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Renal cell carcinoma (RCC) frequently presents with osseous metastasis, predominantly lytic and prone to pathological fracture. The metastatic lesion in the extremity presents with local swelling, pain and immobility due to pathological fracture. The solitary or oligometastatic lesions should be treated with curative intent, which can help the patient to lead a more prolonged and disability-free life. The RCCs and their metastases are hypervascular with an exuberant arterial supply. Surgery can lead to uncontrolled life-threatening haemorrhage. Preoperative transarterial embolisation reduces tumour vascularity significantly and reduces intraoperative blood loss. We present a 46-year-old male patient with solitary hypervascular metastatic recurrence of RCC with a pathological femoral fracture with an infeasible initial surgery due to profuse haemorrhage. He was successfully treated by preoperative transarterial embolisation, followed by surgical resection and implantation of a megaprosthesis. Multidisciplinary management reduces patient morbidity and mortality with successful treatment in solitary hypervascular metastasis from RCC.

Collecting duct carcinoma of the kidney is a rare and aggressive subtype of renal cell carcinoma (RCC) arising from the distal convoluted tubules. At the time of diagnosis, patients are more frequently symptomatic, with advanced locoregional stage, and have metastatic disease. The 2016 WHO Classification of Tumours of the Urinary System defined diagnostic criteria for this entity. However, the diagnostic features continue to evolve, with typical, but not entirely specific, histologic and immunophenotypic characteristics. In addition, the lack of consistent molecular alterations makes collecting duct carcinoma a diagnosis of exclusion, with historical cases being re-classified as fumarate hydratase deficient RCC, ALK rearranged RCC, renal medullary carcinoma or high-grade urothelial carcinoma. The rarity and poor prognosis of the tumor makes it difficult to reach consensus guidelines to guide therapy. In this manuscript we review the clinicopathologic features of collecting duct carcinoma including pathologic diagnostic criteria, molecular characteristics and differential diagnosis, and their possible implications for management.

Although papillary renal cell carcinoma has historically been classified as either type 1 or type 2, data from The Cancer Genome Atlas (TCGA) has demonstrated significant genomic heterogeneity in tumors classified as "type 2 papillary renal cell carcinoma" (T2PRCC). Papillary renal cell carcinoma is expected to have a favorable clinical course compared to clear cell renal cell carcinoma (CCRCC). However, tumors with poor outcome more similar to CCRCC were included in the T2PRCC cohort studied by the TCGA. The differential diagnosis for T2PRCC includes a variety of other renal tumors, including aggressive entities such as TFE3 translocation-associated renal cell carcinoma, TFEB-amplified renal cell carcinoma, fumarate hydratase-deficient renal cell carcinoma, high-grade CCRCC, and collecting duct carcinoma. Accurate classification of these tumors is important for prognostication and selection of therapy.

Background Treatment options for metastatic renal cell carcinoma (mRCC) include cytoreductive nephrectomy (CN) and systemic therapy (ST). Results from the CARMENA and SURTIME trials suggest that CN before ST may not be the optimal treatment strategy for mRCC. Objective To use real-world data to evaluate and compare outcomes for patients with mRCC who underwent CN before, after, or without ST to those patients who only received ST. Design, setting, and participants The Canadian Kidney Cancer information system (CKCis) database was used to identify patients diagnosed with mRCC between January 2011 and April 2020. Only patients with synchronous disease, treated within 12 mo from their initial RCC diagnosis, with International Metastatic Renal Cell Carcinoma Database Consortium intermediate/high risk, and confirmed RCC histology were included. Outcome measurements and statistical analysis Patients were classified into four groups according to the initial treatment received for mRCC. Inverse probability of treatment weighting using propensity scores was used to balance the treatment groups. Cox proportional hazards models were used to assess the impact of CN after adjusting for potential confounding variables in the weighted cohorts. Results and limitations A total of 788 patients were included in the study cohort. Of these 383 patients underwent CN before ST, 73 underwent CN after ST, 80 underwent CN only, and 252 patients received ST only. The median patient age was 63 yr and 73% of the cohort were men. In weighted analysis, the groups undergoing CN before ST (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52–0.82) and CN after ST (HR 0.41, 95% CI 0.28–0.60) both had better survival compared to the ST only group. No survival benefit was observed for CN only compared to ST only, or for CN before ST compared to CN after ST. Conclusions We evaluated the association between different sequences of treatment with CN and survival in patients with mRCC using CKCis real world data. The results demonstrate that the selected patients who undergo CN, whether performed before or after ST, have an associated improvement in survival. Patient summary Two of the treatment options for metastatic kidney cancer are surgery and systemic therapy (chemotherapy or immunotherapy). We used data from the Canadian Kidney Cancer information system to determine whether there are differences in survival according to the sequencing of these treatments. Patients who had both surgery and systemic therapy, regardless of which treatment was first, had better survival than patients who only received systemic therapy.

