Management of Renal Cell Carcinoma With Supradiaphragmatic Inferior Vena Cava Thrombus Diagnosed During Acute COVID-19 Infection.

Renal cell carcinoma (RCC) tends to undergo intravascular tumor growth along the renal vein, forming tumor thrombi that may extend into the inferior vena cava (IVC) or even the right atrium (Level IV). Managing such cases requires a multidisciplinary approach, especially in patients with acute coronavirus disease 2019 (COVID-19) infection, who face increased risks from surgical interventions. We present a case of RCC with Level IV thrombus and concurrent COVID-19 managed with systemic therapy. We also summarize current literature on treating RCC with IVC thrombus and COVID-19's impact on prognosis. The patient was a 70-year-old female with incidental detection of a 9-cm right heterogeneous renal mass with a supradiaphragmatic tumor thrombus during COVID-19 infection. Due to ongoing pulmonary symptoms, systemic therapy with a combination of ipilimumab and nivolumab was initiated. After an excellent initial response, the patient continued systemic therapy, maintaining a necrotic response in the renal mass and tumor thrombus. The patient continues to tolerate systemic therapy well. We report a rare case of RCC with Level IV tumor thrombus and synchronous acute COVID-19 infection. Our report depicts successful management utilizing systemic therapy with a combination of ipilimumab and nivolumab. The management of such cases necessitates a comprehensive, multidisciplinary approach, considering the risks associated with surgery in the context of recent COVID-19 infection. The case presentation and ensuing literature discussion of the dynamic landscape of RCC management highlights the need for more research to improve treatment plans and guide clinicians in handling such complex situations.

Plasma-Derived Cell-Free DNA as a Biomarker for Early Detection, Prognostication, and Personalized Treatment of Urothelial Carcinoma.

Bladder cancer (BC) is one of the most common malignancies in the United States, with over 80,000 new cases and 16,000 deaths each year. Urothelial carcinoma (UC) is the most common histology and accounts for 90% of cases. BC management is complicated by recurrence rates of over 50% in both muscle-invasive and non-muscle-invasive bladder cancer. As such, the American Urological Association (AUA) recommends that patients undergo close surveillance during and after treatment. This surveillance is in the form of cystoscopy or imaging tests, which can be invasive and costly tests. Considering this, there have been recent pushes to find complements to bladder cancer surveillance. Cell-free DNA (CfDNA), or DNA released from dying cells, and circulating tumor DNA (ctDNA), or mutated DNA released from tumor cells, can be analyzed to detect and characterize the molecular characteristics of tumors. Research has shown promising results for ctDNA use in the BC care realm. A PubMed literature review was performed finding studies discussing cfDNA and ctDNA in BC detection, prognostication, and monitoring for recurrence. Keywords used included bladder cancer, cell-free DNA, circulating tumor DNA, urothelial carcinoma, and liquid biopsy. Studies show that ctDNA can serve as prognostic indicators of both early- and late-stage BC, aid in risk stratification prior to major surgery, assist in detection of disease progression and metastatic relapse, and can assess patients who may respond to immunotherapy. The benefit of ctDNA is not confined to BC, as studies have also suggested its promise as a biomarker for neoadjuvant chemotherapy in upper-tract UC. However, there are some limitations to ctDNA that require improvements in ctDNA-specific detection methods and BC-specific mutations before widespread utilization can be achieved. Further prospective, randomized trials are needed to elucidate the true potential ctDNA has in advancements in BC care.

The Association Between Duration of Antibiotics and Infectious Complications Following Radical Cystectomy: Analysis of the 2019-2021 NSQIP Database.

