Decisional and prognostic impact of diagnostic ureteroscopy in high-risk upper tract urothelial carcinoma: A multi-institutional collaborative analysis (ROBUUST collaborative group).

BACKGROUND: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery. MATERIALS AND METHODS: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes. RESULTS: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality. CONCLUSIONS: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings.

Plasma Kidney Injury Molecule-1 for Preoperative Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association With Clinical Outcomes.

PURPOSE: Both clear cell and papillary renal cell carcinomas (RCCs) overexpress kidney injury molecule-1 (KIM-1). We investigated whether plasma KIM-1 (pKIM-1) may be a useful risk stratification tool among patients with suspicious renal masses. METHODS: Prenephrectomy pKIM-1 was measured in two independent cohorts of patients with renal masses. Cohort 1, from the prospective K2 trial, included 162 patients found to have clear cell RCC (cases) and 162 patients with benign renal masses (controls). Cohort 2 included 247 patients with small (cT1a) renal masses from an academic biorepository, of whom 184 had RCC. We assessed the relationship between pKIM-1, surgical pathology, and clinical outcomes. RESULTS: In Cohort 1, pKIM-1 distinguished RCC versus benign masses with area under the receiver operating curve (AUC-ROC, 0.81 [95% CI, 0.76 to 0.86]). In Cohort 2 (cT1a only), pKIM-1 distinguished RCC versus benign masses (AUC-ROC, 0.74 [95% CI, 0.67 to 0.80]) and the addition of pKIM-1 to an established nomogram for predicting malignancy improved the model AUC-ROC (0.65 [95% CI, 0.57 to 0.74] v 0.78 [95% CI, 0.72 to 0.85]). A pKIM-1 cutpoint identified using Cohort 2 demonstrated sensitivity of 92.5% and specificity of 60% for identifying RCC in Cohort 1. In long-term follow-up of RCC cases (Cohort 1), higher prenephrectomy pKIM-1 was associated with worse metastasis-free survival (multivariable MFS hazard ratio [HR] 1.29 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.53) and overall survival (multivariable OS HR 1.31 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.54). In long-term follow-up of Cohort 2, no metastatic events occurred, consistent with the favorable prognosis of resected cT1a RCC. CONCLUSION: Among patients with renal masses, pKIM-1 is associated with malignant pathology, worse MFS, and risk of death. pKIM-1 may be useful for selecting patients with renal masses for intervention versus surveillance.

Development and validation of a multicenter Cox regression model to predict all-cause mortality in patients with renal masses suspicious for renal cancer.

OBJECTIVE: Life expectancy models are useful tools to support clinical decision-making. Prior models have not been used widely in clinical practice for patients with renal masses. We sought to develop and validate a model to predict life expectancy following the detection of a localized renal mass suspicious for renal cell carcinoma. MATERIALS AND METHODS: Using retrospective data from 2 large centers, we identified patients diagnosed with clinically localized renal parenchymal masses from 1998 to 2018. After 2:1 random sampling into a derivation and validation cohort stratified by site, we used age, sex, log-transformed tumor size, simplified cardiovascular index and planned treatment to fit a Cox regression model to predict all-cause mortality from the time of diagnosis. The model's discrimination was evaluated using a C-statistic, and calibration was evaluated visually at 1, 5, and 10 years. RESULTS: We identified 2,667 patients (1,386 at Corewell Health and 1,281 at Johns Hopkins) with renal masses. Of these, 420 (16%) died with a median follow-up of 5.2 years (interquartile range 2.2-8.3). Statistically significant predictors in the multivariable Cox regression model were age (hazard ratio [HR] 1.04; 95% confidence interval [CI] 1.03-1.05); male sex (HR 1.40; 95% CI 1.08-1.81); log-transformed tumor size (HR 1.71; 95% CI 1.30-2.24); cardiovascular index (HR 1.48; 95% CI 1.32-1.67), and planned treatment (HR: 0.10, 95% CI: 0.06-0.18 for kidney-sparing intervention and HR: 0.20, 95% CI: 0.11-0.35 for radical nephrectomy vs. no intervention). The model achieved a C-statistic of 0.74 in the derivation cohort and 0.73 in the validation cohort. The model was well-calibrated at 1, 5, and 10 years of follow-up. CONCLUSIONS: For patients with localized renal masses, accurate determination of life expectancy is essential for decision-making regarding intervention vs. active surveillance as a primary treatment modality. We have made available a simple tool for this purpose.