BackgroundRenal cell carcinoma (RCC) comprises of a spectrum of clinico-pathologically distinct entities thereby making it difficult to accurately predict the clinical outcome. Though many predictive factors have been described in literature, tumor stage and nuclear grade have been established to consistently correlate with the tumor behaviour. However, tumors in the same stage have shown to behave differently. Similarly subjectivity and lack of reproducibility in nuclear grade mandates use of more objective parameters such as digital nuclear morphometry which could provide consistent and more reliable results in predicting prognosis. The study was conducted with the main objective of comparing the histological grade and the nuclear morphometric variables in RCC for predicting the clinical outcome.Material and methodsA total of 219 cases of renal tumors in adults were retrieved retrospectively from the archives of pathology department in Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow and their clinical, gross and microscopic features were noted. Nuclear grading was done in 181 cases of clear cell and papillary RCC of which computer-assisted morphometry for various nuclear parameters was done in 100 cases where a follow-up data of at least 3 years was available. Nuclear grade and morphometric parameters were correlated statistically with the clinical outcome of the patients.ResultsHistological nuclear grade did not show statistically significant correlation with progression free survival (PFS). Higher values of mean nuclear area, mean nuclear circumference, mean nuclear major diameter and mean nuclear minor diameter were significant predictors of PFS with a strong inverse correlation.ConclusionNuclear morphometry is a more reliable predictor of clinical outcome in patients of RCC when compared to histological grade and should be included in predictive model with other clinical and pathological parameters to accurately determine tumor behaviour.

Background Although treatment of burn patients has significantly improved in recent decades, major burns remain fatal. Therefore, the evaluation of the death risk of the patients with extensive burns is very important. The ratio between the serum levels of aspartate transaminase and alanine transaminase (De Ritis ratio) was an independent predictor of poor outcomes in patients with acute ischemic stroke, cardiac surgery, non-metastatic renal cell carcinoma, and upper urinary tract urothelial carcinoma. Our aim was to determine whether the ratio between the serum levels of AST and ALT (De Ritis ratio) was useful to assess prognosis in extensively burned patients. Methods We conducted a single-center cohort study at the Burns Department of Changhai Hospital. This retrospective observational analysis was performed based on the clinical data of major burn patients admitted between May 1, 2005 and April 30, 2018. Univariate and multivariate logistic regression analyses were performed on variables such as age, sex, total body surface area (TBSA), De Ritis ratio, and serum albumin level, which may affect mortality in major burn patients. We assessed their diagnostic value and found the cut-off value by receiver operative characteristic (ROC) curve analysis. We used the Kaplan–Meier curve to display the impact of the De Ritis ratio and serum albumin level on survival in burn patients. Results A total of 351 patients with extensive burns were included in the study. The cohort predominantly consisted of males (74.64%), and most of the patients (78.35%) had been burned by a flame. Age, TBSA, inhalation, and the De Ritis ratio were found to be independent risk factors for the 30-days mortality of major burn patients, while age, TBSA, inhalation, and the De Ritis ratio were independent risk factors for 90-day mortality. Further, the De Ritis ratio was a better mortality predictor than serum albumin in severely burned patients, whose area under ROC for 30-day and 90-day mortality was 0.771 (95% confidence intervals [CI], 0.708–0.835) and 0.750 (95% CI, 0.683, 0.818). Conclusions The De Ritis ratio was useful as a prognostic indicator for major burn patients, which can be conveniently obtained through blood examination. Regardless of whether the prediction was for 30-day or 90-day mortality, the accuracy remained high. Moreover, compared to serum albumin level, the De Ritis ratio was superior in assessing the prognosis of extensively burned patients.

