Cancer Detection Rates of Systematic and Targeted Prostate Biopsies after Biparametric MRI.

OBJECTIVE: To compare prostate cancer detection rates (CDRs) and pathology results with targeted prostate biopsy (TB) and systematic prostate biopsy (SB) in biopsy-naive men. METHODS: An in-patient control study of 82 men undergoing SB and subsequent TB in case of positive prostate MRI between 2015 and 2017 in the Jeroen Bosch Hospital, the Netherlands. RESULTS: Prostate cancer (PCa) was detected in 54.9% with 70.7% agreement between TB and SB. Significant PCa (Gleason score ≥7) was detected in 24.4%. The CDR with TB and SB was 35.4% and 48.8%, respectively (p=0.052). The CDR of significant prostate cancer with TB and SB was both 20.7%. Clinically significant pathology upgrading occurred in 7.3% by adding TB to SB and 22.0% by adding SB to TB. CONCLUSIONS: There is no statistically significant difference between CDRs of SB and TB. Both SB and TB miss significant PCas. Moreover, pathology upgrading occurred more often by adding SB to TB than vice versa. This indicates that the omission of SB in this study population might not be justified.

Comparison of nodal risk formula and MR lymphography for predicting lymph node involvement in prostate cancer.

PURPOSE: To compare the nodal risk formula (NRF) as a predictor for lymph node (LN) metastasis in patients with prostate cancer with magnetic resonance lymphography (MRL) using Ultrasmall Super-Paramagnetic particles of Iron Oxide (USPIO) and with histology as gold standard. METHODS AND MATERIALS: Logistic regression analysis was performed with the results of histopathological evaluation of the LN as dependent variable and the nodal risk according to the NRF and the result of MRL as independent input variables. Receiver operating characteristic (ROC) analysis was performed to assess the performance of the models. RESULTS: The analysis included 375 patients. In the single-predictor regression models, the NRF and MRL results were both significantly (p<0.001) predictive of the presence of LN metastasis. In the models with both predictors included, NRF was nonsignificant (p=0.126), but MRL remained significant (p<0.001). For NRF, sensitivity was 0.79 and specificity was 0.38; for MRL, sensitivity was 0.82 and specificity was 0.93. After a negative MRL result, the probability of LN metastasis is 4% regardless of the NRF result. After a positive MRL, the probability of having LN metastasis is 68%. CONCLUSIONS: MRL is a better predictor of the presence of LN metastasis than NRF. Using only the NRF can lead to a significant overtreatment on the pelvic LN by radiation therapy. When the MRL result is available, the NRF is no longer of added value.

In vivo imaging of the aneurysm wall with MRI and a macrophage-specific contrast agent.

OBJECTIVE: Because of their capability of secreting proteinases, macrophages play a central role in the growth and rupture of aneurysms. Noninvasive imaging of macrophages therefore may yield valuable information about the pathogenesis of aneurysm disease. We studied uptake of the macrophage-specific contrast agent ultrasmall paramagnetic iron oxide (USPIO) in the walls of aneurysms and normal-sized aortas. MATERIALS AND METHODS: Six patients with an aortic and five patients with an iliac aneurysm and 11 age-matched controls were identified in a database of 239 patients who underwent evaluations for the staging of prostate cancer. USPIO-enhanced MRI and contrast-enhanced MDCT were performed for all patients. The presence of USPIO was assessed with an iron-sensitive MRI sequence. Quantification consisted of counting the number of quadrants with USPIO-induced subendothelial signal voids. A chi-square test was used to analyze the significance of the difference between the number of USPIO-positive quadrants in the aneurysm group and that in the control group. RESULTS: The number of USPIO-positive quadrants was significantly higher in the aneurysm than in the control group: 158 quadrants (4.2%) in the aneurysm group and 13 quadrants (0.4%) in the control group (p < 0.001). Two abdominal aortic aneurysms accounted for 90% (154/171) of all USPIO-positive quadrants. CONCLUSION: USPIO uptake is limited or absent in the wall of normal-sized aortas and most aneurysms. However, individual abdominal aortic aneurysms exhibit high levels of USPIO uptake, indicative of extensive macrophage infiltration in the aneurysm wall. Future research should focus on the predictive value of USPIO uptake for growth and rupture of aneurysms.

Cost-effectiveness of MR lymphography for the detection of lymph node metastases in patients with prostate cancer.

