Valeria Panebianco

Advances in Magnetic Resonance Imaging: How They Are Changing the Management of Prostate Cancer

CONTEXT Although magnetic resonance imaging (MRI) is emerging as the most commonly used imaging modality for prostate cancer (PCa) detection, treatment planning, and follow-up, its acceptance has not been uniform. Recently, great interest has been shown in multiparametric MRI, which combines anatomic T2-weighted (T2W) imaging with MR spectroscopic imaging (MRSI), dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI). OBJECTIVE The aim of this article is to review the current roles of these MR techniques in different aspects of PCa management: initial diagnosis, biopsy strategies, planning of radical prostatectomy (RP) and external radiation therapy (RT), and implementation of alternative focal therapies. EVIDENCE ACQUISITION The authors searched the Medline and Cochrane Library databases (primary fields: prostatic neoplasm, magnetic resonance). The search was performed without language restriction from January 2008 to November 2010. EVIDENCE SYNTHESIS Initial diagnosis: The data suggest that the combination of T2W MRI and DWI or MRSI with DCE-MRI has the potential to guide biopsy to the most aggressive cancer foci in patients with previously negative biopsies, increasing the accuracy of the procedure. Transrectal MR-guided prostate biopsy can improve PCa detection, but its availability is still limited and the examination time is rather long. Planning of RP: It appears that adding MRSI, DWI, and/or DCE-MRI to T2W MRI can facilitate better preoperative characterization of cancer with regard to location, size, and relationship to prostatic and extraprostatic structures, and it may also facilitate early detection of local recurrence. Thus, use of these MR techniques may improve surgical, oncologic, and functional management. Planning of external RT and focal therapies: MR techniques have similar potential in these areas, but the published data remain very limited. CONCLUSIONS MRI technology is continuously evolving, and more extensive use of MRI technology in clinical trials and practice will help to improve PCa diagnosis and treatment planning.

Role of Dynamic Contrast-Enhanced Magnetic Resonance (MR) Imaging and Proton MR Spectroscopic Imaging in the Detection of Local Recurrence after Radical Prostatectomy for Prostate Cancer

OBJECTIVES To assess the accuracy of magnetic resonance (MR) spectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced MR (DCEMR) in the depiction of local prostate cancer recurrence in patients with biochemical progression after radical prostatectomy (RP). MATERIALS AND METHODS 1H-MRSI and DCEMR were performed in 70 patients at high risk of local recurrence after RP. The population was divided on the basis of the clinical validation of MR results with the use of a transrectal ultrasound biopsy examination in a group of 50 patients (group A) and the prostate-specific antigen (PSA) serum level restitution after external beam radiotherapy, in a group of 20 patients (group B). RESULTS In group A, 1H-MRSI analysis alone showed a sensitivity of 84% and a specificity of 88%; the DCEMR analysis alone, a sensitivity of 71% and a specificity of 94%; combined 1HMRSI-DCEMR, a sensitivity of 87% and specificity of 94%. Areas under the receiver operating characteristic (ROC) curve for 1HMRSI, DCEMR, and combined 1HMRSI /DCEMR were 0.942, 0.93,1 and 0.964, respectively. In group B, 1HMRSI alone showed a sensitivity of 71% and a specificity of 83%; DCEMR, a sensitivity of 79% and a specificity of 100%; combined 1HMRSI and DCEMR, a sensitivity of 86% and a specificity of 100%. Areas under the ROC curve for each of these groups were 0.81, 0.923, and 0.94, respectively. CONCLUSION Our results show that combined 1H-MRSI and DCMRE is an accurate method to identify local prostate cancer recurrence in patients with biochemical progression after RP.

