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To evaluate a conceptually simple model to predict new-baseline-glomerular-filtration-rate (NBGFR) after radical nephrectomy (RN) based on split-renal-function (SRF) and renal-functional-compensation (RFC), and to compare its predictive accuracy against a validated non-SRF-based model. RN should only be considered when the tumor has increased oncologic potential and/or when there is concern about perioperative morbidity with PN due to increased tumor complexity. In these circumstances, accurate prediction of NBGFR after RN can be important, with a threshold NBGFR 45 ml/min/1.73m236 RCC patients who underwent RN (2010-2012) with preoperative imaging (CT/MRI) and relevant functional data were included. NBGFR was defined as GFR 3-12 months post-RN. SRF was determined using semi-automated software that provides differential parenchymal-volume-analysis (PVA) from preoperative imaging. Our SRF-based model was: Predicted NBGFR = 1.24 (× Global GFRThe correlation-coefficients (r) were 0.87/0.72 for SRF-based/non-SRF-based models, respectively (p = 0.005). For prediction of NBGFR 45 ml/min/1.73mPrevious non-SRF-based models to predict NBGFR post-RN are complex and omit two important parameters: SRF and RFC. Our proposed model prioritizes these parameters and provides a conceptually simple, accurate, and clinically implementable approach to predict NBGFR post-RN. SRF can be easily obtained using PVA software that is affordable, readily available (FUJIFILM-Medical-Systems), and more accurate than nuclear-renal-scans. The SRF-based model demonstrates greater predictive-accuracy than a non-SRF-based model, including the clinically-important predictive-threshold of NBGFR 45 ml/min/1.73m

Radical nephrectomy (RN) is an important consideration for the management of localized renal-cell-carcinoma (RCC) whenever the tumor appears aggressive, although reduced renal function is a concern. Split-renal-function (SRF) in the contralateral kidney and postoperative renal functional compensation (RFC) are fundamentally important for the accurate prediction of new baseline GFR (NBGFR) post-RN. SRF can be estimated either from nuclear renal scans (NRS) or from preoperative imaging using parenchymal-volume-analysis (PVA). We compare two SRF-based models for predicting NBGFR after RN with a subjective prediction of NBGFR by an experienced urologic-oncologist.187 RCC patients managed with RN (2006-16) were included based on the availability of preoperative CT/MRI and NRS, and preoperative/postoperative eGFR. NBGFR was defined as the final GFR 3-12 months post-RN. For the SRF-based approaches, SRF was derived from either NRS or PVA, and RFC was estimated at 25% based on previous independent analyses. Thus, the formula (Global GFRThe r values for subjective-assessment, NRS/SRF-based, and PVA/SRF-based approaches were 0.72/0.72/0.85, respectively (p 0.05). The PVA/SRF-based model also demonstrated significant improvement across other performance parameters.The PVA/SRF-based model more accurately predicts NBGFR post-RN than NRS/SRF-based and Subjective Estimation. PVA software (Fujifilm-medical-systems) is readily available and affordable and provides accurate SRF estimations from routine preoperative imaging. This novel approach may inform clinical management regarding RN/PN for complex RCC cases.

Partial prostatectomy has been described as an alternative to focal therapy for the management of localized low- and intermediate-risk prostate cancer.To describe early outcomes and technique for single-port (SP) transvesical partial prostatectomy.A retrospective analysis was performed for nine patients with low-volume, localized, low- to intermediate-risk prostate cancer (Gleason ≤7) undergoing SP transvesical partial prostatectomy replicating the inclusion criteria for focal therapy by a single surgeon from November 2020 to March 2022.The daVinci SP access port was inserted percutaneously into the bladder and pnuemovesicum was achieved. The camera, robotic instruments, assistant port, and flexible suction tubing were introduced through the access port. The Koelis transrectal ultrasound with preoperative prostate magnetic resonance imaging fusion was used for intraoperative guidance.Demographic information, intraoperative variables, and postoperative outcomes were collected in an institutional review board-approved database, and a descriptive statistical analysis was performed.All cases were completed without requiring extra ports or conversion. No intraoperative complications were noted, and all patients were discharged on the day of surgery. Pathology showed Gleason scores of 3 + 3 = 6 in one case, 3 + 4 = 7 in seven cases, and 4 + 3 = 7 in one case, all with negative intraoperative margin assessment. At 6 wk, the median prostate-specific antigen was 0.5 and the median Sexual Health Inventory for Men score was 17.5 from 23 preoperatively. All patients were continent at 6 wk. The limitations include a small number of patients, short follow-up, and single-surgeon experience.We demonstrated the feasibility of the SP robotic transvesical partial prostatectomy. Early functional outcomes show impressive time to continence and erectile function. Continued follow-up will evaluate long-term oncologic outcomes.We performed partial prostatectomies in selected patients as an alternative to focal therapy using a novel transvesical single-port approach. Our approach was safe and feasible, with fewer complications and promising initial return to continence and erectile function.

Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes.The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined.We performed a retrospective review of CaP patients who had Decipher testing at a single high-volume institution. Index lesions from radical prostatectomy specimens were identified by genitourinary pathologists who simultaneously reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were grouped based on pathologic features, specifically the absence of CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+).Clinical, pathologic, and genomic categorical variables were assessed using the Pearson chi-square test, while quantitative variables were assessed with the Kruskal-Wallis test. Multivariable logistic regression was used to identify the predictors of high-risk Decipher scores (0.60). A gene set enrichment analysis was performed to identify genes and gene networks associated with CF/IDC status.A total of 463 patients were included. Patients who were CF+/IDC+ had the highest Decipher risk scores (CF+/IDC+: 0.79 vs CF+/IDC-: 0.71 vs CF-/IDC-: 0.56, p 0.001). On multivariate logistic regression, predictors of high-risk Decipher scores included the presence of CF, both alone (CF+/IDC-; odds ratio [OR]: 5.45, p 0.001) or in combination with positive IDC status (CF+/IDC+; OR: 6.87, p 0.001). On the gene set enrichment analysis, MYC pathway upregulation was significantly enriched in tumor samples from CF/IDC-positive patients (normalized enrichment score [NES]: 1.65, p = 0.046). Other enriched pathways included E2F targets (NES: 1.69, p = 0.031) and oxidative phosphorylation (NES: 1.68, =0 .033).This is the largest series identifying an association between a clinically validated genomic classifier and the presence of CF and IDC at radical prostatectomy. Tumors with CF and intraductal features were associated with aggressive transcriptomic signatures.Genomic-based tests are becoming readily available for the management of prostate cancer. We observed that Decipher, a commonly used genomic test in prostate cancer, correlates with unfavorable features in tissue specimens.

The American-Urological-Association(AUA) Guidelines for renal cancer(2017) recommend consideration for radical-nephrectomy(RN) over partial(PN) whenever there is increased oncologic-risk; and RN should be prioritized if three other criteria are all also met: 1) increased tumor-complexity; 2) no preexisting chronic-kidney-disease/ proteinuria, and 3) normal contralateral kidney that will likely provide estimated glomerular-filtration-rate (eGFR)45ml/min/1.73mRetrospective review of 267 consecutive RN/PN from 2019(100-RN/167-PN). High tumor-complexity was defined as R.E.N.A.L.≥9. Increased oncologic-risk was defined as tumor7cm, locally-advanced or infiltrative-features on imaging, or high-risk pathology on biopsy, if obtained. New-baseline GFR after RN was estimated using global-GFR, split-renal-function163 patients(61%) fit scenarios that are well-defined in the Guidelines. Of these, 34 had strong indications for RN, and all had RN. Twelve of 129 patients(9.3%) underwent RN despite Guidelines generally favoring PN. The remaining 104 patients(39%) did not fit within situations where the Guidelines provide specific recommendations. In these patients, RN was often performed despite functional-considerations favoring PN due to overriding concerns about oncologic-risk and/or tumor-complexity.Our data demonstrate complexity of decision-making about PN/RN as almost 40% of patients did not fit well-described AUA Guidelines descriptors. Compliance was generally strong although occasional overutilization of RN remains a concern in our series, and will be addressed with additional education. Further studies will be required to assess the generalizability of our findings in other institutions/settings.

Our goal was to evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma.In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored.Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term followup; 23/41 patients (56%) remained in complete response after 12 months (95% CI 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs.Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.

Purpose: Preoperative assessment of T3a renal-cell-carcinoma (RCC) in absence of main renal vein involvement or lymph node enlargement is challenging but has potential implications for counseling and prognosis. Materials and Methods: A retrospective review of 1129 cT1-T3aN0M0 RCC patients managed with partial/radical nephrectomy (PN/RN) in our institution (2012-2014) was performed. Exclusion criteria included radiological evidence of main renal vein involvement or substantial lymphadenopathy. Eleven radiological findings suggestive of aggressive tumor biology or invasive phenotype based on prior literature were assessed for correlation with pT3a status. These included perinephric-findings (stranding, enhancing-nodule, collateral-vessels, or irregular-perinephric-tumor-contour), findings within the sinus (stranding, collecting-system invasion, branch-vein enlargement, or irregular-tumor-sinus-border [ITSB]), and tumor-necrosis, infiltrative-features, and tumor-size. Radiological assessment was blinded to final pathology. Sensitivity/specificity and logistic-regression analyses assessed the performance of each imaging-finding for detecting pT3a tumors. Results: Median tumor-size was 4.0cm and R.E.N.A.L. was 8. Median follow-up was 53 months (IQR:28-64). pT3a tumors were found in 281 patients (25%) and strongly correlated with local and systemic recurrence (p

This chapter summarizes the findings of a notable non-inferiority trial comparing nephron-sparing surgery to radical nephrectomy for small renal masses suspected to be renal cell carcinoma. Overall survival results favored radical nephrectomy and progression-free survival was largely similar. Its findings remain controversial but suggest that the assumed benefits of nephron-sparing surgery over radical nephrectomy based on non-randomized studies may have been overstated and that in many cases both approaches may have similar outcomes.

