Association of Surgical Delay and Overall Survival in Patients With T2 Renal Masses: Implications for Critical Clinical Decision-making During the COVID-19 Pandemic.

OBJECTIVE: To test for an association between surgical delay and overall survival (OS) for patients with T2 renal masses. Many health care systems are balancing resources to manage the current COVID-19 pandemic, which may result in surgical delay for patients with large renal masses. METHODS: Using Cox proportional hazard models, we analyzed data from the National Cancer Database for patients undergoing extirpative surgery for clinical T2N0M0 renal masses between 2004 and 2015. Study outcomes were to assess for an association between surgical delay with OS and pathologic stage. RESULTS: We identified 11,848 patients who underwent extirpative surgery for clinical T2 renal masses. Compared with patients undergoing surgery within 2 months of diagnosis, we found worse OS for patients with a surgical delay of 3-4 months (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.00-1.25) or 5-6 months (HR 1.51, 95% CI 1.19-1.91). Considering only healthy patients with Charlson Comorbidity Index = 0, worse OS was associated with surgical delay of 5-6 months (HR 1.68, 95% CI 1.21-2.34, P= .002) but not 3-4 months (HR 1.08, 95% CI 0.93-1.26, P = 309). Pathologic stage (pT or pN) was not associated with surgical delay. CONCLUSION: Prolonged surgical delay (5-6 months) for patients with T2 renal tumors appears to have a negative impact on OS while shorter surgical delay (3-4 months) was not associated with worse OS in healthy patients. The data presented in this study may help patients and providers to weigh the risk of surgical delay versus the risk of iatrogenic SARS-CoV-2 exposure during resurgent waves of the COVID-19 pandemic.

Robotic Partial Nephrectomy: Update on Techniques.

Surgical techniques for robot-assisted partial nephrectomy are driven by the aims of simplifying the most challenging surgical steps, maximizing functional and oncologic outcomes, and consistently pushing the envelope on possibilities. Over the past several years, we have seen an emergence in not only innovation in surgical technique, and robotic platforms, but integration of a variety of imaging techniques. We believe with developing robotic expertise, practicing urologists will continue to push the envelope in nephron preservation and complication-free recovery.

The changing landscape of systemic therapy in metastatic renal cell carcinoma: an update.

Treatment options for metastatic renal cell carcinoma (RCC) continue to expand. Three recent phase III trials, Checkmate 214, Keynote-426, and Javelin Renal 101, have led to FDA approval of three new regimens for patients with clear cell RCC: nivolumab plus ipilimumab, pembrolizumab plus axitinib, and avelumab plus axitinib, respectively. At the same time, the dearth of treatment options for non-clear cell RCC has changed very little. The role of cytoreductive nephrectomy has also come into question after the publication of the CARMENA and SURTIME trials. This review will examine recent changes in therapeutic options in clear cell RCC and non-clear RCC, and the role of surgery in the treatment of metastatic RCC.

Case report: a nonfunctioning juxtaglomerular cell tumor mimicking renal cell carcinoma.

INTRODUCTION: Based on existing literature, the juxtaglomerular cell tumor (JGCT) is a rare renal tumor, typically present with hypertension and hypokalemia. Nonfunctioning JGCT, without hypertension or hypokalemia, is extremely rare. PATIENT CONCERNS: Herein, we report a case of nonfunctioning JGCT mimicking renal cell carcinoma. The 29-year-old woman with an unremarkable past medical history presented with a left renal tumor without hypertension or hypokalemia. DIAGNOSIS: Both CT and 18F-FDG-PET/CT suggested a malignancy, possibly renal cell carcinoma. INTERVENTIONS: The tumor was then removed completely via robotic assistant laparoscopic partial nephrectomy; and pathology result was JGCT. Since the patient had no hypertension or hypokalemia, a nonfunctional JGCT was diagnosed. OUTCOMES: The patient recovered uneventfully, and was in good health in 6-months' follow-up period. CONCLUSION: Preoperative identification of JGCT is very difficult due to the lack of specific clinical manifestations. This case teaches us that for young patients with renal tumors whose CT enhancement is not obvious at the early phase, JGCT should be considered as a differential diagnosis. Radical nephrectomy should be avoided for JGCT in consideration of its relatively good prognosis.