OBJECTIVES: To identify the impact of the duration of peri-operative antibiotics on infectious complications following radical cystectomy. METHODS: The National Surgical Quality Improvement Project (NSQIP) targeted database was queried for patients undergoing radical cystectomy from 2019 to 2021. Baseline patient characteristics were collected. Antibiotic duration was classified as <24 hours (short), 24-72 hours (intermediate) or >72 hours (long). Infectious complication data were collected including surgical site infection (SSI), urinary tract infection (UTI), organ space infection, pneumonia, sepsis, and clostridium difficile infection up to 30 days after surgery. Univariate and multivariable analyses were performed to compare duration of antibiotic therapy to infectious outcomes. RESULTS: Of the 4363 patients who underwent radical cystectomy, 3250 (74%), 827 (19%) and 286 (6.6%) received short, intermediate, and long duration of peri-operative antibiotics, respectively. Infectious complication occurred in 954 (22%) patients, including 227 (5.2%) SSI, 280 (6.4%) UTI, 268(6.1%) organ space infection, 87 (2%) pneumonia, and 378 (8.7%) sepsis. Clostridium difficile infection occurred in 89 (2%) patients. On multivariable analysis, there was no significant difference in overall infectious complication rates with long-duration antibiotics. However, intermediate duration of antibiotics in open surgery was associated with a decreased risk of SSI (OR 0.58; 95%CI 0.37-0.91) compared to those treated with short-term antibiotics. CONCLUSION: Despite guideline recommendations, 26% of patients in this database received >24 hours of peri-operative antibiotics without decreased risk of overall infectious complication. An intermediate course of antibiotics decreased risk of SSI in open surgery compared to the guideline recommend <24-hour course. Greater education regarding antibiotic stewardship and further studies investigating infectious complications are warranted.

A Narrative Review on Robotic Surgery as Treatment for Renal Cell Carcinoma with Inferior Vena Cava Thrombus.

Renal cell carcinoma (RCC) is a common diagnosis, of which a notable portion of patients present with an extension into the venous circulation causing an inferior vena cava (IVC) tumor thrombus. Venous extension has significant implications for staging and subsequent treatment planning, with recommendations for more aggressive surgical removal, although associated surgical morbidity and mortality is relatively increased. The methods for surgical removal of RCC with IVC thrombus remain complex, particularly surrounding the use of robot-assisted surgery. Robot assistance for radical nephrectomy in this context is recently emerging. Thrombus level has important implications for surgical technique and prognosis. Other preoperative considerations may include location, laterality, size, and wall invasion. The urology literature on treatment of such tumors is largely limited to case series and institutional studies that describe the feasibility of various surgical options for these complex tumors. Further understanding of the outcomes and patient-specific risk factors would shed increased light on the optimal treatment for such cases. This narrative review provides a thorough overview on the previously reported use of robot-assisted nephrectomy in RCC with IVC thrombus to inform further studies which may optimize outcomes and guide shared decision-making.

Effect of United States Medical Licensing Examination Score Cutoffs on Recruitment of Underrepresented Applicants in the Urology Match.

OBJECTIVE: To determine how the use of United States Medical Licensing Examination (USMLE) score cutoffs during the screening process of the Urology Residency Match Program may affect recruitment of applicants who are underrepresented in medicine (URM). MATERIALS AND METHODS: Deidentified data from the Association of American Medical Colleges' (AAMC) Electronic Residency Application Service (ERAS) system was reviewed, representing all applicants to our institution's urology residency program from 2018 to 2022. We analyzed self-reported demographic variables including race/ethnicity, age, sex/gender, as well as USMLE Step 1 and Step 2 scores. Chi-square tests and ANOVA were used to determine the association between race/ethnicity and other sociodemographic factors and academic metrics. Applicants were stratified according to USMLE Step 1 cutoff scores and the distribution of applicants by race/ethnicity was assessed using a Gaussian nonlinear regression fit. RESULTS: A total of 1258 applicants submitted applications to our program during the 5-year period, including 872 males (69.3%) and 386 females (30.7%). Most applicants were White (43.5%), followed by Asian (28.3%), Hispanic/Latino (11.7%), and Black (7.0%). There was an association between race/ethnicity and USMLE scores. Median USMLE Step 1 scores for White, Asian, Hispanic/Latino, and Black applicants were 242, 242, 237, and 232, respectively (P < .001). As cutoff score increases, percentage of URM applicants decreases. CONCLUSION: The use of cutoffs based on USMLE scores disproportionately affects URM applicants. Transitioning from numeric scores to pass/fail may enhance holistic review processes and increase the representation of URM applicants offered interviews at urology residency programs.

First analysis of the safety and efficacy of UGN-101 in the treatment of ureteral tumors.

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.

Pelvic lymphadenectomy: Evaluating nodal stage migration and will rogers effect in bladder cancer.

