Faculty Bibliography

PURPOSE: To explore the role of whole-lesion apparent diffusion coefficient (ADC) analysis for predicting outcomes in prostate cancer patients on active surveillance. METHODS: This study included 72 prostate cancer patients who underwent MRI-ultrasound fusion-targeted biopsy at the initiation of active surveillance, had a visible MRI lesion in the region of tumor on biopsy, and underwent 3T baseline and follow-up MRI examinations separated by at least one year. Thirty of the patients also underwent an additional MRI-ultrasound fusion-targeted biopsy after the follow-up MRI. Whole-lesion ADC metrics and lesion volumes were computed from 3D whole-lesion volumes-of-interest placed on lesions on the baseline and follow-up ADC maps. The percent change in lesion volume on the ADC map between the serial examinations was computed. Statistical analysis included unpaired t tests, ROC analysis, and Fisher's exact test. RESULTS: Baseline mean ADC, ADC0-10th-percentile, ADC10-25th-percentile, and ADC25-50th-percentile were all significantly lower in lesions exhibiting >/=50% growth on the ADC map compared with remaining lesions (all P /=50% growth observed for ADC0-10th-percentile (585 +/- 308 vs. 911 +/- 336; P = 0.001). ADC0-10th-percentile achieved highest performance for predicting >/=50% growth (AUC = 0.754). Mean percent change in tumor volume on the ADC map was 62.3% +/- 26.9% in patients with GS >/= 3 + 4 on follow-up biopsy compared with 3.6% +/- 64.6% in remaining patients (P = 0.050). CONCLUSION: Our preliminary results suggest a role for 3D whole-lesion ADC analysis in prostate cancer active surveillance.

OBJECTIVE: To describe a novel technique of robotic inguinal lymphadenectomy with near infrared fluorescence imaging (NIRF) using indocyanine green (ICG) to facilitate lymph node identification during robotic groin dissection for penile cancer. MATERIALS AND METHODS: The patient is placed in lithotomy position with access to the groin. Three robotic ports and 1 assist port are placed in a V configuration below the tip of femoral triangle. Intradermal ICG is injected at the base of the penis (0.5 mL of 2 mg/kg concentration in normal saline), and the lymphatic channels and nodes are visualized using NIRF in the robotic console approximately 15 minutes after injection. The surgical template established in the open approach is then replicated using NIRF to ensure complete resection of the affected nodes. RESULTS: A total of 10 groin dissections in 5 patients have been completed using this technique, with an average lymph node yield of 7 per groin (range 5-13 lymph nodes). Mean operative time per groin was 207 minutes (range 164-258 minutes) and estimated blood loss was 38 mL (range 25-50 mL). Mean length of hospital stay was 1.8 days (range 0-4 days). Identification of the lymphatic drainage pattern from the superficial to deep groin nodes to pelvic nodes underneath the inguinal ligament was identified in all patients. With a mean follow-up of 10 months (range 3-16 months), there have been no postoperative infections, lymphatic leaks, wound breakdown, or necrosis. Pathologically involved lymph nodes were identified using NIRF. CONCLUSION: Our novel technique of robotic inguinal lymphadenectomy with fluorescence lymphangiography allows for identification and excision of both superficial and deep groin nodes with a significant reduction in morbidity compared with the open approach. Prospective studies are required to ensure long-term efficacy and results of this procedure.

Importance: Potential survival benefits from treating aggressive (Gleason score, >/=7) early-stage prostate cancer are undermined by harms from unnecessary prostate biopsy and overdiagnosis of indolent disease. Objective: To evaluate the a priori primary hypothesis that combined measurement of PCA3 and TMPRSS2:ERG (T2:ERG) RNA in the urine after digital rectal examination would improve specificity over measurement of prostate-specific antigen alone for detecting cancer with Gleason score of 7 or higher. As a secondary objective, to evaluate the potential effect of such urine RNA testing on health care costs. Design, Setting, and Participants: Prospective, multicenter diagnostic evaluation and validation in academic and community-based ambulatory urology clinics. Participants were a referred sample of men presenting for first-time prostate biopsy without preexisting prostate cancer: 516 eligible participants from among 748 prospective cohort participants in the developmental cohort and 561 eligible participants from 928 in the validation cohort. Interventions/Exposures: Urinary PCA3 and T2:ERG RNA measurement before prostate biopsy. Main Outcomes and Measures: Presence of prostate cancer having Gleason score of 7 or higher on prostate biopsy. Pathology testing was blinded to urine assay results. In the developmental cohort, a multiplex decision algorithm was constructed using urine RNA assays to optimize specificity while maintaining 95% sensitivity for predicting aggressive prostate cancer at initial biopsy. Findings were validated in a separate multicenter cohort via prespecified analysis, blinded per prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) criteria. Cost effects of the urinary testing strategy were evaluated by modeling observed biopsy results and previously reported treatment outcomes. Results: Among the 516 men in the developmental cohort (mean age, 62 years; range, 33-85 years) combining testing of urinary T2:ERG and PCA3 at thresholds that preserved 95% sensitivity for detecting aggressive prostate cancer improved specificity from 18% to 39%. Among the 561 men in the validation cohort (mean age, 62 years; range, 27-86 years), analysis confirmed improvement in specificity (from 17% to 33%; lower bound of 1-sided 95% CI, 0.73%; prespecified 1-sided P = .04), while high sensitivity (93%) was preserved for aggressive prostate cancer detection. Forty-two percent of unnecessary prostate biopsies would have been averted by using the urine assay results to select men for biopsy. Cost analysis suggested that this urinary testing algorithm to restrict prostate biopsy has greater potential cost-benefit in younger men. Conclusions and Relevance: Combined urinary testing for T2:ERG and PCA3 can avert unnecessary biopsy while retaining robust sensitivity for detecting aggressive prostate cancer with consequent potential health care cost savings.

