Faculty Bibliography

CONTEXT:Comparative reviews of whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography/computed tomography (CT; with different radiotracers) have shown that metastasis detection in advanced cancers is more accurate than with currently used CT and bone scans. However, the ability of WB-MRI and positron emission tomography/CT to assess therapeutic benefits has not been comprehensively evaluated. There is also considerable variability in the availability and quality of WB-MRI, which is an impediment to clinical development. Expert recommendations for standardising WB-MRI scans are needed, in order to assess its performance in advanced prostate cancer (APC) clinical trials. OBJECTIVE:To design recommendations that promote standardisation and diminish variations in the acquisition, interpretation, and reporting of WB-MRI scans for use in APC. EVIDENCE ACQUISITION:An international expert panel of oncologic imagers and oncologists with clinical and research interests in APC management assessed biomarker requirements for clinical care and clinical trials. Key requirements for a workable WB-MRI protocol, achievable quality standards, and interpretation criteria were identified and synthesised in a white paper. EVIDENCE SYNTHESIS:The METastasis Reporting and Data System for Prostate Cancer guidelines were formulated for use in all oncologic manifestations of APC. CONCLUSIONS:Uniformity in imaging data acquisition, quality, and interpretation of WB-MRI are essential for assessing the test performance of WB-MRI. The METastasis Reporting and Data System for Prostate Cancer standard requires validation in clinical trials of treatment approaches in APC. PATIENT SUMMARY:METastasis Reporting and Data System for Prostate Cancer represents the consensus recommendations on the performance, quality standards, and reporting of whole-body magnetic resonance imaging, for use in all oncologic manifestations of advanced prostate cancer. These new criteria require validation in clinical trials of established and new treatment approaches in advanced prostate cancer.

OBJECTIVE:To investigate the multiparametric prostate magnetic resonance imaging (mpMRI) findings in patients treated with testosterone replacement therapy (TRT) while on active surveillance for low-risk prostate cancer. METHODS:We retrospectively reviewed 12 patients who underwent mpMRI before and after TRT while on active surveillance. Changes in serum testosterone level, prostate-specific antigen (PSA), prostate biopsy findings, prostate volume, and Prostate Imaging Reporting and Data System Version 2 (PI-RADSv2) score before and after TRT were summarized. RESULTS:). In total, 2 patients had biopsy progression during the study period. The PI-RADSv2 scores before and after TRT were unchanged in 10/12 patients; none of these demonstrated biopsy progression on post-TRT. The PI-RADSv2 scores increased after TRT in 2/12 patients; both showed Gleason score upgrade on follow-up biopsy. Of these 2 patients, 1 patient underwent radical treatment due to clinical progression. The area under the curve for detecting biopsy progression calculated from PI-RADSv2 score after TRT was 0.90, which was better than that calculated from post-TRT PSA level (0.48). CONCLUSIONS:After TRT, mpMRI findings remained stable in patients without biopsy progression, whereas PI-RADSv2 score increase was identified in patients with Gleason score upgrade on follow-up biopsy.