INTRODUCTION: Pelvic lymphadenectomy (PLND) alongside radical cystectomy (RC), provides crucial diagnostic and therapeutic value in patients with bladder cancer. With the advent of neoadjuvant chemotherapy and prospective data supporting standard PLND, controversy remains regarding the optimal PLND extent and patient selection. Nearly 40% of patients may not receive adequate PLND, even though 25% of patients have positive lymph nodes (LN) at time of RC. We hypothesized that PLND still remains an important facet of bladder cancer treatment. To clarify the prognostic importance of nodal yield, we performed a retrospective investigation of a heterogenous population (pTanyNx/0M0) of patients undergoing RC. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) program, we identified pTanyNx/0M0 bladder cancer patients undergoing RC from 2004 to 2015. Kaplan Meier curves and Cox proportional hazards models assessed cancer-specific survival. Patients were analyzed with PLND performed as the primary covariate. Survival analysis then stratified patients undergoing PLND by LN yield, both as a continuous and categorial variable (≤10, 11-20, 21-30, and >30), and T stage. RESULTS: The final cohort included pTanyNx/0M0 patients with urothelial bladder cancer (n = 12,096); median follow up was 39 (IQR: 17-77) months. PLND was performed in 81.45% of patients with a median LN yield of 14 (IQR: 7-23). Most commonly, patients had T2 disease (44.68%). After controlling for age and T stage, patients receiving PLND had improved CSS (HR = 0.56, [95% CI: 0.51-0.62]) compared to those that did not receive PLND. When grouping patients by LN yield, survival improved in a "dose dependent" manner (>30 LN: HR = 0.76, [95% CI: 0.66-0.87]). We noted similar results when stratifying patients into non-muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC). CONCLUSIONS: In a large contemporary series of pTanyNx/0M0 bladder cancer patients, we found a significant oncologic benefit to PLND. Higher LN yield correlated to improved CSS in non-muscle-invasive and muscle-invasive disease. Our data support the possibility of occult micrometastasis even in non-muscle-invasive disease. Additionally, in light of recent advances in adjuvant immunotherapy, our results emphasize the importance of adequate nodal yield for accurate staging and optimal treatment.

Transcriptional state dynamics lead to heterogeneity and adaptive tumor evolution in urothelial bladder carcinoma.

Intra-tumor heterogeneity contributes to treatment failure and poor survival in urothelial bladder carcinoma (UBC). Analyzing transcriptome from a UBC cohort, we report that intra-tumor transcriptomic heterogeneity indicates co-existence of tumor cells in epithelial and mesenchymal-like transcriptional states and bi-directional transition between them occurs within and between tumor subclones. We model spontaneous and reversible transition between these partially heritable states in cell lines and characterize their population dynamics. SMAD3, KLF4 and PPARG emerge as key regulatory markers of the transcriptional dynamics. Nutrient limitation, as in the core of large tumors, and radiation treatment perturb the dynamics, initially selecting for a transiently resistant phenotype and then reconstituting heterogeneity and growth potential, driving adaptive evolution. Dominance of transcriptional states with low PPARG expression indicates an aggressive phenotype in UBC patients. We propose that phenotypic plasticity and dynamic, non-genetic intra-tumor heterogeneity modulate both the trajectory of disease progression and adaptive treatment response in UBC.

The Role of Salvage Radical Prostatectomy in Patients with Radiation-Resistant Prostate Cancer.

There are multiple treatment strategies for patients with localized prostate adenocarcinoma. In intermediate- and high-risk patients, external beam radiation therapy demonstrates effective long-term cancer control rates comparable to radical prostatectomy. In patients who opt for initial radiotherapy but have a local recurrence of their cancer, there is no unanimity on the optimal salvage approach. The lack of randomized trials comparing surgery to other local salvage therapy or observation makes it difficult to ascertain the ideal management. A narrative review of existing prospective and retrospective data related to salvage radical prostatectomy after radiation therapy was undertaken. Based on retrospective and prospective data, post-radiation salvage radical prostatectomy confers oncologic benefits, with overall survival ranging from 84 to 95% at 5 years and from 52 to 77% at 10 years. Functional morbidity after salvage prostatectomy remains high, with rates of post-surgical incontinence and erectile dysfunction ranging from 21 to 93% and 28 to 100%, respectively. Factors associated with poor outcomes after post-radiation salvage prostatectomy include preoperative PSA, the Gleason score, post-prostatectomy staging, and nodal involvement. Salvage radical prostatectomy represents an effective treatment option for patients with biochemical recurrence after radiotherapy, although careful patient selection is important to optimize oncologic and functional outcomes.

