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For some urologic cancers, long-term data support laparoscopy as the new standard for treatment. In other cases, the most known is that a procedure can be accomplished laparoscopically, and still others fall in the middle of this spectrum. Based on a review of the literature, the authors provide evidence-based guidance to help determine when and when not to recommend laparoscopy to your patients. [ABSTRACT FROM AUTHOR]

Objectives: We studied the diagnostic accuracy and discordance of upper tract urothelial carcinoma (UTUC) by comparing biopsy and urinary cytology with matched nephroureterectomy specimens., Methods: Sixty-nine patients with UTUC without neoadjuvant treatment were retrospectively identified who had matched biopsy and nephroureterectomy specimens. Twenty patients had concurrent upper tract cytology. H&E and cytology slides were re-reviewed. Statistical analysis was performed., Results: Patients included 48 men and 21 women with a mean age of 69 years. A concordant grade between biopsy and surgical specimen was present in 49 (71%) patients. The mean size of biopsy specimens in the discordant group was significantly smaller than that in the concordant group. Invasion was evaluated in 48 biopsy cases that had adequate subepithelial tissue, and 33 of them were diagnosed with concordant invasion status. Mean tumor size in both tumor grade and invasion discordant groups was significantly larger than that in the concordant group. High-grade urothelial carcinoma was detected in 84% of cases using urinary cytology., Conclusions: Our study demonstrates the diagnostic challenges of UTUC on small biopsy specimens. Biopsy specimen size and tumor size are significantly associated with the diagnostic discordance. Upper tract cytology showed high diagnostic accuracy and should be complementary to the biopsy., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To evaluate the technical success and outcomes of renal biopsies performed under magnetic resonance imaging (MRI) using a closed-bore, 1.5-Tesla MRI unit., Materials and Methods: We retrospectively reviewed our institutional biopsy database and included 150 consecutive MRI-guided biopsies for renal masses between November 2007 and March 2020. We recorded age, sex, BMI, tumor characteristics, RENAL nephrometry score, MRI scan sequence, biopsy technique, complications, diagnostic yield, pathologic outcome, and follow-up imaging. Univariate logistic regression was used to assess the association between different parameters and the development of complications. McNemar's test was used to assess the association between paired diagnostic yield measurements for fine-needle aspiration and core samples., Results: A total of 150 biopsies for 150 lesions were performed in 150 patients. The median tumor size was 2.7 cm. The median BMI was 28.3. The lesions were solid, partially necrotic/cystic, and predominantly cystic in 137, eight, and five patients, respectively. Image guidance using fat saturation steady-state free precession sequence was recorded in 95% of the biopsy procedures. Samples were obtained using both fine-needle aspiration (FNA) and cores in 99 patients (66%), cores only in 40 (26%), and FNA only in three (2%). Tissue sampling was diagnostic in 144 (96%) lesions. No major complication developed following any of the biopsy procedures. The median follow-up imaging duration was 8 years and none of the patients developed biopsy-related long-term complication or tumor seeding., Conclusions: MRI-guided renal biopsy is safe and effective, with high diagnostic yield and no major complications., Clinical Relevance Statement: Image-guided renal biopsy is safe and effective, and should be included in the management algorithm of patients with renal masses. Core biopsy is recommended., Key Points: • MRI-guided biopsy is a safe and effective technique for sampling of renal lesions. • MRI-guided biopsy has high diagnostic yield with no major complications. • Percutaneous image-guided biopsy plays a key role in the management of patients with renal masses., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: We initiated a biomarker-informed preoperative study of infigratinib, a fibroblast growth factor receptor (FGFR) inhibitor, in patients with localized upper tract urothelial carcinoma (UTUC), a population with high unmet needs and tumor with a high frequency of FGFR3 alterations., Materials and Methods: Patients with localized UTUC undergoing ureteroscopy or nephroureterectomy/ureterectomy were enrolled on a phase 1b trial (NCT04228042). Once-daily infigratinib 125 mg by mouth × 21 days (28-day cycle) was given for 2 cycles. Tolerability was monitored by Bayesian design and predefined stopping boundaries. The primary endpoint was tolerability, and the secondary endpoint was objective response based on tumor mapping, done after endoscopic biopsy and post-trial surgery. Total planned enrollment: 20 patients. Targeted sequencing performed using a NovaSeq 6000 solid tumor panel., Results: From May 2021 to November 2022, 14 patients were enrolled, at which point the trial was closed due to termination of all infigratinib oncology trials. Two patients (14.3%) had treatment-terminating toxicities, well below the stopping threshold. Responses occurred in 6 (66.7%) of 9 patients with FGFR3 alterations. Responders had median tumor size reduction of 67%, with 3 of 5 patients initially planned for nephroureterectomy/ureterectomy converted to ureteroscopy. Median follow-up in responders was 24.7 months (14.9-28.9)., Conclusions: In this first trial of targeted therapy for localized UTUC, FGFR inhibition was well tolerated and had significant activity in FGFR3 altered tumors. Renal preservation was enabled in a substantial proportion of participants. These data support the design of a biomarker-driven phase 2 trial of FGFR3 inhibition in this population with significant unmet clinical needs.

Background: Our purpose is to evaluate the long-term oncologic efficacy and survival rates of MRI-guided cryoablation for patients with biopsy-proven cT1a renal cell carcinoma (RCC)., Materials and Methods: We retrospectively reviewed our renal ablation database between January 2007 and June 2021 and only included patients with solitary-biopsy-proven cT1a RCC (≤4 cm) who underwent MRI-guided cryoablation. We excluded patients with genetic syndromes, bilateral RCC, recurrent RCC or benign lesions, those without pathologically proven RCC lesions and patients who underwent radiofrequency ablation or CT-guided cryoablation. For each patient, we collected the following: age, sex, lesion size, right- or left-sided, pathology, ablation zone tumor recurrence, development of new tumor in the kidney other than ablation zone, development of metastatic disease, patient alive or not, date and cause of death. We used the Kaplan and Meier product limit estimator to estimate the survival outcomes., Results: Twenty-nine patients (median age 70 years) met our inclusion criteria. Twenty-nine MRI-guided cryoablation procedures were performed for twenty-nine tumor lesions with a median size of 2.2 cm. A Clavien-Dindo grade III complication developed in one patient (3.4%). Clear cell RCC was the most reported histology (n = 19). The median follow up was 4.5 years. No tumor recurrence or metastatic disease developed in any of the patients. Two patients developed new renal lesions separate from the ablation zone. The 5- and 10-year OS were 72% and 55.6%, respectively. The 5- and 10-year DFS were 90.5% and the 5-year and 10-year LRFS, MFS and CSS were all 100%., Conclusions: MRI-guided cryoablation is a safe treatment with a low complication rate. Long-term follow-up data revealed long-standing oncologic control.