IMPORTANCE/OBJECTIVE:A critical decision in the management of metastatic castration-resistant prostate cancer (mCRPC) is when to administer an androgen receptor signaling (ARS) inhibitor or a taxane. OBJECTIVE:To determine if pretherapy nuclear androgen-receptor splice variant 7 (AR-V7) protein expression and localization on circulating tumor cells (CTCs) is a treatment-specific marker for response and outcomes between ARS inhibitors and taxanes. DESIGN, SETTING, AND PARTICIPANTS/METHODS:For this cross-sectional cohort study at Memorial Sloan Kettering Cancer Center, 265 men with progressive mCRPC undergoing a change in treatment were considered; 86 were excluded because they were not initiating ARS or taxane therapy; and 18 were excluded for processing time constraints, leaving 161 patients for analysis. Between December 2012 and March 2015, blood was collected and processed from patients with progressive mCRPC immediately prior to new line of systemic therapy. Patients were followed up to 3 years. MAIN OUTCOMES AND MEASURES/METHODS:Prostate-specific antigen (PSA) response, time receiving therapy, radiographic progression-free survival (rPFS), and overall survival (OS). RESULTS:Overall, of 193 prospectively collected blood samples from 161 men with mCRPC, 191 were evaluable (128 pre-ARS inhibitor and 63 pretaxane). AR-V7-positive CTCs were found in 34 samples (18%), including 3% of first-line, 18% of second-line, and 31% of third- or greater line samples. Patients whose samples had AR-V7-positive CTCs before ARS inhibition had resistant posttherapy PSA changes (PTPC), shorter rPFS, shorter time on therapy, and shorter OS than those without AR-V7-positive CTCs. Overall, resistant PTPC were seen in 65 of 112 samples (58%) without detectable AR-V7-positive CTCs prior to ARS inhibition. There were statistically significant differences in OS but not in PTPC, time on therapy, or rPFS for patients with or without pretherapy AR-V7-positive CTCs treated with a taxane. A multivariable model adjusting for baseline factors associated with survival showed superior OS with taxanes relative to ARS inhibitors when AR-V7-positive CTCs were detected pretherapy (hazard ratio, 0.24; 95% CI, 0.10-0.57; P = .035). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:The results validate CTC nuclear expression of AR-V7 protein in men with mCRPC as a treatment-specific biomarker that is associated with superior survival on taxane therapy over ARS-directed therapy in a clinical practice setting. Continued examination of this biomarker in prospective studies will further aid clinical utility.

PURPOSE:Accurate identification of the source of a detectable serum prostate-specific antigen (PSA) in the postprostatectomy setting is a major challenge among the urologic community. The aim of this study was to assess positivity rates of imaging examinations performed in patients with early PSA rise after prostatectomy and to summarize the management strategies adopted in this clinical scenario. METHODS:F-sodium fluoride-PET/CT at a single tertiary cancer center. Imaging results were summarized per modality and compared with pathology findings. RESULTS:Pelvic MRI was positive in 15/142 (11%) patients (14 patients with local recurrence in the surgical bed and 1 patient with pelvic osseous metastases). Of these 15, 10 patients underwent additional imaging examinations; none revealed positive findings. Of the 127 patients with negative pelvic MRI, 54 (43%) underwent additional imaging examinations; only 1/54 had positive findings (false-positive T8 lesion on bone scintigraphy and FDG-PET/CT; biopsy was negative for cancer). Overall, 12/16 patients with positive imaging findings and 75/126 (60%) patients with negative imaging received treatment (radiation, hormones or chemotherapy). CONCLUSION:The conventional imaging identified sites of disease, almost always in the form of local recurrence, in a minority of patients with early PSA rise postprostatectomy.

PURPOSE/OBJECTIVE:We compared the diagnostic outcomes of magnetic resonance-ultrasound fusion and visually targeted biopsy for targeting regions of interest on prostate multiparametric magnetic resonance imaging. MATERIALS AND METHODS/METHODS:Patients presenting for prostate biopsy with regions of interest on multiparametric magnetic resonance imaging underwent magnetic resonance imaging targeted biopsy. For each region of interest 2 visually targeted cores were obtained, followed by 2 cores using a magnetic resonance-ultrasound fusion device. Our primary end point was the difference in the detection of high grade (Gleason 7 or greater) and any grade cancer between visually targeted and magnetic resonance-ultrasound fusion, investigated using McNemar's method. Secondary end points were the difference in detection rate by biopsy location using a logistic regression model and the difference in median cancer length using the Wilcoxon signed rank test. RESULTS:We identified 396 regions of interest in 286 men. The difference in the detection of high grade cancer between magnetic resonance-ultrasound fusion biopsy and visually targeted biopsy was -1.4% (95% CI -6.4 to 3.6, p=0.6) and for any grade cancer the difference was 3.5% (95% CI -1.9 to 8.9, p=0.2). Median cancer length detected by magnetic resonance-ultrasound fusion and visually targeted biopsy was 5.5 vs 5.8 mm, respectively (p=0.8). Magnetic resonance-ultrasound fusion biopsy detected 15% more cancers in the transition zone (p=0.046) and visually targeted biopsy detected 11% more high grade cancer at the prostate base (p=0.005). Only 52% of all high grade cancers were detected by both techniques. CONCLUSIONS:We found no evidence of a significant difference in the detection of high grade or any grade cancer between visually targeted and magnetic resonance-ultrasound fusion biopsy. However, the performance of each technique varied in specific biopsy locations and the outcomes of both techniques were complementary. Combining visually targeted biopsy and magnetic resonance-ultrasound fusion biopsy may optimize the detection of prostate cancer.

