Sherif Mehralivand

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.

A Magnetic Resonance Imaging–Based Prediction Model for Prostate Biopsy Risk Stratification

Importance Multiparametric magnetic resonance imaging (MRI) in conjunction with MRI–transrectal ultrasound (TRUS) fusion-guided biopsies have improved the detection of prostate cancer. It is unclear whether MRI itself adds additional value to multivariable prediction models based on clinical parameters. Objective To determine whether an MRI-based prediction model can reduce unnecessary biopsies in patients with suspected prostate cancer. Design, Setting, and Participants Patients underwent MRI, MRI-TRUS fusion-guided biopsy, and 12-core systematic biopsy in 1 session. The development cohort used to derive the prediction model consisted of 400 patients from 1 institution enrolled between May 14, 2015, and August 31, 2016, and the validation cohort included 251 patients from 2 independent institutions who underwent biopsies between April 1, 2013, and June 30, 2016, at 1 institution and between July 1, 2015, and October 31, 2016, at the other institution. The MRI model included MRI-derived parameters in addition to clinical variables. Area under the curve of receiver operating characteristic curves and decision curve analysis were performed. Main Outcomes and Measures Risk of clinically significant prostate cancer on biopsy, defined as a Gleason score of 3 + 4 or higher in at least 1 biopsy core. Results Overall, 193 (48.3%) of the 400 patients in the development cohort (mean [SD] age at biopsy, 64.3 [7.1] years) and 96 (38.2%) of the 251 patients in the validation cohort (mean [SD] age at biopsy, 64.9 [7.2] years) had clinically significant prostate cancer, defined as a Gleason score greater than or equal to 3 + 4. By applying the model to the external validation cohort, the area under the curve increased from 64% to 84% compared with the baseline model (P < .001). At a risk threshold of 20%, the MRI model had a lower false-positive rate than the baseline model (46% [95% CI, 32%-66%] vs 92% [95% CI, 70%-100%]), with only a small reduction in the true-positive rate (89% [95% CI, 85%-96%] vs 99% [95% CI, 89%-100%]). Eighteen of 100 fewer biopsies could have been performed, with no increase in the number of patients with missed clinically significant prostate cancers. Conclusions and Relevance The inclusion of MRI-derived parameters in a risk model could reduce the number of unnecessary biopsies while maintaining a high rate of diagnosis of clinically significant prostate cancers.

A Prospective Comparison of 18F-Sodium Fluoride PET/CT and PSMA-targeted 18F-DCFBC PET/CT in Metastatic Prostate Cancer

The purpose of this study was to compare the diagnostic performance of 18F-DCFBC PET/CT, a first-generation 18F-labeled prostate-specific membrane antigen (PSMA)–targeted agent, and 18F-NaF PET/CT, a sensitive marker of osteoblastic activity, in a prospective cohort of patients with metastatic prostate cancer. Methods: Twenty-eight prostate cancer patients with metastatic disease on conventional imaging prospectively received up to 4 PET/CT scans. All patients completed baseline 18F-DCFBC PET/CT and 18F-NaF PET/CT scans, and 23 patients completed follow-up imaging, with a median follow-up interval of 5.7 mo (range, 4.2–12.6 mo). Lesion detection was compared across the 2 PET/CT agents at each time point. Detection and SUV characteristics of each PET/CT agent were compared with serum prostate-specific antigen (PSA) levels and treatment status at the time of baseline imaging using nonparametric statistical testing (Spearman correlation, Wilcoxon rank). Results: Twenty-six patients had metastatic disease detected on 18F-NaF or 18F-DCFBC at baseline, and 2 patients were negative on both scans. Three patients demonstrated soft tissue–only disease. Of 241 lesions detected at baseline, 56 were soft-tissue lesions identified by 18F-DCFBC only and 185 bone lesions detected on 18F-NaF or 18F-DCFBC. 18F-NaF detected significantly more bone lesions than 18F-DCFBC (P < 0.001). Correlation of PSA with patient-level SUV metrics was strong in 18F-DCFBC (ρ > 0.5, P < 0.01) and poor in 18F-NaF (ρ < 0.3, P > 0.1). When PSA levels were combined with treatment status, patients with below-median levels of PSA (<2 ng/mL) on androgen deprivation therapy (n = 11) demonstrated more lesions on 18F-NaF than 18F-DCFBC (P = 0.02). In PSA greater than 2 ng/mL, patients on androgen deprivation therapy (n = 8) showed equal to or more lesions on 18F-DCFBC than on 18F-NaF. Conclusion: The utility of PSMA-targeting imaging in metastatic prostate cancer appears to depend on patient disease course and treatment status. Compared with 18F-NaF PET/CT, 18F-DCFBC PET/CT detected significantly fewer bone lesions in the setting of early or metastatic castrate-sensitive disease on treatment. However, in advanced metastatic castrate-resistant prostate cancer, 18F-DCFBC PET/CT shows good concordance with NaF PET/CT.