Background: Careful patient selection is critical when considering cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) but few studies have investigated the prognostic value of radiologic features that measure tumor burden., Objective: To develop a prognostic model to improve CN selection with integration of common radiologic features with known prognostic factors associated with mortality in the first year following surgery., Design, Settings, and Participants: Data were analyzed for consecutive patients with mRCC treated with upfront CN at five institutions from 2006 to 2017. Univariable and multivariable models were used to evaluate radiographic features and known risk factors for associations with overall survival. Relevant factors were used to create the SCREEN model and compared to the International mRCC Database Consortium (IMDC) model for predictive accuracy and clinical usefulness., Results and Limitations: A total of 914 patients with mRCC were treated with upfront CN during the study period. Seven independently predictive variables were used in the SCREEN score: three or more metastatic sites, total metastatic tumor burden ≥5 cm, bone metastasis, systemic symptoms, low serum hemoglobin, low serum albumin, and neutrophil/lymphocyte ratio ≥4. Predictive accuracy measured as the area under the receiver operating characteristic curves was 0.76 for the SCREEN score and 0.55 for the IMDC model. Decision curve analysis showed that the SCREEN model was useful beyond the IMDC classifier for threshold first-year mortality probabilities between 15% and 70%., Conclusions: The SCREEN score had higher predictive accuracy for first-year mortality compared to the IMDC scheme in a multi-institutional cohort and may be used to improve CN selection., Patient Summary: This study provides a model to improve selection of patients with metastatic kidney cancer who may benefit from surgical removal of the primary kidney tumor. We found that radiographic measurements of the tumor burden predicted the risk of death in the first year after surgery. The model can be used to improve decision-making by these patients and their physicians., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To evaluate perioperative and oncologic outcomes of a cohort of clinically node negative high-risk penile cancer patients undergoing robotic assisted inguinal lymph node dissection (RAIL) compared to patients undergoing open superficial inguinal lymph node dissection (OSILND)., Patients and Methods: We retrospectively reviewed the clinical characteristics and outcomes of clinically node negative high-risk penile cancer patients undergoing RAIL at MDACC from 2013-2019. We sought to compare this to a contemporary open cohort of clinically node negative patients treated from 1999 to 2019 at MDACC and Moffit Cancer Center (MCC) with an OSILND. Descriptive statistics were used to characterize the study cohorts. Comparison analysis between operative variables was performed using Fisher's exact test and Wilcoxon's rank-sum test. The Kaplan-Meier method was used to estimate survival endpoints., Results: There were 24 patients in the RAIL cohort, and 35 in the OSILND cohort. Among the surgical variables, operative time (348.5 minutes vs. 239.0 minutes, P < 0.01) and the duration of operative drain (37 vs. 22 days P = 0.017) were both significantly longer in the RAIL cohort. Complication incidences were similar for both cohorts (34.3% for OSILND vs. 33.3% for RAIL), with wound complications making up 33% of all complications for RAIL and 31% of complications for OSILND. No inguinal recurrences were noted in either cohort. The median follow-up was 40 months for RAIL and 33 months for OSILND., Conclusions: We observed similar complication rates and surgical variable outcomes in our analysis apart from operative time and operative drain duration. Oncological outcomes were similar between the two cohorts. RAIL was a reliable staging and potentially therapeutic procedure among clinically node negative patients with penile squamous cell carcinoma with comparable outcomes to an OSILND cohort., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: The timing of perioperative nephrotoxic chemotherapy for upper tract urothelial carcinoma (UTUC) remains controversial and strongly depends on predicted platinum eligibility after radical nephroureterectomy (RNU). The study objective was to develop and validate a multivariable nomogram to predict estimated glomerular filtration rate (eGFR) following RNU., Methods: This was a multi-institutional retrospective study of patients with UTUC treated with RNU from 2000 to 2020 at seven high-volume referral centers. Use of adjuvant chemotherapy was risk-stratified. Patients were retrospectively randomly allocated 2:1 to discovery and validation cohorts. Discovery data were used to identify independent factors associated with GFR at 1-3 mo after RNU on linear regression, and backward selection was applied for model construction. Accuracy was defined as the percentage of predicted eGFR results within 30% of the corresponding observed eGFR., Key Findings and Limitations: We included 1100 patients, of whom 733 were in the discovery and 367 were in the validation cohort. Multivariable predictors of postoperative eGFR decline included advanced age (odds ratio [OR] -0.18, 95% confidence interval [CI] -0.28 to -0.08), diabetes (OR -2.38, 95% CI -4.64 to -0.11), and hypertension (OR -2.24, 95% CI -4.16 to -0.32). Factors associated with favorable postoperative eGFR included larger tumor size (OR 10.57, 95% CI 7.4-13.74 for tumors >5 cm vs ≤2 cm) and preoperative eGFR (OR 0.44, 95% CI 0.39-0.49). A composite nomogram predicted postoperative eGFR with good accuracy in both the discovery (80.5%) and validation (78.6%) cohorts. Limitations include exclusion of patients who received neoadjuvant chemotherapy., Conclusions: A nomogram that incorporates ubiquitous preoperative clinical variables can predict post-RNU eGFR and was validated with an independent cohort., Patient Summary: We developed a tool that uses patient data to predict eligibility for chemotherapy after surgery to remove the kidney and ureter in patients with cancer in the upper urinary tract., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: UGN-101 has been approved for the chemoablation of low-grade upper tract urothelial cancer (UTUC) involving the renal pelvis and calyces. Herein is the first reported cohort of patients with ureteral tumors treated with UGN-101., Patients and Methods: We performed a retrospective review of patients treated with UGN-101 for UTUC at 15 high-volume academic and community centers focusing on outcomes of patients treated for ureteral disease. Patients received UGN-101 with either adjuvant or chemo-ablative intent. Response rates are reported for patients receiving chemo-ablative intent. Adverse outcomes were characterized with a focus on the rate of ureteral stenosis., Results: In a cohort of 132 patients and 136 renal units, 47 cases had tumor involvement of the ureter, with 12 cases of ureteral tumor only (8.8%) and 35 cases of ureteral plus renal pelvic tumors (25.7%). Of the 23 patients with ureteral involvement who received UGN-101 induction with chemo-ablative intent, the complete response was 47.8%, which did not differ significantly from outcomes in patients without ureteral involvement. Fourteen patients (37.8%) with ureteral tumors had significant ureteral stenosis at first post-treatment evaluation, however, when excluding those with pre-existing hydronephrosis or ureteral stenosis, only 5.4% of patients developed new clinically significant stenosis., Conclusions: UGN-101 appears to be safe and may have similar efficacy in treating low-grade urothelial carcinoma of the ureter as compared to renal pelvic tumors., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Solomon Woldu receives honoraria for consulting for UroGen Pharma Ltd. Yair Lotan is involved in research with Pacific Edge Inc., Cepheid Inc., MDx Health and received honoraria for consulting for Nanorobotics, C2I genomics, Photocure, Astra-Zeneca, Merck, Fergene, Abbvie, Nucleix, Ambu, Seattle Genetics, Hitachi, Ferring Research, Verity Pharmaceutics, Virtuoso Surgical, Stimit, Urogen Pharma Ltd, Vessi medical, CAPs medical, Xcures, BMS, Nonagen, Aura Biosciences, Inc., Convergent Genomics, Pacific Edge, Pfizer, Phinomics Inc, CG oncology, Uroviu, On target lab., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate factors associated with perioperative outcomes in a multi-institutional cohort of patients treated with cytoreductive nephrectomy (CN)., Methods: Data were analyzed for metastatic renal cell carcinoma patients treated with CN at 6 tertiary academic centers from 2005 to 2019. Outcomes included: Clavien-Dindo complications, mortality, length of hospitalization, 30-day readmission rate, and time to systemic therapy. Univariate and multivariable models evaluated associations between outcomes and prognostic variables including the year of surgery., Results: A total of 1272 consecutive patients were treated with CN. Patients treated in 2015-2019 vs 2005-2009 had better performance status (P<.001), higher pathologic N stage (P = .04), more frequent lymph node dissections (P<.001), and less frequent presurgical therapy (P = .02). Patients treated in 2015-2019 vs 2005-2009 had lower overall and major complications from surgery, 22% vs 39%, P<.001% and 10% vs 16%, P = .03. Mortality at 90days was higher for patients treated 2005-2009 vs 2015-2019; 10% vs 5%, P = .02. After multivariable analysis, surgical time period was an independent predictor of major complications and 90-day mortality following cytoreductive surgery., Conclusion: Postoperative major complications and mortality rates following CN are significantly lower in patients treated within the most recent time period., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Background: UGN-101 can be used for chemoablation of low-grade upper tract urothelial carcinoma (UTUC). The gel can be administered via a retrograde route through a ureteral catheter or an antegrade route via a nephrostomy tube., Objective: To report outcomes of UGN-101 by route of administration., Design, Setting, and Participants: We performed a retrospective review of 132 patients from 15 institutions who were treated with UGN-101 for low-grade UTUC via retrograde versus antegrade administration., Outcome Measurements and Statistical Analysis: Survival outcomes are reported per patient. Treatment, complications, and recurrence outcomes are reported per renal unit. Statistical analysis was performed for primary endpoints of oncological response and ureteral stricture occurrence., Results and Limitations: A total of 136 renal units were evaluated, comprising 78 retrograde and 58 antegrade instillations. Median follow-up was 7.4 mo. There were 120 cases (91%) of biopsy-proven low-grade UTUC. Tumors were in the renal pelvis alone in 89 cases (65%), in the ureter alone in 12 cases (9%), and in both in 35 cases (26%). Seventy-six patients (56%) had residual disease before UGN-101 treatment. Chemoablation with UGN-101 was used in 50/78 (64%) retrograde cases and 26/58 (45%) antegrade cases. A complete response according to inspection and cytology was achieved in 31 (48%) retrograde and 30 (60%) antegrade renal units (p = 0.1). Clavien grade 3 ureteral stricture occurred in 21 retrograde cases (32%) and only six (12%) antegrade cases (p < 0.01). Limitations include treatment bias, as patients in the antegrade group were more likely to undergo endoscopic mechanical ablation before UGN-101 instillation., Conclusions: These preliminary results show a significantly lower rate of stricture occurrence with antegrade administration of UGN-101, with no apparent impact on oncological efficacy., Patient Summary: We compared results for two different delivery routes for the drug UGN-101 for treatment of cancer in the upper urinary tract. For the antegrade route, a tube is inserted through the skin into the kidney. For the retrograde route, a catheter is inserted past the bladder into the upper urinary tract. Our results show a lower rate of narrowing of the ureter (the tube draining urine from the kidney into the bladder) using the antegrade route, with no difference in cancer control., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Repeat partial nephrectomy (PN) for tumors recurring in the ipsilateral kidney is associated with surgical complexity and a higher rate of complications., Objective: To evaluate the local oncologic efficacy of thermal ablation (TA) for renal cell carcinoma (RCC) in the ipsilateral kidney following PN., Design Setting Participation: We included patients who underwent ablation for renal tumors in the ipsilateral kidney after PN between January 2005 and December 2019. Demographics, tumor size, procedural details, complications, pathology, local oncologic outcomes, and survival outcomes are described., Outcome Measurements and Statistical Analysis: The procedural, pathologic, and oncologic outcomes are described. Survival rates were estimated using the Kaplan-Meier method., Results and Limitations: A total of 66 patients (46 male and 20 female) with a median age of 62 yr (interquartile range [IQR] 52-69) met our inclusion criteria. In these patients, 74 TA procedures were performed for 86 lesions (median tumor size 1.9 cm, IQR 1.6-2.5). Radiofrequency ablation and cryoablation accounted for 60 (81%) and 14 (19%) procedures, respectively. Three patients (3.7%) had Clavien-Dindo grade III complications. Of 65 lesion biopsies, 62 (95.5%) were diagnostic. The most common subtype was clear cell RCC ( n  = 37). The median imaging follow-up duration was 60 mo (IQR 43-88). Recurrence in the ablation zone occurred for four lesions (4.6%) at a median of 6.9 mo (IQR 6.4-10.7). The rates of overall, recurrence-free, and disease-free survival were 93.1%, 94.4%, and 65.6% at 5 yr, and 71.6%, 94.4%, and 60.1% at 10 yr, respectively. Limitations include the retrospective design and the lack of a control group., Conclusions: TA is effective for the treatment of RCC in the ipsilateral kidney following PN., Patient Summary: Heat treatment to remove tumor tissue is an effective option for small kidney masses recurring after partial kidney removal for cancer. Long-term follow-up data revealed that this treatment resulted in low recurrence and complication rates., (© 2023 The Author(s).)

