Faculty Bibliography

BACKGROUND:Several consensus statements recommend serial serum prostate-specific antigen (PSA), multi parametric magnetic resonance imaging (mpMRI), and prostate biopsy following partial gland ablation. We determined the rate of persistent in-field disease following primary partial gland cryo-ablation and whether PSA or mpMRI are reliable predictors of in-field disease persistence. METHODS:Between March 2017 and July 2019, subjects meeting eligibility criteria for partial gland cryoablation were enrolled into an IRB approved outcomes registry. PSA, mpMRI, and prostate biopsy (four cores targeting the ablation zone + six ipsilateral systematic cores) were performed per protocol 6 months following intervention. Binary logistic regression was employed to calculate odds ratio (OR) of PSA decrease, and suspicious mpMRI effect on cancer persistence. The performance of mpMRI for predicting in-field persistence of PCa was evaluated by area under the receiver operation characteristics curve (AUC). RESULTS:Of the 83 eligible men undergoing partial gland cryoablation, 70 (84.3%) underwent 6-month protocol prostate biopsy. Five (7.1%) biopsies exhibited any in-field disease persistence. Only one (1.4%) of these cancers was Gleason grade > 1. Neither PSA decrease or suspicious mpMRI reliably predicted cancer persistence, with OR of 1.6 (0.25-8.6) and 1.5 (0.02-1.3), respectively. AUC of mpMRI for predicting in-field disease persistence was 0.554. CONCLUSIONS:In this cohort of patients undergoing partial gland cryo-ablation, the incidence of persistent disease was low. PSA and mpMRI were not reliable predictors of in-field disease persistence. Based on these data, consideration may be given to deferring early follow-up biopsy in appropriate patients.

PURPOSE/OBJECTIVE:This study reports on the development of a novel 3D procedure planning technique to provide pre-ablation treatment planning for partial gland prostate cryoablation (cPGA). METHODS:Twenty men scheduled for partial gland cryoablation (cPGA) underwent pre-operative image segmentation and 3D modeling of the prostatic capsule, index lesion, urethra, rectum, and neurovascular bundles based upon multi-parametric MRI data. Pre-treatment 3D planning models were designed including virtual 3D cryotherapy probes to predict and plan cryotherapy probe configuration needed to achieve confluent treatment volume. Treatment efficacy was measured with 6 month post-operative MRI, serum prostate specific antigen (PSA) at 3 and 6 months, and treatment zone biopsy results at 6 months. Outcomes from 3D planning were compared to outcomes from a series of 20 patients undergoing cPGA using traditional 2D planning techniques. RESULTS:Forty men underwent cPGA. The median age of the cohort undergoing 3D treatment planning was 64.8 years with a median pretreatment PSA of 6.97 ng/mL. The Gleason grade group (GGG) of treated index lesions in this cohort included 1 (5%) GGG1, 11 (55%) GGG2, 7 (35%) GGG3, and 1 (5%) GGG4. Two (10%) of these treatments were post-radiation salvage therapies. The 2D treatment cohort included 20 men with a median age of 68.5 yrs., median pretreatment PSA of 6.76 ng/mL. The Gleason grade group (GGG) of treated index lesions in this cohort included 3 (15%) GGG1, 8 (40%) GGG2, 8 (40%) GGG3, 1 (5%) GGG4. Two (10%) of these treatments were post-radiation salvage therapies. 3D planning predicted the same number of cryoprobes for each group, however a greater number of cryoprobes was used in the procedure for the prospective 3D group as compared to that with 2D planning (4.10 ± 1.37 and 3.25 ± 0.44 respectively, p = 0.01). At 6 months post cPGA, the median PSA was 1.68 ng/mL and 2.38 ng/mL in the 3D and 2D cohorts respectively, with a larger decrease noted in the 3D cohort (75.9% reduction noted in 3D cohort and 64.8% reduction 2D cohort, p 0.48). In-field disease detection was 1/14 (7.1%) on surveillance biopsy in the 3D cohort and 3/14 (21.4%) in the 2D cohort, p = 0.056) In the 3D cohort, 6 month biopsy was not performed in 4 patients (20%) due to undetectable PSA, negative MRI, and negative MRI Axumin PET. For the group with traditional 2D planning, treatment zone biopsy was positive in 3/14 (21.4%) of the patients, p = 0.056. CONCLUSIONS:3D prostate cancer models derived from mpMRI data provide novel guidance for planning confluent treatment volumes for cPGA and predicted a greater number of treatment probes than traditional 2D planning methods. This study prompts further investigation into the use of 3D treatment planning techniques as the increase of partial gland ablation treatment protocols develop.

