological specimens. An ISUP score of 2 or greater (ie Gleason 3 + 4 or greater) was defined as clinically significant prostate cancer. Cancer detection rates were determined for each PI-RADS, version 2 category as well as for the T2 weighted PI-RADS, version 2 categories in the peripheral zone. RESULTS: The cancer detection rate for PI-RADS, version 2 categories 1, 2, 3, 4 and 5 was 25%, 20.2%, 24.8%, 39.1% and 86.9% for all prostate cancer, and 0%, 9.6%, 12%, 22.1% and 72.4% for clinically significant prostate cancer, respectively. On T2-weighted magnetic resonance imaging the cancer detection rate in the peripheral zone was significantly higher for PI-RADS, version 2 category 4 than for overall PI-RADS, version 2 category 4 in the peripheral zone (all prostate cancer 36.6% vs 48.1%, p = 0.001, and clinically significant prostate cancer 22.9% vs 32.6%, p = 0.002). CONCLUSIONS: The cancer detection rate increases with higher PI-RADS, version 2 categories.

Optimal high b-value for diffusion weighted MRI in diagnosing high risk prostate cancers in the peripheral zone.

PURPOSE: To retrospectively determine the optimal b-value(s) of diffusion-weighted imaging (DWI) associated with intermediate-high risk cancer in the peripheral zone (PZ) of the prostate. MATERIALS AND METHODS: Forty-two consecutive patients underwent multi b-value (16 evenly spaced b-values between 0 and 2000 s/mm2 ) DWI along with multi-parametric MRI (MP-MRI) of the prostate at 3 Tesla followed by trans-rectal ultrasound/MRI fusion guided targeted biopsy of suspicious lesions detected at MP-MRI. Computed DWI images up to a simulated b-value of 4000 s/mm2 were also obtained using a pair of b-values (b = 133 and 400 or 667 or 933 s/mm2 ) from the multi b-value DWI. The contrast ratio of average intensity of the targeted lesions and the background PZ was determined. Receiver operator characteristic curves and the area under the curve (AUCs) were obtained for separating patients eligible for active surveillance with low risk prostate cancers from intermediate-high risk prostate cancers as per the cancer of the prostate risk assessment (CAPRA) scoring system. RESULTS: The AUC first increased then decreased with the increase in b-values reaching maximum at b = 1600 s/mm2 (0.74) with no statistically significant different AUC of DWI with b-values 1067-2000 s/mm2 . The AUC of computed DWI increased then decreased with the increase in b-values reaching a maximum of 0.75 around b = 2000 s/mm2 . There was no statistically significant difference between the AUC of optimal acquired DWI and either of optimal computed DWI. CONCLUSION: The optimal b-value for acquired DWI in differentiating intermediate-high from low risk prostate cancers in the PZ is b = 1600 s/mm2 . The computed DWI has similar performance as that of acquired DWI with the optimal performance around b = 2000 s/mm2 . LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:125-131.

Prospective Evaluation of the Prostate Imaging Reporting and Data System Version 2 for Prostate Cancer Detection.

PURPOSE: Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) was developed to standardize the interpretation and reporting of multiparametric prostate magnetic resonance imaging and provide guidelines for biopsy of multiparametric magnetic resonance imaging findings. We prospectively evaluated the cancer detection rate at each overall PI-RADSv2 score. MATERIALS AND METHODS: This prospective study included 62 consecutive patients with 116 lesions who underwent multiparametric prostate magnetic resonance imaging at 3T with PI-RADSv2 evaluation and subsequent targeted magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and concurrent 12-core systematic prostate biopsy between May and September 2015. Median patient age and prostate specific antigen values were 65.5 years (range 50.3 to 76.6) and 7.10 ng/ml (range 0.47 to 863.0), respectively. Mean lesion size was 12.7 mm overall. Lesion based cancer detection rates for all tumors and for Gleason 3+4 or greater tumors at each PI-RADSv2 score were calculated. Univariate analysis was performed to assess differences in the cancer detection rate among PI-RADSv2 scores. RESULTS: A total of 116 lesions in 62 patients were evaluated prospectively (0 PI-RADS 1, 18 PI-RADS 2, 19 PI-RADS 3, 47 PI-RADS 4, 32 PI-RADS 5), and the patients underwent magnetic resonance/transrectal ultrasound fusion guided biopsy and systematic biopsy. Histopathology revealed 55 of 116 (47.4%) cancers (17 Gleason 3+3, 16 Gleason 3+4, 6 Gleason 4+3, 12 Gleason 4+4, 3 Gleason 4+5 and 1 Gleason 5+4). Based on targeted biopsy on a per lesion basis, the overall cancer detection rates of PI-RADS 2, 3, 4 and 5 scores for all tumors was 22.2%, 15.8%, 29.8% and 78.1%, respectively. The cancer detection rate of PI-RADS 2, 3, 4 and 5 scores for Gleason 3+4 or greater tumors was 5.6%, 0%, 21.3% and 75%, respectively. Differences in the cancer detection rate between overall PI-RADS 4 and 5 scores were significant (p <0.001 for Gleason greater than 3+3 and Gleason 3+4 or greater cancers). CONCLUSIONS: A PI-RADS score of 5 had the highest prospective cancer detection rate (78%). A PI-RADS score of 4 had only a 30% cancer detection rate, which is lower than expected. Surprisingly, no or few significant cancers were detected at a PI-RADS score of 3 (16%). These early prospective data suggest that current criteria result in a high false-positive rate that lowers the cancer detection rate. Therefore, stricter criteria may be needed in the future to decrease false-positives and increase the cancer detection rate for PI-RADS scores of 3, 4 and 5.

