Challenges and opportunities in the management of metastatic renal cell carcinoma: combination therapy and the role of cytoreductive surgery.

PURPOSE OF REVIEW: As the biology of metastatic renal cell carcinoma (mRCC) continues to be elucidated, novel treatments focused around immunotherapies and targeted therapies will continue to emerge. In this review, we will highlight recent treatment advances and their implications for surgical and systemic therapy. RECENT FINDINGS: Several new treatments, including the tyrosine kinase inhibitor cabozantinib, the combination of a programmed cell death protein 1 antibody (nivolumab) with a cytotoxic T-lymphocyte-associated antigen 4 antibody (ipilimumab), and the combination of axitinib with pembrolizumab or avelumab have been approved by the US Food and Drug Administration as first-line therapy for the treatment of mRCC. Although promising survival benefits have been seen with these new therapies, careful patient selection is still critical. SUMMARY: The introduction of novel therapies and the investigation of combinatorial therapies have shifted the treatment paradigm for advanced RCC. Present trials have provided promising data that could lead to further therapeutic advances.

Bowel preparation prior to reconstructive urologic surgery in pediatric myelomeningocele patients.

INTRODUCTION: Mechanical bowel preparation (MBP) has historically been the standard of care for patients undergoing reconstructive urologic surgery, including urinary diversion. To date, several studies have examined the role of mechanical bowel preparation in postoperative outcomes in pediatric patients undergoing augmentation cystoplasty. However, these patient populations have been heterogeneous in nature, with no studies dedicated to examining the role of MBP prior to reconstructive urologic surgery in pediatric patients with myelomenginoceles. Thus, our objective was to retrospectively assess perioperative measures and postoperative complications after reconstructive urologic surgery with or without mechanical bowel preparation in pediatric myelomeningocele patients. MATERIALS AND METHODS: From 2008 to 2013, 80 patients with myelomeningocele underwent reconstructive urologic surgery involving the use of bowel. Seventy patients underwent a preoperative MBP while 10 did not. Perioperative measures and postoperative complications for these two cohorts were assessed. RESULTS: Eighty patients with myelomeningocele were identified; 70 patients underwent MBP while 10 patients did not. There were no statistically significant differences in demographics or operative time. There were no statistically significant differences in postoperative outcomes including time to first bowel movement and time to tolerating diet. There was also no significant difference in overall complication rate; patients with MBP had 31/70 (44%) complications while 2/10 (20%) of those without MBP had complications (p = 0.18). CONCLUSION: There was no significant difference in perioperative measures and postoperative complications for patients who did not receive a mechanical bowel preparation. Our findings indicate that it is safe and warranted to perform a prospective, randomized study to better characterize the risks and benefits of preoperative bowel preparation for patients with myelomeningocele.

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.

Chromophobe Renal Cell Carcinoma with Sarcomatoid Differentiation.

Chromophobe renal cell carcinoma (chRCC) is one of the less common types of kidney cancer and generally portends a more favorable prognosis. RCC with sarcomatoid differentiation has a more aggressive clinical course with poor outcomes. Four cases of chRCC with varying degrees of sarcomatoid differentiation were retrospectively reviewed at our institution, and clinicopathologic data as well as clinical courses were reported. Patients with higher degrees of sarcomatoid differentiation and larger tumors at presentation generally had and worse overall survival. chRCC with sarcomatoid differentiation portends a poor prognosis with limited data on systemic treatment options for metastatic disease.

Renal Cell Carcinoma with Testicular Metastases: A Case Report and Review of the Literature.

Renal cell carcinoma (RCC) metastases to the testicle are an extremely rare clinical entity. Here, we describe the case of a man with metastatic RCC who developed a new testicular mass. Pathologic analysis after surgical removal of this testicle confirmed the diagnosis of metastatic RCC. This report highlights the unique diagnostic and therapeutic challenges associated with such a disease process.

Renal Cell Carcinoma with Cardiac Metastases: A Case Report and Review of the Literature.