PURPOSE/OBJECTIVE:To demonstrate the generalizability of PRECISION findings and apply the PRECISION biopsy strategy to a contemporary cohort to characterize cancers missed by employing this strategy. MATERIALS AND METHODS/METHODS:629 men biopsied between 2/2015-9/2018 met PRECISION inclusion criteria. Men with PI-RADS 1-2 MRI were only biopsied if high clinical suspicion for cancer. Missed cancers were defined as prostate cancer (PCa) identified uniquely on systematic biopsy (SB) in men with PI-RADS 3-5 MRI, or on either SB or MRI-targeted prostate biopsy (MRI-TB) in men with PI-RADS 1-2 MRI. Outcomes included 1) clinically-significant PCa (csPCa), ≥Gleason grade group (GG) 2, detection rate (CDR), 2) missed csPCa rate upon application of PRECISION biopsy strategy, 3) GG distribution, core size, spatial orientation, and oncologic risk among missed cancers. RESULTS:Application of the PRECISION biopsy strategy to the study cohort resulted in avoidance of biopsy in 28%, similar MRI-TB CDR to PRECISION, reduction of GG1 CDR by 60%, and reduction of csPCa CDR by 19%. Missed csPCa were often <6 mm (54.5%), GG2 (67.3%), and low-risk by clinical nomogram (74.6%). GG1 cancers identified uniquely on SB were often contralateral to MRI target (46.4%), while missed csPCa was predominantly ipsilateral (81%). Limitations include biopsy of only men with high-risk clinical features among PIRADS 1-2 MRI, potentially overestimating the csPCa CDR. CONCLUSIONS:The study cohort demonstrated generalizability of PRECISION findings. Applying the PRECISION biopsy strategy greatly reduces GG1 CDR, while missing a small number of csPCa, typically small volume, low-risk, and GG2. Missed csPCa are predominantly ipsilateral to MRI target, possibly representing targeting error.

OBJECTIVES/OBJECTIVE:To compare both the concordance between the 4Kscore® and SelectMDx® for informing decision to perform prostate biopsy (PB) and the performance of these tests for detecting clinically significant prostate cancer (csPCa). Several biomarkers were developed to inform decisions whether to perform a PB based on the probability of detecting csPCa. There is a paucity of studies directly comparing them METHODS: Between 11/2018 and 4/2019, all new referrals with the diagnosis of elevated PSA were advised to undergo 4Kscore® and SelectMDx® in order to guide the selection of candidates for PB. Men were advised to undergo PB if the reported biomarker risk for detecting csPCA was ≥7.5%, or if they presented a PI-RADS ≥1 MRI. Cohen's Kappa was used to assess the concordance between the binary 4Kscore® and SelectMDx® results using externally validated cutoffs of 7.5% and 12%. Receiver operating characteristics curve and area under the curve (AUC) assessed the performance of each biomarker for predicting csPCa. RESULTS:Of 128 consecutive patients referred, 114 (89.1%) underwent 4Kscore® and SelectMDx®, The kappa coefficient between the biomarkers using the 7.5% cutoff was 0.184 (poor concordance) and 0.22 using the 12% cutoff. The two biomarkers yielded discordant guidance whether to proceed with PB in 46% and 38% of cases, respectively. csPCa was found in 22 of the 50 patients who underwent PB (44%). The AUC for 4Kscore® and SelectMDx® was 0.830 (95%CI: 0.710 - 0.949) and 0.672 (95%CI: 0.517 - 0.828) (p=0.036), respectively. CONCLUSION/CONCLUSIONS:The discordance observed between the 4Kscore® and SelectMDx® is disconcerting. The 4Kscore® when combined with MRI was superior to the SelectMDx® for detecting csPCa. Prospective comparative studies must be performed to optimize implementation of biomarkers for selecting candidates for PB.

