Faculty Bibliography

BACKGROUND:Primary robot-assisted retroperitoneal lymph node dissection (RA-RPLND) for men with nonseminomatous germ cell tumor (NSGCT) is an alternative to open RPLND for stage I and select stage II patients. OBJECTIVE:To report the complication rates and oncologic outcomes from a multi-institutional series, and to estimate reduction in chemotherapy by using upfront minimally invasive surgery. DESIGN, SETTING, AND PARTICIPANTS/METHODS:A retrospective chart review of men undergoing primary robot-assisted RPLND between 2014 and 2019 in five institutions by eight urologists experienced in testis cancer and robotic surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/UNASSIGNED:Variables such as demographic and clinicopathologic information, operative parameters and complication rates, oncologic outcomes, sexual recovery, and hospital length of stay were collected. Descriptive statistics are presented. RESULTS AND LIMITATIONS/CONCLUSIONS:Forty-nine patients were analyzed with a median follow-up of 15.0 mo (interquartile range 6.5-29.1 mo). Median operative time was 288 min, estimated blood loss was 100 ml, and lymph node yield was 32. Median length of stay was 1 d. There were nine postoperative complications, 44% (4/9) of which were Clavien grade 1. There were no Clavien grade IV complications. Twenty-one patients had metastatic NSGCT (42.8%), of whom nine (18.4%) received adjuvant chemotherapy. Four patients experienced recurrence (three out-of-field and one in-field recurrence). Limitations include the retrospective study design and various surgical techniques among surgeons. CONCLUSIONS:Primary robot-assisted RPLND for NSGCT can be performed safely, with low complication rates and acceptable oncologic outcomes reducing the need for chemotherapy. For a population in which compliance with surveillance is typically challenging, robot-assisted RPLND may improve quality of care and outcomes for patients with NSGCT. PATIENT SUMMARY/UNASSIGNED:In experienced centers, robot-assisted retroperitoneal lymph node dissection can be performed safely with similar oncologic outcomes to an open approach, while providing an option that may reduce the need for chemotherapy.

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.

Background/UNASSIGNED:Radical cystectomy for bladder cancer has one of the highest rates of morbidity among urologic surgery, but the ability to predict postoperative complications remains poor. Our study objective was to create machine learning models to predict complications and factors leading to extended length of hospital stay and discharge to a higher level of care after radical cystectomy. Methods/UNASSIGNED:Using the American College of Surgeons National Surgical Quality Improvement Program, peri-operative adverse outcome variables for patients undergoing elective radical cystectomy for bladder cancer from 2005 to 2016 were extracted. Variables assessed include occurrence of minor, infectious, serious, or any adverse events, extended length of hospital stay, and discharge to higher-level care. To develop predictive models of radical cystectomy complications, we fit generalized additive model (GAM), least absolute shrinkage and selection operator (LASSO) logistic, neural network, and random forest models to training data using various candidate predictor variables. Each model was evaluated on the test data using receiver operating characteristic curves. Results/UNASSIGNED:A total of 7557 patients were identified who met the inclusion criteria, and 2221 complications occurred. LASSO logistic models demonstrated the highest area under curve for predicting any complications (0.63), discharge to a higher level of care (0.75), extended length of stay (0.68), and infectious (0.62) adverse events. This was comparable with random forest in predicting minor (0.60) and serious (0.63) adverse events. Conclusions/UNASSIGNED:Our models perform modestly in predicting radical cystectomy complications, highlighting both the complex cystectomy process and the limitations of large healthcare datasets. Identifying the most important variable leading to each type of adverse event may allow for further strategies to model cystectomy complications and target optimization of modifiable variables pre-operative to reduce postoperative adverse events.

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.

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.