A 75-year-old man was referred to our urology service with painless haematuria. The delayed phase on a subsequent computed tomography (CT) abdomen and pelvis showed a filling defect in the left renal pelvicalyceal system, suspicious for a transitional cell carcinoma. The patient underwent ureteroscopic biopsy suggestive of a papillary neoplasia, before progressing to a laparoscopic radical left nephrouretectomy. Final histology revealed a fumarate hydratase-deficient renal cell carcinoma with clear margins. The patient was subsequently referred for genetic counselling.

Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.

BACKGROUND CONTEXT With improvements in adjuvant radiotherapy and minimally invasive surgical techniques, separation surgery has become the default surgical intervention for spine metastases at many centers. However, it is unclear if there is clinical benefit from anterior column resection in addition to simple epidural debulking prior to stereotactic body radiotherapy (SBRT). PURPOSE To examine the effect of anterior column debulking versus epidural disease resection alone in the local control of metastases to the bony spine. STUDY DESIGN Retrospective cohort study. PATIENT SAMPLE Ninety-seven patients who underwent open surgery followed by SBRT for spinal metastases at a single comprehensive cancer center. OUTCOME MEASURES Local tumor recurrence following surgery and SBRT. METHODS Data were collected regarding radiation dose, cancer histology, extent of anterior column resection, and recurrence. Tumor involvement was categorized using the International Spine Radiosurgery Consortium guidelines. Univariable analyses were conducted to determine predictors of local recurrence and time to local recurrence. RESULTS Among the 97 included patients, mean age was 60.5±11.4 years and 51% of patients were male. The most common primary tumor types were lung (20.6%), breast (17.5%), kidney (13.4%) and prostate (12.4%). Recurrence was seen in 17 patients (17.5%) and local control rates were: 85.5% (1-year), 81.1% (2-year), and 54.9% (5-year). Overall predictors of local recurrence were tumor pathology (p

Introduction/Background Radiotherapy (RT) is an alternative local therapy to metastasectomy in the treatment of thoracic metastases from renal cell carcinoma (RCC), including the management of life-threatening disease. Patients and Methods We reviewed patients with lung and mediastinal RCC metastases treated with RT at our institution. Overall survival (OS) and metastasis control (MC) was measured from the start of RT using the Kaplan-Meier (KM) method. Results Seventy-one patients were treated with RT for 89 lung (n=58) or mediastinal (n=31) metastases. Of 89 treated lesions, 11 (12%) had local tumor recurrence, at a median of 1.6 years (range 0.4-2.9). MC at 1, 3, and 5-years was 96.6%, 83.5%, and 67.9%, respectively. For the 58 lung metastasis-directed RT courses, MC rates at 1, 3, and 5-years were 95.0%, 84.5%, and 84.5%, respectively (median MC not reached). For the 31 mediastinum metastasis-directed RT courses, MC rates at 1, 3, and 5-years were 100%, 43.4%, and 43.4%, respectively (median MC 2.9 years). MC was significantly improved for lung lesions compared to mediastinal lesions (p=0.046). OS for the entire cohort at 1, 3, and 5 years was 65.2%, 48.5%, and 38.0%. There was no difference in OS based on metastatic sites in the 71 patients. Nineteen patients received RT to 19 lesions with the intention of preventing an event such as airway compromise or vascular invasion. One and two-year MC for these 19 lesions were 88.9% and 71.1%, respectively (median local control 2.4 years). OS in these 19 patients at 1, 2, and 5 years were 62.1%, 48.3%, and 32.2% respectively, with median survival 1.2 years. No patients developed grade 4 or 5 acute or late toxicities. Conclusion Radiation therapy can safely achieve high metastasis control rates for lung and mediastinal metastases from RCC, including lesions at high risk for causing a life-threatening event. MicroAbstract: Radiotherapy is an alternative local therapy to metastasectomy in the treatment of thoracic metastases from renal cell carcinoma. We retrospectively reviewed 71 patients who were treated with radiation for 89 lung (n=58) or mediastinal (n=31) metastases and reported overall survival and metastasis control. Local control was safely achieved, including lesions at high risk for causing a life-threatening event.

