Sequential Intravesical Valrubicin and Docetaxel for the Salvage Treatment of Non-Muscle-Invasive Bladder Cancer.

PURPOSE: Intravesical gemcitabine-docetaxel has emerged as an efficacious and well-tolerated salvage therapy for non-muscle-invasive bladder cancer. However, further rescue therapies are needed for subsequent recurrences or intolerance, particularly when cystectomy is refused or precluded. Valrubicin is a U.S. Food and Drug Administration-approved agent for bacillus Calmette-Guérin unresponsive disease, yet as monotherapy has demonstrated poor efficacy. We report our experience with sequential intravesical valrubicin and docetaxel as a rescue therapy for non-muscle-invasive bladder cancer. MATERIALS AND METHODS: We retrospectively identified all patients with recurrent non-muscle-invasive bladder cancer treated with valrubicin and docetaxel between April 2013 and June 2021. Patients received weekly sequential intravesical instillations of 800 mg valrubicin and 37.5 mg docetaxel for 6 weeks. If disease-free at first follow-up, monthly maintenance of 2 years was initiated. The primary outcome was recurrence-free survival, assessed using the Kaplan-Meier method. RESULTS: The analysis included 75 patients with median follow-up of 21 months (IQR: 13-37). Twelve patients with low-grade disease had a 73% recurrence-free survival at 2 years. Sixty-three patients with recurrent high-grade disease had a 38% 2-year high-grade recurrence-free survival. Forty-two (56%) patients had carcinoma in situ present; recurrence-free survival was similar for those with and without carcinoma in situ (P = .63). Two patients died of metastatic bladder cancer while 10 underwent cystectomy. Among patients with high-grade disease, overall, cancer-specific, and cystectomy-free survivals were 87%, 96%, and 84% at 2 years, respectively. Adverse events included bladder spasms (n = 18), urinary frequency (n = 10), and dysuria (n = 8). Two patients could not tolerate valrubicin and docetaxel induction. CONCLUSIONS: In a heavily pretreated population, our results suggest valrubicin and docetaxel is an effective rescue treatment for patients with recurrent non-muscle-invasive bladder cancer. Further prospective evaluation is needed.

Sequential Intravesical Gemcitabine and Docetaxel for bacillus Calmette-Guérin-Naïve High-Risk Nonmuscle-Invasive Bladder Cancer.

PURPOSE: Bacillus Calmette-Guérin (BCG) is currently recommended as adjuvant therapy following complete transurethral resection of bladder tumor for high-risk nonmuscle-invasive bladder cancer (NMIBC). In response to the BCG shortage, gemcitabine plus docetaxel (Gem/Doce) has been utilized at our institution in the BCG-naïve setting. We report the outcomes of patients with high-risk BCG-naïve NMIBC treated with Gem/Doce. MATERIALS AND METHODS: We retrospectively reviewed patients with BCG-naïve high-risk NMIBC treated with Gem/Doce from May 2013 through April 2021. Patients received 6 weekly intravesical instillations of sequential 1 gm gemcitabine and 37.5 mg docetaxel after complete transurethral resection of bladder tumor. Monthly maintenance of 2 years was initiated if disease-free at first followup. The primary outcome was recurrence-free survival. Survival was assessed with the Kaplan-Meier method, indexed from the first Gem/Doce instillation. Adverse events were reported using CTCAE (Common Terminology Criteria for Adverse Events) v5 (National Cancer Institute, Bethesda, Maryland). Differences were assessed with the log-rank test. RESULTS: There were 107 patients with a median followup of 15 months included in the analysis. Patients had high-risk characteristics including 47 with any carcinoma in situ and 55 with T1 disease. Recurrence-free survival was 89%, 85% and 82% at 6, 12 and 24 months, respectively. Recurrence rates were similar between patients with or without carcinoma in situ (p=0.42). No patient had disease progression or died of bladder cancer. One patient underwent cystectomy due to end-stage lower urinary tract symptoms. Overall survival was 84% at 24 months. There were 92 adverse events (1 ≥grade 3), and 4 (4%) patients were unable to receive a full induction course. CONCLUSIONS: Gem/Doce is an effective and well-tolerated therapy for BCG-naïve NMIBC. Further investigation is warranted.

Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy for Nonmuscle Invasive Bladder Cancer.

PURPOSE: Rescue intravesical therapies for patients with bacillus Calmette-Guérin failure nonmuscle invasive bladder cancer remain a critical focus of ongoing research. Sequential intravesical gemcitabine and docetaxel therapy has shown safety and efficacy in 2 retrospective, single institution cohorts. This doublet has since been adopted as an intravesical salvage option at multiple institutions. We report the results of a multi-institutional evaluation of gemcitabine and docetaxel. MATERIALS AND METHODS: Each institution retrospectively reviewed all records of patients treated with intravesical gemcitabine and docetaxel for nonmuscle invasive bladder cancer between June 2009 and May 2018. Only patients with recurrent nonmuscle invasive bladder cancer and a history of bacillus Calmette-Guérin treatment were included in the analysis. If patients were disease-free after induction, maintenance was instituted at the treating physician's discretion. Posttreatment surveillance followed American Urological Association guidelines. Survival analysis was performed using the Kaplan-Meier method and risk factors for treatment failure were assessed with Cox regression models. RESULTS: Overall 276 patients (median age 73 years, median followup 22.9 months) received treatment. Nine patients were unable to tolerate a full induction course. One and 2-year recurrence-free survival rates were 60% and 46%, and high grade recurrence-free survival rates were 65% and 52%, respectively. Ten patients (3.6%) had disease progression on transurethral resection. Forty-three patients (15.6%) went on to cystectomy (median 11.3 months from induction), of whom 11 (4.0%) had progression to muscle invasion. Analysis identified no patient, disease or prior treatment related factors associated with gemcitabine and docetaxel failure. CONCLUSIONS: Intravesical gemcitabine and docetaxel therapy is well tolerated and effective, providing a durable response in patients with recurrent nonmuscle invasive bladder cancer after bacillus Calmette-Guérin therapy. Further prospective study is warranted.

The association of marital status and mortality among men with early-stage prostate cancer treated with radical prostatectomy: insight into post-prostatectomy survival strategies.

PURPOSE: The purpose of this study was to determine the association of marital status, a marker of social support, with all-cause and prostate cancer-specific mortality in a cohort of men with early-stage prostate cancer treated with radical prostatectomy. METHODS: We conducted a retrospective cohort study of 3,579 men treated for localized (stage 1-2) prostate cancer with radical prostatectomy at a single institution between 1994 and 2004. Marital status (not married vs. married) and marital history (never married, divorced, widowed vs. married) at the time of prostatectomy were examined in relation to (1) all-cause mortality and (2) prostate cancer-specific mortality using Cox proportional hazards regression. RESULTS: Not being married (vs. married) at the time of radical prostatectomy was associated with an increased risk of all-cause mortality [Hazard Ratio (HR) 1.42; 95% Confidence Interval (CI) 1.10, 1.85]. Similarly, in analyses of marital history, never-married men were at highest risk of all-cause mortality (HR 1.77, 95% CI 1.19, 2.63). Unmarried status (vs. married) was also associated with an increased risk of prostate cancer-specific mortality (HR 1.97; 95% CI 1.01, 3.83). CONCLUSIONS: Unmarried men with prostate cancer were at greater risk for death after radical prostatectomy. Among married men with prostate cancer, marriage likely serves as a multi-faceted proxy for many protective factors including social support. Future studies should explore the mechanisms underlying these findings to inform the development of novel prostate cancer survival interventions for unmarried men and those with low social support.

Update of the International Consultation on Urological Diseases on bladder cancer 2018: non-urothelial cancers of the urinary bladder.