Increased Circulatory Extrarenal 1α,25-Dihydroxyvitamin D3 in Bilaterally Nephrectomized Rats.

BACKGROUND: Extrarenal 1α,25-dihydroxyvitamin D3 (1,25-D) locally produced by immune cells plays crucial roles in the regulation of the immune system. However, in vivo status of extrarenal 1,25-D and 25-hydroxyvitamin D (25-D) in acute inflammatory conditions are unknown. OBJECTIVE: The aim of this study was to determine the extrarenal 1,25-D level in circulation in bilaterally nephrectomized rats, induced by low-dose lipopolysaccharide (LPS). METHODS: Renal 1,25-D synthesis was terminated through bilateral nephrectomy in rats. The rats received intraperitoneal LPS (50 µg/kg BW) three times and the experiment was ended 24 hours after nephrectomy. Serum 1,25-D, 25-D, calcium, phosphorus, intact parathyroid hormone, and calcitonin levels were measured and immunohistochemistry was applied to detect the sources of extrarenal 1,25- D synthesis. RESULTS: Circulatory 1,25-D concentration remarkably increased in both LPS-treated and non-treated bilaterally nephrectomized rats. Elevated circulatory 1,25-D did not have hypercalcemic endocrinal effects. The increased 1,25-D level also resulted in a concurrent rapid and dramatic depletion of circulatory 25-D. CONCLUSION: Extrarenal 1,25-D could enter into the systemic circulation and, therefore, might have systemic effects besides its autocrine and paracrine functions.

Stereotactic Body Radiotherapy for Stage I Renal Cell Carcinoma: National Treatment Trends and Outcomes Compared to Partial Nephrectomy and Thermal Ablation.

PURPOSE: To assess use of stereotactic body radiotherapy (SBRT) for stage I renal cell carcinoma (RCC) and compare outcomes with thermal ablation and partial nephrectomy (PN). MATERIALS AND METHODS: The 2004-2015 National Cancer Database was investigated for histopathologically proven stage I RCC treated with PN, cryoablation, radiofrequency (RF) or microwave (MW) ablation, or SBRT. Patients were propensity score-matched to account for potential confounders, including patient age, sex, race, comorbidities, tumor size, histology, grade, tumor sequence, administration of systemic therapy, treatment in academic vs nonacademic centers, treatment location, and year of diagnosis. Overall survival (OS) was evaluated with Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models. RESULTS: A total of 91,965 patients were identified (SBRT, n = 174; PN, n = 82,913; cryoablation, n = 5,446; RF/MW ablation, n = 3,432). Stage I patients who received SBRT tended to be older women with few comorbidities treated at nonacademic centers in New England states. After propensity score matching, a cohort of 636 patients was obtained with well-balanced confounders between treatment groups. In the matched cohort, OS after SBRT was inferior to OS after PN and thermal ablation (PN vs SBRT, hazard ratio [HR] = 0.29, 95% confidence interval [CI] 0.19-0.46, P < .001; cryoablation vs SBRT, HR = 0.40, 95% CI 0.26-0.60, P < .001; RF/MW ablation vs SBRT, HR = 0.46, 95% CI 0.31-0.67, P < .001). Compared with PN, neither cryoablation nor RF/MW ablation showed significant difference in OS (cryoablation vs PN, HR = 1.35, 95% CI 0.80-2.28, P = .258; RF/MW ablation vs PN, HR = 0.64, 95% CI 0.95-2.55, P = .079). CONCLUSIONS: Current SBRT protocols show lower OS compared with thermal ablation and PN, whereas thermal ablation and PN demonstrate comparable outcomes.

Changing trends in surgical management of renal tumours from 2000 to 2016: a nationwide study of Medicare claims data.