This chapter summarizes the findings of one of the earliest trials of targeted therapy with a protein kinase inhibitor in patients with previously untreated, metastatic renal cell carcinoma who received either systemic sunitinib or interferon alfa. The study found better progression-free survival and overall survival in patients who received sunitinib. Diarrhea was the most common adverse event in the sunitinib group and was much more frequent compared to the interferon alfa group

This chapter summarizes the findings of the landmark CheckMate 025 trial for the new class of drugs of immune checkpoint blockade in advanced renal cell cancer. The trial randomized patients with metastatic renal cell carcinoma who had failed antiangiogenic therapy to systemic therapy with nivolumab versus everolimus and found improved overall survival and fewer treatment-related adverse events in the nivolumab arm.

4593 Background: Upper tract urothelial carcinoma (UTUC) is a rare and heterogeneous disease accounting for approximately 5-10% of UC. While tumor grade and stage are known prognostic factors, data on other factors affecting outcomes in UTUC patients (pts) undergoing surgery is scant. We studied effect of various clinical factors and treatment on outcomes in UTUC. Methods: This is a single-institution retrospective study of 607 pts with UTUC undergoing surgery (nephroureterectomy (NU) or ureterectomy (U)) between Jan 2000 and Dec 2020. We studied effect of demographics, clinicopathological features, tumor location, preoperative Neutrophil-to-Lymphocyte ratio (NLR) and Albumin-to-Globulin ratio (AGR) and use of neoadjuvant or adjuvant chemotherapy on overall survival (OS) and recurrence free survival (RFS). Results: Of the 607 pts 401 (66.06%) were males and 355 (58.48%) were > 70 yrs; 232 pts (38.22%) had UTUC of renal pelvis, 242 (39.87%) of ureter and 133 (21.91%) of both. 542 pts (89.29%) underwent radical NU and 65 (10.71%) segmental U; 328 patients (54.04%) were diagnosed with muscle invasive UC (MIUC) ( > / = pT2) and 276 (45.47%) with non-MIUC ( < / = pT2). Only 51 (8.4%) pts had lymph node positive (N+) disease. Lymphovascular invasion (LVI) was identified in 163 (26.85%) and carcinoma- in-situ (CIS) in 163 (26.85%) pts. Surgical margins were positive in 92 pts (15.16%). Median NLR cutoff was 3.25 and AGR cutoff was 1.25 (dichotomized based on literature). 44 pts (7.2%) received Neoadjuvant chemotherapy and 49 pts (8%) received adjuvant chemotherapy. Tumor recurrence occurred in 216 pts (35.58%) of which 65% were at urothelial and 35% at non-urothelial sites. With median follow up of 35.2 mos, median OS was 82.69 mos and 5-yr OS rate was 60%; median RFS was 29.47 mos and 5-yr RFS rate was 40%. High grade, age > / = 70 yrs, high NLR, low AGR, presence of LVI, positive margins, CIS, MIUC, N+ disease were associated with worse outcomes. Pts with only renal pelvis involvement had better OS. Conclusions: In this large, long term follow-up series of UTUC pts, we identified several prognostic factors besides grade and stage that impact outcomes. These findings warrant further validation for use in clinical practice. [Table: see text]

To report the overall effect of ERAS protocol implementation in patients undergoing radical cystectomy and its impact on the length of hospital stay (LOS) and surgical outcomes considering their comorbid conditions.Retrospective cohort study including 296 patients (146 non-ERAS patients vs. 150 ERAS patients) undergoing radical cystectomy and urinary diversion from 2010 to 2018. Age-adjusted Charlson Comorbidity Index (ACCI) score eight was set as cut off value between low-risk and high-risk patients. The primary outcome was LOS. Secondary outcomes were time to bowel movements, tolerance of regular diet, the incidence of postoperative ileus, postoperative complications, and 30- and 90-day readmission rates.A higher comorbidity burden was identified in the ERAS group compared to non-ERAS patients (p = 0.04). Median (IQR) LOS for non-ERAS was group 8(4) and 8(5) for ERAS group (p = 0.07). ERAS group demonstrated shorter time to resume bowel movements as well as time to tolerance of regular diet (p = 0.007, p = 0.023, respectively). Low-risk patients managed by the ERAS protocol demonstrated a significantly shortened gastrointestinal (GIT) recovery time (p = 0.001) as well as a reduction of LOS (p = 0.04). No significant reduction of LOS was identified for patients with higher comorbidity when placed on the ERAS protocol (p = 0.65). There were no significant differences in postoperative complications or readmission rates between groups.ERAS protocol implementation following radical cystectomy showed significant improvements in GIT recovery, nevertheless, it did not result in a decrease in LOS or readmission rates. Low-risk patients appeared to derive more benefit from ERAS protocol implementation than high-risk patients.