Kidney computed tomography perfusion in patients with ureteral obstruction.

INTRODUCTION: Kidney perfusion on CT is an encouraging surrogate for renal scintigraphy in assessing renal function. However, data on dynamic volumetric CT in patients with kidney obstruction is lacking. Thus, the aim of this study is to determine the feasibility of CT-based renal perfusion using a dynamic volume to assess renal hemodynamics at different degrees and durations of obstruction. MATERIALS AND METHODS: We included patients with unilateral kidney obstruction in our single-center, prospective study. The patients were divided into three groups. Patients without dilatation of the pelvicalyceal system (PCS) and normal parenchyma thickness were included into Group 1; patients with PCS dilatation and parenchyma thickness 1.8-2.4 cm-into Group 2; and patients with ureteropyelocalicoectasia and parenchyma thickness less than 1.8 cm-into Group 3. RESULTS: Total of 56 patients were enrolled. In Group 1 mean values of cortical and medullar arterial blood flow, blood volume, and extraction fraction were within the normal range. Changes in contralateral kidney were not determined. Patients from Group 2 showed significant differences in blood flow parameters in the cortical and medulla of the obstructed kidney. No changes in perfusion values in the contralateral kidney was observed. In patients from Group 3 there was a marked decrease in perfusion on the side of obstruction compared to Group 2, indicating that the degree of expansion of the PCS directly correlates with the change in blood flow. However, in the contralateral kidney, these indicators exceeded the normal values of perfusion. CONCLUSION: CT perfusion allows to objectively assess changes in blood flow in the setting of renal obstruction. The degree of obstruction directly affects the measured rate of blood flow.

Automated Upper Tract Urothelial Carcinoma Tumor Segmentation During Ureteroscopy Using Computer Vision Techniques.

INTRODUCTION: Endoscopic tumor ablation of upper tract urothelial carcinoma (UTUC) allows for tumor control with the benefit of renal preservation but is impacted by intraoperative visibility. We sought to develop a computer vision model for real-time, automated segmentation of UTUC tumors to augment visualization during treatment. MATERIALS AND METHODS: We collected twenty videos of endoscopic treatment of UTUC from two institutions. Frames from each video (N=3387) were extracted and manually annotated to identify tumors and areas of ablated tumor. Three established computer vision models (U-Net, U-Net++ and UNext) were trained using these annotated frames and compared. Eighty percent of the data was used to train the models while 10% was used for both validation and testing. We evaluated the highest performing model for tumor and ablated tissue segmentation using a pixel-based analysis. The model and a video overlay depicting tumor segmentation were further evaluated intraoperatively. RESULTS: All twenty videos (mean 36 seconds ± 58s) demonstrated tumor identification and 12 depicted areas of ablated tumor. The U-Net model demonstrated the best performance for segmentation of both tumors (AUC-ROC of 0.96) and areas of ablated tumor (AUC-ROC of 0.90). Additionally, we implemented a working system to process real-time video feeds and overlay model predictions intraoperatively. The model was able to annotate new videos at 15 fps. CONCLUSIONS: Computer vision models demonstrate excellent real-time performance for automated upper tract urothelial tumor segmentation during ureteroscopy.

A systematic review of cytoreductive prostatectomy outcomes and complications in oligometastatic disease.

Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space. Methods: We performed a systematic literature search using three databases (Medline, Scopus, and Web of Science). The primary endpoints were oncologic outcomes. The secondary endpoints were complication rates and functional results. Results: In all studies, overall survival was better or at least comparable variable in the groups with CRP compared to no local treatment. The greatest benefit from CRP in 5-year overall survival in one study was 67.4% for CRP versus 22.5% for no local treatment. Cancer-specific survival (CSS) showed the same trend. Several authors found significant benefits from CSS in the CRP group: from 79% vs. 46% to 100% vs. 61%. CRP was a predictor of better CSS (hazard ratio 0.264, p=0.004). Positive surgical margin rates differed widely from 28.6% to 100.0%. Urinary continence in CRP versus RP for localized PCa was significantly lower (57.4% vs. 90.8%, p<0.0001). Severe incontinence occurred seldom (2.5%-18.6%). Total complication rates after CRP differed widely, from 7.0% to 43.6%. Rates of grades 1 and 2 events prevailed. Patients on ADT alone also showed a considerable number of complications varying from 5.9% to 57.7%. Conclusion: CRP improves medium-term cancer control in patients with oligometastatic PCa. The morbidity and complication rates of this surgery are comparable with other approaches, but postoperative incontinence rate is higher compared with RP for localized disease.

A Phase II Trial of Intravesical Gemcitabine and Docetaxel in the Treatment of Bacillus Calmette-Guérin‒Naïve Nonmuscle-Invasive Urothelial Carcinoma of the Bladder.

PURPOSE: Combination intravesical gemcitabine and docetaxel (GemDoce) has demonstrated efficacy as second-line therapy for patients with bacillus Calmette-Guérin (BCG)‒unresponsive nonmuscle-invasive urothelial carcinoma of the bladder (NMIBC). In the context of widespread BCG shortages, we performed a phase 2 prospective trial to assess GemDoce for BCG-naïve NMIBC. MATERIALS AND METHODS: This study is a prospective, single-arm, open-label phase 2 trial for patients with BCG-naïve high-risk NMIBC. Intravesical GemDoce was given weekly for 6 weeks as induction followed by monthly maintenance therapy for 2 years among responders. The primary end point was 3-month complete response, and key secondary end points included adverse events (AEs) and 12-month recurrence-free survival. RESULTS: Twenty-five patients were enrolled between August 2020 and August 2022 with median follow-up of 19.6 months. The pretrial pathologic stages were high-grade (HG) T1 with carcinoma in situ (CIS; n = 7), HGT1 without CIS (n = 6), HGTa (n = 9), and CIS alone (n = 3). The 3-month complete response rate was 100% and recurrence-free survival at 12 months was 92%. Two patients with pretrial HGT1 had HGT1 recurrences at 9 and 12 months. No patients progressed to T2 disease, underwent radical cystectomy, or had any radiographic evidence of progressive disease. Grade 1 AEs were common (23/25 patients) including hematuria, urinary frequency, urgency, and fatigue. Five patients (20%) experienced a grade 3 AE including hematuria and UTI. CONCLUSIONS: In this single-arm phase 2 trial, GemDoce was well tolerated with promising efficacy for patients with BCG-naïve high-risk NMIBC.

High-Grade, Nonsarcomatoid Chromophobe Renal Cell Carcinoma: A Series of 22 Cases With Novel Molecular Features on a Subset.

Chromophobe renal cell carcinoma (ChRCC) is the third most common subtype of renal cell carcinoma and typically exhibits indolent behavior, though a rare subset can exhibit high-grade morphologic features and is associated with a poor prognosis. Although there are limited data on the molecular characteristics of metastatic and sarcomatoid ChRCC, the molecular features of high-grade, nonsarcomatoid ChRCC remain unexplored. Herein, we characterize 22 cases of ChRCC with high-grade, nonsarcomatoid components. High-grade ChRCC frequently demonstrated advanced stage at diagnosis (64% ≥pT3a or N1), with regions of extrarenal extension, nodal metastases, and vascular invasion consisting solely of high-grade ChRCC morphologically. We performed spatially guided panel-based DNA sequencing on 11 cases comparing high-grade and low-grade regions (n = 22 samples). We identified recurring somatic alterations emblematic of ChRCC, including deletions of chromosomes 1, 2, 6, 10, 13, 17, and 21 in 91% (10/11) of cases and recurring mutations in TP53 (81.8%, n = 9/11) and PTEN (36.4%, n = 4/11). Notably, although PTEN and TP53 alterations were found in both high-grade and low-grade regions, private mutations were identified in 3 cases, indicating convergent evolution. Finally, we identified recurring RB1 mutations in 27% (n = 3) of high-grade regions leading to selective protein loss by immunohistochemistry not observed in adjacent low-grade regions. This finding was confirmed in The Cancer Genome Atlas cohort where 2 of 66 cases contained RB1 mutations and demonstrated unequivocal high-grade, nonsarcomatoid morphology. We also detected multiple chromosomal gains confined to the high-grade regions, consistent with imbalanced chromosome duplication. These findings broaden our understanding of the molecular pathogenesis of ChRCC and suggest that subclonal RB1 mutations can drive the evolution to high-grade, nonsarcomatoid ChRCC.