Prospective comparison of PI-RADS version 2 and qualitative in-house categorization system in detection of prostate cancer: Prospective Comparison of PI-RADSv2

Prostate Imaging‐Reporting and Data System v. 2 (PI‐RADSv2) provides standardized nomenclature for interpretation of prostate multiparametric MRI (mpMRI). Inclusion of additional features for categorization may provide benefit to stratification of disease.

Sentinel lymph node imaging in urologic oncology

Lymph node (LN) metastases in urological malignancies correlate with poor oncological outcomes. Accurate LN staging is of great importance since patients can benefit from an optimal staging, accordingly aligned therapy and more radical treatments. Current conventional cross-sectional imaging modalities [e.g., computed tomography (CT) and magnetic resonance imaging (MRI)] are not accurate enough to reliably detect early LN metastases as they rely on size criteria. Radical lymphadenectomy, the surgical removal of regional LNs, is the gold standard of invasive LN staging. The LN dissection is guided by anatomic considerations of lymphatic drainage pathways of the primary tumor. Selection of patients for lymphadenectomy heavily relies on preoperative risk stratification and nomograms and, as a result a considerable number of patients unnecessarily undergo invasive staging with associated morbidity. On the other hand, due to individual variability in lymphatic drainage, LN metastases can occur outside of standard lymphadenectomy templates leading to potential understaging and undertreatment. In theory, metastases from the primary tumor need to pass through the chain of LNs, where the initial node is defined as the sentinel LN. In theory, identifying and removing this LN could lead to accurate assessment of metastatic status. Radiotracers and more recently fluorescent dyes and superparamagnetic iron oxide nanoparticles (SPION) are injected into the primary tumor or peritumoral and the sentinel LNs are identified intraoperatively by a gamma probe, fluorescent camera or a handheld magnetometer. Preoperative imaging [e.g., single-photon emission computed tomography (SPECT)/CT or MRI] after tracer injection can further improve preoperative planning of LN dissection. While sentinel LN biopsy is an accepted and widely used approach in melanoma and breast cancer staging, its use in urological malignancies is still limited. Most data published so far is in penile cancer staging since this cancer has a typical echelon-based lymphatic metastasizing pattern. More recent data is encouraging with low false-negative rates, but its use is limited to centers with high expertise. Current guidelines recommend sentinel LN biopsy as an accepted alternative to modified inguinal lymphadenectomy in patients with pT1G2 disease and non-palpable inguinal LNs. In prostate cancer, a high diagnostic accuracy could be demonstrated for the sentinel approach. Nevertheless, due to lack of data or high false-negative rates in other urological malignancies, sentinel LN biopsy is still considered experimental in other urological malignancies. More high-level evidence and longitudinal data is needed to determine its final value in those malignancies. In this manuscript, we will review sentinel node imaging for urologic malignancies.

Predicting Gleason Group Progression for Men on Prostate Cancer Active Surveillance: The Role of a Negative Confirmatory MRI-US Fusion Biopsy

