Young age is associated with decreased recurrence for renal cell carcinoma.

INTRODUCTION: We aimed to examine stage-specific oncologic outcomes for young versus conventional-age patients with localized disease in a modern cohort. MATERIALS AND METHODS: The Surveillance, Epidemiology and End Results database was queried for patients with T1-T2N0M0 kidney cancer from 1975-2016, including clear cell, papillary, and chromophobe renal cell carcinoma. Patients were stratified into ≤ 40 years-old or > 40 years-old cohorts and underwent definitive treatment via percutaneous ablation, partial nephrectomy, or radical nephrectomy. Primary outcome was cancer-specific survival. Cox regression and Kaplan-Meier analysis were performed. RESULTS: A total of 44,673 patients were identified with 41,812 patients in the conventional-age and 2,861 patients in the young cohort with mean ages of 62.1 and 34.7 years old, respectively. The young cohort had a higher proportion of T1a disease compared to the conventional-age cohort (65.2% vs. 58.6%) and a lower proportion of the cT1b (24.4% vs. 29.3%), cT2a (6.8% vs. 8.4%), and cT2b (3.6% vs. 3.7%) disease. Chromophobe histology was more prevalent in the younger population (10.5% vs. 6.6%). Nuclear grade 3 or 4 were more prominent in the conventional-age population (24.8% vs. 19.1%). Cancer-specific death was significantly higher in the conventional-age cohort (2.4% vs. 0.7%). Cox regression analysis demonstrated patients > 40 years old, increasing stage, and higher grade were at independently increased risk of cancer-specific death. Kaplan-Meier analysis showed significantly improved 5-year cancer-specific survival for the young versus conventional-age cohorts when sub-stratified by stage. CONCLUSION: When stratified by stage, young patients with localized kidney cancer experience improved cancer-specific survival.

Increasing rate of pathologic upgrading in low risk prostate cancer patients in the active surveillance era.

INTRODUCTION: Management of prostate cancer has seen an increasing predilection for active surveillance in low risk (LR) patients. We aimed to evaluate the rate of pathologic upgrading in patients with very low (VLR) or LR prostate cancer after prostatectomy. MATERIALS AND METHODS: The National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Database were queried for patients diagnosed with Gleason 6 prostate cancer and prostate specific antigen (PSA) < 10 ng/mL from 2010 to 2016. All patients underwent 12-core biopsy and a subsequent prostatectomy for final pathologic staging. Our primary outcome was rate of pathologic upgrading over the study period. RESULTS: A total of 35,332 patients from the NCDB and 7,186 patients from the SEER database were collected. Patient population had an average age of about 59 years old and was over 80% white. Mean pre-biopsy PSA was higher for the upgraded cohorts in the NCDB and SEER populations (5.3 versus 4.9 and 5.5 versus 5.1 respectively, p < 0.001). Upgraded cohorts were more likely to have a higher percentage of positive cores at biopsy (p < 0.001). Multivariable analysis demonstrated that increasing age, increasing PSA and year of diagnosis were all predictors of upgrading (p < 0.05) in both databases. African American race was significantly associated with upgrading in the NCDB database only (p = 0.001). Over the studied time period, the rate of upgrading at prostatectomy increased from 41.2% to 56.7% in the NCDB population and from 41.9% to 45.4% in the SEER population. CONCLUSIONS: The rate of pathologic upgrading of VLR and LR prostate cancer at prostatectomy has been increasing in recent years. Increasing age, pre-biopsy PSA and an increasing percentage of positive cores at biopsy are predictors of this outcome. This may relate to improved patient selection for active surveillance and definitive treatment.

Invasive non-urachal adenocarcinoma of the bladder: analysis of the National Cancer Database.