Pembrolizumab plus axitinib improved efficacy over sunitinib in treatment-naive advanced renal cell carcinoma in the KEYNOTE-426 (NCT02853331) study. However, a relatively high incidence of grade 3/4 aminotransferase elevations was observed.To further characterize treatment-emergent aminotransferase elevations in patients treated with pembrolizumab-axitinib.Patients enrolled in KEYNOTE-426 were included in this study.Three Standardized MedDRA Queries for potential hepatic disorders were used to identify patients for the hepatic event analysis subpopulation (HEAS). Alanine aminotransferase events were characterized for time to onset, time to recovery, corticosteroid use, and rechallenge with study treatment(s).The HEAS comprised 189/429 (44%) pembrolizumab-axitinib patients and 128/425 (30%) sunitinib patients. Grade 3/4 hepatic adverse events were more common in the combination arm: 22% (94/429) versus 7% (29/425); 3% (13/429) discontinued the combination due to hepatic adverse events. In the pembrolizumab-axitinib arm, 125/426 patients (29%) had alanine aminotransferase (ALT) ≥3× upper limit of normal (ULN), with median time to onset of 84 d (range, 7-840 d). Among patients with ALT ≥3× ULN, 120/125 (96%) recovered to3× ULN following study treatment interruption/discontinuation, with a median time to recovery of 15 d (3-176 d): 68/120 (57%) received corticosteroids. One hundred patients were rechallenged with one or both study treatment(s): 45/100 (45%) had ALT ≥3× ULN recurrence, and all 45 recovered to ALT3× ULN following study treatment interruption/discontinuation. No fatal hepatic events occurred.A higher incidence of grade 3/4 aminotransferase elevations occurs with pembrolizumab-axitinib. These events should be carefully evaluated and managed with prompt study treatment interruption or discontinuation, with or without corticosteroid treatment. The decision to rechallenge with one or both drugs should be based on severity of event and thorough causality assessment.Renal cell carcinoma patients receiving pembrolizumab-axitinib are at a higher risk of liver enzyme elevations, which could be reversed with appropriate management.

Aim The aim of this study was to retrospectively analyze treatment outcomes and tolerance in patients in whom cabozantinib was used after previous targeted therapy. Patients and methods Cabozantinib was administered in dose 60 mg/day, a subset of patients received initial dose of 40 mg/day. The treatment was administered until to progression or unacceptable toxicity. CT scans were assessed according to the RECIST 1.1 and toxicity of treatment was assessed based on the CTCAE (version 4). Kaplan-Meier analysis was used to calculate progression free survival (PFS) and overall survival (OS). We performed a multivariate analysis of risk factors for treatment outcomes (PFS, OS) by Cox regression analysis. All statistics were evaluated at the significance level alpha = 0.05. Results 54 patients with metastatic renal cell carcinoma (mRCC) were evaluated. Median PFS in all patients treated with cabozantinib was 9.3 months (95% CI 5.3 - 13.3). One-year survival was 85.2% (95% CI 72.9 - 93.4%). Treatment response was observed in 45.9% of cases, including one complete remission. Cox regression analysis demonstrated that presence of subsequent treatment was the only factor with a significant effect on OS (P=0.008). Adverse events occurred in 88.9% of patients, grade 3 - 4 in 46.3%. Conclusion The analysis of our cohort of patients treated with cabozantinib in the second or higher lines of treatment showed that cabozantinib represents an effective and safe therapy and contributes to longer survival of our mRCC patients.