Value of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy

Purpose: This study aimed to prospectively analyze the role of magnetic resonance spectroscopy imaging (MRSI) and dynamic-contrast enhancement magnetic resonance (DCEMR) in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen levels (in the range of ≥4 ng/mL to <10 ng/mL) and prior negative random trans-rectal ultrasound (TRUS)-guided biopsy. Experimental Design: This was a prospective randomized single-center study. One hundred and eighty eligible cases were included in the study. Patients in group A were submitted to a second random prostate biopsy, whereas patients in group B were submitted to a 1H-MRSI-DCEMR examination and samples targeted on suspicious areas were associated to the random biopsy. Results: At the second biopsy, a prostate adenocarcinoma histologic diagnosis was found in 22 of 90 cases (24.4%) in group A and in 41 of 90 cases (45.5%) in group B (P = 0.01). On a patient-by-patient basis, MRSI had 92.3% sensitivity, 88.2% specificity, 85.7% positive predictive value (PPV), 93.7% negative predictive value (NPV), and 90% accuracy; DCEMR had 84.6 % sensitivity, 82.3% specificity, 78.5% PPV, 87.5% NPV, and 83.3% accuracy; and the association MRSI plus DCEMR had 92.6% sensitivity, 88.8% specificity, 88.7% PPV, 92.7% NPV, and 90.7% accuracy, for predicting prostate cancer detection. Conclusions: The combination of MRSI and DCEMR showed the potential to guide biopsy to cancer foci in patients with previously negative TRUS biopsy. To avoid a potential bias, represented from having taken more samples in group B (mean of cores, 12.17) than in group A (10 cores), in the future a MRSI/DCEMR directed biopsy could be prospectively compared with a saturation biopsy procedure. Clin Cancer Res; 16(6); 1875–83

Multiparametric magnetic resonance imaging vs. standard care in men being evaluated for prostate cancer: A randomized study

OBJECTIVES To assess whether the proportion of men with clinically significant prostate cancer (PCa) is higher among men randomized to multiparametric magnetic resonance imaging (mp-MRI)/biopsy vs. those randomized to transrectal ultrasound (TRUS)-guided biopsy. METHODS In total, 1,140 patients with symptoms highly suggestive of PCa were enrolled and divided in 2 groups of 570 patients to follow 2 different diagnostic algorithms. Group A underwent a TRUS-guided random biopsy. Group B underwent an mp-MRI and a TRUS-guided targeted+random biopsy. The accuracy of mp-MRI in the diagnosis of PCa was calculated using prostatectomy as the standard of reference. RESULTS In group A, PCa was detected in 215 patients. The remaining 355 patients underwent an mp-MRI: the findings were positive in 208 and unremarkable in 147 patients. After the second random+targeted biopsy, PCa was detected in 186 of the 208 patients. In group B, 440 patients had positive findings on mp-MRI, and PCa was detected in 417 at first biopsy; 130 group B patients had unremarkable findings on both mp-MRI and biopsy. In the 130 group B patients with unremarkable findings on mp-MRI and biopsy, a PCa Gleason score of 6 or precancerous lesions were detected after saturation biopsy. mp-MRI showed an accuracy of 97% for the diagnosis of PCa. CONCLUSIONS The proportion of men with clinically significant PCa is higher among those randomized to mp-MRI/biopsy vs. those randomized to TRUS-guided biopsy; moreover, mp-MRI is a very reliable tool to identify patients to schedule in active surveillance.

Prostate cancer: 1HMRS-DCEMR at 3 T versus [(18)F]choline PET/CT in the detection of local prostate cancer recurrence in men with biochemical progression after radical retropubic prostatectomy (RRP)