Cardiac metastases from renal cell carcinoma (RCC) are very rare. We describe the case of a woman with RCC with cardiac metastases involving the entire right atrium, penetrating through the myocardium, with extension into the tricuspid valve and right ventricle. This report highlights the unique challenge of the diagnosis and treatment of cardiac metastases in RCC.

Factors Associated With Palliative Intervention Utilization for Metastatic Renal Cell Carcinoma.

INTRODUCTION: Several guidelines have adopted early integration of palliative intervention (PI) into oncologic care to improve quality of life among patients with advanced malignancies. However, PI utilization patterns and factors associated with its use in metastatic renal cell carcinoma are poorly understood. PATIENTS AND METHODS: Using the National Cancer Database (NCDB), we abstracted patients diagnosed with Stage IV RCC from 2004 to 2014 and evaluated the utilization of PI within this cohort. Socioeconomic and clinical factors were compared for patients receiving and not receiving PI for metastatic RCC. Multivariable logistic regression (MLR) models identified factors that were associated with receipt of PI within overall cohort and treatment-based cohorts. RESULTS: We identified 42,014 patients with Stage IV RCC, of which 7,912 patients received PI. From 2004 to 2014, the use of PI minimally increased from 17% to 20% for Stage IV RCC. MLR analysis demonstrated that increased comorbidities, insurance status, higher education status, facility location, care at a comprehensive cancer program or integrated network, sarcomatoid histology, and treatment type significantly increased the likelihood of PI use. Various socioeconomic, clinical, and geographical factors that are associated with use of PI-based on the treatment received for Stage IV RCC. CONCLUSIONS: While PI utilization has minimally increased for Stage IV RCC, there are several geographic, socioeconomic, and clinical factors that predict its use among patients with Stage IV RCC in a treatment-specific manner. Taken together, this suggests the need for earlier initiation of PI in a more equitable and systematic fashion among patients with metastatic RCC.

Delaying surgery for clinical T1b-T2bN0M0 renal cell carcinoma: Oncologic implications in the COVID-19 era and beyond.

PURPOSE: During COVID-19, many operating rooms were reserved exclusively for emergent cases. As a result, many elective surgeries for renal cell carcinoma (RCC) were deferred, with an unknown impact on outcomes. Since surveillance is commonplace for small renal masses, we focused on larger, organ-confined RCCs. Our primary endpoint was pT3a upstaging and our secondary endpoint was overall survival. MATERIALS AND METHODS: We retrospectively abstracted cT1b-T2bN0M0 RCC patients from the National Cancer Database, stratifying them by clinical stage and time from diagnosis to surgery. We selected only those patients who underwent surgery. Patients were grouped by having surgery within 1 month, 1-3 months, or >3 months after diagnosis. Logistic regression models measured pT3a upstaging risk. Kaplan Meier curves and Cox proportional hazards models assessed overall survival. RESULTS: A total of 29,746 patients underwent partial or radical nephrectomy. Delaying surgery >3 months after diagnosis did not confer pT3a upstaging risk among cT1b (OR = 0.90; 95% CI: 0.77-1.05, P = 0.170), cT2a (OR = 0.90; 95% CI: 0.69-1.19, P = 0.454), or cT2b (OR = 0.96; 95% CI: 0.62-1.51, P = 0.873). In all clinical stage strata, nonclear cell RCCs were significantly less likely to be upstaged (P <0.001). A sensitivity analysis, performed for delays of <1, 1-3, 3-6, and >6 months, also showed no increase in upstaging risk. CONCLUSION: Delaying surgery up to, and even beyond, 3 months does not significantly increase risk of tumor progression in clinically localized RCC. However, if deciding to delay surgery due to COVID-19, tumor histology, growth kinetics, patient comorbidities, and hospital capacity/resources, should be considered.

The human microbiome and genitourinary malignancies.