Although chimeric antigen receptor T cell (CAR-T) therapy has been successful for hematological malignancies, it is less effective for solid tumors. The primary reason is that the immune microenvironment restricts CAR-T cells from infiltrating and proliferating in tumors. Oncolytic virotherapy has emerged as a novel immunogenic therapy to augment antitumor immune response. Here we combined an oncolytic adenovirus carrying decorin with a CAR-T targeting carbonic anhydrase IX (CAIX) to perform the antitumor activity for renal cancer cells. We found that OAV-Decorin combined with CAIX-CAR-T exhibited significantly reduced tumor burden, altered the composition of extracellular matrix (ECM) by inhibiting the distribution of collagen fibers, decreased the expression of TGF-β in tumor cells, enhanced IFN-γ secretion, and obtained higher numbers of CAR-T cells. The combination treatment modality showed prolonged mice survival. The intratumoral injection of OAV-Decorin into tumor-bearing immunocompetent mice activated the inflammatory immune status and resulted in tumor regression. These data supported further investigation of the combination of OAV-Decorin and CAIX-CAR-T cells in solid tumors., Graphical abstract, It was shown that decorin expression mediated by oncolytic adenovirus activated the inflammatory immune status. OAV-Decorin combined with CAIX-targeted CAR-T cells exhibited significantly reduced renal tumor burden and altered the composition of extracellular matrix. OAV-Decorin is potent to be developed as an effective enhancer of CAR-T cells therapeutic approach.

Objective To describe a Case of a personal and family history of early uterine leiomyomatosis that revealed a pathogenic variant in the FH gene encoding fumarate hydratase. After the patient’s diagnosis, a first degree relative was detected with early stage renal cell carcinoma. The patient decided to undergo preimplantation genetic testing to reduce the risk to her future children. Design A Case report of autosomal dominant hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome where the patient underwent two cycles of in vitro fertilization (IVF) with preimplantation genetic testing for monogenic disease/aneuploidy (PGT-MA) that resulted in three unaffected, euploid embryos. Setting Large academic single center hospital Patient(s) A 35 year old nulligravida with a personal history of early onset uterine leiomyomatosis and family history of renal cell carcinoma and uterine leiomyomas, who is heterozygous for a pathogenic variant in FH and diagnosed with HLRCC syndrome. Informed consent was obtained. Interventions Two laparoscopic myomectomies were performed, and tissue was sent for histopathology and immunostaining. HLRCC syndrome was confirmed by germline testing and two cycles of PGT-MA were performed. Main outcome measures Through preimplantation genetic testing for monogenic disease and aneuploidy (PGT-MA), the patient was able to mitigate the risk of passing a known familial variant to her future children. Results After two cycles of IVF-PGT-MA, three unaffected embryos were available for transfer. An unaffected, euploid embryo was transferred for pregnancy and patient is currently pregnant in her second trimester. Conclusions Pathogenic variants in FH should be suspected in patients with early onset uterine leiomyomas and a family history of cutaneous and/or uterine leiomyomas. Familial variant testing is crucial in identifying relatives at risk in order to start early screening.

The incidence of ectopic kidney is 1 in 2100–3000 autopsies. Renal cell cancer (RCC) in pelvic kidney is a rare entity with limited case reports available in the literature. Symptoms can vary from abdominal pain to haematuria, or RCC can be detected incidentally. Contrast imaging with computed tomography (CT) angiography is recommended to determine the location of the renal mass and the anatomy of surrounding organs and major vessels feeding it. Treatment of choice is radical nephrectomy. We report a case of RCC in ectopic pelvic kidney managed with radical nephrectomy that was deemed unresectable on CT imaging.

Cancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. More importantly, effective screening and treatment strategies are limited in this high-risk population. In this review, we begin with a patient’s journey that maps the experience of living with a kidney transplant and understand the patient’s knowledge, education, and experience of cancer in the context of transplantation. The epidemiology and burden of cancer in recipients of kidney transplants, along with the up-to-date screening and treatment strategies, are discussed. We also focus on the current understanding of optimal care for recipients of kidney transplants who are living with cancer from the patients’ perspectives.