BACKGROUND: Guidelines recommend nephron sparing surgery where possible for patients with T1 renal tumours. The trends of nephron sparing surgery outside the USA are limited, particularly since the introduction of robotic-assisted partial nephrectomy (RAPN). The aim of this study was to describe contemporary surgical management patterns of renal tumours in Australia according to Medicare claims data. METHODS: Claims data according to the Medicare Benefits Schedule on surgical management of renal tumours in adult Australians between January 2000 and December 2016 was collated. Analysis of absolute number, population-adjusted rate and renal cancer-adjusted rate of interventions according to age and gender were performed, as well as proportion of RAPN. RESULTS: Between 2000 and 2016, the rate of partial nephrectomy (PN) increased while radical nephrectomy (RN) remained stable (PN: 0.87-4.16, RN: 6.52-6.70 per 100 000 population). Since 2015, PN has become more common than RN in patients aged 25 to 44 years (0.98 versus 0.95 procedures per 100 000 population). Renal cancer-adjusted rate exhibited a trend towards increasing utilization of PN and reduced RN across all age groups. An increase in overall surgical treatment was observed (25%-41%), mainly due to increased treatment of patients older than 75 years. The proportion of RAPN was seen to rapidly increase (4.7% in 2010 to 58% in 2016). CONCLUSIONS: Treatment utilization for renal masses has markedly changed in Australia according to Medicare claims. PN is increasingly replacing RN in younger patients, and older patients are receiving more surgical treatment. The impact of increased RAPN utilization is yet to be determined.

Trends in Renal Tumor Surgery in the United States and Germany Between 2006 and 2014: Organ Preservation Rate Is Improving.

BACKGROUND: Nephron-sparing surgery (NSS) is the treatment of choice for T1 renal tumors. This study compared the implementation of NSS in the United States and Germany. METHODS: Data were derived from the National Inpatient Sample and from the Nationwide German Hospital Billing Database. All cases of NSS and radical nephrectomy from 2006 to 2014 were analyzed. To assess tumor stage distribution, data from the Surveillance, Epidemiology, and End Results database (United States) and from German cancer registries were used. RESULTS: The study identified 74,663 cases in the United States and 130,051 cases in Germany. The proportion of NSS for T1 tumors increased from 30.6 to 57% in the United States compared with 38.5 to 72.9% (estimation) in Germany (p < 0.001). The proportion of robotic NSS increased from 0 to 54.5% in the United States (p < 0.001) and from 0.2 to 8.6% in Germany (p < 0.001). In a multivariate model, hospitals with higher annual caseloads and a surgical robot favored NSS. CONCLUSION: Patients with renal tumors might receive inhomogeneous care based on the resources of the treating institution. The robotic approach is a key driver for better implementation of NSS in the United States, and relevant potential still may exist for more organ preservation.

[50 years of renal cell carcinoma]. / 50 Jahre Nierenzellkarzinom.

In the past 50 years, many knowledge gaps regarding renal cell carcinoma (RCC) have been closed. A pathological tumour classification has been developed and different histological subtypes are known today. In clear cell RCC, the (mutated) von Hippel-Lindau gene located on chromosome 3 is highly important. Operative therapy of non-metastatic RCC has evolved from radical nephrectomy to less radical techniques including procedures sparing the adrenal gland as well as nephron-sparing surgery. Surgical procedures are increasingly performed using laparoscopic or robot-assisted approaches. Even less invasive techniques such as cryoablation, radiofrequency ablation or active surveillance are applied for small renal masses, if indicated. Metastatic RCC is most commonly treated by systemic therapy. Chemotherapy has no effect in RCC. For more than 20 years, cytokine therapy was the standard of care for metastatic RCC. Mutations of the von Hippel-Lindau gene associated with accumulation of hypoxia-inducible factor, followed by increased transcription of vascular endothelial growth factor, provided the scientific rationale for the successful use of tyrosine kinase inhibitors, mTOR inhibitors, and anti-VEGF antibodies introduced in 2006. The development of checkpoint inhibitors has changed the systemic treatment of RCC in yet another relevant manner.

Evolving role of cytoreductive nephrectomy in metastatic renal cell carcinoma of variant histology.