The human microbiome contains a vast network of understudied organisms that have an intimate role in our health and wellness. These microbiomes differ greatly between individuals, creating what may be thought of as a unique and dynamic microbial signature. Microbes have been shown to have various roles in metabolism, local and systemic inflammation, as well as immunity. Recent findings have confirmed the importance of both the gut and urinary microbiomes in genitourinary malignancies. Numerous studies have identified differences in microbial signatures between healthy patients and those with urologic malignancies. The microbiomes have been shown to contain microbes that may contribute to the etiology of disease state as well as yield information in regard to a person's health and their responsiveness to certain drugs such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Less well understood are the effects of antibiotics on oncologic outcomes in such treatment courses. This review will explore our current understanding and advancements in the field of microbiome research and discuss its intimate association with genitourinary diseases including bladder cancer, prostate cancer, and kidney cancer. With a better understanding of the association between the microbiome and genitourinary malignancy, further investigation may produce reliable predictors of disease, prognostic indicators as well as therapeutic targets.

Urologic oncology surgery during COVID-19: a rapid review of current triage guidance documents.

The Coronavirus Disease 2019 pandemic placed urologic surgeons, and especially urologic oncologists, in an unprecedented situation. Providers and healthcare systems were forced to rapidly create triage schemas in order to preserve resources and reduce potential viral transmission while continuing to provide care for patients. We reviewed United States and international triage proposals from professional societies, peer-reviewed publications, and publicly available institutional guidelines to identify common themes and critical differences. To date, there are varying levels of agreement on the optimal triaging of urologic oncology cases. As the need to preserve resources and prevent viral transmission grows, prioritizing only high priority surgical cases is paramount. A similar approach to prioritization will also be needed as nonemergent cases are allowed to proceed in the coming weeks. While these decisions will often be made on a case-by-case basis, more nuanced surgeon-driven consensus guidelines are needed for the near future.

Retroperitoneal Lymph Node Dissection as Primary Treatment for Men With Testicular Seminoma: Utilization and Survival Analysis Using the National Cancer Data Base, 2004-2014.

BACKGROUND: The role of retroperitoneal lymph node dissection (RPLND) as first-line treatment for testicular seminoma is less well defined than for testicular nonseminomatous germ-cell tumors. We describe utilization of primary RPLND in the United States and report on overall survival (OS) after surgery for these men. PATIENTS AND METHODS: Using 2004-2014 data from the National Cancer Data Base, we identified 62,727 men with primary testicular cancer, 31,068 of whom were diagnosed as having seminoma. After excluding men with benign, non-germ cell, and nonseminomatous germ-cell tumor histologies, those who did not undergo RPLND, those where clinical stage and survival data were unavailable, and those with testicular seminoma who underwent RPLND in the postchemotherapy setting (n = 47), 365 men comprised our final cohort. Descriptive statistics were used to summarize clinical and demographic factors. The Kaplan-Meier method was used to determine OS. RESULTS: A total of 365 men with testicular seminoma underwent primary RPLND. At a median follow-up of 4.1 years, there were 16 deaths in the entire cohort. Five-year OS was 94.2%. Subset analysis of men with stage I and IIA/B disease who underwent primary RPLND revealed 5-year OS rates of 97.3% and 92.0%, respectively (P = .035). OS did not significantly differ in patients with stage IIA versus IIB disease (91.8% vs. 92.3%, respectively, P = .907). CONCLUSION: Although RPLND is rarely used as primary therapy in testicular seminoma, OS rates appear to be comparable to rates reported in the literature for primary chemotherapy or radiotherapy. Ongoing prospective trials will clarify the role of RPLND in the management of testicular seminoma.

A Case Study Evaluating the Diagnosis and Treatment of a Rare Mesenchymal Tumor.

The objective of this study is to report a benign mesenchymal neoplasm, cellular angiofibroma. We describe a 34-year-old male with a 4-month history of a painless right inguinal mass. CT scan of the abdomen and pelvis showed a 6.6 cm, oval-shaped mass without any distinguishing radiographical features. Surgical excision of the mass was performed. Tissue was extracted for immunohistochemical analysis, which stained positive for CD34 and Desmin, confirming cellular angiofibroma of the spermatic cord. Thus, this report highlights the importance of a challenging diagnostic case for providers due to the narrow range of imaging modalities and therefore limited treatment options.