PURPOSE: To apply a decision analytic model to determine whether the addition of magnetic resonance (MR) lymphography to the diagnostic workup of patients with intermediate or high probability of lymph node metastases is cost effective from a health care perspective. MATERIALS AND METHODS: The data that were used for the decision analytic model were obtained from an empiric study population of 375 patients. As the input of the decision analytic model was made given prospective patient data from several hospitals, the ethics review board of each hospital approved the study. Written consent was obtained from all patients. To investigate possible differences between strategies that utilize MR lymphography and those that do not (pelvic lymph node dissection [PLND]), two outcome measures were examined and combined in an incremental cost-effectiveness ratio (ICER) of health care resources consumed and quality-adjusted life-years (QALYs). Probabilistic and one-way sensitivity analyses were performed. RESULTS: The PLND strategy is dominated by the MR lymphography strategy. Probabilistic sensitivity analysis showed that in 63% of simulations, MR lymphography was cost saving and resulted in better patient outcome for patients with prostate cancer and intermediate or high probability of lymph node metastases. The probability of MR lymphography being inferior (more expensive and worse patient outcome) is less than 3%. CONCLUSION: MR lymphography is an efficient strategy in the detection of lymph node metastases of prostate cancer when compared with the PLND strategy.

Prostate cancer: detection of lymph node metastases outside the routine surgical area with ferumoxtran-10-enhanced MR imaging.

PURPOSE: To prospectively evaluate the feasibility of magnetic resonance (MR) imaging with ferumoxtran-10 in patients with prostate cancer to depict lymph node metastases outside the routine pelvic lymph node dissection (PLND) area. MATERIALS AND METHODS: The study was approved by the institutional review boards at all four hospitals; patients provided written informed consent. Two hundred ninety-six consecutive men (mean age, 67 years; range, 47-83 years) with prostate cancer and an intermediate-to-high risk for nodal metastases (prostate-specific antigen level >10 ng/mL, Gleason score >6, or stage T3 disease) were enrolled. MR lymphography of the pelvis was performed 24 hours after intravenous drip infusion of ferumoxtran-10. Positive nodes at MR lymphography were indicated to be inside or outside the routine dissection area (RDA). On the basis of MR lymphography computed tomographic (CT)-guided biopsy, routine PLND, or MR imaging-guided minimal extended PLND was performed. RESULTS: MR lymphography findings were positive in 58 patients. Of these, 44 had histopathologic confirmation of lymph node metastases. In 18 of 44 patients (41%), MR lymphography findings showed nodes exclusively outside the RDA, which were confirmed with MR lymphography-guided extended PLND (n = 13) and CT-guided biopsy (n = 5). In another 18 patients (41%), positive nodes were located both inside and outside the RDA at MR lymphography. In these 18 patients, routine PLND was used to confirm the nodes inside the RDA (n = 11); CT-guided biopsy was used to confirm nodes outside the RDA (n = 7). In the remaining eight patients, MR lymphography findings showed only nodes inside the RDA, which was confirmed with PLND (n = 5) and CT-guided biopsy (n = 3). In 14 of the 58 patients (24%), there was no histologic confirmation. CONCLUSION: In 41% of patients with prostate cancer, nodal metastases outside the area of routine PLND were detected by using MR imaging with ferumoxtran-10.

MRI with a lymph-node-specific contrast agent as an alternative to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study.

BACKGROUND: In patients with prostate cancer who are deemed to be at intermediate or high risk of having nodal metastases, invasive diagnostic pelvic lymph-node dissection (PLND) is the gold standard for the detection of nodal disease. However, a new lymph-node-specific MR-contrast agent ferumoxtran-10 can detect metastases in normal-sized nodes (ie, <8 mm in size) by use of MR lymphoangiography (MRL). In this prospective, multicentre cohort study, we aimed to compare the diagnostic accuracy of MRL with up-to-date multidetector CT (MDCT), and test the hypothesis that a negative MRL finding obviates the need for a PLND. METHODS: We included consecutive patients with prostate cancer who had an intermediate or high risk (risk of >5% according to routinely used nomograms) of having lymph-node metastases. All patients were assessed by MDCT and MRL, and underwent PLND or fine-needle aspiration biopsy. Imaging results were correlated with histopathology. The primary outcomes were sensitivity, specificity, accuracy, NPV, and PPV of MRL and MDCT. This study is registered with ClinicalTrials.gov, number NCT00185029. FINDINGS: The study was done in 11 hospitals in the Netherlands between April 8, 2003, and April 19, 2005. 375 consecutive patients were included. 61 of 375 (16%) patients had lymph-node metastases. Sensitivity was 34% (21 of 61; 95% CI 23-48) for MDCT and 82% (50 of 61; 70-90) for MRL (McNemar's test p<0.05). Specificity was 97% (303 of 314; 94-98) for MDCT and 93% (291 of 314; 89-95) for MRL. Positive predictive value (PPV) was 66% (21 of 32; 47-81) for MDCT and 69% (50 of 73; 56-79) for MRL. Negative predictive value (NPV) was 88% (303 of 343; 84-91) for MDCT and 96% (291 of 302; 93-98) for MRL (McNemar's test p<0.05). Of the 61 patients with lymph-node metastases, 50 were detected by MRL, of which 40 (80%) had metastases in normal-sized lymph nodes. The high sensitivity and NPV of MRL imply that in patients with a negative MRL, the chance of positive lymph nodes is less than 11/302 (4%). INTERPRETATION: MRL had significantly higher sensitivity and NPV than MDCT for patients with prostate cancer who had intermediate or high risk of having lymph-node metastases. In such patients, after a negative MRL, the post-test probability of having lymph-node metastases is low enough to omit a PLND.