PURPOSE: To provide a comprehensive update of the joint consultation of the International Consultation on Urological Diseases (ICUD) for the diagnosis and management of non-urothelial cancer of the urinary bladder. METHODS: A detailed analysis of the literature was conducted reporting on the epidemiology, etiology, diagnosis, treatment and outcomes of non-urothelial cancer of the urinary bladder. An international, multidisciplinary expert committee evaluated and graded the evidence according to the Oxford System of Evidence-based Medicine modified by the ICUD. RESULTS: The major non-urothelial cancers of the urinary bladder are squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumors. Several other non-urothelial tumors are rare but important to identify because of their aggressive behavior when compared to urothelial bladder tumors. Radical cystectomy and urinary diversion, preceded by neoadjuvant radiation or chemotherapy in some of these tumors, is the main method or treatment for resectable disease. Adjuvant therapy is not usually successful and no novel targeted or immunotherapeutic agents have been identified to provide benefit. Patients with small cell neuroendocrine tumors of the bladder should be offered chemotherapy before surgery. Because non-urothelial cancers are usually locally advanced and/or metastatic at the time of diagnosis, 5-year survival is generally poor. CONCLUSIONS: Non-urothelial cancers of the urinary bladder are rare and mostly lack established protocols for treatment. The prognosis of most of these tumors is poor because they are usually advanced at the time of diagnosis. A multimodal treatment approach should be considered to improve outcomes.

Alpha-dystroglycan staining pattern and mortality in patients undergoing radical prostatectomy with lymph node positive prostate cancer.

INTRODUCTION: Dystroglycan (DG) is a cell surface receptor for extracellular matrix proteins involved in tissue mechanical stability and matrix organization. Initial work has demonstrated that alpha-DG expression is decreased in many types of adenocarcinoma, including prostate, and potentially associated with the development of metastatic disease. However, the consistency between prostate and lymph node alpha-DG staining has not been previously reported. In addition, identification of an immunohistochemical marker associated with prostate cancer grade, stage, need for adjuvant or salvage therapy and mortality would have potential clinical value. MATERIALS AND METHODS: Node positive, margin negative radical prostatectomy specimens at a single institution from 1982 to 2012 were reviewed and identified 35 prostate specimens, including 26 patients with available tissue from both the primary prostatectomy and lymph node specimens. The expression levels of the alpha-DG subunit were analyzed using immunohistochemistry and graded from 0 to 4. Survival was compared in different staining pattern groups. RESULTS: Strength of alpha-DG staining was found to be consistent between prostate and lymph node specimens (p < 0.004). The median overall survival was shorter in those without alpha-DG staining in the prostate compared to those with positive staining, but this difference was not statistically significant (13.2 years versus 19.4 years, p = 0.21). In addition, negative staining was associated with higher mean PSA, pathologic T stage, Gleason grade and the need for adjuvant or salvage therapy compared to positive group but none reached statistical significance (16.06 ng/mL versus 11.67 ng/mL, p = 0.79; 89% versus 68%, p = 0.38; 33.3% versus 23.1%, p = 0.66; 88.9% versus 76.9%, p = 0.44). CONCLUSIONS: DG expression by immunohistochemistry staining was consistent between prostate and metastatic lymph node specimens. In a small cohort of prostate cancer patients with margin negative but node positive disease, DG staining was not associated with Gleason grade or with overall mortality.

Optimizing Nutrition Prior to Radical Cystectomy.

PURPOSE OF REVIEW: Malnutrition in a prevalent problem in patients undergoing radical cystectomy. Preoperative malnutrition has been shown to contribute to increased rates of postoperative complications. Given the significant morbidity and mortality of the procedure of radical cystectomy, there is potential for improvement in patient outcomes by nutritional intervention. RECENT FINDINGS: Prospective studies have demonstrated a reduction in postoperative infection rates in patients who receive supplemental immunonutrition prior to major surgery including radical cystectomy. These initial evaluations of nutritional optimization show significant potential for improved outcomes. Additionally, several studies using enhanced recovery after surgery protocols, which include a preoperative nutritional component, have shown a benefit in reducing length of stay. Emerging literature has shown the benefits of preoperative immunonutrition in improving postoperative outcomes of radical cystectomy. However, further work is needed to determine the best mechanism to optimize nutrition prior to radical cystectomy.

Emerging Impact of Malnutrition on Surgical Patients: Literature Review and Potential Implications for Cystectomy in Bladder Cancer.