268 Background: Invasive cribriform and intraductal carcinoma (CF/IDC) portends an unfavorable prognosis for patients diagnosed with prostate cancer (CaP). Limited studies with small sample sizes have explored whether genomic classifiers are associated with IDC and/or CF status. We investigated the correlation between Decipher genomic risk score and IDC/CF status and assessed PCa transcriptomic features. Methods: We performed a retrospective review of CaP patients who had Decipher testing at a single high volume center between 2009-2020. The highest grade index lesion from radical prostatectomy specimens was identified by GU pathologists and used for Decipher testing. Genitourinary pathologists reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were divided into three groups based on pathologic features, absent CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+). Categorical clinical, genomic, and pathologic variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test. Multivariable logistic regression was used to identify predictors of high-risk Decipher GC scores. The Kaplan-Meier method with log-rank was used to compare biochemical recurrence free survival. Differential gene expression and gene network analysis was used to identify genes and pathways associated with IDC/CF features. Results: 463 patients were included with a median follow-up of 25 months. Patients who were CF+/IDC+ had higher GC scores (CF+/IDC+: 0.77 vs. CF+/IDC-: 0.71 vs. CF-/IDC-: 0.61, p3 (CF+/IDC+: 79% vs. CF+/IDC-: 52% vs. CF-/IDC-: 52%, p3 (OR: 1.58, p=0.04). Transcriptomic analysis revealed that the hallmark androgen response pathway was significantly upregulated in CF+/IDC+ patients (Log fold change: 15.7, p

528 Background: The BLASST-1 study is multi-center phase II trial evaluating the combination of nivolumab (N) with gemcitabine-cisplatin (GC) as a neoadjuvant therapy for patients (pts) with MIBC undergoing radical cystectomy (RC). The primary endpoint was pathologic down staging (PaR; ≤pT1N0). Safety, Relapse-free survival (RFS), Progression-free survival (PFS) and biomarker analyses were secondary endpoints. We previously reported a PaR rate of 65.8% and pCR rate of 49%. There were no safety concerns or delays to surgery. (ASCO GU 2020) Here, we correlate PaR with biomarkers (Tumor mutational burden (TMB), PD-L1 and molecular subtypes) and provide updated clinical follow-up (FU) data. Methods: Forty-one pts with MIBC (cT2-T4a, N≤1, M0) and candidates for RC were enrolled between Feb 2018 and June 2019; (cT2N0 90%, cT3N0 7%, cT4N1 3%). Pts received C (70mg/m2) IV on D1, G (1000mg/m2) on D1, D8 and N (360 mg) IV on D8 every 21 days for 4 cycles followed by RC within 8 weeks. For RNA-based analysis, GeneChip Human Exon 1.0 ST Array (Affymetrix) was used; baseline tumors from 37 patients passed quality control and had available transcriptome data. A cohort (n=223) of patients treated with NAC+RC was used as a comparator for molecular subtyping analysis. DNA was extracted from baseline pre-treatment tumor samples and sequenced to an average depth of 150X and the DNA extracted from matched normal tissue (peripheral blood) to a mean depth of 50X. PD-L1 expression was assessed using IHC 28-8 antibody on baseline tumors. Results: At a median FU of 15.8 months,12-month RFS rate was 85.4% and PFS including death from any cause was 83%. There were no long-term safety concerns. Molecular subtyping found patients with a basal-type tumor (Basal or Claudin-low) had a more favorable overall PaR in 13/18 = 73% with PaR in 9/13 in basal (69%) and 4/5 in claudin-low (80%) compared to overall PaR of 58% for the luminal-type tumors (Luminal or Infiltrated luminal) with a breakdown of PaR in 5/8 (63%) in luminal and 6/11 (54%) in infiltrated luminal. In contrast, in the comparator NAC cohort, the PaR rates were similar for basal-type and luminal-type tumors, with 44% and 48% respectively. There was no correlation of PaR with TMB or PD-L1 expression from bassline pre-treatment tumors. Biomarker analyses from residual tumors in RC tissues are ongoing. Conclusions: The combination of N+GC was safe and efficacious in MIBC with encouraging outcomes of pathologic down staging and relapse-free survival at a median FU of 15.8 months. Molecular subtyping results suggest basal-type tumors may respond more favorably to this chemo-immunotherapy treatment regimen. Clinical trial information: NCT03294304.