PURPOSE: To review the United States National Cancer Database (NCDB) from 2004 to 2015 and analyze survival outcomes of invasive non-urachal adenocarcinoma based on treatment modality. METHODS: The NCDB 2004-2015 bladder dataset was queried for adenocarcinoma histology, excluding urachal variant, and limited to patients with clinical stage T2-T4 disease. Treatment modality was categorized as no treatment, cystectomy (partial or radical), external beam radiation therapy (EBRT), or EBRT plus cystectomy. Our primary outcome was overall survival. Cox regression (CR) and Kaplan-Meier (KM) analysis were performed. RESULTS: 851 patients were identified with invasive (cT2-T4) adenocarcinoma of the bladder. Treatment modalities included 398 (47.8%) no treatment, 298 (35.8%) cystectomy, 124 (14.9%) EBRT, and 31 (3.7%) EBRT plus cystectomy. On KM analysis excluding those with metastatic disease, the 5-year survival was significantly better (p < 0.001) for patients who underwent cystectomy (39.6%), versus no treatment (21.0%), EBRT (18.6%), or EBRT plus cystectomy (26.9%) (log rank, p < 0.001). On CR for mortality, age (HR 1.030, p < 0.001), Charlson score 1 (HR 1.287, p = 0.034), cT4 (HR 1.768, p < 0.001), and receiving treatment at a low-volume center (HR 1.289, p = 0.026) were associated with worsened survival; however, cystectomy (HR 0.593, p < 0.001) was the only factor associated with improved survival. For those undergoing cystectomy, the mean length of stay was 8.5 days and the 30-day readmission rate was 7.0%. CONCLUSIONS: Invasive non-urachal adenocarcinoma of the bladder is a rare diagnosis. Survival benefits in patients without metastatic disease are seen only in those patients undergoing definitive surgery.

Squamous cell carcinoma of the bladder: poor response to neoadjuvant chemotherapy.

BACKGROUND: Squamous cell carcinoma (SCC) of the bladder is a rare, aggressive malignancy. Unlike urothelial cell carcinoma, SCC is resistant to chemotherapy and guidelines recommend radical cystectomy (RC) without neoadjuvant chemotherapy (NAC). We aimed to evaluate the current management and survival of patients with invasive SCC treated with or without NAC. METHODS: 671 patients with invasive SCC bladder cancer from 2004 to 2015 in the National Cancer Data Base were identified. Patients were stratified by treatment with RC alone or NAC prior to RC (NAC + RC). Survival analysis was performed with Kaplan-Meier and Cox regression. Secondary outcomes included length of stay and readmission. RESULTS: Of 671 patients, 92.8% were treated with RC alone and 7.2% with NAC + RC. Cox regression for mortality was performed including age, Charlson score, clinical stage, and NAC. Increased risk of mortality was noted with increasing age (OR 1.01, p = 0.023) and Charlson score of 1-3 (HR 1.58-1.68, p < 0.05). NAC did not confer survival advantage (HR 1.17, p = 0.46). On Kaplan-Meier analysis, the overall survival was equivalent (log-rank p = 0.804). Hospital stay and readmission were similar between RC and NAC + RC groups. CONCLUSIONS: Analysis of a national tumor registry suggests a lack of overall survival benefit for NAC with localized, muscle invasive SCC of the bladder. Further research directed at chemotherapy regimens for SCC is needed to optimize treatment and improve survival outcomes.

Lymph node density for stratification of survival outcomes with node positive upper tract urothelial carcinoma.

INTRODUCTION: The use of lymph node density (LND) as a predictor of survival outcomes has been studied with urothelial carcinoma of the bladder. Similar results can be postulated to upper tract urothelial carcinoma (UTUC). This study aims to determine the overall survival of patients with lymph node positive UTUC based on LND, utilizing the National Cancer Database (NCDB). MATERIALS AND METHODS: Data was derived from NCDB Participant User Kidney Dataset using the histology code 'transitional cell carcinoma', utilizing pN+ patients from 2004-2015. LND was calculated as number of positive nodes divided by total number of nodes removed. Patients were stratified by traditional AJCC pN stage and compared to LND groups (< 30%, ≥ 30%). Primary outcome was overall survival. Kaplan-Meier and Cox regression analyses were performed. RESULTS: A total of 2049 patients were identified (pN1 = 1022, pN2 = 1027; LND < 30% = 370, ≥ 30% = 1679). Mean LND was 71%. Cox regression for mortality using pN stage was not significant (p = 0.11); however, Cox regression for mortality using LND group noted significantly worsened survival with LND ≥ 30% (HR 1.54, p = 0.001). Kaplan Meier analysis for overall survival at 2 years showed no difference between pN1 and pN2 stages (35.3% versus 34.1%; log rank p = 0.37). Kaplan Meier analysis for overall survival at 2 years revealed significant difference between LND groups (LND < 30%, 47.3% versus LND ≥ 30%, 32.0%; log rank p < 0.001). CONCLUSIONS: LND provides improved prognostic information regarding overall survival, compared to traditional AJCC pN staging. Future studies need to evaluate LND to improve prognostic understanding of lymph node positive UTUC.