Background: Intracavitary UGN-101 is approved for the treatment of low-grade noninvasive upper tract urothelial carcinoma (UTUC). Post-commercialization studies underscore the benefit of UGN-101 administration for patients with imperative indications for whom radical nephroureterectomy (RNU) is not a viable option., Objective: To describe the use, efficacy, and safety of UGN-101 in patients with UTUC with imperative indications for renal preservation, including high-grade disease., Design, Setting, and Participants: Patients receiving UGN-101 with imperative indications were retrospectively analyzed using a multicenter centralized registry from 15 high-volume academic and community centers., Outcome Measurements and Statistical Analysis: We defined imperative indications as patients with a solitary kidney, the presence of chronic kidney disease (CKD) with a glomerular filtration rate <30 ml/min, bilateral UTUC, and patients unfit for or unwilling to undergo surgical extirpation. Tumor characteristics, disease progression/recurrence, and adverse events were recorded on a per-renal-unit basis., Results and Limitations: UGN-101 was instilled into 52 renal units (38%) in 48 patients for imperative indications, including 29 patients (56%) with a solitary kidney, 11 kidneys (21%) in the setting of bilateral UTUC, six patients (12%) with CKD, and six patients (12%) who were unfit for or unwilling to undergo RNU. Twelve renal units had biopsy-proven high-grade papillary disease. Tumors were completely ablated before induction therapy in 34% of cases, while 66% had tumor present. Following induction therapy, 17 patients (40%) had no evidence of disease (NED) on ureteroscopy, 88% of whom maintained this status at median follow-up of 10.8 mo. In the cohort with high-grade disease, five patients (45%) had NED at initial post-induction primary disease evaluation. Adverse events included pyelonephritis (8%), ureteral stenosis (8%), anemia (6%), and acute renal failure (4%). Limitations include the retrospective study design, the lack of long-term follow up, and patient selection bias., Conclusions: Intracavitary therapy with UGN-101 in patients with UTUC and imperative indications shows promise as a kidney-sparing treatment modality. While long-term follow-up is needed, this intracavitary treatment may help in prolonging time to RNU and delaying the morbidity of hemodialysis in this comorbid population., Patient Summary: We reviewed results for patients with cancer in the upper urinary tract and an additional condition that would not allow kidney removal who received treatment with a gel called UGN-101. Our results suggest that UGN-101 shows promise as a kidney-sparing treatment. It may delay the time until kidney removal is needed in these patients and avoid the negative effects associated with dialysis., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Assess the real-world ablative effect of mitomycin reverse thermal gel for low-grade upper tract urothelial carcinoma (UTUC) in patients who undergo biopsy only or partial ablation and evaluate utility of complete ablation prior to UGN-101., Material and Methods: We retrospectively reviewed low-grade UTUC patients treated with UGN-101 from 15 high-volume centers. Patients were categorized based on initial endoscopic ablation (biopsy only, partial ablation, or complete ablation) and by size of remaining tumor (complete ablation, <1cm, 1-3cm, or >3cm) prior to UGN-101. The primary outcome was rendered disease free (RDF) rate at first post-UGN-101 ureteroscopy (URS), defined as complete response or partial response with minimal mechanical ablation to endoscopically clear the upper tract of visible disease., Results: One hundred and sixteen patients were included for analysis after excluding those with high-grade disease. At first post-UGN-101 URS, there were no differences in RDF rates between those who at initial URS (pre-UGN-101) had complete ablation (RDF 77.0%), partial ablation (RDF 55.9%) or biopsy only (RDF 66.7%) (P = 0.14). Similarly, a complimentary analysis focusing on tumor size (completely ablated, <1cm, 1-3cm or >3cm) prior to UGN-101 induction did not demonstrate significant differences in RDF rates (P = 0.17)., Conclusion: The results of the early real-world experience suggest that UGN-101 may play a role in initial chemo-ablative cytoreduction of larger volume low-grade tumors that may not initially appear to be amenable to renal preservation. Further studies will help to better quantify the chemo-ablative effect and to identify clinical factors for patient selection., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this guideline is to provide a useful reference on the effective evidence-based diagnoses and management of non-metastatic upper tract urothelial carcinoma (UTUC)., Materials/methods: The Pacific Northwest Evidence-based Practice Center of Oregon Health & Science University (OHSU) team conducted searches in Ovid MEDLINE (1946 to March 3rd, 2022), Cochrane Central Register of Controlled Trials (through January 2022), and Cochrane Database of Systematic Reviews (through January 2022). The searches were updated August 2022. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (Table 1).[Table: see text]Results:This Guideline provides updated, evidence-based recommendations regarding diagnosis and management of non-metastatic UTUC including risk stratification, surveillance and survivorship. Treatments discussed include kidney sparing management, surgical management, lymph node dissection (LND), neoadjuvant/adjuvant chemotherapy and immunotherapy., Conclusion: This standardized guideline seeks to improve clinicians' ability to evaluate and treat patients with UTUC based on available evidence. Future studies will be essential to further support these statements for improving patient care. Updates will occur as the knowledge regarding disease biology, clinical behavior and new therapeutic options develop.