PURPOSE OF REVIEW: Summarize current evidence for cytoreductive nephrectomy in patients with metastatic renal cell carcinoma (mRCC) of variant histology. RECENT FINDINGS: The mainstream treatment for advanced malignancy is systematic therapy, including chemotherapy, targeted therapy, and immunotherapy. Nonetheless, cytoreductive nephrectomy has been used in the management of mRCC including variant (nonclear cell) histology. Prospective data supported cytoreductive nephrectomy for clear cell mRCC in the cytokine immunotherapy era in the late 1990s. In the targeted therapy era, the practice of cytoreductive nephrectomy in nonclear and clear cell histology had been largely based on retrospective data, but a recent phase III trial showed that targeted therapy alone is noninferior to targeted therapy combined with cytoreductive nephrectomy, therefore, questioning the clinical benefit of cytoreductive nephrectomy in this context. However, this trial had excluded patient with nonclear cell histology. With the potential for checkpoint inhibitor combinations to achieve long-term complete durable response, cytoreductive nephrectomy is a subject of ongoing debate especially, in nonclear cell histology as those were excluded from prospective trials. SUMMARY: Data are very sparse in nonclear histology. Although retrospective data favor the use of cytoreductive nephrectomy in nonclear cell mRCC, clinicians must carefully select patients and balance risks of surgery and delayed systemic therapy.

Is cytoreductive nephrectomy relevant in the immunotherapy era?

PURPOSE OF REVIEW: The recent approval of immune checkpoint inhibitors (ICI) revolutionized the treatment paradigm for metastatic renal cell carcinoma (mRCC). However, the role of cytoreductive nephrectomy is not well defined in this setting. Here, we review the contemporary role and timing of cytoreductive nephrectomy for advanced RCC in the era of immunotherapy. RECENT FINDINGS: Evidence concerning combination systemic therapy and cytoreductive nephrectomy in the multimodal management of mRCC is primarily limited to studies conducted in the targeted therapy era. The oncologic role of cytoreductive nephrectomy in the setting of ICI remains largely undefined and is supported primarily by case reports. Nonetheless, patient selection for cytoreductive nephrectomy is paramount, and appropriate candidacy in the ICI era will likely be refined as increasing evidence emerges. Until then, a cautious balance between perceived oncologic benefit and risks of intervention must be exercised. Several trials are ongoing to help shed light on patient selection, technical feasibility, and optimal timing of cytoreductive nephrectomy in the immunotherapy era. SUMMARY: Although the role and timing for cytoreductive nephrectomy remain to be further elucidated in the immunotherapy era, patient selection remains critical for treatment planning. Further studies are urgently needed to better define the role of cytoreductive nephrectomy in this setting.

The evolving role of cytoreductive nephrectomy in metastatic renal cell carcinoma.

PURPOSE OF REVIEW: To review the evidence related to cytoreductive nephrectomy in metastatic renal cell carcinoma (mRCC) treated in the targeted therapy era, with a focus on observational studies and randomized trials. RECENT FINDINGS: A number of retrospective observational studies exploring the role of cytoreductive nephrectomy have been reported. These have suggested an association between cytoreductive nephrectomy and survival, with hazard ratio estimates ranging from 0.39 to 0.68 in favour of cytoreductive nephrectomy. In contrast, the CARMENA randomized trial demonstrated that sunitinib alone was noninferior to cytoreductive nephrectomy followed by sunitinib in intermediate-risk and poor-risk patients. The results of the SURTIME trial suggest that initial sunitinib followed by a deferred cytoreductive nephrectomy may also be a reasonable approach in select patients. SUMMARY: On the basis of the evidence to date, there is still a role for cytoreductive nephrectomy in the multimodality treatment of mRCC. Careful patient selection is of paramount importance and discussion in multidisciplinary tumour boards is encouraged. As the treatment landscape of mRCC continues to change, the role of cytoreductive nephrectomy in the modern immuno-oncology era will need to be explored.

The evolving role of cytoreductive nephrectomy: incorporating genomics of metastatic renal cell carcinoma into treatment decisions.