Development and Validation of a Multivariable Nomogram Predictive of Post-Nephroureterectomy Renal Function.

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.

Kidney double positive T cells have distinct characteristics in normal and diseased kidneys.

Multiple types of T cells have been described and assigned pathophysiologic functions in the kidneys. However, the existence and functions of TCR+CD4+CD8+ (double positive; DP) T cells are understudied in normal and diseased murine and human kidneys. We studied kidney DPT cells in mice at baseline and after ischemia reperfusion (IR) and cisplatin injury. Additionally, effects of viral infection and gut microbiota were studied. Human kidneys from patients with renal cell carcinoma were evaluated. Our results demonstrate that DPT cells expressing CD4 and CD8 co-receptors constitute a minor T cell population in mouse kidneys. DPT cells had significant Ki67 and PD1 expression, effector/central memory phenotype, proinflammatory cytokine (IFNγ, TNFα and IL-17) and metabolic marker (GLUT1, HKII, CPT1a and pS6) expression at baseline. IR, cisplatin and viral infection elevated DPT cell proportions, and induced distinct functional and metabolic changes. scRNA-seq analysis showed increased expression of Klf2 and Ccr7 and enrichment of TNFα and oxidative phosphorylation related genes in DPT cells. DPT cells constituted a minor population in both normal and cancer portion of human kidneys. In conclusion, DPT cells constitute a small population of mouse and human kidney T cells with distinct inflammatory and metabolic profile at baseline and following kidney injury.

Changes in the Perioperative Management and Outcomes of Patients With Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy at Memorial Sloan Kettering Cancer Center: Over 20 Years of Experience.

INTRODUCTION: We evaluated surgical trends, perioperative management evolution, and oncologic outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) at a tertiary cancer center over a 24-year period. METHODS: Between 1995 and 2018, we evaluated 743 consecutive patients with UTUC who underwent RNU. Generalized additive models were used to estimate the associations between date of surgery and continuous outcomes using a linear model, dichotomous outcomes using a logit link, categorical outcomes using multinomial models, and 2- and 5-year survival outcomes using Cox proportional hazards models. RESULTS: Over the study period, preoperative diagnostic endoscopic biopsies increased from 10% to 66%, along with the proportion of patients who underwent RNU for high-grade disease from 55% to 91%. The rate of open RNU declined from 100% to 56% with a rise in minimally invasive approaches. Median lymph node yield increased with more retroperitoneal lymph node dissections performed. Neoadjuvant chemotherapy utilization increased with a contemporary utilization rate of 32%, coinciding with an increase in pT0 rate from 2% to 8%. Cancer-specific survival probabilities improved over the study period, while metastasis-free and overall survival remained stable. CONCLUSIONS: We found several changes in treatment patterns and outcomes for patients with UTUC over the past 2 decades. How individual alterations in management factors, such as patient selection, perioperative chemotherapy, lymphadenectomy, and salvage therapies, impact patient outcomes is challenging in the setting of multiple overlapping practice changes for this rare disease and warrants further investigation.

Prognostic significance of pT3a staging subclassifications in renal cell carcinoma: Not all pT3a are equal.