Chemotherapy increases survival and downstaging of upper tract urothelial cancer.

INTRODUCTION: To evaluate the overall survival and pathologic downstaging effect of neoadjuvant chemotherapy for upper tract urothelial cell carcinoma. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried for patients with stage II-IV upper tract urothelial cell carcinoma undergoing definitive surgical resection (nephroureterectomy) from 2004-2015. Patients with metastatic disease were excluded. Cohorts were stratified by receipt of neoadjuvant chemotherapy (NAC). Kaplan-Meier analysis and Cox regression were used to evaluate overall survival. Logistic regression was used to predict the odds of pathologic downstaging to non-invasive disease (< pT2). Propensity score matched analysis was performed between groups. RESULTS: A total of 3634 patients were identified with non-metastatic stage II-IV disease undergoing surgical resection; 3364 received no chemotherapy and 270 received NAC. Patients undergoing NAC had a 10.9% rate of downstaging to non-invasive disease (OR 6.35, p < 0.001). Moreover, on Kaplan-Meier analysis, median survival was 27.3 months and 44.8 months for no chemotherapy versus NAC, respectively (log-rank, p = 0.001). Cox regression for death also revealed benefits for receiving NAC (HR 0.67, p < 0.001). Findings were confirmed on propensity score matching (532 matched patients). After matching, Cox regression for death noted improvement with neoadjuvant as compared to no chemotherapy (HR 0.61, p < 0.001). CONCLUSION: Neoadjuvant chemotherapy increases likelihood of downstaging to non-invasive disease in patients with upper tract urothelial cell carcinoma. Chemotherapy also provides an overall survival benefit in patients undergoing nephroureterectomy.

3-Hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin)-induced 28-kDa interleukin-1ß interferes with mature IL-1ß signaling.

Multiple clinical trials have shown that the 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors known as statins have anti-inflammatory effects. However, the underlying molecular mechanism remains unclear. The proinflammatory cytokine interleukin-1ß (IL-1ß) is synthesized as a non-active precursor. The 31-kDa pro-IL-1ß is processed into the 17-kDa active form by caspase-1-activating inflammasomes. Here, we report a novel signaling pathway induced by statins, which leads to processing of pro-IL-1ß into an intermediate 28-kDa form. This statin-induced IL-1ß processing is independent of caspase-1- activating inflammasomes. The 28-kDa form of IL-1ß cannot activate interleukin-1 receptor-1 (IL1R1) to signal inflammatory responses. Instead, it interferes with mature IL-1ß signaling through IL-1R1 and therefore may dampen inflammatory responses initiated by mature IL-1ß. These results may provide new clues to explain the anti-inflammatory effects of statins.

Age related trends in the utilization of neoadjuvant chemotherapy for muscle invasive bladder cancer.

PURPOSE: The current standard of care for muscle invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Previous research has shown under-utilization of NAC for treatment of MIBC, especially among the elderly. Our aim was to stratify NAC use by decade of life and analyze trends in use over time along with recording pathologic downstaging and perioperative outcomes. MATERIALS AND METHODS: The National Cancer Database was queried for patients with cT2-4NanyM0 MIBC treated with RC from 2010 to 2016 with urothelial carcinoma. Nineteen thousand nine hundred fifty seven patients met criteria for analysis. We retrospectively analyzed trends in use of NAC, readmission rate, mortality rate, and pathologic downstaging with NAC all stratified by decade of life. RESULTS: Of the 19,957 patients treated with RC for MIBC, only 30.9% underwent NAC. There was a statistically significant increase in NAC use across all age groups from 2010 to 2016. Receipt of NAC was associated with decreased age on univariate analysis (P < 0.001) and on logistic regression (OR: 0.617 for age 70-79, OR: 0.221 for age ≥80 vs. age <60; P < 0.001). Patients receiving NAC were more likely to exhibit pathologic downstaging at time of RC (OR: 3.907; P < 0.001), and this trend held for each age group examined. Among patients receiving NAC, the risk of 30 and 90-day mortality was associated with increasing age; however, age was not associated with 30-day readmission for those receiving NAC. CONCLUSION: Rates of NAC use prior to RC have increased among all age groups with the lowest utilization rate among the elderly. NAC use was associated with greater pathologic downstaging in all age groups. These data show a promising trend in the uptake of the gold standard for treatment of MIBC; however, the underlying etiology of differing rates of NAC utilization remains to be determined.