Sitravatinib is an immunomodulatory tyrosine kinase inhibitor that can augment responses when combined with programmed death-1 inhibitors such as nivolumab. We report a single-arm, interventional, phase 2 study of neoadjuvant sitravatinib in combination with nivolumab in patients with locally advanced clear cell renal cell carcinoma (ccRCC) prior to curative nephrectomy (NCT03680521). The primary endpoint was objective response rate (ORR) prior to surgery with a null hypothesis ORR = 5% and the alternative hypothesis set at ORR = 30%. Secondary endpoints were safety; pharmacokinetics (PK) of sitravatinib; immune effects, including changes in programmed cell death-ligand 1 expression; time-to-surgery; and disease-free survival (DFS). Twenty patients were evaluable for safety and 17 for efficacy. The ORR was 11.8%, and 24-month DFS probability was 88·0% (95% CI 61.0 to 97.0). There were no grade 4/5 treatment-related adverse events. Sitravatinib PK did not change following the addition of nivolumab. Correlative blood and tissue analyses showed changes in the tumour microenvironment resulting in an immunologically active tumour by the time of surgery (median time-to-surgery: 50 days). The primary endpoint of this study was not met as short-term neoadjuvant sitravatinib and nivolumab did not substantially increase ORR., (© 2023. The Author(s).)

Purpose: We describe a novel application of the reverse thermal polymer gel of mitomycin C (UGN-101) as adjuvant therapy after complete endoscopic ablation of upper tract urothelial carcinoma., Materials and Methods: We retrospectively reviewed patients treated with UGN-101 from 15 high-volume centers. Adjuvant therapy was defined as treatment administered following visually complete endoscopic ablation. Response at primary endoscopic evaluation was defined as no visual tumor or negative biopsy. Ipsilateral disease-free and progression-free survival were estimated by the Kaplan-Meier method. Ureteral stenosis and other adverse events were abstracted from the medical records. Ureteral stenosis was defined as a condition requiring ureteral stent or nephrostomy, or that would typically warrant stent or nephrostomy., Results: Adjuvant UGN-101 after complete endoscopic ablation was used in 52 of 115 (45%) renal units in the oncologic analysis. At first endoscopic evaluation, 36/52 (69%) were without visible disease. At 6.8 months' median follow-up, the ipsilateral disease-free rate was 63%. Recurrence after adjuvant UGN-101 therapy was more likely in multifocal tumors compared to unifocal (HR 3.3, 95% CI 1.07-9.91). Compared with UGN-101 treatment for chemoablation of measurable disease, there were significantly fewer disease detections with adjuvant therapy ( P < .001). Ureteral stenosis after UGN-101 was diagnosed in 10 patients (19%) undergoing adjuvant therapy compared to 17 (29%) undergoing chemoablative therapy ( P = .28)., Conclusions: In patients being considered for UGN-101, maximal endoscopic ablation prior to UGN-101 treatment may result in fewer patients with disease at first endoscopy and possibly fewer adverse events than primary chemoablative therapy. Longer follow-up is needed to determine if UGN-101 after complete endoscopic ablation will lead to durable disease-free interval.

Background: UGN-101 is a novel delivery system for intracavitary treatment of upper tract urothelial cancer (UTUC). UGN-101 was approved based on a pivotal trial for small volume residual low-grade UTUC. Our aim was to report our experience with UGN-101 in a more heterogenous and real-world setting., Methods: We performed a retrospective review of all UGN-101 cases from 15 institutions with a focus on practice patterns, efficacy, and adverse effects. We include UGN-101 utilization in both the chemoablative and adjuvant setting., Results: There were a total 136 renal units treated from 132 patients. The majority of cases were biopsy proven low-grade UTUC. Practice patterns varied considerably - the most common administration technique was antegrade instillation via a percutaneous nephrostomy. When utilized in the adjuvant setting, 69% of patients were disease free at the time of their first endoscopic evaluation, while in the chemoablative setting, 37% were endoscopically clear on the first evaluation (P < 0.001). Complete response was higher in patients with smaller tumor size prior to UGN-101 induction; low volume (<1 cm) residual disease was associated with a 70% complete response, similar to disease free rate at first endoscopic evaluation when UGN-101 was used in the adjuvant setting. The use of maintenance doses of UGN-101 was reported in 27% of cases. The overall incidence of new onset, clinically significant ureteral stenosis was 23%., Conclusions: This study represents the largest review of patients treated with UGN-101 and can serve as a basis of ongoing hypotheses regarding treatment with UGN-101 for UTUC., Competing Interests: Conflict of interest Solomon Woldu receives honoraria for consulting for UroGen Pharma Ltd. Yair Lotan is involved in research with Pacific Edge Inc., Cepheid Inc., MDx Health and received honoraria for consulting for UroGen Pharma Ltd., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The aim is to determine the long-term oncologic and survival outcomes of the radiofrequency ablation (RFA) of solitary de novo T1a renal cell carcinoma (RCC)., Materials and Methods: We retrospectively reviewed our renal ablation registry and included only patients with new solitary, biopsy-proven T1a RCC (<4 cm) who underwent RFA from January 2001 through December 2020. We collected patient and tumor characteristics. Survival rates were estimated using the Kaplan-Meier method., Results: Of the 243 patients who met our inclusion criteria (160 male and 83 female, median age 68 years), 128 (52.6%) had another primary malignancy other than renal malignancy. Two-hundred forty-three RFA procedures were performed for 243 renal tumors of a median tumor size of 2.5 cm. The median follow-up period was 3.7 years. Most tumors (68.6%) were clear cell RCC. Ten patients (4.1%) experienced Clavien-Dindo Grade III complications. Seven patients(3.1%) developed recurrence at the ablation zone, and 11 (4.5%) developed recurrence elsewhere in the kidney. The 15-year local-recurrence- and disease-free survival were 96.5% and 88.6%, respectively. The 15-year metastasis-free survival and cancer-specific survival were 100%., Conclusions: RFA is a highly effective modality for the management of T1a RCC, with low complication and recurrence rates. Long-term data revealed favorable oncologic and survival outcomes.