OBJECTIVES This study compares proton magnetic resonancespectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined techniques at 3T magnet versus [(18)F]choline PET/computed tomography (CT) in the detection of local prostate cancer recurrence in patients with biochemical progression after radical retropubic prostatectomy (RRP). MATERIALS AND METHODS 84 consecutive patients at high risk of local recurrence underwent combined 1HMRSI-DCEMR and 18-Fcholine- PET/CT. MR scan protocol included turbo spin echo (TSE) T2-weighted sequences in the axial, sagittal and coronal planes; three-dimensional (3D) chemical shift imaging (CSI) sequences with spectral/spatial pulses optimized for quantitative detection of choline and citrate; dynamic contrast enhanced gradient-echo (GRE) T1-weighted sequence. The population was divided into two groups. Group A included 28 patients with a lesion size ranging between 5.00mm and 7.2mm and PSA reduction following radiation therapy. Group B included 56 patients with a lesion size between 7.6mm and 19.4mm. Sensitivity, specificity, positive predictive value (PPV) and accuracy were evaluated and receiver operating characteristic (ROC) curves were performed. RESULTS In Group A combined 1H-MRSI and DCE-MRI showed a sensitivity of 92%, a specificity of 75% (PPV 96%) while PET-CT examination showed a sensitivity of 62% and a specificity of 50% (PPV 88%) in identifying local recurrence. The accuracy of MRI was 89% while PET-CT showed an accuracy of 60%. Areas under the ROC curve (AUC) values for MR and PET-CT were 0.833 and 0.562, respectively. In Group B combined 1H-MRSI and DCEMR showed a sensitivity of 94% and a specificity of 100% (PPV 100%) with accuracy of 94%. PET-CT had a sensitivity of 92% and a specificity of 33% (PPV 98%) with accuracy of 91%. The AUCs for MR and PET-CT values were 0.971 and 0.837, respectively. CONCLUSION The diagnostic accuracy of combined 1HMRSI-DCEMR was higher than PET/CT to identify local prostate cancer recurrence, mostly in patients with low biochemical progression after RRP (0.2-2ng/mL).

Real-time magnetic resonance-guided high-intensity focused ultrasound focal therapy for localised prostate cancer: preliminary experience.

Five patients with unifocal, biopsy-proven prostate cancer (PCa) evident on multiparametric magnetic resonance imaging (MRI) were treated with magnetic resonance-guided focused ultrasound (MRgFUS) ablation before radical prostatectomy (RP). An endorectal probe featuring a phased-array focused ultrasound transducer was positioned for lesion ablation under MRI guidance. The tissue temperature and accumulation of thermal damage in the target zone was monitored during the procedure by MRI thermometry. Overlap between the ablation area and the devascularisation of the target lesion was evaluated by contrast-enhanced MRI performed immediately after treatment. The procedure was uneventful, and no adverse events were observed. RP was safely performed without significant surgical difficulties in relation to the previous MRgFUS treatment. The histopathology report showed extensive coagulative necrosis, with no residual tumour in the ablated area. Significant bilateral residual tumour, not evident on pretreatment MRI, was observed outside the treated area in two patients. MRgFUS ablation of focal localised PCa is feasible and, if confirmed in appropriate studies, could represent a valid option for the focal treatment of localised PCa.

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography–guided biopsy for prostate‐cancer detection in men with a raised prostate‐specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography–guided biopsy. Men in the MRI‐targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10‐to‐12–core, transrectal ultrasonography–guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI‐targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI‐targeted biopsy group, as compared with 64 of 248 (26%) in the standard‐biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI‐targeted biopsy group than in the standard‐biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, ‐13 percentage points; 95% CI, ‐19 to ‐7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI‐targeted biopsy was superior to standard transrectal ultrasonography–guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027.)

Pancreatic adenocarcinoma: combination of MR imaging, MR angiography and MR cholangiopancreatography for the diagnosis and assessment of resectability

Abstract. The purpose of this study was to determine the possibility of integrating MR cholangiopancreatography (MRCP) and MR angiography (MRA) to conventional MR images in the diagnosis and assessment of resectability of pancreatic adenocarcinoma. Twenty-three patients with pancreatic adenocarcinoma were prospectively examined with MR. Conventional MR images were acquired in all patients. Three-dimensional MRCP and MRA images were acquired in all patients with suspected biliary and vascular involvement. Acquisition time was less than 45 min in all cases. Images were independently evaluated by two radiologists, with final reading decided by consensus among readers. Diagnosis was confirmed with surgery in 16 patients and with percutaneous biopsy in 7. Concordance among readers was high with a kappa value of 0.83. Pancreatic adenocarcinoma was observed in all patients. Correct assessment of unresectability due to vascular involvement was found in 22 of 23 patients. Biliary obstruction was evident in 13 patients, involving the biliary and pancreatic ducts in 9 and the biliary ducts only in 4. Technical advances permit extensive use of MRI in the evaluation of abdominal pathologies. The combination of MR imaging, MRCP, and MRA can provide sufficient information for the diagnosis and assessment of resectability of pancreatic adenocarcinoma, which otherwise would require three different exams.