Thyroid-like follicular renal cell carcinoma (TFRCC) is rare, with

Introduction To compare complication rates in radical nephrectomy for renal cell carcinoma across different age groups. Methods Retrospective analysis of the British Association of Urological Surgeons Nephrectomy Audit database between 1st January 2012 and 31st December 2017 was performed. Comparisons were made between different age groups (

Objective To propose EV-derived mRNA as a potential diagnostic biomarker detecting the presence of clear cell renal cell carcinoma (ccRCC). There is currently no kidney cancer specific screening or diagnostic technology. Therefore, one-third of kidney cancer diagnoses occur after the cancer has metastasized and is past curative measures Materials and Methods Urine, plasma, normal tumor adjacent tissue, and tumor tissue was collected from a limited population of ccRCC patients. Extracellular vesicle (EV) isolation was performed on each sample, followed by mRNA extraction from isolated EVs. NanoString® nCounter technology was utilized to count the mRNA transcripts present in matched plasma, urine, tumor tissue, and normal tumor adjacent tissue samples. Results 770 mRNA transcripts related to gene's affecting cancer's progression and metastasis processes were evaluated. Four EV derived mRNA transcripts (ALOX5, RBL2, VEGFA, TLK2) were found specific to urine and cancer tissue samples. Conclusion Four candidate RCC-specific urine EV biomarkers were identified. However, due to the lack of a true negative control and urine collection techniques, further re-examination is necessary for validation. This study demonstrates the promise of defining disease-specific EV biomarkers in liquid biopsy patient samples.

Von Hippel–Lindau disease (VHL) is a multineoplasm inherited disease manifesting with hemangioblastoma of the central nervous system and retina, adrenal pheochromocytoma, renal cell carcinoma, pancreatic neuroendocrine tumors and cysts, and neoplasms/cysts of the ear, broad ligament, and testicles. During 2018-2020, the VHL Alliance gathered several committees of experts in the various clinical manifestations of VHL to review the literature, gather the available evidence on VHL, and develop recommendations for patient management. The current report details the results of the discussion of a group of experts in the pancreatic manifestations of VHL along with their proposed recommendations for the clinical surveillance and management of patients with VHL. The recommendations subcommittee performed a comprehensive systematic review of the literature and conducted panel discussions to reach the current recommendations. The level of evidence was defined according to the Shekelle variation of the Grading of Recommendations, Assessment, Development, and Evaluation grading system. The National Comprehensive Cancer Network Categories of Evidence and Consensus defined the committee members' interpretation of the evidence and degree of consensus. The recommendations encompass the main aspects of VHL-related pancreatic manifestations and their clinical management. They are presented in a clinical orientation, including general planning of screening and surveillance for pancreatic neuroendocrine tumors, utility of biochemical biomarkers, the optimal choice for imaging modality, indirect risk stratification, indications for tissue sampling of VHL-related pancreatic neuroendocrine tumors, and interventions. These recommendations are designed to serve as the reference for all aspects of the screening, surveillance, and management of VHL-related pancreatic manifestations.

Background : Full dose cabozantinib for metastatic renal cell carcinoma (mRCC) is 60mg, but adverse events (AEs) may require dose reductions. Limited data exist comparing efficacy among cabozantinib doses. We compared AEs and clinical outcomes in mRCC patients treated with full versus reduced starting cabozantinib dose. Methods : We performed a retrospective analysis of 87 mRCC patients treated with cabozantinib at Winship Cancer Institute from 2016-2019. Overall survival (OS), progression-free survival (PFS), and objective response (OR) rate measured clinical outcomes. AEs were collected from clinic notes and the most common were hypertension, mucositis/hand-foot skin reaction (HFSR), or gastrointestinal toxicity. Univariate analysis (UVA) between starting doses and AEs with clinical outcomes was performed using logistic regression model. Multivariable analysis (MVA) was also performed using Cox proportional hazard model. Results : Most patients were male (71%) with clear-cell RCC (72%). The majority were IMDC intermediate (58%) or poor (35%) risk. One third received first-line cabozantinib and 64% had ≥3 baseline metastatic sites. Most patients (68%) required dose reduction from 60mg or started at reduced dose without escalation. Reduced dose patients were more likely to have ≥3 distant metastatic sites (70% vs 58%) and ≥ 2 prior lines of systemic therapy (50% vs 40%) compared to full dose patients. UVA revealed a trend towards shorter OS (HR: 1.78, p=0.095), PFS (HR: 1.50, p=0.107), and lower chance of OR (HR:0.42, p=0.149) among reduced dose patients. This trend did not hold in MVA (OS HR: 1.20, p=0.636; PFS HR: 1.23, p=0.4662). Mucositis/HFSR and hypertension were significantly associated with improved outcomes in UVA. Conclusions : Although we found a trend favoring full dose cabozantinib, this is likely due to worse baseline disease characteristics among patients starting on a reduced dose. Hypertension and mucositis/HFSR may be associated with improved outcomes. Larger studies are warranted to validate these findings.