OBJECTIVE: To examine the prognostic significance of perinephric fat, renal sinus fat, and renal vein invasion in patients with pT3a renal cell carcinoma (RCC) by histologic type. METHODS: A population-based retrospective cohort study of patients with pT3aN0M0 RCC was performed using Surveillance, Epidemiology, and End Results (SEER) data for the years 2010 through 2019. Cox proportional hazards models were used to examine the relationship between pT3a subclassification groups and cancer-specific survival (CSS) by histological subtype (clear cell, papillary, chromophobe, and other). RESULTS: The cohort consisted of 10,170 patients with pT3a RCC, including 8,446 (83.0%) with clear cell RCC and 1,724 (17.0%) with nonclear cell RCC (nccRCC). Median follow up was 36 months. Differences in CSS by pT3a subclassification groups were observed in all histological subtypes but were most pronounced in nccRCC, specifically papillary RCC. Compared to perinephric fat (PF) invasion only, renal vein (RV) invasion (HR = 4.9, 95%CI: 2.5-9.3, P < 0.01), renal sinus fat invasion (HR = 3.0, 95%CI: 1.4-6.2), RV and PF invasion (HR = 7.5, 95%CI: 3.5-16.0), and combination of all three characteristics (HR = 4.4, 95%CI: 1.2-15.5) were associated with worse CSS in patients with papillary RCC. CONCLUSION: We examined the prognostic role of pT3a staging subclassifications in RCC by histologic subtype and observed survival differences, particularly in papillary RCC. Our findings highlight the need to refine pT3a staging criteria to help guide individualized, multimodal treatment strategies for locally advanced RCC.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted and Systematic Prostate Biopsy to Prevent Infectious Complications: The PREVENT Randomized Trial.

BACKGROUND AND OBJECTIVE: The transrectal biopsy approach is traditionally used to detect prostate cancer. An alternative transperineal approach is historically performed under general anesthesia, but recent advances enable transperineal biopsy to be performed under local anesthesia. We sought to compare infectious complications of transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis. METHODS: We assigned biopsy-naïve participants to undergo transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis (rectal culture screening for fluoroquinolone-resistant bacteria and antibiotic targeting to culture and sensitivity results) through a multicenter, randomized trial. The primary outcome was post-biopsy infection captured by a prospective medical review and patient report on a 7-d survey. The secondary outcomes included cancer detection, noninfectious complications, and a numerical rating scale (0-10) for biopsy-related pain and discomfort during and 7-d after biopsy. KEY FINDINGS AND LIMITATIONS: A total of 658 participants were randomized, with zero transperineal versus four (1.4%) transrectal biopsy infections (difference -1.4%; 95% confidence interval [CI] -3.2%, 0.3%; p = 0.059). The rates of other complications were very low and similar. Importantly, detection of clinically significant cancer was similar (53% transperineal vs 50% transrectal, adjusted difference 2.0%; 95% CI -6.0, 10). Participants in the transperineal arm experienced worse periprocedural pain (0.6 adjusted difference [0-10 scale], 95% CI 0.2, 0.9), but the effect was small and resolved by 7-d. CONCLUSIONS AND CLINICAL IMPLICATIONS: Office-based transperineal biopsy is tolerable, does not compromise cancer detection, and did not result in infectious complications. Transrectal biopsy with targeted prophylaxis achieved similar infection rates, but requires rectal cultures and careful attention to antibiotic selection and administration. Consideration of these factors and antibiotic stewardship should guide clinical decision-making. PATIENT SUMMARY: In this multicenter randomized trial, we compare prostate biopsy infectious complications for the transperineal versus transrectal approach. The absence of infectious complications with transperineal biopsy without the use of preventative antibiotics is noteworthy, but not significantly different from transrectal biopsy with targeted antibiotic prophylaxis.

Immunomodulatory response to neoadjuvant nivolumab in non-metastatic clear cell renal cell carcinoma.

Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.

Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy.