OBJECTIVE:To quantify how surgeons translate two-dimensional (2D) CT or MRI data to a three-dimensional (3D) model and evaluate if 3D printed models improve tumor localization. MATERIALS AND METHODS/METHODS:Twenty patients with renal masses were randomly selected from our IRB approved prospective 3D modeling study. Three surgeons reviewed the clinically available CT or MRI data; and using computer-aided design (CAD) software, translated the renal tumor to the position on the kidney that corresponded with the image interpretation. The renal tumor location determined by each surgeon was compared to the true renal mass location determined by the segmented imaging data and the Dice Similarity Coefficient (DSC) was calculated to evaluate the spatial overlap accuracy. The exercise was repeated for a subset of patients with a 3D printed model. RESULTS:The mean DSC was 0.243 ± 0.236 for the entire cohort (n=60). There was no overlap between the actual renal tumor and renal tumor identified by the surgeons in 16/60 cases (26.67%). Seven cases were reviewed again by two surgeons in a different setting with a 3D printed renal cancer model. For these cases, the DSC improved from 0.277 ± 0.248 using imaging only to 0.796 ± 0.090 with the 3D printed model (p < 0.01). CONCLUSIONS:In this study, cognitive renal tumor localization based on CT and MRI data was poor. This study demonstrates that experienced surgeons cannot always translate 2D imaging studies into 3D. Furthermore, 3D printed models can improve tumor localization and potentially assist with appropriate surgical approach.

OBJECTIVE:To assess knowledge of both promoting and preventive dietary factors on nephrolithiasis in a diverse patient population. Precipitating factors of kidney stone disease include diet, lifestyle, socioeconomic status, and race/ethnicity. However, patient awareness of these influences is poorly described. MATERIALS AND METHODS/METHODS:A 24-question survey, assessing intake-related risk factors for stone disease, was administered prospectively to 1018 patients. Responses were summarized with frequency and percent. Statistical comparisons were made using a propensity scoring method in order to account for potential confounding variables. Propensity scores were stratified into quintiles. Further analysis with multiple imputation was performed to account for any missing data in the survey. The results of the propensity-adjusted log-binomial regression model are presented as prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS:Respondents demonstrated limited knowledge of nutrient factors that influence stone development. However, most study participants (70.3%) reported a willingness to make lifestyle changes aimed at lowering their risk for stone disease. Respondents reporting previous nephrolithiasis education were less likely to report that diet had no effect on kidney stone formation (PR = 0.795, 95% CI 0.65, 0.96, p = 0.01) The type of physician who counseled the respondent had no association with patient knowledge for stone disease (PR = 0.83, 95% CI 0.63, 1.10, p = 0.2). CONCLUSIONS:Knowledge of diet-related risk factors for nephrolithiasis is limited among this population. Respondents who received prior education appeared to maintain the knowledge of dietary risk for nephrolithiasis. Participants also expressed a willingness to make requisite dietary changes if that information is provided. Given that most stone formers experience a recurrence, these findings highlight the need for more comprehensive patient education strategies on the modifiable risk factors for nephrolithiasis.

PURPOSE/OBJECTIVE:The Studies of Prostate Ablation Related Energy Devices (SPARED) coordinated registry network (CRN) is a private-public partnership between academic and community urologists, the US Food and Drug Administration (FDA), Medical Device Epidemiology Network (MDEpiNet) and device manufacturers to examine safety and effectiveness of technologies for partial gland ablation (PGA) in men with localized prostate cancer. MATERIALS AND METHODS/METHODS:We report on a recent workshop at the FDA with thought leaders to discuss a critical framework for PGA, focusing on patient selection, surgical planning, follow up, study design and appropriate comparators in terms of adverse events and cancer control outcomes. We summarize salient points from experts in urology, oncology, and epidemiology that were presented and discussed in an open forum. RESULTS:Given the challenges in achieving patient and physician equipoise to conduct a randomized trial, as well as an inherent paradigm shift when comparing PGA (inability to assess PSA recurrence) to whole gland treatments, the group focused on objective performance criteria/goals (OPC/OPG) as a platform to guide the creation of single arm studies within the SPARED CRN. CONCLUSIONS:This summit lays the foundation for prospective, multi-center data collection and evaluation of novel medical devices and drug/device combinations for PGA.