Context: Bladder recurrences have been reported in 22-47% of patients after surgery for upper urinary tract urothelial carcinoma (UTUC). This collaborative review focuses on risk factors for and treatment strategies to reduce bladder recurrences after upper tract surgery for UTUC., Objective: To review the current evidence on risk factors and treatment strategies for intravesical recurrence (IVR) after upper tract surgery for UTUC., Evidence Acquisition: This collaborative review is based on a literature search of PubMed/Medline, Embase, Cochrane Library, and currently available guidelines on UTUC. Relevant papers on bladder recurrence (etiology, risk factors, and management) after upper tract surgery were selected. Special attention has been paid to (1) the genetic background of bladder recurrences, (2) bladder recurrences after ureterorenoscopy (URS) with or without a biopsy, and (3) postoperative or adjuvant intravesical instillations. The literature search was performed in September 2022., Evidence Synthesis: Recent evidence supports the hypothesis that bladder recurrences after upper tract surgery for UTUC are often clonally related. Clinicopathologic risk factors (patient, tumor, and treatment related) have been identified for bladder recurrences after UTUC diagnosis. Specifically, the use of diagnostic ureteroscopy before radical nephroureterectomy (RNU) is associated with an increased risk of bladder recurrences. Further, a recent retrospective study suggests that performing a biopsy during ureteroscopy may further worsen IVR (no URS: 15.0%; URS without biopsy: 18.4%; URS with biopsy: 21.9%). Meanwhile, a single postoperative instillation of intravesical chemotherapy has been shown to be associated with a reduced bladder recurrence risk after RNU compared with no instillation (hazard ratio 0.51, 95% confidence interval 0.32-0.82). Currently, there are no data on the value of a single postoperative intravesical instillation after ureteroscopy., Conclusions: Although based on limited retrospective data, performing URS seems to be associated with a higher risk of bladder recurrences. Future studies are warranted to assess the influence of other surgical factors as well as the role of URS biopsy or immediate postoperative intravesical chemotherapy after URS for UTUC., Patient Summary: In this paper, we review recent findings on bladder recurrences after upper tract surgery for upper urinary tract urothelial carcinoma., (© 2023 The Author(s).)

Purpose: Venous thromboembolic events (VTEs) are a major cause of morbidity following abdominopelvic oncologic surgery. Enoxaparin, a subcutaneous injectable low molecular weight heparin, is commonly used for extended-duration VTE prophylaxis (EP), but has been associated with noncompliance. Newer direct oral anticoagulants have not been prospectively studied in the urologic oncology post-discharge setting. We aimed to improve compliance with EP following abdominopelvic oncologic surgery and secondarily test the hypothesis that apixaban is noninferior to enoxaparin for EP., Materials and Methods: A single-center prospective quality improvement study measuring patient compliance and safety with EP was conducted between August 10, 2020 and September 21, 2021. Baseline data were continuously collected for 6 months, followed by a uniform departmental change from enoxaparin to apixaban. The duration of data collection was determined a priori using a noninferiority sample size estimation (145 per group). The primary outcome was compliance events (real or potential barriers to EP use). The secondary outcome was 30-day post-discharge safety events (symptomatic VTE or major bleed)., Results: A total of 161 patients were discharged with enoxaparin (baseline period) and 154 with apixaban (intervention period). Safety events occurred in 3.1% vs 0% of patients receiving enoxaparin and apixaban, respectively. The absolute risk difference of 3.1% (95% CI: 0.043%-5.8%) met the prespecified noninferiority threshold (p=0.028 for apixaban superiority). Compliance events occurred in 33.5% of enoxaparin patients and 14.3% of apixaban patients (p=0.0001)., Conclusions: There were fewer compliance events using apixaban for EP than enoxaparin after urologic oncology surgery. Regarding safety, apixaban is noninferior to enoxaparin and may in fact have fewer associated major complications.

Purpose: Renal function dictates sequencing and eligibility for definitive therapy in upper tract urothelial carcinoma. We investigated longitudinal glomerular filtration rate (GFR) changes after neoadjuvant chemotherapy (NAC) and nephroureterectomy (RNU)., Materials and Methods: Patients treated with ≥3 cycles of chemotherapy prior to RNU for UTUC from 2000 to 2019 were included. GFR was calculated by CKD-Epi before chemotherapy, before RNU, 1 to 3 months, and 12 months post-RNU. Pathologic stage and overall survival were compared in those with stable GFR (+/-10% of baseline) to the rest of the cohort., Results: One hundred and fifty-two patients received ≥3 cycles of NAC, with 121 (79%) receiving at least 1 cycle of cisplatin. Renal function dropped by mean of 22.3 ml/min/1.73 m 2 from the beginning of chemotherapy to 1-year post-surgery. In patients receiving cisplatin, a mean decline of 26.2 ml/min/1.73 m 2 was observed vs. 8.8 ml/min/1.73 m 2 without cisplatin-based NAC (P < 0.01). GFR after RNU was unchanged between 3 and 12 months postoperatively. At 1 to 3 months after RNU, 19% of patients had GFR<30 ml/min/1.73m 2 . Improvement in GFR during NAC was associated with invasive final pathologic stage (P = 0.018) and worse overall survival (P = 0.049)., Conclusions: In patients managed with NAC prior to RNU, renal function stabilizes at 1 to 3 months post-operatively and remains clinically similar for cisplatin or non-cisplatin-based therapy. Improvement in GFR during NAC was associated with higher pathologic stage and poorer survival, especially in those receiving non-cisplatin-based therapy, an observation that requires further investigation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Surgical resection of renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is a complex procedure with significant morbidity. Patient selection is critical to determining whether the benefits of the procedure outweigh the risks. In this study, we identified and stratified the risk factors that were associated with overall survival (OS) and recurrence-free survival (RFS) in patients undergoing surgical resection of RCC with IVC thrombus., Methods: We identified all patients with RCC with IVC tumor thrombus (stages cT3b and cT3c) who had undergone radical nephrectomy with tumor thrombectomy between December 1, 1993 and June 30, 2009. Kaplan-Meier method was used to estimate OS and RFS. Cox proportional hazards models were used to determine the association between risk factors and OS. Patients were stratified into 3 groups based on the number of risk factors present at diagnosis., Results: Two hundred twenty-four patients were included in the study. A total of 45.3% of patients had metastasis at presentation, 84.5% had cT3b, and 90.2% had clear cell RCC. cT3c, cN1, and cM1 were significantly associated with the risk of death. Group 1 patients (0 risk factors) had a median OS duration of 77.6 months (95% CI 50.5-90.4), group 2 (1 risk factor) 26.0 months (95% CI 19.5-35.2), and group 3 (≥2 risk factors) 8.9 months (95% CI 5.2-12.9; P < .001)., Conclusions: Stratification of patients with RCC and IVC thrombus by risk factors allowed us to predict survival duration. In patients with ≥2 risk factors, new treatment strategies with preoperative systemic therapy may improve survival., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To study the effects of adjuvant therapy in patients with sarcomatoid renal cell carcinoma (sRCC) enrolled in the randomised phase III clinical trial E2805., Patients and Methods: The original trial (E2805) was a randomised, double-blinded phase III clinical trial comparing outcomes in 1943 patients with RCC accrued between 2006 and 2010 and treated with up to 1 year of adjuvant placebo, sunitinib, or sorafenib. The present study analyses the cohort of patients with sRCC that participated in E2805., Results: A total of 171 patients (8.8%) had sarcomatoid features. Of these, 52 patients received sunitinib, 58 received sorafenib, and 61 received placebo. Most patients were pT3-4 (71.1%, 63.7%, and 70.5%, respectively); 17.3%, 19.0%, and 27.9% had pathologically positive lymph nodes; and 59.6%, 62.1%, and 62.3% of the patients were University of California Los Angeles (UCLA) Integrated Staging System (UISS) very-high risk. In 49% of patients with subsequent development of metastatic disease, recurrence occurred in the lung, followed by 30% in the lymph nodes, and 13% in the liver. There was a high local recurrence rate in the renal bed (16%, 29%, and 18%, respectively). The 5-year disease-free survival (DFS) rates were 33.6%, 36.0%, and 27.8%, for sunitinib, sorafenib and placebo, respectively (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.45-1.20 for sunitinib vs placebo, and HR 0.82, 95% CI 0.53-1.28 for sorafenib vs placebo)., Conclusions: Adjuvant therapy with sunitinib or sorafenib did not show an improvement in DFS or OS in patients with sRCC., (© 2021 The Authors BJU International © 2021 BJU International.)