BACKGROUND AND OBJECTIVE: Growing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk-matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve. METHODS: We retrospectively identified 1993 patients (including 112 NAC recipients) who underwent RNU for nonmetastatic, high-grade UTUC between 1985 and 2022 in a large, international, multicenter cohort. We divided the cohort into low-risk and high-risk groups defined according to pathologic findings of muscle invasion and lymph node involvement at RNU. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) estimates were calculated using the Kaplan-Meier method. Multivariable analyses were performed to determine clinical and demographic factors associated with these outcomes. KEY FINDINGS AND LIMITATIONS: Among patients with low-risk pathology at RNU, RFS, OS, and CSS were similar between the NAC and chemotherapy-naïve groups. Among patients with high-risk pathology at RNU, the NAC group had poorer RFS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 2.10-4.48), OS (HR 2.06, 95% CI 1.33-3.20), and CSS (subdistribution HR 2.54, 95% CI 1.37-4.69) in comparison to the pathologic risk-matched, chemotherapy-naïve group. Limitations include the lack of centralized pathologic review. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients with residual invasive disease at RNU after NAC represent a uniquely high-risk population with respect to oncologic outcomes. There is a critical need to determine an optimal adjuvant approach for these patients. PATIENT SUMMARY: We studied a large, international group of patients with cancer of the upper urinary tract who underwent surgery either with or without receiving chemotherapy beforehand. We identified a high-risk subgroup of patients with residual aggressive cancer after chemotherapy and surgery who should be prioritized for clinical trials and drug development.

Urologist-level variation in the management of T1a renal cell carcinoma: A population-based cohort study.

OBJECTIVES: Lack of strict indications in current guidelines have led to significant variation in management patterns of small renal masses. The impact of the urologist on the management approach for patients with small renal masses has not been explored previously. MATERIALS AND METHODS: Using the linked Surveillance, Epidemiology, and End Results-Medicare database, patients aged ≥66 years diagnosed with small renal masses from January 1, 2004 to December 31, 2013 were identified and assigned to primary urologists. Mixed-effects logistic models were used to evaluate factors associated with different management approaches, estimate urologist-level probabilities of each approach, assess management variation, and determine urologist impact on choice of approach. RESULTS: A total of 12,402 patients with 2,794 corresponding primary urologists were included in the study. At the individual urologist level, the estimated case-adjusted probability of different approaches varied markedly: nonsurgical management (mean, 12.8%; range, 4.9%-36.1%); thermal ablation (mean, 10.8%; range, 2.4%-66.3%); partial nephrectomy (mean, 30.1%; range, 10.1%-66.6%); and radical nephrectomy (mean, 40.4%; range, 17.7%-71.6%). Compared to patient and tumor characteristics, the primary urologist was a more influential measured factor, accounting for 13.6% (vs. 12.9%), 33.8% (vs. 2.1%), 15.1% (vs. 8.4%), and 13.5% (vs. 4.0%) of the variation in management choice for nonsurgical management, thermal ablation, partial nephrectomy, and radical nephrectomy, respectively. CONCLUSIONS: Significant variation exists in the management of small renal masses and appears to be driven primarily by urologist preference and practice patterns. Our findings emphasize the need for unified guidance regarding management of these masses to reduce unwarranted variation in care.

Beyond the knife: strategic patient selection for cytoreductive nephrectomy.

PURPOSE OF REVIEW: To evaluate the current role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) within the context of evolving treatment paradigms, focusing on implications for patient selection. RECENT FINDINGS: Two randomized trials failed to show significant benefits from CN for intermediate and poor-risk patients undergoing targeted therapy. Despite this, subgroup analysis and retrospective data suggest potential benefits for a subset of good and intermediate-risk patients. Although currently used risk stratification tools guide CN eligibility, they have limitations, including, subjectivity, perioperative variability, and missing validation. Deferred CN may benefit patients responding to systemic treatment, whereas other patients may benefit from upfront CN. Emerging data supports the value of CN with immune checkpoint inhibitors (ICI) in selected patients, emphasizing the need for ongoing trials in the ICI era. SUMMARY: The role and timing of CN in mRCC have evolved across therapeutic eras. Although awaiting prospective evidence in the current era of ICI, CN still has a role in the therapeutic approach for a subset of patients. The decision to recommend CN must be personalized and involve multidisciplinary discussions considering both patient- and tumor-related factors.