PURPOSE: Malnutrition is emerging as a significant factor in patient outcomes. A contemporary review of malnutrition has not been performed for the urologist. We review the available literature and current standards of care for malnutrition screening, assessment and intervention, focusing on patients with bladder cancer treated with cystectomy. MATERIALS AND METHODS: Our multidisciplinary team searched PubMed® for available literature on malnutrition, focusing on definition and significance, importance to urologists, screening, assessment, diagnosis, immunological and economic impacts, and interventions. RESULTS: The prevalence of malnutrition in hospitalized patients is estimated to range from 15% to 60%, reaching upward of 71% in those with cancer. Malnutrition has been shown to increase inflammatory markers, further intensifying catabolism and weight loss. Bladder cancer is catabolic and patients undergoing cystectomy have increased resting energy expenditure postoperatively. Data are emerging on the impact of malnutrition in the cystectomy population. Recent studies have identified poor nutritional status based on low albumin or sarcopenia (loss of muscle) as having an adverse impact on length of hospitalization, complications and survival. The current standard of care malnutrition assessment tool, the 2012 consensus statement of the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition, has not been evaluated in the urological literature. Perioperative immunonutrition in patients undergoing colorectal surgery has been associated with significant decreases in postoperative complications, and recent pilot work has identified the potential for immunonutrition to positively impact the cystectomy population. CONCLUSIONS: Malnutrition has a significant impact on surgical patients, including those with bladder cancer. There are emerging data in the urological literature regarding how best to identify and improve the nutritional status of patients undergoing cystectomy. Additional research is needed to identify malnutrition in these patients and interventions to improve surgical outcomes.

Experience with Sequential Intravesical Gemcitabine and Docetaxel as Salvage Therapy for Non-Muscle Invasive Bladder Cancer.

Patients with high-grade muscle invasive bladder cancer (NMIBC) receive intravesical therapy with bacillus Calmette-Guérin (BCG) as the well-established standard-of-care. However, even with prompt induction of intravesical therapy, approximately 40 % of patients will recur within 2 years. For patients who fail BCG, options include radical cystectomy, repeat BCG therapy, or alternative intravesical salvage therapy. In this review, we will discuss the most recent published evidence on salvage intravesical therapy with an emphasis on a more in-depth report of our therapeutic strategy with sequential gemcitabine and docetaxel intravesical therapy for this treatment-refractory population. In addition, we will provide practical advice on our approach to this challenging patient population including the use of operative staging to aid early identification of treatment failures.

Gleason 6 Prostate Cancer: Translating Biology into Population Health.

PURPOSE: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. MATERIALS AND METHODS: Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. RESULTS: The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. CONCLUSIONS: The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

Evaluating the safety of intraoperative instillation of intravesical chemotherapy at the time of nephroureterectomy.

BACKGROUND: Urothelial carcinoma (UC) is a common cancer affecting many patients in the United States. Nephroureterectomy remains the gold standard for the treatment of high grade upper tract disease or low grade tumors that are not amenable to endoscopic management. Recent reports have shown a decrease in UC recurrence in patients who underwent nephroureterectomy and who had Mitomycin C (MMC) instilled into the bladder at the time of catheter removal. At our institution instillation of intravesical MMC at the time of nephroureterectomy has been common for more than 10 years. Given the recent data, we sought to formally describe our experience with and evaluate the safety of intravesical instillation of cytotoxic chemotherapy at the time of nephroureterectomy. METHODS: We retrospectively reviewed 51 patients who underwent intraoperative intravesical instillation of cytotoxic chemotherapy (MMC (n = 48) or adriamycin (n = 3)) at the time of nephroureterectomy (2000-2012). The procedure was performed in a similar fashion by 8 different surgeons from the same institution, with drainage of the bladder prior to management of the bladder cuff. Patient characteristics and perioperative data including complications out to 90 days after surgery were collected. Perioperative complications for all patients were graded using the modified Clavien-Dindo classification. RESULTS: Twenty-four men and 27 women underwent intraoperative intravesical instillation of cytotoxic chemotherapy at the time of nephroureterectomy. Median age at the time of operation was 74 years (range 48-88). Median dwell time was 60 min. Twenty three patients had a total of 45 perioperative complications. The majority (36/45) were Clavien grades I and II. No patients experienced any intraoperative or postoperative complications attributable to MMC or Adriamycin instillation. CONCLUSION: Intraoperative intravesical instillation of cytotoxic chemotherapy at the time of nephroureterectomy is safe and feasible. Multicenter trials to study the efficacy of early cytotoxic chemotherapy administration to prevent recurrence of bladder urothelial carcinoma following nephroureterectomy are warranted.