Does Abstinence From Ejaculation Before Prostate MRI Improve Evaluation of the Seminal Vesicles?

OBJECTIVE: The purpose of the present study is to determine whether abstinence from ejaculation before undergoing multiparametric prostate MRI increases seminal vesicle (SV) volume and therefore improves diagnostic interpretation of the SVs. MATERIALS AND METHODS: This retrospective study included 238 patients who underwent 3-T MRI of the prostate over a 4-month period. Patients were requested to complete a questionnaire that asked how long it had been since their last ejaculation (i.e., < 3 days vs ≥ 3 days). Forty-two patients (mean patient age, 62.0 years) indicated that it had been less than 3 days since their last ejaculation and were designated as group 1, whereas the remainder indicated an interval of 3 days or more since their last ejaculation. A group of 42 age-matched subjects (mean patient age, 62.1 years) were randomly selected from the remaining 196 patients and were designated as group 2. SV volumes were measured manually. Two radiologists who were blinded to group assignment and patient characteristics scored the right and left SVs separately to determine diagnostic interpretability, which was scored on a 3-point scale as follows: a score of 1 denoted that the SVs were not dilated and the score was nondiagnostic, a score of 2 indicated that the SVs were not dilated but the score was diagnostic, and a score of 3 denoted that the SVs were dilated and the score was diagnostic. Volume differences and interpretability scores were analyzed using a t test. Interobserver agreement was analyzed using the Cohen kappa statistic. A separate analysis was performed to evaluate differences in diagnostic interpretability for patients 60 years and younger versus patients older than 60 years, by use of the chi-square test and relative risk ratio analysis. RESULTS: The right, left, and total SV volumes for group 1 were 3.1 mL, 2.9 mL, and 6.0 mL, respectively, whereas those for group 2 were 4.7 mL, 4.1 mL, and 8.8 mL, respectively (p = 0.011). The mean interpretability scores for group 1 and group 2 were 2.0 and 2.5, respectively. For group 1, reader 1 and reader 2 assigned a nondiagnostic score for 10 and 13 patients, respectively, whereas for group 2, they assigned a nondiagnostic score for two and five patients, respectively (p = 0.01, for reader 1; and p = 0.03, for reader 2). For men in group 1 who were older than 60 years, reader 1 and reader 2 gave a nondiagnostic score for nine and 11 patients, respectively; whereas for men in group 2 who were older than 60 years, the readers gave a nondiagnostic score for two and five patients, respectively (p = 0.01, for reader 1; and p = 0.05, for reader 2). CONCLUSION: For men older than 60 years, abstinence from ejaculation for 3 or more days before undergoing MRI examination resulted in larger SV volumes and lower rates of nondiagnostic evaluation and therefore might improve evaluation of SV invasion on multi-parametric MRI. The difference is less striking in men 60 years and younger.

PET imaging of recurrent and metastatic prostate cancer with novel tracers.

Early detection of recurrent prostate cancer (PCa) is of paramount importance to deliver prompt and accurate therapy reducing the chance of progression to metastatic disease. However, current imaging modalities such as conventional computed tomography, MRI and PET scanning do not provide sufficient sensitivity, especially at lower prostate-specific antigen values. Moreover, biological characterization of PCa has become increasingly important to provide patient-specific therapy and current imaging poorly characterizes disease aggressiveness. The current uprise of novel PET tracers in recurrent and metastatic PCa shows promising, yet variable sensitivities and specificities in detection, indicating the need for further studies. In this review, we highlight current and new PET tracers that have been developed to improve the detection of recurrent and metastatic PCa.

Evaluating the Role of mpMRI in Prostate Cancer Assessment.

Prostate cancer is the most common malignancy among American men. The role of multi-parametric MRI has recently gained more importance in detection of prostate cancer, its targeted biopsy, and focal therapy guidance. In this review, uses of multi-parametric MRI in prostate cancer assessment and treatment are discussed.

Multiparametric Magnetic Resonance Imaging of Recurrent Prostate Cancer.

There is growing consensus that multiparametric magnetic resonance imaging (mpMRI) is an effective modality in the detection of locally recurrent prostate cancer after prostatectomy and radiation therapy. The emergence of magnetic resonance (MR)-guided focal therapies, such as cryoablation, high-intensity focused ultrasound, and laser ablation, have made the use of mpMRI even more important, as the normal anatomy is inevitably altered and the detection of recurrence is made more difficult. The aim of this article is to review the utility of mpMRI in detecting recurrent prostate cancer in patients following radical prostatectomy, radiation therapy, and focal therapy and to discuss expected post-treatment mpMRI findings, the varied appearance of recurrent tumors, and their mimics.