Purpose To determine the diagnostic performance of intravoxel incoherent motion (IVIM) parameters and apparent diffusion coefficient (ADC) to assess response to combined chemotherapy and radiation therapy (CRT) in patients with rectal cancer by using histogram analysis derived from whole-tumor volumes and single-section regions of interest (ROIs). Materials and Methods The institutional review board approved this retrospective study of 31 patients with rectal cancer who underwent magnetic resonance (MR) imaging before and after CRT, including diffusion-weighted imaging with 34 b values prior to surgery. Patient consent was not required. ADC, perfusion-related diffusion fraction (f), slow diffusion coefficient (D), and fast diffusion coefficient (D*) were calculated on MR images acquired before and after CRT by using biexponential fitting. ADC and IVIM histogram metrics and median values were obtained by using whole-tumor volume and single-section ROI analyses. All ADC and IVIM parameters obtained before and after CRT were compared with histopathologic findings by using t tests with Holm-Sidak correction. Receiver operating characteristic curves were generated to evaluate the diagnostic performance of IVIM parameters derived from whole-tumor volume and single-section ROIs for prediction of histopathologic response. Results Extreme values aside, results of histogram analysis of ADC and IVIM were equivalent to median values for tumor response assessment (P > .06). Prior to CRT, none of the median ADC and IVIM diffusion metrics correlated with subsequent tumor response (P > .36). Median D and ADC values derived from either whole-volume or single-section analysis increased significantly after CRT (P ≤ .01) and were significantly higher in good versus poor responders (P ≤ .02). Median IVIM f and D* values did not significantly change after CRT and were not associated with tumor response to CRT (P > .36). Interobserver agreement was excellent for whole-tumor volume analysis (range, 0.91-0.95) but was only moderate for single-section ROI analysis (range, 0.50-0.63). Conclusion Median D and ADC values obtained after CRT were useful for discrimination between good and poor responders. Histogram metrics did not add to the median values for assessment of tumor response. Volumetric analysis demonstrated better interobserver reproducibility when compared with single-section ROI analysis. (©) RSNA, 2016 Online supplemental material is available for this article.

PURPOSE/OBJECTIVE:We determined whether multiparametric magnetic resonance imaging targeted biopsies may replace systematic biopsies to detect higher grade prostate cancer (Gleason score 7 or greater) and whether biopsy may be avoided based on multiparametric magnetic resonance imaging among men with Gleason 3+3 prostate cancer on active surveillance. MATERIALS AND METHODS/METHODS:We identified men with previously diagnosed Gleason score 3+3 prostate cancer on active surveillance who underwent multiparametric magnetic resonance imaging and a followup prostate biopsy. Suspicion for higher grade cancer was scored on a standardized 5-point scale. All patients underwent a systematic biopsy. Patients with multiparametric magnetic resonance imaging regions of interest also underwent magnetic resonance imaging targeted biopsy. The detection rate of higher grade cancer was estimated for different multiparametric magnetic resonance imaging scores with the 3 biopsy strategies of systematic, magnetic resonance imaging targeted and combined. RESULTS:Of 206 consecutive men on active surveillance 135 (66%) had a multiparametric magnetic resonance imaging region of interest. Overall, higher grade cancer was detected in 72 (35%) men. A higher multiparametric magnetic resonance imaging score was associated with an increased probability of detecting higher grade cancer (Wilcoxon-type trend test p <0.0001). Magnetic resonance imaging targeted biopsy detected higher grade cancer in 23% of men. Magnetic resonance imaging targeted biopsy alone missed higher grade cancers in 17%, 12% and 10% of patients with multiparametric magnetic resonance imaging scores of 3, 4 and 5, respectively. CONCLUSIONS:Magnetic resonance imaging targeted biopsies increased the detection of higher grade cancer among men on active surveillance compared to systematic biopsy alone. However, a clinically relevant proportion of higher grade cancer was detected using only systematic biopsy. Despite the improved detection of disease progression using magnetic resonance imaging targeted biopsy, systematic biopsy cannot be excluded as part of surveillance for men with low risk prostate cancer.