Metastatic Prostate Cancer to the Renal Pelvis and Proximal Ureter: A Case Report and Review of the Literature.

Prostate cancer metastases are commonly seen in the skeleton, lymph nodes, lungs, or liver, and are associated with a poor five-year survival rate. Renal pelvis and ureteral metastasis are exceedingly uncommon and can present with obstructive symptoms or as an asymptomatic mass on imaging. We report the case of a 60-year-old patient who was initially diagnosed with prostate adenocarcinoma and experienced eventual metastasis to the right renal pelvis and proximal ureter. Following the diagnosis, he was started on docetaxel and pembrolizumab as part of a clinical trial protocol. A high index of suspicion and thorough metastatic work-up is necessary when patients with prostate cancer present with symptoms of obstructive uropathy or new visceral disease is identified.

Primary Renal Ewing Sarcoma: A Case Report and Review of the Literature.

Primary Ewing sarcoma of the kidney is an extremely rare and aggressive tumor affecting young adults. We present the case of a 22-year-old male with primary Ewing sarcoma/primitive neuroectodermal tumor (EWS/PNET) of the kidney who underwent right radical nephrectomy and adjuvant chemo-radiation.

Trends and outcomes of lymphadenectomy for nonmetastatic renal cell carcinoma: A propensity score-weighted analysis of the National Cancer Database.

PURPOSE: Lymph node (LN) involvement in renal cell carcinoma (RCC) is associated with a poor prognosis. While lymph node dissection (LND) may provide diagnostic information, its therapeutic benefit remains controversial. Thus, the aim of our study is to analyze survival outcomes after LND for nonmetastatic RCC and to characterize contemporary practice patterns. MATERIALS AND METHODS: The National Cancer Database was queried for patients with nonmetastatic RCC who underwent either partial or radical nephrectomy from 2010 to 2014. A total of 11,867 underwent surgery and LND. Chi-square tests were used to examine differences in patient demographics. To minimize selection bias, propensity score matching (PSM) was used to select one control for each LND case (n = 19,500). Cox regression analyses were conducted to examine overall survival (OS) in patients who received LND compared to those who did not. RESULTS: Of all patients undergoing LND for RCC (n = 11,867), 5%, 23%, 31%, 47% were performed for tumors of clinical T stage 1, 2, 3, and 4, respectively. Proportions of LND have not significantly changed from 2010 to 2014. No significant improvement in median OS for patients undergoing LND compared to no LND was shown (34.7 vs. 34.9 months, respectively; P = 0.98). Similarly, no significant improvement in median OS was found for clinically LN positive patients undergoing LND compared to no LND (P = 0.90). On Cox regression analysis, LND dissection was not associated with an OS benefit (hazard ratio: 1.00; 95% confidence interval 0.97 to 1.04). CONCLUSIONS: Among all RCC patients, LNDs are often performed for low stage disease, suggesting a potential overutilization of LND. No OS benefit was seen in any subgroup of patients undergoing LND. Further investigation is needed to determine which patient populations may benefit most from LND.

Results of Phase 1 study on cytoreductive radical prostatectomy in men with newly diagnosed metastatic prostate cancer.

BACKGROUND: Preclinical and retrospective data suggest that cytoreductive radical prostatectomy may benefit a subset of men who present with metastatic prostate cancer (mPCa). Herein, we report the results of the first planned Phase 1 study on cytoreductive surgery. METHODS: From four institutions, 36 patients consented to the study. However, four did not complete surgery because of rapid disease progression (n = 3) and another because of an intraoperatively discovered pericolonic abscess. Men with newly diagnosed clinical mPCa to lymph nodes or bones were eligible. The primary endpoint was the rate of major perioperative complications (Clavien-Dindo Grade 3 or higher) occurring within 90 days of surgery. RESULTS: The mean age at surgery was 64.0 years. The 90-day overall complication rate was 31.2% (n = 10), of which two (6.25%) were considered major complications: one acute tubular necrosis requiring temporary dialysis and one death. In men with more than 6 months of follow-up, 67.9% had prostate specific antigen nadir ≤0.2 ng/mL, while one patient experienced a rapid rise in prostate specific antigen and another a widely disseminated disease that resulted in death 5 months after surgery. Altogether, these results demonstrate that cytoreductive radical prostatectomy is safe and surgically feasible in selected patients who present with mPCa . Yet, there may be a small subset of patients in whom surgery may cause a significant harm. CONCLUSION: Therefore, cytoreductive surgery in men with mPCa should be limited to clinical trials until robust data are available.