T1-weighted dual-echo MRI for fat quantification in pediatric nonalcoholic fatty liver disease

AIM To determine in obese children with nonalcoholic fatty liver disease (NAFLD) the accuracy of magnetic resonance imaging (MRI) in assessing liver fat concentration. METHODS A case-control study was performed. Cases were 25 obese children with biopsy-proven NAFLD. Controls were 25 obese children matched for age and gender, without NAFLD at ultrasonography and with normal levels of aminotransferases and insulin. Hepatic fat fraction (HFF) by MRI was obtained using a modification of the Dixon method. RESULTS HFF ranged from 2% to 44% [mean, 19.0% (95% CI, 15.1-27.4)] in children with NAFLD, while in the controls this value ranged from 0.08% to 4.69% [2.0% (1.3-2.5), P < 0.0001]. HFF was highly correlated with histological steatosis (r = 0.883, P < 0.0001) in the NAFLD children. According to the histological grade of steatosis, the mean HFF was 8.7% (95% CI, 6.0-11.6) for mild, 21.6% (15.3-27.0) for moderate, and 39.7% (34.4-45.0) for severe fatty liver infiltration. With a cutoff of 4.85%, HFF had a sensitivity of 95.8% for the diagnosis of histological steatosis ≥ 5%. All control children had HFF lower than 4.85%; thus, the specificity was 100%. After 12 mo, children with weight loss displayed a significant decrease in HFF. CONCLUSION MRI is an accurate methodology for liver fat quantification in pediatric NAFLD.

Reporting Magnetic Resonance Imaging in Men on Active Surveillance for Prostate Cancer: The PRECISE Recommendations—A Report of a European School of Oncology Task Force

BACKGROUND Published data on prostate magnetic resonance imaging (MRI) during follow-up of men on active surveillance are lacking. Current guidelines for prostate MRI reporting concentrate on prostate cancer (PCa) detection and staging. A standardised approach to prostate MRI reporting for active surveillance will facilitate the robust collection of evidence in this newly developing area. OBJECTIVE To develop preliminary recommendations for reporting of individual MRI studies in men on active surveillance and for researchers reporting the outcomes of cohorts of men having MRI on active surveillance. DESIGN, SETTING, AND PARTICIPANTS The RAND/UCLA Appropriateness Method was used. Experts in urology, radiology, and radiation oncology developed a set of 394 statements relevant to prostate MRI reporting in men on active surveillance for PCa. Each statement was scored for agreement on a 9-point scale by each panellist prior to a panel meeting. Each statement was discussed and rescored at the meeting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Measures of agreement and consensus were calculated for each statement. The most important statements, derived from both group discussion and scores of agreement and consensus, were used to create the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) checklist and case report form. RESULTS AND LIMITATIONS Key recommendations include reporting the index lesion size using absolute values at baseline and at each subsequent MRI. Radiologists should assess the likelihood of true change over time (ie, change in size or change in lesion characteristics on one or more sequences) on a 1-5 scale. A checklist of items for reporting a cohort of men on active surveillance was developed. These items were developed based on expert consensus in many areas in which data are lacking, and they are expected to develop and change as evidence is accrued. CONCLUSIONS The PRECISE recommendations are designed to facilitate the development of a robust evidence database for documenting changes in prostate MRI findings over time of men on active surveillance. If used, they will facilitate data collection to distinguish measurement error and natural variability in MRI appearances from true radiologic progression. PATIENT SUMMARY Few published reports are available on how to use and interpret magnetic resonance imaging for men on active surveillance for prostate cancer. The PRECISE panel recommends that data should be collected in a standardised manner so that natural variation in the appearance and measurement of cancer over time can be distinguished from changes indicating significant tumour progression.