Cost-utility of Initial Management of High-grade T1 Bladder Cancer With Intravesical BCG vs Immediate Radical Cystectomy.

OBJECTIVE: To compare the cost-utility of initial management of high-grade T1 non-muscle invasive bladder cancer (HGT1 NMIBC) with intravesical BCG vs immediate radical cystectomy. High-risk NMIBC patients may climb a costly ladder of treatments, culminating in radical cystectomy for oncologic or symptomatic benefit in up to one-third. This high healthcare resource utilization presents a challenging dilemma in balancing sufficiently aggressive management with cost, toxicity, and quality-of-life. METHODS: Cost-utility of initially managing HGT1 with intravesical BCG and early radical cystectomy with ileal conduit urinary diversion was compared using decision-analytic Markov models. Five-year oncologic outcomes, adverse event rates, and published utility values were extracted from literature. Costs were calculated from a US Medicare perspective in 2021 US dollars. Sensitivity analysis identified drivers of cost and break-even points for recurrence and progression. RESULTS: Mean costs were $26,093 for intravesical BCG and $39,720 for immediate radical cystectomy, though cystectomy generated a gain of 2.2 quality-adjusted life years (QALYs) compared to intravesical BCG. Immediate cystectomy was a more cost-effective management strategy for HGT1 NMIBC with an incremental CE ratios (ICER) of $7120/QALY. The costs associated with cystectomy, TURBT, and BCG toxicity had the greatest impact on ICER. One-way sensitivity analysis demonstrated that intravesical BCG became a cost-effective management strategy if the 5-year recurrence rate of HG T1 was less than 56% or the 5-year progression rate to MIBC was less than 4%. CONCLUSION: At current prices, treatment of high-grade T1 NMIBC with early radical cystectomy is more cost-effective management strategy than initial treatment with intravesical BCG.

Novel Use of Circulating Tumor DNA to Identify Muscle-invasive and Non-organ-confined Upper Tract Urothelial Carcinoma.

BACKGROUND: Optimal patient selection for neoadjuvant chemotherapy prior to surgical extirpation is limited by the inaccuracy of contemporary clinical staging methods in high-risk upper tract urothelial carcinoma (UTUC). OBJECTIVE: To investigate whether the detection of plasma circulating tumor DNA (ctDNA) can predict muscle-invasive (MI) and non-organ-confined (NOC) UTUC. DESIGN, SETTING, AND PARTICIPANTS: Plasma cell-free DNA was prospectively collected from chemotherapy-naïve, high-risk UTUC patients undergoing surgical extirpation and sequenced using a 152-gene panel and low-pass whole-genome sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: To test for concordance, whole-exome sequencing was performed on matching tumor samples. The performance of ctDNA for predicting MI/NOC UTUC was summarized using the area under a receiver-operating curve, and a variant count threshold for predicting MI/NOC disease was determined by maximizing Youden's J statistic. Kaplan-Meier methods estimated survival, and Mantel-Cox log-rank testing assessed the association between preoperative ctDNA positivity and clinical outcomes. RESULTS AND LIMITATIONS: Of 30 patients enrolled prospectively, 14 were found to have MI/NOC UTUC. At least one ctDNA variant was detected from 21/30 (70%) patients, with 52% concordance with matching tumor samples. Detection of at least two panel-based molecular alterations yielded 71% sensitivity at 94% specificity to predict MI/NOC UTUC. Imposing this threshold in combination with a plasma copy number burden score of >6.5 increased sensitivity to 79% at 94% specificity. Furthermore, the presence of ctDNA was strongly prognostic for progression-free survival (PFS; 1-yr PFS 69% vs 100%, p < 0.001) and cancer-specific survival (CSS; 1-yr CSS 56% vs 100%, p = 0.016). CONCLUSIONS: The detection of plasma ctDNA prior to extirpative surgery was highly predictive of MI/NOC UTUC and strongly prognostic of PFS and CSS. Preoperative ctDNA demonstrates promise as a biomarker for selecting patients to undergo neoadjuvant chemotherapy prior to nephroureterectomy. PATIENT SUMMARY: Here, we show that DNA from upper tract urothelial tumors can be detected in the blood prior to surgical removal of the kidney or ureter. This circulating tumor DNA can be used to predict that upper tract urothelial carcinoma is invasive into the muscular lining of the urinary tract and may help identify those patients who could benefit from chemotherapy prior to surgery.