A Restaging Transurethral Resection of Bladder Tumor Is Always Necessary For High-grade T1 Non-muscle-invasive Bladder Cancer.

Patients with high-grade T1 non-muscle-invasive bladder cancer (NMIBC) have a high risk of recurrence and upstaging. Restaging transurethral resection of bladder tumor allows better staging so that patients can proceed to the appropriate treatment in a timely manner. This should be done in all patients with high-grade T1 NMIBC.

Annual trends of cystectomy complications: A contemporary analysis of the NSQIP database.

INTRODUCTION: Despite significant morbidity, radical cystectomy (RC) is standard of care for muscle invasive bladder cancer, certain high-risk nonmuscle invasive tumors and after failure of intravesical or trimodal therapy. Modern efforts have hastened the recovery after this surgery without impact on overall complication rates. Our primary aim was to examine changes in complication rates of RC over time. METHODS: The National Surgical Quality Improvement Program database included 11,351 RC from 2006 to 2018 for nondisseminated bladder cancer. Baseline characteristics and complication rates were studied across time periods: 2006 to 2011, 2012 to 2014, and 2015 to 2018. Thirty-day complications, readmissions, and mortality were identified. RESULTS: Overall complication rates decreased over time (56.5%, 57.4%, 50.6%, P < 0.01). Infectious complications were stable, including UTIs (10.1%, 8.8%, 8.3% respectively, P = 0.11) and sepsis (10.4%, 8.8%, 8.7% respectively, P = 0.20). On multivariable analysis, ASA≥3 (OR 1.399, 95% CI 1.279-1.530) was associated with increased complications, while procedures in 2015 to 2018 (OR 0.825, 95% CI 0.722-0.942), laparoscopic/robotic approach (OR 0.555, 95%CI 0.494-0.622), and ileal conduit (OR 0.796, 95% CI 0.719-0.882) were associated with decreased complication rates. Other outcomes of interest included mean length of stay (LOS), which decreased over time (10.5, 9.8, 8.6 days, respectively, P < 0.01) and readmission (20.0%, 21.3%, 21.0%, respectively, P = 0.84) and mortality rates were stable (2.7%, 1.7%, 2.0%, respectively, P = 0.13). CONCLUSION: Decreased early complications and LOS after RC over time may reflect beneficial effects of recent advances in bladder cancer treatment such as enhanced recovery after surgery protocols and minimally invasive techniques. Further opportunities to improve long term outcomes, readmissions and infection rates are needed.

The ablative effect of mitomycin reverse thermal gel: Expanding the role for nephron preservation therapy in low grade upper tract urothelial carcinoma.

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.

Impact of smoking on urologic cancers: a snapshot of current evidence.

PURPOSE: The purpose of this paper is to present evidence regarding the associations between smoking and the following urologic cancers: prostate, bladder, renal, and upper tract urothelial cancer (UTUC). METHODS: This is a narrative review. PubMed was queried for evidence-based analyses and trials regarding the associations between smoking and prostate, bladder, renal, and UTUC tumors from inception to September 1, 2022. Emphasis was placed on articles referenced in national guidelines and protocols. RESULTS: Prostate-multiple studies associate smoking with higher Gleason score, higher tumor stage, and extracapsular invasion. Though smoking has not yet been linked to tumorigenesis, there is evidence that it plays a role in biochemical recurrence and cancer-specific mortality. Bladder-smoking is strongly associated with bladder cancer, likely due to DNA damage from the release of carcinogenic compounds. Additionally, smoking has been linked to increased cancer-specific mortality and higher risk of tumor recurrence. Renal-smoking tobacco has been associated with tumorigenesis, higher tumor grade and stage, poorer mortality rates, and a greater risk of tumor recurrence. UTUC-tumorigenesis has been associated with smoking tobacco. Additionally, more advanced disease, higher stage, lymph node metastases, poorer survival outcomes, and tumor recurrence have been linked to smoking. CONCLUSION: Smoking has been shown to significantly affect most urologic cancers and has been associated with more aggressive disease, poorer outcomes, and tumor recurrence. The role of smoking cessation is still unclear, but appears to provide some protective effect. Urologists have an opportunity to engage in primary prevention by encouraging cessation practices.