Routine pathology evaluation of hydrocele and spermatocele specimens is associated with significant costs and no identifiable benefit.

PURPOSE: Hydrocelectomy and spermatocelectomy are routine scrotal surgeries. A significant number of the surgical specimens are sent for pathology analysis. However, to our knowledge no study has been done to examine outcomes and necessity, which results in significant potentially unnecessary costs to the patient and the health care system. We evaluated outcomes and surgical pathology analysis of hydroceles and spermatoceles. MATERIALS AND METHODS: We performed a retrospective, single institution chart review of all patients who underwent initial surgery for hydrocele or spermatocele between January 2000 and August 2013. We determined the number of cases in which a surgical specimen was sent for pathology examination. The cost for each specimen was estimated at the department of pathology. RESULTS: A total of 264 routine scrotal cases were performed during the 14-year period. Surgical specimens were sent for pathology analysis in 102 hydrocelectomy cases (51%) and in 57 spermatocelectomy cases (90%). No pathology specimen showed any indication of malignancy. The estimated direct total cost of pathology analysis was $49,449 in this cohort. CONCLUSIONS: No malignancy was detected in 159 hydrocele and spermatocele specimens during the 14 study years, suggesting that the pathology analysis is of little clinical benefit. Forgoing surgical pathology analysis of these specimens would result in significant cost savings to the patient and the health care system.

Defining the potential of neoadjuvant chemotherapy use as a quality indicator for bladder cancer care.

PURPOSE: Despite known survival benefits, overall use of neoadjuvant chemotherapy before cystectomy is low, raising concerns about quality of care. However, not all patients undergoing cystectomy are eligible for this therapy. We establish the maximum proportion of patients expected to receive neoadjuvant chemotherapy if all those eligible had a consultation with medical oncology. MATERIALS AND METHODS: From institutional data (January 2010 through December 2012) we identified 215 patients treated with radical cystectomy for bladder cancer. After excluding patients not eligible for neoadjuvant chemotherapy, we fit models assessing patient disease and health factors affecting referral to medical oncology and receipt of neoadjuvant chemotherapy. Expected use of chemotherapy was then determined for increasingly broad groups of patients treated with cystectomy after controlling for factors precluding the use of neoadjuvant chemotherapy. RESULTS: Of the 215 patients identified 127 (59%) were eligible for neoadjuvant chemotherapy. After additional consideration of patient factors (patient refusal, health status and poor renal function), maximum receipt of neoadjuvant chemotherapy increased from 42% to 71% as more restrictive definitions for the eligible patient cohort were used. CONCLUSIONS: Substantial variability exists in the proportion of patients eligible for neoadjuvant chemotherapy based on the population identified. While there is substantial underuse of neoadjuvant chemotherapy, the development of quality metrics for this essential therapy depends on correct identification of the cystectomy population being assessed. Even with referral of all appropriate patients for medical oncology evaluation, use of chemotherapy would likely not exceed 50% of patients in nationally representative cystectomy data.

Comparison of a single center, academic surgeon real-world experience with three percutaneous nephrolithotomy lithotripters.