Immune Checkpoint Inhibitor Toxicity Management in Non-muscle-invasive Bladder Cancer: What Urologists Need To Know.

Immune checkpoint inhibitors (ICIs) have emerged as a treatment option for non-muscle-invasive bladder cancer. Urologists need to be aware of the indications for ICI treatment in this setting and the systemic toxicities associated with these agents. We provide a brief overview of the most common treatment-related adverse events reported in the literature and summarize guidelines for their management. PATIENT SUMMARY: Immunotherapy is now being used as a treatment option for bladder cancer that does not invade the bladder muscle. Urologists need to become comfortable in recognizing and managing adverse effects associated with immunotherapy drugs.

Variant histology in upper tract carcinomas: Analysis of the National Cancer Database.

INTRODUCTION: Upper urinary tract malignancies are relatively uncommon, with the majority representing urothelial carcinoma (UC). Variant histology (VH) is rare but has been increasingly shown to confer worse prognoses, and standardized approaches to treatment for upper tract cancers with VH have not been established. Our study aimed to analyze outcomes amongst various treatment modalities for upper tract malignancies based on VH subtype. Additionally, we stratified mortality outcomes associated with the upper tract tumors based on their primary location in the renal pelvis (RP) versus ureter. METHODS: The National Cancer Database was queried for patients who were diagnosed with upper tract malignancy of the RP or ureter from 2005 to 2016. Populations were grouped based on tumor location (RP vs. ureter) and substratified based on tumor histology (UC vs. VH). Cox regression (CR) was used for multivariable survival analysis. RESULTS: A total of 63,826 patients with upper tract malignancies met inclusion criteria: 36,692 (57.5%) cases involving the RP and 27,134 (42.5%) cases involving the ureter. VH was noted in 2.5% of all tumors with the squamous cell variant being the most common subtype (62.5%). VH presented with higher stage, increased mortality, and higher proportion of metastatic disease relative to UC.  Patients with VH were less likely to undergo surgical intervention and more likely to receive radiation or adjuvant chemotherapy. Neoadjuvant chemotherapy was not associated with tumor downstaging for VH. On multivariable CR, receiving definitive surgical excision improved survival for patients with any VH, and chemotherapy improved survival for patients with renal VH. On subanalysis of CR by VH subtype, survival benefits for surgery were significant for adenocarcinoma, neuroendocrine, and squamous in a renal location and adenocarcinoma, neuroendocrine, sarcoma, and squamous in a ureteral location. Additionally, benefits of chemotherapy were significant for adenocarcinoma in a renal location and neuroendocrine in a ureteral location. CONCLUSION: Patients with upper tract VH are more likely to present at advanced stages and experience higher mortality rates when compared to pure UC. Generally, survival benefits are seen with either surgical excision or chemotherapy for renal VH and with surgical excision for ureteral VH, but mortality rates for these treatment modalities differ amongst specific subtypes.

Perioperative outcomes of open versus robot-assisted radical cystectomy in octogenarians: a population based analysis.

Octogenarians undergoing cystectomy experience higher morbidity and mortality compared to younger patients. Though the non-inferiority of robot-assisted radical cystectomy (RARC) compared to open radical cystectomy (ORC) has been established in a generalized population, the benefits of the robotic approach have not been well studied in an aged population. The National Cancer Database (NCDB) was queried for all patients who underwent cystectomy for bladder cancer from 2010 to 2016. Of these, 2527 were performed in patients age 80 or older; 1988 and 539 underwent ORC and RARC, respectively. On Cox regression analysis, RARC was associated with significantly reduced odds for both 30- and 90-day mortality (HR 0.404, p = 0.004; HR 0.694, p = 0.031, respectively), though the association with overall mortality was not significant (HR 0.877, p = 0.061). The robotic group had a significantly shorter length of stay (LOS) compared to open surgery (10.3 days ORC vs. 9.3 days RARC, p = 0.028). The proportion of cases performed robotically increased over the study period from 12.2% in 2010 to 28.4% in 2016 (p = 0.009, R2 = 0.774). The study is limited by a retrospective design and a section bias, which was not completely control for in the analysis. In conclusion, RARC provides improved perioperative outcomes in aged patients compared to ORC and a trend toward greater utilization of this technique was observed.