Metastasis-Directed Therapy for Oligometastatic Castration-Sensitive Prostate Cancer: An Alternative to ADT?

PURPOSE OF REVIEW: The standard treatment of patients with metastatic prostate cancer is systemic treatment with androgen-deprivation therapy (ADT). The spectrum-based model of metastatic disease includes the presence of an oligometastatic state, an intermediary between localized and widespread metastatic disease, in which radical local treatment might improve systemic control. Our purpose is to review the literature on metastasis-directed therapy in the treatment of oligometastatic prostate cancer. RECENT FINDINGS: Several prospective clinical trials have reported improvements in ADT-free survival and progression-free survival with metastasis-directed therapy of oligometastatic prostate cancer. Retrospective studies have found improvements in oncologic outcomes for patients with oligometastatic prostate cancer undergoing metastasis-directed therapy, and several recent prospective clinical trials have confirmed these results. Advancements in imaging as well as an understanding of the genomics of oligometastatic prostate cancer may allow for better patient selection for metastasis-directed therapy and the potential for cure in selected patients.

Factors associated with clinical trial participation for patients with renal cell carcinoma.

OBJECTIVE: Recruitment of a diverse and representative study population is critical to the external validity of oncology clinical trials. The primary objective of this study was to characterize the factors associated with clinical trial participation for patients with renal cell carcinoma and the secondary objective was to examine differences in survival outcomes. MATERIALS AND METHODS: We used a matched case-control design by querying the National Cancer Database for patients with renal cell carcinoma who were coded as having enrolled in a clinical trial. Trial patients were matched in a 1:5 ratio to the control cohort based on clinical stage and then sociodemographic variables were compared between the 2 groups. Multivariable conditional logistic regression models evaluated factors associated with clinical trial participation. The trial patient cohort was then matched again in a 1:10 ratio based on age, clinical stage, and comorbidities. Log-rank test was used to compare overall survival (OS) between these groups. RESULTS: From 2004 to 2014, 681 patients enrolled in clinical trials were identified. Clinical trial patients were significantly younger and had a lower Charlson-Deyo comorbidity score. On multivariate analysis, male patients and white patients were more likely to participate compared to their Black counterparts. Having Medicaid or Medicare negatively associated with trial participation. Median OS was greater among clinical trial participants. CONCLUSION: Patient sociodemographic factors remain significantly associated with clinical trial participation and trial participants experienced superior OS to their matched counterparts.

Examining the Role of Microbiota-Centered Interventions in Cancer Therapeutics: Applications for Urothelial Carcinoma.

Modern advances in genomic and molecular technologies have sparked substantial research on the human intestinal microbiome over the past decade. A deeper understanding of the microbiome has illuminated that dysbiosis, or a disruption in the microbiome, is associated with inflammatory disease states and carcinogenesis. Novel therapies that target the microbiome and restore healthy flora may have value in dampening the immunopathologic state induced by dysbiosis. A narrative review of the literature on the use of microbiota-centered interventions (MCIs) was conducted. Several randomized clinical trials show that MCIs can augment response to immune checkpoint inhibitor (ICI) therapy in patients with metastatic cancer. Clinical trials have also demonstrated that modulation of the intestinal microbiome can enhance recovery and reduce infectious complications in the surgical management of colorectal adenocarcinoma. Overall, these major discoveries suggest future clinical applications of MCIs for a wide range of immune-mediated conditions. These results may also translate to improved patient outcomes in systemic immunotherapy for urothelial carcinoma as well as in patients recovering from radical cystectomy (RC), which is complicated by high infection rates. Further research is needed to evaluate the optimal bacterial composition of microbiota-centered therapies and the specific cellular changes that lead to improved tumor antigen recognition after microbiota-centered therapies.