Faculty Bibliography

INTRODUCTION/UNASSIGNED:Tc-DTPA) tracer clearance is the gold standard for bilateral kidney function, involving extended clearance times and radioactivity. Imaging-derived total kidney volumes are functional proxies but do not probe tissue quality. METHODS/UNASSIGNED:tests. RESULTS/UNASSIGNED:= 0.880 and 0.700, respectively). In addition, MR metrics differentiated proteinuria status. DISCUSSION/UNASSIGNED:Advanced DW MRI metrics may provide surrogates of mGFR and proteinuria. Parameters from bipolar encoding in diastole (emphasizing tubular flow) and flow compensation in systole (emphasizing vascular flow) were often informative.

OBJECTIVE:To evaluate the relationship between the Global Budget Revenue (GBR) model and surgical outcomes. SUMMARY BACKGROUND DATA/BACKGROUND:Medicare tested GBR in Maryland, wherein hospitals received a fixed annual revenue to cover healthcare delivery for their population. The relationship between GBR implementation and outcomes after cancer surgery is unclear. METHODS:Observational difference-in-differences analysis using 100% national Medicare data to compare changes in outcomes between GBR hospitals and matched control hospitals before (2011-2013) and after (2014-2018) policy implementation in Traditional Medicare beneficiaries undergoing cystectomy, prostatectomy, or nephrectomy for cancer. The primary outcome was achievement of a textbook outcome, defined as the absence of in-hospital and 30-day mortality, postoperative complications, a prolonged length of stay (i.e., above the 75th percentile by procedure and year) and readmission within 30 days of discharge. The secondary outcome was Medicare inpatient spending. RESULTS:This study included 23 Maryland hospitals with 4,910 beneficiaries and 371 control hospitals with 57,456 beneficiaries. Textbook outcomes increased from 72.8% to 76.1% in GBR hospitals and from 70.2% to 70.5% in matched controls, a differential increase of 2.9 percentage points (95% CI, 0.5 to 5.3; P=0.02). The greater improvement at GBR hospitals was a result of reducing complications (-1.5 percentage points; 95% CI, -2.9 to -0.1) and limiting prolonged lengths of stay (-1.8 percentage points; 95% CI, -2.9 to -0.7). Medicare inpatient spending declined by $771 (95% CI, -$1,275 to -$267) more at GBR hospitals. CONCLUSIONS:The GBR was associated with improved surgical outcomes and lower Medicare inpatient spending.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Trimodality therapy (TMT) is an accepted bladder-preserving option for selected patients with muscle-invasive bladder cancer (MIBC). Pembrolizumab has demonstrated activity in MIBC and may enhance the effects of chemotherapy and radiation. We evaluated the safety and efficacy of adding pembrolizumab to TMT. METHODS:In this multicenter phase 2 trial, patients with MIBC received one dose of pembrolizumab followed by maximal transurethral resection, then definitive bladder radiation with concurrent low-dose gemcitabine and pembrolizumab every 3 wk for three doses. The primary end point was 2-yr bladder-intact disease-free survival (BIDFS). Secondary end points included safety, metastasis-free survival (MFS), and overall survival (OS). KEY FINDINGS AND LIMITATIONS/UNASSIGNED:Fifty-four patients were enrolled, including 48 in the efficacy cohort; 67% had clinical stage T2 disease. The 2-yr BIDFS was 60% (95% confidence interval [CI], 45-73). Two-yr MFS and OS were 81% (95% CI, 66-92) and 83% (95% CI, 69-91), respectively. Grade ≥3 treatment-related adverse events occurred in 25% of patients. Limitations include the single-arm design and modest sample size. CONCLUSIONS AND CLINICAL IMPLICATIONS/CONCLUSIONS:Pembrolizumab combined with gemcitabine-based chemoradiation was feasible and showed efficacy comparable to standard TMT. Ongoing phase 3 trials will further define its role in bladder preservation.