Sequential Intravesical Gemcitabine and Docetaxel is an Alternative to Bacillus Calmette-Guérin for the Treatment of Intermediate-risk Non-muscle-invasive Bladder Cancer.

Adjuvant treatment with either chemotherapy or bacillus Calmette-Guérin (BCG) is recommended for patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC). In this multi-institutional retrospective review, we evaluated oncological outcomes for 182 patients with IR-NMIBC treated with BCG (n = 100) or intravesical sequential gemcitabine and docetaxel (Gem/Doce; n = 82). Median follow-up was 48.6 mo (interquartile range 24.9-70.9). No patient had a previous diagnosis of high-grade disease. Recurrence rates were similar in the two treatment groups (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.65-1.73; p = 0.8). Results were consistent after adjusting for International Bladder Cancer Group (IBCG) risk subgroups, use of single-instillation postoperative chemotherapy, use of blue light cystoscopy, and receipt of maintenance therapy (HR 0.88, 95% CI 0.47-1.64; p = 0.7). Similarly, there was no difference in the rate of stage/grade progression between the treatment groups (HR 0.66, 95% CI 0.21-2.12; p = 0.5). Rates of progression to muscle-invasive disease/metastasis (2.2%) and cancer-specific mortality (1.7%) were low in the cohort. Our results support the use of Gem/Doce as an alternative to BCG in patients with IR-NMIBC. PATIENT SUMMARY: We compared cancer control outcomes for two different treatments for intermediate-risk non-muscle-invasive bladder cancer. Our results show that a chemotherapy combination of docetaxel and gemcitabine is as effective as the BCG (bacillus Calmette-Guérin) treatment traditionally used for this type of bladder cancer.

Survival Benefits of Adjuvant Chemotherapy for Positive Soft Tissue Surgical Margins Following Radical Cystectomy in Bladder Cancer with Extravesical Extension.

INTRODUCTION AND OBJECTIVE: Muscle invasive bladder cancer with extravesical extension is an aggressive disease entity that requires multimodal therapy. The benefits of adjuvant chemotherapy (AC) in patients with a positive soft-tissue surgical margin (STSM), however, are relatively unknown due to exclusion of this population in randomized controlled trials of AC. We sought to define survival benefits in this patient population through our institutional bladder cancer database. METHODS: Retrospective review of all patients undergoing radical cystectomy for urothelial carcinoma of the bladder from 2004-2020 with ≥pT3b disease irrespective of neoadjuvant chemotherapy (NAC) use was conducted. Progression-free survival (PFS) and overall survival (OS) estimates were obtained using the Kaplan-Meier method with log-rank test, and the Cox-proportional hazards model was used to identify predictors of improved PFS and OS. AC was defined by any chemotherapy use within 90 days of cystectomy, regardless of STSM status. RESULTS: 476 patients with pT3b disease or worse were identified. Median follow-up was 12.3 months. An amount of 21% of patients were treated with AC. An amount of 24% of patients had positive STSM. Median OS for patients with positive STSM was 8.4 months [95% CI 7-11.5] and 18.3 months [95% CI 15.6-20.8] (p < 0.001) for patients with negative STSM. In the overall cohort, positive STSM (HR 1.93, 95% CI 1.45-2.57, p < 0.001), AC use (HR 0.68, 95% CI 0.51-0.90, p = 0.007), and pN1-3 disease (HR 1.47, 95% CI 1.16-1.87, p = 0.002) were independent predictors of OS when adjusted for performance status, pT-stage, and neoadjuvant chemotherapy use. In patients with positive STSM, median survival was seven months [95% CI 5.2-8.4] without AC, compared to 16.2 months [95% CI 11.5-52.5] with AC (p = 0.0038). For patients with negative STSM, median survival was 17.4 months [95% CI 14-20.1] without AC compared to 22.3 months [95% CI 17.2-36.9] with AC (p = 0.23). In patients with positive STSM, AC use was the only factor associated with an OS benefit with a HR of 0.41 (95% CI 0.21-0.78, p = 0.007). In patients with negative STSM, pT4 and pN1-3 disease were the only factors associated with worse overall survival with a HR of 1.32 (95% CI 1.00-1.74, p = 0.050) and 1.97 (95% CI 1.49-2.60, p < 0.001), respectively. CONCLUSIONS: Administration of adjuvant chemotherapy is of particular benefit in patients with positive STSM following radical cystectomy for gross extravesical disease. Positive STSM may be a representative of "early metastatic" or micrometastatic disease.