Objective: To study whether delivering definitive radiotherapy (RT) to sites of oligoprogression in metastatic renal cell carcinoma (mRCC) enabled deferral of systemic therapy (ST) changes without compromising disease control or survival., Patients and Methods: We identified patients with mRCC who received RT to three or fewer sites of extracranial progressive disease between 2014 and 2019 at a large tertiary cancer centre. Inclusion criteria were: (1) controlled disease for ≥3 months before oligoprogression, (2) all oligoprogression sites treated with a biologically effective dose of ≥100 Gy, and (3) availability of follow-up imaging. Time-to-event end-points were calculated from the start of RT., Results: A total of 72 patients were identified (median follow-up 22 months, 95% confidence interval [CI] 19-32 months), with oligoprogressive lesions in lung/mediastinum (n = 35), spine (n = 30), and non-spine bone (n = 5). The most common systemic therapies before oligoprogression were none (n = 33), tyrosine kinase inhibitor (n = 23), and immunotherapy (n = 13). At 1 year, the local control rate was 96% (95% CI 87-99%); progression-free survival (PFS), 52% (95% CI 40-63%); and overall survival, 91% (95% CI 82-96%). At oligoprogression, ST was escalated (n = 16), maintained (n = 49), or discontinued (n = 7), with corresponding median (95% CI) PFS intervals of 19.7 (8.2-27.2) months, 10.1 (6.9-13.2) months, and 9.8 (2.4-28.9) months, respectively. Of the 49 patients maintained on the same ST at oligoprogression, 21 did not subsequently have ST escalation., Conclusion: Patients with oligoprogressive mRCC treated with RT had comparable PFS regardless of ST strategy, suggesting that RT may be a viable approach for delaying ST escalation. Randomised controlled trials comparing treatment of oligoprogression with RT vs ST alone are needed., (© 2021 The Authors BJU International © 2021 BJU International.)

Purpose: 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., Materials and Methods: 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., Results: 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., Conclusions: 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.

Background: Emerging data suggests improved outcomes in patients receiving neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) for high-risk upper tract urothelial carcinoma. In one of the largest single-center experiences to date, we provide an updated analysis of outcomes of patients receiving NAC followed by RNU., Patients and Methods: A retrospective review of patients with high-risk UTUC who received NAC followed by surgery between 2004 to 2017 was conducted. 126 patients were evaluated as part of the analysis. Kaplan-Meier method was used to estimate survival probabilities. Multivariable Cox modeling was used to evaluate for association with outcomes, and the cumulative incidence factor was used for competing risk analysis., Results: Median OS time was 106 months. 14.3% of patients had a pathologic complete response and 60% were down-staged to ypT0-1 ypN0. The estimated 5 and 10-year DSS rates were 89.8% and 80.6%, respectively. The estimated 5 and 10-year metastasis-free survival rates were 81% and 75.4%, respectively. The estimated 5 and 10-year OS rates were 73.7% and 35.9 %, respectively. Recurrences mainly occurred in lymph nodes and lung at a median time of 15.5 months (IQR 8.9-27). The estimated 5 and 10-year cumulative incidence factor for death from UTUC was 9.5% and 16.1%, respectively. Limitations include retrospective nature and challenge of accurate pre-surgical staging., Conclusions: NAC prior to RNU in high-risk UTUC shows durable 5 and 10-year OS and DSS rates in a large single-institution series, confirming prior findings in prospective trials and retrospective studies., (Copyright © 2021. Published by Elsevier Inc.)

Background: The European Association of Urology risk stratification dichotomizes patients with upper tract urothelial carcinoma (UTUC) into two risk categories., Objective: To evaluate the predictive value of a new classification to better risk stratify patients eligible for kidney-sparing surgery (KSS)., Design, Setting, and Participants: This was a retrospective study including 1214 patients from 21 centers who underwent ureterorenoscopy (URS) with biopsy followed by radical nephroureterectomy (RNU) for nonmetastatic UTUC between 2000 and 2017., Outcome Measurements and Statistical Analysis: A multivariate logistic regression analysis identified predictors of muscle invasion (≥pT2) at RNU. The Youden index was used to identify cutoff points., Results and Limitations: A total of 811 patients (67%) were male and the median age was 71 yr (interquartile range 63-77). The presence of non-organ-confined disease on preoperative imaging (p < 0.0001), sessile tumor (p < 0.0001), hydronephrosis (p = 0.0003), high-grade cytology (p = 0.0043), or biopsy (p = 0.0174) and higher age at diagnosis (p = 0.029) were independently associated with ≥pT2 at RNU. Tumor size was significantly associated with ≥pT2 disease only in univariate analysis with a cutoff of 2 cm. Tumor size and all significant categorical variables defined the high-risk category. Tumor multifocality and a history of radical cystectomy help to dichotomize between low-risk and intermediate-risk categories. The odds ratio for muscle invasion were 5.5 (95% confidence interval [CI] 1.3-24.0; p = 0.023) for intermediate risk versus low risk, and 12.7 (95% CI 3.0-54.5; p = 0.0006) for high risk versus low risk. Limitations include the retrospective design and selection bias (all patients underwent RNU)., Conclusions: Patients with low-risk UTUC represent ideal candidates for KSS, while some patients with intermediate-risk UTUC may also be considered. This classification needs further prospective validation and may help stratification in clinical trial design., Patient Summary: We investigated factors predicting stage 2 or greater cancer of the upper urinary tract at the time of surgery for ureter and kidney removal and designed a new risk stratification. Patients with low or intermediate risk may be eligible for kidney-sparing surgery with close follow-up. Our classification scheme needs further validation based on cancer outcomes., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: The incidence and risk factors for metachronous upper tract urothelial carcinoma (UTUC) following radical cystectomy (RC) remain incompletely defined, which has limited the ability to individualize postoperative surveillance., Materials and Methods: A retrospective review of 2 institutional registries was performed to identify patients undergoing RC for urothelial carcinoma. Multivariable Cox proportional hazard models for metachronous post-RC UTUC were developed in one institutional data set and validated in the second institutional data set. A post-RC UTUC risk score was then developed from these models., Results: A total of 3,170 RC patients were included from the training cohort and 959 RC patients from the validation cohort. At a median followup after RC of 4.6 years (IQR 2.1-8.7), 167 patients were diagnosed with UTUC. On multivariable analysis in the training cohort, risk factors for metachronous UTUC were the presence of positive urothelial margin (HR 2.60, p <0.01), history of bacillus Calmette-Guérin treatment prior to RC (HR 2.20, p <0.01), carcinoma in situ at RC (HR 2.01, p <0.01) and pre-RC hydronephrosis (HR 1.48, p=0.04). These factors had similar discriminative capacity in the training and validation cohorts (C-statistic 0.71 and 0.73, respectively). A UTUC risk score was developed with these variables which stratified patients into low (0 points), intermediate (1-3 points), and high risk (4+ points) for post-RC UTUC, with respective 5-year UTUC-free survivals of 99%, 96%, 89% in the training cohort and 98%, 96%, and 91% in the validation cohort., Conclusions: We developed and validated a risk score for post-RC UTUC that may optimize UTUC surveillance protocols after RC.