PURPOSE OF REVIEW: Recent publications evaluating cytoreductive nephrectomy in the era of targeted therapy emphasize the importance of patient selection. We reviewed the predictive role of genetic alterations in patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy. RECENT FINDINGS: Studies evaluating the association between genetic alterations and outcomes following systemic treatment for mRCC include mainly patients after cytoreductive nephrectomy. Expression of proangiogenic genes, single nucleotide polymorphisms involving genes of the vascular-endothelial growth factor (VEGF) pathway and somatic mutations of chromatin remodeling genes were associated with response to VEGF-targeted therapy. Outcomes following treatment with mammalian target of rapamycin (mTOR) inhibitors were initially associated with mTOR/TSC1/TSC2 mutations; however, subsequent studies did not validate these findings but rather found an association between loss of PTEN expression and PBRM1 mutations and improved outcomes. Loss of PBRM1 was initially linked to response to immunotherapy; however, larger studies question this association and showed high expression of T-effector gene signature predicted improved outcome. Primary tumors with low intratumor heterogeneity but elevated somatic copy-number alterations were associated with rapid progression at multiple sites. SUMMARY: Genetic alterations may help select patients for cytoreductive nephrectomy and optimize timing of treatment. Intratumor heterogeneity and genetic discordance between primary and metastatic tumors may limit clinical applicability. Future studies should evaluate approaches to overcome these limitations.

Evolving Trends for Selected Treatments of T1a Renal Cell Carcinoma.

OBJECTIVE: To evaluate contemporary trends in the management of small renal masses and how patient age has impacted practice patterns. METHODS: Using the NCDB Participant User File (PUF) from 2002 to 2015, we identified patients with T1a renal masses. The initial treatment was categorized as radical nephrectomy (RN), partial nephrectomy (PN), ablation, or active surveillance (AS). A multinominal logistic regression model was used to identify significant factors impacting treatment. RESULTS: We identified 75,691 patients for analysis. RN, PN, and ablation accounted for 28%, 52%, and 12%, respectively, while 8% were managed with AS. In the past decade the likelihood of undergoing PN, ablation, or surveillance compared to RN has consistently increased, independent of age, sex, race, comorbidity, tumor size, or institution. As age increased, patients were independently less likely to undergo PN and more likely to be managed with ablation or AS. Compared to patients under 40 years of age, patients between 70 and 79 were far less likely to undergo PN (RR 0.58, P< .01), and far more likely to undergo either ablation (RR 5.53, P< .01) or AS (RR 3.7, P< .01). CONCLUSION: Trends in small renal mass management continue to evolve, with PN supplanting RN over the past decade as the predominant surgical treatment. Age significantly impacts treatment selection, particularly in older cohorts whom are much more likely to undergo ablation or AS. While the use of minimally invasive therapies has increased over the past decade, AS lags behind despite quality data supporting its use. When controlling for multiple clinical factors, PN, ablation and surveillance have consistently increased in utilization compared to RN.

Trends in surgical management of multicystic dysplastic kidney at USA children's hospitals.