BACKGROUND:Patient-specific 3D models are being used increasingly in medicine for many applications including surgical planning, procedure rehearsal, trainee education, and patient education. To date, experiences on the use of 3D models to facilitate patient understanding of their disease and surgical plan are limited. The purpose of this study was to investigate in the context of renal and prostate cancer the impact of using 3D printed and augmented reality models for patient education. METHODS:Patients with MRI-visible prostate cancer undergoing either robotic assisted radical prostatectomy or focal ablative therapy or patients with renal masses undergoing partial nephrectomy were prospectively enrolled in this IRB approved study (n = 200). Patients underwent routine clinical imaging protocols and were randomized to receive pre-operative planning with imaging alone or imaging plus a patient-specific 3D model which was either 3D printed, visualized in AR, or viewed in 3D on a 2D computer monitor. 3D uro-oncologic models were created from the medical imaging data. A 5-point Likert scale survey was administered to patients prior to the surgical procedure to determine understanding of the cancer and treatment plan. If randomized to receive a pre-operative 3D model, the survey was completed twice, before and after viewing the 3D model. In addition, the cohort that received 3D models completed additional questions to compare usefulness of the different forms of visualization of the 3D models. Survey responses for each of the 3D model groups were compared using the Mann-Whitney and Wilcoxan rank-sum tests. RESULTS:All 200 patients completed the survey after reviewing their cases with their surgeons using imaging only. 127 patients completed the 5-point Likert scale survey regarding understanding of disease and surgical procedure twice, once with imaging and again after reviewing imaging plus a 3D model. Patients had a greater understanding using 3D printed models versus imaging for all measures including comprehension of disease, cancer size, cancer location, treatment plan, and the comfort level regarding the treatment plan (range 4.60-4.78/5 vs. 4.06-4.49/5, p < 0.05). CONCLUSIONS:All types of patient-specific 3D models were reported to be valuable for patient education. Out of the three advanced imaging methods, the 3D printed models helped patients to have the greatest understanding of their anatomy, disease, tumor characteristics, and surgical procedure.

INTRODUCTION/BACKGROUND:Penectomy for PC is useful in staging, disease prognosis, and treatment. Limited studies have evaluated its surgical complications. We sought to assess these complications and determine predictive models to create a novel risk score for penectomy complications. PATIENTS AND METHODS/METHODS:A retrospective review of patients undergoing PC surgical management from the 2005-2016 American College of Surgeons National Surgical Quality Improvement Program was performed. Data were queried for partial and total penectomy among those with PC. To develop predictive models of complications, we fit LASSO logistic, random forest, and stepwise logistic models to training data using cross-validation, demographic, comorbidity, laboratory, and wound characteristics as candidate predictors. Each model was evaluated on the test data using receiver operating characteristic curves. A novel risk score was created by rounding coefficients from the LASSO logistic model. RESULTS:A total of 304 cases met the inclusion criteria. Overall incidence of penectomy complications was 19.7%, where urinary tract infection (3.0%), superficial surgical site infection (3.0%), and bleeding requiring transfusion (3.9%) were most common. LASSO logistic, random forest, and stepwise logistic models for predicting complications had area under the curve (AUC) [95% confidence interval] values of 0.66 [0.52-0.81], 0.73 [0.63-0.83], and 0.59 [0.45-0.74], respectively. Eleven variables were included in the risk score. The LASSO model-derived risk score had moderately good performance (area under the curve [95% confidence interval] 0.74 [0.66-0.82]). Using a cutoff point of 6, the score attains sensitivity 0.58, specificity 0.74, and kappa 0.26. CONCLUSION/CONCLUSIONS:PC management through penectomy is associated with appreciable complications rates. Predictive models of penectomy complications performed moderately well. Our novel prognostic risk score may allow for improved preoperative counseling and risk stratification of men undergoing surgical management of PC.