Purpose: Active surveillance has gained acceptance as an alternative to definitive therapy in many men with prostate cancer. Confirmatory biopsies to assess the appropriateness of active surveillance are routinely performed and negative biopsies are regarded as a favorable prognostic indicator. We sought to determine the prognostic implications of negative multiparametric magnetic resonance imaging-transrectal ultrasound guided fusion biopsy consisting of extended sextant, systematic biopsy plus multiparametric magnetic resonance imaging guided targeted biopsy of suspicious lesions on magnetic resonance imaging. Materials and Methods: All patients referred with Gleason Grade Group 1 or 2 prostate cancer based on systematic biopsy performed elsewhere underwent confirmatory fusion biopsy. Patients who continued on active surveillance after a positive or a negative fusion biopsy were followed. The baseline characteristics of the biopsy negative and positive cases were compared. Cox regression analysis was used to determine the prognostic significance of a negative fusion biopsy. Kaplan-Meier survival curves were used to estimate Grade Group progression with time. Results: Of the 542 patients referred with Grade Group 1 (466) or Grade Group 2 (76) cancer 111 (20.5%) had a negative fusion biopsy. A total of 60 vs 122 patients with a negative vs a positive fusion biopsy were followed on active surveillance with a median time to Grade Group progression of 74.3 and 44.6 months, respectively (p <0.01). Negative fusion biopsy was associated with a reduced risk of Grade Group progression (HR 0.41, 95% CI 0.22-0.77, p <0.01). Conclusions: A negative confirmatory fusion biopsy confers a favorable prognosis for Grade Group progression. These results can be used when counseling patients about the risk of progression and for planning future followup and biopsies in patients on active surveillance.PURPOSE Active surveillance has gained acceptance as an alternative to definitive therapy in many men with prostate cancer. Confirmatory biopsies to assess the appropriateness of active surveillance are routinely performed and negative biopsies are regarded as a favorable prognostic indicator. We sought to determine the prognostic implications of negative multiparametric magnetic resonance imaging-transrectal ultrasound guided fusion biopsy consisting of extended sextant, systematic biopsy plus multiparametric magnetic resonance imaging guided targeted biopsy of suspicious lesions on magnetic resonance imaging. MATERIALS AND METHODS All patients referred with Gleason Grade Group 1 or 2 prostate cancer based on systematic biopsy performed elsewhere underwent confirmatory fusion biopsy. Patients who continued on active surveillance after a positive or a negative fusion biopsy were followed. The baseline characteristics of the biopsy negative and positive cases were compared. Cox regression analysis was used to determine the prognostic significance of a negative fusion biopsy. Kaplan-Meier survival curves were used to estimate Grade Group progression with time. RESULTS Of the 542 patients referred with Grade Group 1 (466) or Grade Group 2 (76) cancer 111 (20.5%) had a negative fusion biopsy. A total of 60 vs 122 patients with a negative vs a positive fusion biopsy were followed on active surveillance with a median time to Grade Group progression of 74.3 and 44.6 months, respectively (p <0.01). Negative fusion biopsy was associated with a reduced risk of Grade Group progression (HR 0.41, 95% CI 0.22-0.77, p <0.01). CONCLUSIONS A negative confirmatory fusion biopsy confers a favorable prognosis for Grade Group progression. These results can be used when counseling patients about the risk of progression and for planning future followup and biopsies in patients on active surveillance.

Added Value of Multiparametric Magnetic Resonance Imaging to Clinical Nomograms for Predicting Adverse Pathology in Prostate Cancer

Purpose We examined the additional value of preoperative prostate multiparametric magnetic resonance imaging and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy when performed in combination with clinical nomograms to predict adverse pathology at radical prostatectomy. Materials and Methods We identified all patients who underwent 3 Tesla multiparametric magnetic resonance imaging prior to fusion biopsy and radical prostatectomy. The Partin and the MSKCC (Memorial Sloan Kettering Cancer Center) preradical prostatectomy nomograms were applied to estimate the probability of organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement using transrectal ultrasound guided systematic biopsy and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy Gleason scores. With radical prostatectomy pathology as the gold standard we developed multivariable logistic regression models based on these nomograms before and after adding multiparametric magnetic resonance imaging to assess any additional predictive ability. Results A total of 532 patients were included in study. When multiparametric magnetic resonance imaging findings were added to the systematic biopsy based MSKCC nomogram, the AUC increased by 0.10 for organ confined disease (p <0.001), 0.10 for extraprostatic extension (p = 0.003), 0.09 for seminal vesicle invasion (p = 0.011) and 0.06 for lymph node involvement (p = 0.120). Using Gleason scores derived from targeted biopsy compared to systematic biopsy provided an additional predictive value of organ confined disease (&Dgr; AUC 0.07, p = 0.003) and extraprostatic extension (&Dgr; AUC 0.07, p = 0.048) at radical prostatectomy with the MSKCC nomogram. Similar results were obtained using the Partin nomogram. Conclusions Magnetic resonance imaging alone or in addition to standard clinical nomograms provides significant additional predictive ability of adverse pathology at the time of radical prostatectomy. This information can be greatly beneficial to urologists for preoperative planning and for counseling patients regarding the risks of future therapy.