INTRODUCTION AND OBJECTIVE: Multicystic dysplastic kidney (MCDK) is a congenital renal cystic disease often incidentally diagnosed in children. Historically, children with MCDK underwent early nephrectomy because of concerns for the development of hypertension or malignancy. Over the last decade, management recommendations have not supported routine early surgical removal of MCDK. The study authors sought to determine the current trends in the use of nephrectomy for MCDK in US children's hospitals because national practice patterns have not been investigated. METHODS: A population-based retrospective cohort study using the Pediatric Health Information System (PHIS) was conducted. The study population was comprised of patients aged 0-18 years with a diagnosis of MCDK (International Classification of Diseases-9th revision, code 753.19) admitted to the inpatient department of the study hospital between January 2006 and September 2015. Patients with additional renal anomalies including polycystic kidney, medullary cystic kidney, and medullary sponge kidney were excluded, as were patients treated in a hospital that did not contribute data to the PHIS continuously throughout the study period. Trends in the annual proportion of nephrectomies performed were analyzed among admissions in the study population, along with patient clinical and demographic information. RESULTS: A total of 3792 MCDK admissions, in 34 hospitals, were included in the study. Overall, 569 nephrectomies were performed during the study period. The proportion of nephrectomy decreased annually by 9.2% on average, from 22.1% in 2006 to 7.3% in the first 3 quarters of 2015. No significant trends were observed in the annual number of overall MCDK admissions or patient age at procedure among patients who had a nephrectomy. Among nephrectomies, 84.2% were open and 15.8% were minimally invasive procedures (laparoscopic non-robotic, 10% and robotic, 5.8%). The proportion of minimally invasive nephrectomies increased annually by 13.7%, from 8% in 2006 to 29% in 2015. DISCUSSION: Trends in the use of nephrectomy for MCDK at a national level have not been previously reported. This study is limited by the use of inpatient discharge data, which did not allow estimating the true rate of nephrectomy in patients born with MCDK. CONCLUSIONS: During the study period, there has been a decrease in the use of nephrectomy for MCDK in pediatric hospitals, along with a concurrent increase in utilization of minimally invasive techniques to perform nephrectomies. These results suggest that in general, urologists at freestanding children's hospitals are heeding recommendations for observation and against routine early surgical removal of these kidneys; although trends in the use of nephrectomy varied between hospitals, there is room for continued improvement in following these recommendations.

Considerations for the Next Clinical Trial Evaluating the Role of Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma.

Trials SWOG 8949 and EORTC 30947 had the same eligibility criteria and established the role of cytoreductive nephrectomy for metastatic renal cell carcinoma. The more recently published CARMENA trial calls into question the need for cytoreductive nephrectomy. A systematic comparison of CARMENA and SWOG 8949 suggests that cytoreductive nephrectomy may be beneficial for patients receiving immunotherapy but not targeted therapy. The approval of immune checkpoint inhibitors for previously untreated metastatic renal cell carcinoma underlines the need for another randomized phase 3 trial of cytoreductive nephrectomy for patients receiving powerful modern immunotherapies.

Contemporary Analysis of Calculous Nephrectomy Utilization and Outcomes in the United States.

Introduction: Calculous nephrectomy was a mainstay of treatment of complex upper tract stone disease up until the 1970s, but data on its contemporary utilization in the current era of rising rates of stone disease are lacking. We characterized the nationwide utilization and outcomes for calculous nephrectomy in the United States. Patients and Methods: The National/Nationwide Inpatient Sample databases for 2001 to 2014 were queried for adults with a principal diagnosis of upper urinary tract calculi (UUTCs), who underwent nephrectomy as well as other inpatient surgeries for UUTCs. Per-population trend in utilization of calculous nephrectomy was analyzed using negative binomial regression. The proportion of calculous nephrectomy as a fraction of all inpatient surgical procedures for UUTCs was analyzed using the Cochran-Armitage test. Patient demographics, hospital characteristics, perioperative outcomes, and complications were analyzed using appropriate statistical tests. Results: Of almost 1.42 million inpatient UUTC procedures performed over the study period, 9232 (0.65%) were calculous nephrectomies. Per-population utilization rate for calculous nephrectomy decreased significantly over time (incidence rate ratio = 0.82; 95% confidence interval = 0.73-0.91, p < 0.001). The proportion of calculous nephrectomy as a fraction of all inpatient surgical procedures for UUTC also decreased significantly over time (p < 0.0001). Majority of the procedures were performed in females, in urban teaching hospitals, and in the Southern United States. The overall complication rate was 38.3%, most commonly hemorrhage requiring transfusion (15.6%). Older age, female gender, and nonprivate insurance or lack of insurance were significant predictors of increased risk of complications, whereas hospitalization in urban hospitals was a predictor of lower risk. Conclusions: Despite increasing prevalence of stone disease in the United States in the contemporary era, utilization of calculous nephrectomy is low and is declining. Inpatient complication rates are moderately high and influenced by patient sociodemographic and hospital characteristics.