INTRODUCTION: We compared a single surgeon, single-institution experience with the Wolf Ultrasonic Model #2167.05 (Richard Wolf Medical Instruments Co., Vernon Hills, IL, USA), Lithoclast Ultra (Boston Scientific, Natick, MA, USA), and CyberWand (Gyrus/ACMI, Southborough, MA, USA) lithotripters for percutaneous nephrolithotomy (PCNL). We assessed each lithotripter's performance and durability. MATERIALS AND METHODS: We conducted a retrospective chart review on 70 sequential PCNLs. Treatments were split into three cohorts based on the type of lithotripter used, Wolf (August 2003 to February 2004), Lithoclast (March 2004 to November 2008), or CyberWand (December 2008 to October 2009). Operative time, repeat PCNL procedures, lithotripter efficacy, patient body mass index (BMI), and stone-free rates (defined as < 4 mm fragment on postoperative day one noncontrast CT scan) were compared. RESULTS: Sixty-one patients underwent 70 PCNLs using the Wolf (12), Lithoclast (39) or CyberWand (19). The CyberWand cohort had higher rates of obesity (74% versus 53% for Lithoclast and 45% for Wolf) and staghorn calculi (68% versus 39% for Lithoclast and 36% for Wolf). Operative time were 151 minutes (75-384, Wolf), 190 (55-360, Lithoclast) and 200 (81-387, CyberWand) cohorts. Stone-free rates were 50% (Wolf), 49% (Lithoclast) and 37% (CyberWand). PCNL was repeated within 45 days following 6 (50%) Wolf, 7 (18%) Lithoclast and 1 (5%) CyberWand procedures. Lithotripter malfunction complicated 1 Wolf (8%), 5 (13%) Lithoclast and no CyberWand PCNLs. Intraoperative complications occurred during 1 (8%) Wolf, 9 (23%) Lithoclast, and 2 (11%) CyberWand cases. CONCLUSIONS: Despite treating larger stones in more obese patients, the CyberWand lithotripter had a lower malfunction and need for repeat PCNL rates. These findings suggest that the CyberWand may be a more durable lithotripter. However, the overall efficacy of each lithotripter in performing PCNL was similar.

Does Rounding Order Bias Discharge Efficiency? Predictors of Discharge Timing on an Academic Urology Service.

ABSTRACT: No previous works have analyzed whether the order in which surgical teams see patients on morning rounds affects discharge efficiency at teaching hospitals. We obtained perioperative urologic surgery timing data at our academic institution from 2014 to 2019. We limited the analysis to routine postoperative day 1 discharges. Univariate and multivariate analyses were performed to determine whether various hospital and patient factors were associated with discharge timing. We analyzed 1,494 patients. Average discharge order time was 11:22 a.m. and hospital discharge 1:24 p.m. Univariate regression revealed earlier discharge order time for patients seen later in rounds by 4 minutes per sequential room cluster (p = .013) and by 12 minutes per cluster when excluding short-stay patients. Multivariate analysis revealed discharge order placement did not vary significantly by rounding order. However, time of hospital discharge did (p < .001), likely due to speed of discharge in the designated short-stay units. Attending physician was the most consistent predictor in variations of discharge timing, with statistical significance across all measured outcomes. Patients seen later in rounding progression received earlier discharge orders, but this relationship does not remain in multivariate modeling or translate to earlier discharge. These findings have helped guide quality improvement efforts focused on discharge efficiency.

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.

Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics.

PURPOSE: This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV). METHODS: Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium. The data set comprised abstracted clinical data with germline and tumor genomic data, and comparative analyses were conducted. RESULTS: Clinically actionable germline PVs in cancer predisposition genes were identified in 16 (4.5%) of 354 patients. A higher proportion of patients with the urethra and the upper tract as the primary sites of disease had PVs with a prevalence of 11% (5/45), compared with only 3.6% (11/308) in those with the bladder as the primary site of disease (P = .04). There were no significant differences in markers of genomic instability (such as tumor mutational burden, microsatellite instability [MSI], and loss of heterozygosity, copy number, and chromosomal instability) between those with PVs and those without (P > .05). Of the PVs identified, 10 (62%) were in homologous recombination repair (HRR) genes, three (19%) in mismatch repair (MMR) genes, and three (19%) in genes associated with other pathways. CONCLUSION: Tissue-based assessment of genomic instability, such as MSI, does not reliably indicate germline PV. A comprehensive clinical germline testing approach that includes HRR genes in addition to MMR genes is likely to yield PVs in approximately one of 10 patients with nonbladder primary disease sites such as the upper tract and the urethra.

Interruptions in bladder cancer care during the COVID-19 public health emergency.

BACKGROUND: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. METHODS: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. RESULTS: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. CONCLUSIONS: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic.

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.