PURPOSE/UNASSIGNED:To report the duration of response (DoR) to UGN-102 treatment in patients with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) 24 months after achieving complete response (CR). MATERIALS AND METHODS/UNASSIGNED:ENVISION (NCT05243550) is an ongoing, multinational, single-arm, phase 3 study in patients with biopsy-proven recurrent LG-IR-NMIBC. Patients received 6 once-weekly intravesical instillations of UGN-102. Patients underwent cystoscopy, urine cytology testing, and for-cause biopsy to determine bladder cancer presence at 3 months. DoR (from CR at 3 months to disease recurrence, progression, or death from any cause) at 24 months was estimated using the Kaplan-Meier (KM) method. RESULTS/UNASSIGNED:A total of 240 patients were enrolled and received ≥1 dose of UGN-102. Most patients were White (98%), male (61%), and aged ≥65 years (68%). At 3 months, 191 patients (80%; 95% confidence interval [CI]: 74, 85) achieved CR. Among these responders, the probability of remaining event-free 24 months after CR was 72% (95% CI: 64, 79; KM estimate). Among patients with CR at 3 months (n = 191), 36 developed LG disease recurrence. Treatment-emergent adverse events that occurred in ≥10% of enrolled patients (N = 240) was dysuria. CONCLUSIONS/UNASSIGNED:Patients who achieved CR following UGN-102 treatment had a high probability of remaining event-free 24 months later. These data indicate UGN-102 is a novel, nonsurgical treatment that provides a durable CR for patients with recurrent LG-IR-NMIBC. Study limitations included the single-arm design and the limited racial diversity of the patients.

The detection of localized prostate cancer has transformed tremendously in the twenty-first century with the emergence of more accurate imaging technologies. The standard transrectal ultrasound is now supported by the widespread adoption of MRI, with growing investigation into modalities such as micro-ultrasound and prostate-specific membrane antigen imaging. The value of these imaging techniques is still being understood, as seen by their increasing application for management decisions, treatment planning, and treatment monitoring. This article aims to provide a comprehensive understanding of contemporary imaging techniques for localized prostate cancer, including relevant data.

PURPOSE/OBJECTIVE:Partial nephrectomy has been advocated as the preferred surgical approach for small kidney tumors over total nephrectomy. However, partial nephrectomy is associated with increased perioperative risk. Estimating renal function after nephrectomy can facilitate personalized patient counseling, guide surgical approach, and identify patients who could benefit from perioperative interventions. Existing prediction models have several limitations including the lack of external validation or a user-friendly tool or application, and most have used traditional statistical methods. METHODS:We used data from two academic medical institutions and machine learning (ML) methods to develop and externally validate renal function after nephrectomy-machine learning (RFAN-ML), a model to estimate long-term renal function after partial or total nephrectomy. Boruta feature selection was used to select four routinely available clinical features, specifically age, BMI, preoperative renal function, and nephrectomy type. In the training set of 1,932 patients, we compared six ML regression models representing a set of both ensemble and nonensemble ML algorithms and optimized for root mean squared error (RMSE). This model was evaluated in a test set of 1,995 patients, and the best performing model was selected as RFAN-ML. RESULTS:, and mean absolute error. CONCLUSION/CONCLUSIONS:We developed and externally validated RFAN-ML, a ML model to predict renal function after nephrectomy, and have deployed our model online. RFAN-ML has the potential to improve the care and outcomes in patients with kidney tumors by informing personalized patient counseling and guiding surgical planning.

INTRODUCTION/BACKGROUND:The OPTIMA II phase 2b study (NCT03558503) treated patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) with UGN-102, a reverse thermal hydrogel containing mitomycin. Efficacy and safety results have been reported for the 12-month parent study; here, we report 5-year follow-up data. PATIENTS AND METHODS/METHODS:Patients who participated in the OPTIMA II study and achieved a complete response (CR) after 6 weekly doses of UGN-102 were followed for up to 9 months after initial CR. Those with CR at study completion were eligible to enroll in a further long-term follow-up (LTFU) study, during which there were no protocol-specified interventions/treatments, protocol-specified visits, or evaluations. Supervising physicians provided semiannual updates on patients' disease status. Duration of response (DoR) was calculated using the Kaplan-Meier method. RESULTS:Of the 41 patients achieving a CR at 3 months, 25 remained in CR at 12 months and 17 entered LTFU. For the 41 patients achieving a CR at 3 months the median Kaplan-Meier estimate of DoR was 24.2 months (95% confidence interval [CI], 9.72-42.09), with a median follow-up time of 35.8 months (95% CI, 10.78-60.98). For the 17 patients in the LTFU study the median DoR was 42.1 months (95% CI, 24.18-not estimable [NE]), with a median follow-up of 50.40 months (95% CI, 26.97-NE), CONCLUSION: These results demonstrate that treatment with UGN-102 results in clinically meaningful, and highly durable response in patients with LG-IR-NMIBC. UGN-102 may offer a promising non-surgical alternative to transurethral resection of bladder cancer (TURBT) for LG-IR-NMIBC patients.