Objective: Tumor shrinkage of at least 10% after presurgical targeted molecular therapy (TMT) in renal cell carcinoma (RCC) patients has been associated with better overall survival (OS) outcomes. We characterized primary and metastatic tumor diameter response and OS in patients with metastatic clear cell RCC (ccRCC) who received preoperative TMT, immunotherapy, or both followed by deferred cytoreductive nephrectomy (dCN)., Materials and Methods: Patients with metastatic ccRCC (n = 198) who underwent preoperative therapy and dCN from 2005 to 2019 were identified retrospectively. Longest primary and metastatic tumor diameters were calculated using cross-sectional images obtained before systemic therapy and dCN using the Response Evaluation Criteria in Solid Tumors. Patients were stratified by tumor shrinkage of at least 10% in the primary and/or metastatic tumors after systemic therapy. The Kaplan-Meier method was used to estimate OS, and Cox proportional hazards models were used to assess the association of patient characteristics with OS., Results: In total, 31.31% of patients had only metastatic tumor shrinkage (MTS) ≥ 10%, 8.08% had only primary tumor shrinkage (PTS) ≥ 10%, 32.32% had PTS and MTS ≥ 10%, and 28.28% had PTS/MTS < 10%. The median OS, number of patients with tumor shrinkage ≥ 10%, and International Metastatic Database Consortium (IMDC) scores were similar among the 3 systemic therapy groups (all P ≥ 0.80). Patients with MTS ≥ 10%, PTS ≥ 10%, and PTS/MTS ≥ 10% had significantly longer median OS compared to patients with PTS/MTS < 10% (P < 0.01). Patients with intermediate-risk IMDC scores had significantly longer median OS compared to patients in the poor-risk group. After adjusting for preoperative therapy and IMDC risk group, MTS ≥ 10%, PTS ≥ 10%, and PTS/MTS ≥ 10% were associated with better OS outcomes (HR 0.48 95% CI 0.32-0.73, P < 0.001; HR 0.48, 95% CI 0.23-0.98, P = 0.04; HR 0.44, 95% CI 0.29-0.67, P < 0.001, respectively)., Conclusions: Intermediate risk score and shrinkage of at least 10% in the primary tumor, metastases, or both were associated with better OS outcomes in patients with metastatic ccRCC who underwent dCN independent of the type of preoperative systemic therapy., Competing Interests: Conflict of interest Matthew T. Campbell: Consulting/Advisory Roles for AstraZeneca, Astellas, Eisai, EMD Serono, Exelixis, Genentech, Pfizer, Seattle Genetics, Consulting: AXDev, Exelixis, Pfizer, Research grants: ApricityHealth, EMD Serono, Exelixis, Janssen, Pfizer, Non-CME education: Bristol Myers Squibb, Merck, Roche, Pfizer. Nizar Tannir: Consulting/advisory roles for Bristol-Myers-Squibb; Pfizer; Nektar Therapeutics; Exelisis, Inc, Eisai Medical Research; Eli Lilly; Oncorena; Calithera Bioscience; Surface Oncology; Novartis, Ipsen; Merck Sharp & Dohme. Research Funding: Bristol-Myers-Squibb; Nektar Therapeutics; Calithera Bioscience; Arrowhead Pharmaceuticals; Eisai; Novartis. Jose A Karam: Consultant/Advisory Board/Honoraria: Pfizer, Merck, Johnson and Johnson Research funding to MD Anderson: Merck, Roche/Genentech, Mirati, Elypta. Stocks: MedTek., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cryoablation in combination with immune checkpoint therapy was previously reported to improve anti-tumor immune responses in pre-clinical studies. Here we report a pilot study of anti-CTLA-4 (tremelimumab) with (n = 15) or without (n = 14) cryoablation in patients with metastatic renal cell carcinoma (NCT02626130), 18 patients with clear cell and 11 patients with non-clear cell histologies. The primary endpoint is safety, secondary endpoints include objective response rate, progression-free survival, and immune monitoring studies. Safety data indicate ≥ grade 3 treatment-related adverse events in 16 of 29 patients (55%) including 6 diarrhea/colitis, 3 hepatitis, 1 pneumonitis, and 1 glomerulonephritis. Toxicity leading to treatment discontinuation occurs in 5 patients in each arm. 3 patients with clear cell histology experience durable responses. One patient in the tremelimumab arm experiences an objective response, the median progression-free survival for all patients is 3.3 months (95% CI: 2.0, 5.3 months). Exploratory immune monitoring analysis of baseline and post-treatment tumor tissue samples shows that treatment increases immune cell infiltration and tertiary lymphoid structures in clear cell but not in non-clear cell. In clear cell, cryoablation plus tremelimumab leads to a significant increase in immune cell infiltration. These data highlight that treatment with tremelimumab plus cryotherapy is feasible and modulates the immune microenvironment in patients with metastatic clear cell histology., (© 2021. The Author(s).)

Introduction: Neoadjuvant chemotherapy (NAC) is increasingly used prior to radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Systemic recurrence (SR) carries a dismal prognosis. We sought to determine risk factors associated with SR in this setting., Methods: We evaluated a multi-center database of patients with UTUC who received cisplatin-based NAC before RNU. Final pathology at RNU was dichotomized into ypT<2 vs ypT≥2. Univariable and multivariable analyses were performed to identify risk factors associated with SR. Three groups were defined based on the number of significant risk factors (groups 1, 2, 3 for 0-1, 2, 3 risk factors, respectively) and evaluated for recurrence-free survival (RFS) using the Kaplan-Meier method., Results: 106 patients were identified between 2004 and 2018. Median age was 67.0 years [IQR = 61-73.3]; 57 (54%) and 49 (46 %) patients received MVAC and GC, respectively. Final pathological stage was ypT<2 in 57 (54%); 23% (24/106) had SR. On univariable analysis, pathological variables on final specimen including ypT≥2, lymphovascular invasion (ypLVI), and nodal involvement were associated with SR. On multivariable analysis, ypLVI OR = 4.1 (95% CI 1.2-13.6; P = 0.024) and pathological nodal involvement OR = 4.5 (95% CI 1.3-15.7; P = 0.017) were predictive of recurrence. Stratifying by the number of risk factors, the 2-year RFS was 95%, 55%, and 18% for groups 1, 2, and 3 respectively (log-rank <0.001)., Conclusion: This model evaluates the risk of SR following NAC and RNU to guide counseling and decision-making after surgery. Adverse pathological variable including ypLVI and nodal involvement, in combination with ypT-stage, are strongly associated with SR., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The presence of sarcomatoid features and/or lymph node-positive disease may be associated with a worse prognosis in chromophobe renal cell carcinoma (ChRCC). We sought to better characterize patients' long-term outcomes with these features compared with those without these features., Materials and Methods: We identified 300 patients treated for sporadic, unilateral, nonmetastatic ChRCC between 1993 and 2019. Clinical and pathologic features were summarized, and cancer-specific survival (CSS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier plots. Cox regression analysis was performed to determine factors associated with recurrence. Patients with sarcomatoid features and/or nodal disease were grouped as high-risk in a secondary analysis., Results: The median age was 60 years, 43.7% were female, 29.3% had pT3/T4 disease, 3.3% had sarcomatoid features, and 4% had pathologic N1 disease. Sixteen patients were categorized as high-risk based on the presence of sarcomatoid features (n = 4), pathologic N1 disease (n = 6), or both (n = 6). There were 22 recurrences; the recurrence rate in the low-risk group was 4.9% and 50% in the high-risk group. 10-year RFS was 91.4% in the low-risk group and 34.4% in the high-risk group (P < 0.001). 10-year CSS was 96.4% in the low-risk group and 54.3% in the high-risk group (P < 0.001). In multivariable analysis, sarcomatoid features (HR 5.5, CI 1.5-20.2, P = 0.01) and pN1 disease (HR 16.5, CI 5.3-51.4, P < 0.0001) were independently associated with RFS., Conclusions: The presence of sarcomatoid features and/or lymph node-positive disease portends a poor prognosis in ChRCC. Further studies evaluating the impact of novel therapeutic agents in these patients are warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of upper tract urothelial carcinoma (UTUC) on bacillus Calmette-Guerin (BCG) response and progression in patients with non-muscle-invasive bladder cancer (NMIBC)., Patients and Methods: We performed an institutional review board-approved review of patients with NMIBC treated with adequate intravesical BCG, as defined by the US Food and Drug Administration, at our institution between 2000 and 2018. Patients were stratified by presence of any UTUC and time of UTUC diagnosis (preceding vs synchronous to NMIBC diagnosis or metachronous disease after NMIBC diagnosis). Descriptive statistics were used to summarize the data overall and by groups, and t-tests or Wilcoxon's rank sum tests and Pearson's chi-squared or Fisher's exact tests were used to analyse continuous and categorical data, respectively., Results: Of 541 patients with NMIBC treated with adequate BCG, 59 (10.9 %) were diagnosed with UTUC. Of these, 34 had a history of UTUC prior to NMIBC (UTUC-P; median [interquartile range {IQR}] 13.1 [7.4-27.6] months prior), while 25 developed UTUC after diagnosis of NMIBC (six synchronous and 19 metachronous; median [IQR] 12.1 [1.7-28.1] months after). Compared to the non-UTUC group, patients with UTUC-P were more likely to exhibit Tis without papillary tumour in the bladder (20.6% vs 5.0%; P < 0.001), but were less likely to have T1 disease on index transurethral resection (8.8% vs 49.4%; P < 0.001). Patients with UTUC-P developed more recurrences (55.9% vs 34.0%; P = 0.010), any stage/grade progression (23.5% vs 9.8%; P = 0.012) and progression to muscle-invasive or metastatic disease (17.6% vs 6.4%; P = 0.014). The presence of high-grade UTUC-P compared to low-grade UTUC-P was associated with increased NMIBC recurrence (68.2% vs 25.0%; P = 0.049). There was no significant difference in rates of recurrence or progression based on timing of UTUC with respect to the index bladder tumour, although this analysis was limited by small numbers., Conclusions: Presence of UTUC prior to a diagnosis of NMIBC was associated with an almost twofold increased recurrence and progression rates after adequate BCG therapy. This should be considered when counselling patients and designing cohorts for clinical trials., (© 2021 The Authors BJU International © 2021 BJU International.)