Prostate and lymph node proton magnetic resonance (MR) spectroscopic imaging with external array coils at 3 T to detect recurrent prostate cancer after radiation therapy.

In a patient suspected of having recurrent prostate cancer after radiation therapy, we demonstrate the feasibility of noninvasive proton magnetic resonance spectroscopic (1H-MRS) imaging of the prostate and a lymph node at 3 T using a matrix of external surface coils. Written informed consent was obtained from the patient. With 1H-MRS imaging, high choline with low citrate signal was observed in the prostate, and in the lymph node a signal of choline-containing compounds was identified. The tissue level of the compounds in the enlarged lymph node was estimated to be 8.1 mmol/kg water. Subsequent histopathological analysis of systematic transrectal ultrasound-guided prostate biopsy and computed tomography-guided biopsy of the lymph node confirmed the presence of prostate cancer in both.

Prostate cancer evaluated with ferumoxtran-10-enhanced T2*-weighted MR Imaging at 1.5 and 3.0 T: early experience.

PURPOSE: To prospectively evaluate the feasibility of ferumoxtran-10-enhanced magnetic resonance (MR) imaging at high magnetic field strength (3.0 T) and to compare image quality between 1.5- and 3.0-T MR imaging in terms of lymph node detection in patients with prostate cancer. MATERIALS AND METHODS: This study was institutional review board approved, and all patients gave written informed consent. Forty-eight consecutive patients aged 51-79 years (mean, 65.5 years) with prostate cancer were enrolled. T2*-weighted 1.5- and 3.0-T MR images of the pelvis were acquired in a sagittal plane parallel to the psoas muscle 24 hours after ferumoxtran-10 administration. A pelvic and body phased-array coil was used and yielded an in-plane resolution of 0.56 x 0.56 x 3.00 mm at 1.5 T and 0.50 x 0.50 x 2.50 mm at 3.0 T. All images were evaluated by three readers for total image quality, lymph node border delineation, muscle-fat contrast, and vessel-fat contrast. Statistical significance was calculated by using the Mann-Whitney U test. Subsequently, the general linear mixed model was used to estimate the contributions of three factors-patient, reader, and technique-to the variability of the imaging results. RESULTS: Significantly (P < .05) better muscle-fat contrast, vessel-fat contrast, lymph node border delineation, and total image quality were observed at 3.0-T MR imaging. The general linear mixed model revealed that the variability of all results could be attributed to the use of 3.0-T imaging. CONCLUSION: Ferumoxtran-10-enhanced MR imaging can be performed at high magnetic field strengths and result in improved image quality, which may lead to improved detection of small positive lymph nodes.

Cost-analysis of staging methods for lymph nodes in patients with prostate cancer: MRI with a lymph node-specific contrast agent compared to pelvic lymph node dissection or CT.

The aim of this study was to compare the costs of three strategies in patients with prostate cancer in a specific setting: firstly, a strategy including MR lymphography (MRL) in which pelvic lymph node dissection (PLND) is foregone in case of a negative result. The second strategy involves computed tomography (CT) followed by a biopsy or PLND. The third strategy consists of PLND without imaging beforehand. A decision analytic model was constructed. This model represented the diagnostic process for patients with prostate cancer and intermediate or high risk for nodal metastases, comparing the costs of the three strategies. Cost analysis was done from the health care perspective. The model indicated that the expected costs for the MRL strategy were 2,527 euro. The expected costs for the strategy using CT were 3,837 euro and for PLND 3,994 euro. These results show that potential savings performing MRL instead of CT were 1,310 euro and 1,467 euro for PLND. Sensitivity analyses show that variation in costs of PLND was most influential on the costs of all strategies. However, the overall savings pattern did not alter. Average costs of MRL staging in our institution are less than for CT and PLND in staging lymph nodes of patients with prostate cancer and who are intermediate or high risk for nodal metastases.