INTRODUCTION/BACKGROUND:High-volume (≥ 50 %) biopsy core involvement (HVCI) is an independent risk factor for unfavorable intermediate-risk prostate cancer by NCCN guidelines. The studies demonstrating increased recurrence in high-volume disease were conducted in an era of conventional fractionation, often without dose-escalation. In the SBRT era, we explore the value of this pathologic criteria in intermediate-risk disease. METHODS:A large institutional database was reviewed to identify patients diagnosed with localized intermediate-risk (Gleason Grade [GG] 2 and 3) disease, who were treated with definitive five-fraction SBRT without ADT. HVCI was analyzed (1) traditionally with all positive cores given equal weight as well as weighted with a positive core of GG1 to GG3 given (2) linearly and (3) exponentially increased weight. Oncologic outcomes were analyzed using Cox and linear regression analysis. RESULTS:From 2009 to 2018, 888 patients with intermediate-risk prostate cancer were treated with five-fraction SBRT monotherapy to a median dose of 3500 cGy. The majority (68 %) had GG2 disease. HVCI was present in the 22 % and was inversely related to prostate volume and directly related to T-stage. Biochemical disease-free survival (BDFS) was not significantly associated with HVCI in the cohort (p = 0.47) nor in the GG2 (p = 0.85) and GG3 (p = 0.26) sub-cohorts. Similarly, when linear or exponential weight was given to a core with higher-grade disease, there was no association with BDFS. Finally, PSA nadir was not associated with HVCI; however, time to PSA nadir (TTN) was negatively associated with HVCI in the GG3 sub-cohort (p = 0.04). CONCLUSION/CONCLUSIONS:With a median follow-up of 4.1 years, HVCI was not associated with BDFS following SBRT monotherapy, particularly in patients with otherwise favorable intermediate-risk disease (GG2). TTN analysis suggests that HVCI may remain prognostic in GG3 disease (by definition unfavorable intermediate-risk). Further work should prospectively confirm whether HVCI is unnecessary in risk-stratifying GG2 disease in the SBRT era.

INTRODUCTION AND OBJECTIVE/OBJECTIVE:For localized kidney tumors, size and growth kinetics generally predict malignant potential. Thus, for patients with multifocal renal masses, treatment priority often revolves around the largest or index tumor first. We reviewed our kidney surgery database to examine histologic concordance of sporadic multifocal renal tumors and to determine if size is also the greatest determinant of tumor aggressiveness. METHODS:We conducted a retrospective chart review at a tertiary referral center of 1983 patients undergoing nephrectomy (radical and partial) from January 2010 to December 2019. We identified 138 patients with multifocal renal masses (n = 138). Surgical pathology parameters, including tumor size, TNM grading, and staging, were collected through electronic medical records. Patients with syndromic diseases were excluded (n = 10), resulting in a total sample of 128 patients with sporadic multifocal tumors. Overall, the sample included 307 tumors total, with a mean number of 2.4 lesions per patient. RESULTS:About 128 patients (6.45%) had sporadic multifocal renal tumors. Among these, 82 out of 128 (64%) had concordant histologic subtypes, while 46 out of 128 (36%) had discordant histology. In 99 patients (77.3%), the index tumor demonstrated a more aggressive histology. There were 29 patients (22.6%) with a benign or less aggressive index tumor. Among those, 21 patients (16%) had a benign index tumor, 5 (24%) of which had a malignant secondary tumor. CONCLUSION/CONCLUSIONS:Multifocal tumors frequently have discordant histology. While size tends to predict oncologic risk, many patients harbor more aggressive disease in nonindex lesions, highlighting the limitations of relying on size alone for managing sporadic multifocal RCC.