Objectives: Multimodal kidney-preserving (MKP) strategies may be an option for patients with localised or locally advanced high-risk upper tract urothelial carcinoma (UTUC) who have a relative contraindication for nephroureterectomy (NU)., Materials and Methods: We studied patients with UTUC who were managed with MKP strategies, consisting of systemic anticancer therapy, with or without local/topical strategies after endoscopic control of intraluminal tumours. Primary end points were overall survival (OS) and progression-free survival (PFS)., Results: Fourteen patients received MKP treatment between August 2013 and April 2020. Median baseline estimated glomerular filtration rate was 43 mL/min/1.73m 2 . MKP was mainly pursued to avoid dialysis (10/14, 71%), followed by low performance status and/or comorbidities (2/14, 14%). All patients had received systemic therapy: chemotherapy (64%) and immunotherapy (36%). Endoscopic control and/or laser ablation was feasible in 7 (50%) patients. Calculated overall risk of non-organ confined disease was 35%. Predicted 2-year and 5-year relapse-free probability (RFP) was 74% (24-92%) and 62% (10-85%), respectively. Median follow-up was 31 months (95% CI: 22.6, NE), median OS was 48.1 months (95% CI: 48.1, NE) and 2-year OS probability was 0.89 (95% CI: 0.71, 1). Median metastases-free survival was 48.1 months (95% CI: 26.8, NE), median PFS was 22.4 months (95% CI: 15.6, NE) and 2-year PFS probability was 0.48 (0.26, 0.89)., Conclusion: Management of high-risk localised or locally advanced UTUC with MKP strategies was associated with good tolerance, preservation of renal function, and comparable PFS and OS to predicted in vulnerable patients. Prospective studies with more patients are needed to evaluate these possible benefits relative to current standards., Competing Interests: The authors declare no relevant conflict of interest pertinent to this study. Full conflict of inflict disclosures include research funding from BMS, Eisai, EMD Serono for A.Y.S; Honoraria from Pfizer, Roche, BMS and Exelixis for A.Y.S; and Urogen Pharma (consultant) and Urology Education (speaker) for S.F.M. SFM: grant from QED therapeutics; consulting fees Merck, J&J; honoraria Ology education, Clinical Care Options. NN: consulting Schlesinger Group; Ad Board Aduro Bio Tech; Stock Allogene Therapeutics. AMK: grants Adolor, BMS, FKD Industries, FerGene, Heat Biologics, Merck, Photocure, SWOG, NIH/GU SPORE, AIBCCR, Janssen (+ Taris), Seattle Genetics; consulting Arquer Diagnostics. Asieris, Biological Dynamics, Bristol Myers Squibb, CG Oncology, H3 Biomedicine/Eisai, Engene, FerGene, Imagin Medical, Janssen, Medac, Merck, Photocure, ProTara, Seattle Genetics, Sessen Bio, Theralase, US Biotest, Urogen Inc., Roche, TMC Innovation; patents CyPRIT (Cytokine Predictors of Response to Intravesical Therapy) Joint with UT MD Anderson Cancer Center; ad board: Arquer Diagnostics. Asieris, Biological Dynamics, Bristol Myers Squibb, CG Oncology, H3 Biomedicine/Eisai, Engene, FerGene, Imagin Medical, Janssen, Medac, Merck, Photocure, ProTara, Seattle Genetics, Sessen Bio, Theralase, US Biotest, Urogen Inc., Roche, TMC Innovation; leadership IBCG. MTC: grants or contracts ApricityHealth, Aravive, AstraZeneca, EMD Serono, Exelixis, Janssen, Pfizer; consulting Astellas, AXDev, AstraZeneca, Astellas, Exelixis, Eisai, EMD Serono, Exelixis, Genentech, Pfizer, SeaGen; honoraria Bristol Myers Squibb, Merck, Roche, Pfizer. AZ: grants or contracts Infinity pharma; consulting Amedo, Astra Zeneca, Bayer; honoraria Biocept, CancerNet, Incyte; other Janssen‐Cliag, McKesson Specialty Health, Pfizer. AOS: research grants or contracts: Basilea, Bristol Myers Squibb, Janssen, Merck Sharp and Dohme, Nektar Therapeutics; honoraria Janssen; Ad Board Astrazeneca, Basilea, Bavarian Nordic, Bristol‐Myers Squibb, Genentech, Ideaya Biosciences, Immunomedics, Janssen, LOXO‐Oncology, Merck sharp and Dohme, Mirati, Nektar Therapeutics, Seattle Genetics, Taiho., (© 2021 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Background: Several groups have proposed features to identify low-risk patients who may benefit from endoscopic kidney-sparing surgery in upper tract urothelial carcinoma (UTUC)., Objective: To evaluate standard risk stratification features, develop an optimal model to identify ≥pT2/N+ stage at radical nephroureterectomy (RNU), and compare it with the existing unvalidated models., Design, Setting, and Participants: This was a collaborative retrospective study that included 1214 patients who underwent ureterorenoscopy with biopsy followed by RNU for nonmetastatic UTUC between 2000 and 2017., Outcome Measurements and Statistical Analysis: We performed multiple imputation of chained equations for missing data and multivariable logistic regression analysis with a stepwise selection algorithm to create the optimal predictive model. The area under the curve and a decision curve analysis were used to compare the models., Results and Limitations: Overall, 659 (54.3%) and 555 (45.7%) patients had ≤pT1N0/Nx and ≥pT2/N+ disease, respectively. In the multivariable logistic regression analysis of our model, age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.0-1.03, p = 0.013), high-grade biopsy (OR 1.81, 95% CI 1.37-2.40, p < 0.001), biopsy cT1+ staging (OR 3.23, 95% CI 1.93-5.41, p < 0.001), preoperative hydronephrosis (OR 1.37 95% CI 1.04-1.80, p = 0.024), tumor size (OR 1.09, 95% CI 1.01-1.17, p = 0.029), invasion on imaging (OR 5.10, 95% CI 3.32-7.81, p < 0.001), and sessile architecture (OR 2.31, 95% CI 1.58-3.36, p < 0.001) were significantly associated with ≥pT2/pN+ disease. Compared with the existing models, our model had the highest performance accuracy (75% vs 66-71%) and an additional clinical net reduction (four per 100 patients)., Conclusions: Our proposed risk-stratification model predicts the risk of harboring ≥pT2/N+ UTUC with reliable accuracy and a clinical net benefit outperforming the current risk-stratification models., Patient Summary: We developed a risk stratification model to better identify patients for endoscopic kidney-sparing surgery in upper tract urothelial carcinoma., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)