Management of Postradical Prostatectomy Urinary Incontinence: A Review.

Postprostatectomy urinary incontinence has a significant impact on the quality of life of patients who undergo radical prostatectomy. Stress and overflow incontinence may result from the procedure, with sphincteric incompetence and detrusor hypocontractility implicating their development, respectively. In many cases, treatment begins with conservative approaches, including pelvic floor muscle training or biofeedback. Pharmacotherapy can be used to treat overactive bladder. For stress incontinence, transurethral bulking agents are utilized in select patients; however, artificial urinary sphincter and male slings are the most efficacious options with good success rates. In this review, the various treatment modalities are critically discussed with special emphasis on safety and efficacy.

Role of the androgen signaling axis in genitourinary malignancies.

As we learn more about the molecular biology of genitourinary malignancies, novel therapeutic strategies can be developed. This is especially crucial for prostate, renal, and bladder cancer, where mortality rates remain high especially in advanced disease states. The androgen signaling axis and the androgen receptor (AR) are areas that are actively being explored for their role in these diseases. Although long been associated with prostate cancer development and progression, the role of AR in renal cell carcinoma (RCC) and bladder cancer is becoming recognized as well. This review will highlight the current research into the role of the androgen signaling axis in genitourinary malignancies and how this pathway is being used to expand our therapeutic armamentarium.

Disparities in the Use of Continent Urinary Diversions after Radical Cystectomy for Bladder Cancer.

BACKGROUND: Radical cystectomy (RC) with ileal conduit (IC) or continent diversion (CD) is standard treatment for high-risk non-invasive and muscle-invasive bladder cancer. OBJECTIVE: Our aim is to study contemporary trends in the utilization of ICs and CDs in patients undergoing RC. METHODS: Using the National Inpatient Sample 2001-2012, we identified all patients diagnosed with a malignant bladder neoplasm who underwent RC followed by IC or CD. Patient demographics, comorbidities, length of stay (LOS), and in-hospital complications, mortality, and costs were compared. Multivariable logistic regression analysis, Chi square, and t-tests were used for analysis. RESULTS: Between 2001-2012, approximately 69,049 ICs and 6,991 CDs were performed. CDs increased from 2001 to 2008, but declined after 2008 (p < 0.0001). Patients of all ages received ICs at a higher rate than CDs (40-59 years: 79.5% vs. 20.5%; 60-69 years: 88.0% vs. 12.0%; p < 0.0001). There was a difference in males vs. females (10.2% vs. 4.0%; OR 2.36) and Caucasians vs. African Americans (9.0% vs. 6.7%; OR 1.49) when comparing CD rates. CD rates were highest in the West, urban teaching centers, and large hospitals (p < 0.001). ICs were associated with higher rates of overall postoperative complications (p = 0.0185) including infection (p = 0.002) and mortality (p < 0.0001). In-hospital costs were greater for the CD group. CONCLUSIONS: The number of CDs has declined recently. Patients of all ages are more likely to receive ICs than CDs. Gender, racial, and geographic disparities exist among those receiving CDs. CDs are associated with lower rates of in-hospital complications and mortality, but higher in-hospital costs.

Risk of complications and urinary incontinence following cytoreductive prostatectomy: a multi-institutional study.

Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer (PCa). Urinary incontinence was defined as the use of any pad. CRP had longer operative times (200 min vs 140 min, P < 0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared to the control group. However, both overall (8.82% vs 5.85%) and major complication rates (4.41% vs 2.17%) were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI: 1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01-1.36; P = 0.034). In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.