OBJECTIVE: Prior studies in prostate diffusion-weighted magnetic resonance imaging (MRI) have largely explored the impact of b-value and diffusion directions on estimated diffusion coefficient D. Here we suggest varying diffusion time, t, to study time-dependent D(t) in prostate cancer, thereby adding an extra dimension in the development of prostate cancer biomarkers. METHODS: Thirty-eight patients with peripheral zone prostate cancer underwent 3-T MRI using an external-array coil and a diffusion-weighted image sequence acquired for b = 0, as well as along 12 noncollinear gradient directions for b = 500 s/mm using stimulated echo acquisition mode (STEAM) diffusion tensor imaging (DTI). For this sequence, 6 diffusion times ranging from 20.8 to 350 milliseconds were acquired. Tumors were classified as low-grade (Gleason score [GS] 3 + 3; n = 11), intermediate-grade (GS 3 + 4; n = 16), and high-grade (GS >/=4 + 3; n = 11). Benign peripheral zone and transition zone were also studied. RESULTS: Apparent diffusion coefficient (ADC) D(t) decreased with increasing t in all zones of the prostate, though the rate of decay in D(t) was different between sampled zones. Analysis of variance and area under the curve analyses suggested better differentiation of tumor grades at shorter t. Fractional anisotropy (FA) increased with t for all regions of interest. On average, highest FA was observed within GS 3 + 3 tumors. CONCLUSIONS: There is a measurable time dependence of ADC in prostate cancer, which is dependent on the underlying tissue and Gleason score. Therefore, there may be an optimal selection of t for prediction of tumor grade using ADC. Controlling t should allow ADC to achieve greater reproducibility between different sites and vendors. Intentionally varying t enables targeted exploration of D(t), a previously overlooked biophysical phenomenon in the prostate. Its further microstructural understanding and modeling may lead to novel diffusion-derived biomarkers.

Purpose To compare standard diffusion-weighted (DW) imaging and diffusion kurtosis (DK) imaging for prostate cancer (PC) detection and characterization in a large patient cohort, with attention to the potential added value of DK imaging. Materials and Methods This retrospective institutional review board-approved study received a waiver of informed consent. Two hundred eighty-five patients with PC underwent 3.0-T phased-array coil prostate magnetic resonance (MR) imaging, including a DK imaging sequence (b values 0, 500, 1000, 1500, and 2000 sec/mm2) before prostatectomy. Maps of apparent diffusion coefficient (ADC) and diffusional kurtosis (K) were derived by using maximal b values of 1000 and 2000 sec/mm2, respectively. Mean ADC and K were obtained from volumes of interest (VOIs) placed on each patient's dominant tumor and benign prostate tissue. Metrics were compared between benign and malignant tissue, between Gleason score (GS) /= 3 + 4 tumors, and between GS /= 4 + 3 tumors by using paired t tests, analysis of variance, receiver operating characteristic (ROC) analysis, and exact tests. Results ADC and K showed significant differences for benign versus tumor tissues, GS /= 3 + 4 tumors, and GS /= 4 + 3 tumors (P < .001 for all). ADC and K were highly correlated (r = -0.82; P < .001). Area under the ROC curve was significantly higher (P = .002) for ADC (0.921) than for K (0.902) for benign versus malignant tissue but was similar for GS /= 3 + 4 tumors (0.715-0.744) and GS /= 4 + 3 tumors (0.694-0.720) (P > .15). ADC and K were concordant for these various outcomes in 80.0%-88.6% of patients; among patients with discordant results, ADC showed better performance than K for GS /= 4 + 3 tumors (P = .016) and was similar to K for other outcomes (P > .136). Conclusion ADC and K were highly correlated, had similar diagnostic performance, and were concordant for the various outcomes in the large majority of cases. These observations did not show a clear added value of DK imaging compared with standard DW imaging for clinical PC evaluation. (c) RSNA, 2017 Online supplemental material is available for this article.