Cytoreductive Nephrectomy Following Immune Checkpoint Inhibitor Therapy Is Safe and Facilitates Treatment-free Intervals.

Patients with metastatic renal cell cancer (mRCC) who respond to upfront immune checkpoint inhibitor (ICI) combination therapies may be treated with cytoreductive nephrectomy (CN) to remove radiographically viable primary tumors. Early data for post-ICI CN suggested that ICI therapies induce desmoplastic reactions in some patients, increasing the risk of surgical complications and perioperative mortality. We evaluated perioperative outcomes for 75 consecutive patients treated with post-ICI CN at four institutions from 2017 to 2022. Our cohort of 75 patients had minimal or no residual metastatic disease but radiographically enhancing primary tumors after ICI and were treated with CN. Intraoperative complications were identified in 3/75 patients (4%) and 90-d postoperative complications in 19/75 (25%), including two patients (3%) with high-grade (Clavien ≥III) complications. One patient was readmitted within 30 d. No patients died within 90 d after surgery. Viable tumor was present in all but one specimen. Approximately half of the patients (36/75, 48%) remained off systemic therapy at last follow-up. These data suggest that CN following ICI therapy is safe and associated with low rates of major postoperative complications in appropriately selected patients at experienced centers. Post-ICI CN may facilitate observation without additional systemic therapy in patients without significant residual metastatic disease. Patient summary: Current first-line treatment for patients with kidney cancer that has spread to other sites (metastatic cancer) is immunotherapy. For cases in which metastatic sites respond to this therapy but primary tumor is still detected in the kidney, surgical treatment of the tumor is feasible and has a low rate of complications, and may delay the need for further chemotherapy.

Impact of surgical margin and extent of lymphadenectomy on oncologic outcomes in plasmacytoid urothelial carcinoma.

OBJECTIVE: Guideline recommendations disagree on template boundaries for pelvic lymph node dissection (PLND) in conventional urothelial carcinoma. Less is known about PLND in variant histology. We aimed to analyze the role of LND in plasmacytoid urothelial carcinoma (PUC). METHODS: A retrospective review of patients with cTanyNanyM0 PUC who underwent radical cystectomy (RC) with PLND was performed from 2012 to 2022. Lymph node count (LNC) was a surrogate for extent of lymph node dissection and dichotomized based on maximally selected rank statistics. Multivariable cox hazard regression analysis (MVA) for overall survival (OS) corrected for age, perioperative chemotherapy, soft tissue margin status, and stage ≥pT3 and/or pN+ was performed. Disease free survival (DFS) and OS were estimated using Kaplan-Meier (KM) analysis. RESULTS: Sixty-seven patients with median age of 71, who were 79.1% male were included. Neoadjuvant and adjuvant chemotherapy were administered in 61.2% and 19.4% of patients, respectively. At RC, 70.1% were ≥pT3. Median LNC was 22 (IQR 14-27) with 43.3% of patients being pN+. Calculated optimal-LNC cut point for DFS and OS was 19. Grouping by optimal (≥20) vs. suboptimal-LNC (<20), no significant clinicodemographic differences were found. Optimal-LNC provided improved DFS (P = 0.05) and OS (P = 0.02). Optimal-LNC (HR 0.47, 0.24-0.93 CI 95%, P = 0.03) and negative soft tissue margin (HR 0.38, 0.19-0.76 CI 95%, P = 0.01) was associated with improved OS on MVA. Receipt of perioperative chemotherapy did not improve OS (P = 0.46). CONCLUSION: In PUC, complete surgical extirpation achieving negative soft tissue margins and removing ≥20 lymph should be prioritized if operative intervention is pursued.