Comparison of Elastic and Rigid Registration during Magnetic Resonance Imaging/Ultrasound Fusion-Guided Prostate Biopsy: A Multi-Operator Phantom Study

Purpose The relative value of rigid or elastic registration during magnetic resonance imaging/ultrasound fusion guided prostate biopsy has been poorly studied. We compared registration errors (the distance between a region of interest and fiducial markers) between rigid and elastic registration during fusion guided prostate biopsy using a prostate phantom model. Materials and Methods Four gold fiducial markers visible on magnetic resonance imaging and ultrasound were placed throughout 1 phantom prostate model. The phantom underwent magnetic resonance imaging and the fiducial markers were labeled as regions of interest. An experienced user and a novice user of fusion guided prostate biopsy targeted regions of interest and then the corresponding fiducial markers on ultrasound after rigid and then elastic registration. Registration errors were compared. Results A total of 224 registration error measurements were recorded. Overall elastic registration did not provide significantly improved registration error over rigid registration (mean ± SD 4.87 ± 3.50 vs 4.11 ± 2.09 mm, p = 0.05). However, lesions near the edge of the phantom showed increased registration errors when using elastic registration (5.70 ± 3.43 vs 3.23 ± 1.68 mm, p = 0.03). Compared to the novice user the experienced user reported decreased registration error with rigid registration (3.25 ± 1.49 vs 4.98 ± 2.10 mm, p <0.01) and elastic registration (3.94 ± 2.61 vs 6.07 ± 4.16 mm, p <0.01). Conclusions We found no difference in registration errors between rigid and elastic registration overall but rigid registration decreased the registration error of targets near the prostate edge. Additionally, operator experience reduced registration errors regardless of the registration method. Therefore, elastic registration algorithms cannot serve as a replacement for attention to detail during the registration process and anatomical landmarks indicating accurate registration when beginning the procedure and before targeting each region of interest.

Can computer-aided diagnosis assist in the identification of prostate cancer on prostate MRI? A multi-center, multi-reader investigation

For prostate cancer detection on prostate multiparametric MRI (mpMRI), the Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) and computer-aided diagnosis (CAD) systems aim to widely improve standardization across radiologists and centers. Our goal was to evaluate CAD assistance in prostate cancer detection compared with conventional mpMRI interpretation in a diverse dataset acquired from five institutions tested by nine readers of varying experience levels, in total representing 14 globally spread institutions. Index lesion sensitivities of mpMRI-alone were 79% (whole prostate (WP)), 84% (peripheral zone (PZ)), 71% (transition zone (TZ)), similar to CAD at 76% (WP, p=0.39), 77% (PZ, p=0.07), 79% (TZ, p=0.15). Greatest CAD benefit was in TZ for moderately-experienced readers at PI-RADSv2 <3 (84% vs mpMRI-alone 67%, p=0.055). Detection agreement was unchanged but CAD-assisted read times improved (4.6 vs 3.4 minutes, p<0.001). At PI-RADSv2 ≥ 3, CAD improved patient-level specificity (72%) compared to mpMRI-alone (45%, p<0.001). PI-RADSv2 and CAD-assisted mpMRI interpretations have similar sensitivities across multiple sites and readers while CAD has potential to improve specificity and moderately-experienced radiologists’ detection of more difficult tumors in the center of the gland. The multi-institutional evidence provided is essential to future prostate MRI and CAD development.

A Mixed Reality Guidance System for Robot Assisted Laparoscopic Radical Prostatectomy

Robotic surgery with preoperative imaging data for planning have become increasingly common for surgical treatment of patients. For surgeons using robotic surgical platforms, maintaining spatial awareness of the anatomical structures in the surgical area is key for good outcomes. We propose a Mixed Reality system which allows surgeons to visualize and interact with aligned anatomical models extracted from preoperative imagery as well as the in vivo imagery from the stereo laparoscope. To develop this system, we have employed techniques to 3D reconstruct stereo laparoscope images, model 3D shape of the anatomical structures from preoperative MRI stack and align the two 3D surfaces. The application we have developed allows surgeons to visualize occluded and obscured organ boundaries as well as other important anatomy that is not visible through the laparoscope alone, facilitating better spatial awareness during surgery. The system was deployed in 9 robot assisted laparoscopic prostatectomy procedures as part of a feasibility study.