Background: Combinations based on immune checkpoint inhibitors are the new first-line standard treatment for metastatic renal cell carcinoma. Sarcomatoid renal cell carcinoma (sRCC) has a dismal prognosis but good immunogenicity. Methods: The authors performed a network meta-analysis of Phase III randomized trials of immune checkpoint inhibitor-based combinations versus standard tyrosine kinase inhibitor monotherapy reporting data for sRCC. The end points were overall survival, progression-free survival and objective response rate. Results: Five trials comprising 569 sRCC patients (out of a total of 4409 metastatic renal cell carcinoma patients) were included. Nivolumab–cabozantinib was the highest ranking treatment for overall survival (p-score = 88%) and progression-free survival (p-score = 81%). Atezolizumab–bevacizumab had the highest rank for objective response rate (p-score = 80%). Conclusion: Despite some limitations, nivolumab–cabozantinib might be the preferred first-line option for sRCC in terms of efficacy.

On March 10, 2021, the FDA granted regular approval to tivozanib for treatment of patients with relapsed or refractory (R/R) advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. Approval was based on the TIVO-3 study, a randomized trial of tivozanib versus sorafenib in patients with R/R advanced RCC. In TIVO-3, patients were randomized to receive either tivozanib 1.34 mg orally once daily for 21 consecutive days of every 28-day cycle or sorafenib 400 mg orally twice daily continuously. The primary endpoint was progression-free survival (PFS) per RECIST v1.1. Tivozanib demonstrated efficacy compared with sorafenib with an improvement in PFS [HR, 0.73; 95% confidence interval (CI), 0.56–0.95; P = 0.016]. The estimated median PFS was 5.6 months and 3.9 months in the tivozanib and sorafenib arms, respectively. There was no evidence of a detrimental effect on overall survival: HR, 0.97 (95% CI, 0.75–1.24). The most common grade 3 to 4 adverse reaction on the tivozanib arm was hypertension (24%). Compared with sorafenib, tivozanib was associated with lower rates of grade 3 to 4 diarrhea, rash, and palmar-plantar erythrodysesthesia. Patients receiving tivozanib in TIVO-3 had lower rates of dose reduction, interruption, or permanent discontinuation than those receiving sorafenib.

Background : Axitinib monotherapy obtained approval in pre-treated metastatic renal cell carcinoma (mRCC) patients and recently in combination with pembrolizumab or avelumab in the first-line setting. However, patient profiles that may obtain increased benefit from this drug and its combinations still need to be identified. Patients and Methods : Retrospective multicentre analysis describing clinical characteristics associated with axitinib long-responder (LR) population by comparing two extreme-response sub-groups (progression-free survival [PFS] ≥9 months versus disease progression/refractory patients [RP]). A multivariate logistic-regression model was used to analyse clinical factors. Efficacy and safety were also analysed. Results : In total, 157 patients who received axitinib in second or subsequent line were evaluated (91 LR and 66 RP). Older age at start of axitinib and haemoglobin levels > LLN were independent predictive factors for LR in multivariate analyses. In LR patients, median (m) PFS was 18.1 months, median overall survival (OS) was 36.0 months and objective response rate (ORR) was 45.5%. In 59 LR patients receiving axitinib in second-line, mPFS was 18.7 months, mOS was 44.8 months and ORR was 43.9%. mOS was significantly longer in second line compared to subsequent lines (44.8 versus 26.5 months; P=0.009). In LR versus RP, mPFS with sunitinib in first-line was correlated with mPFS with axitinib in second-line (27.2 versus 10.9 months P Conclusions : This study confirms the long-term benefits of axitinib in a selected population, helping clinicians to select the best sequential approach and patients who could obtain a greater benefit from axitinib. Microabstract Patients with metastatic renal cell carcinoma (mRCC) who may benefit most from axitinib still need to be identified. AXILONG study confirms long-term benefits in a selected population in which age at axitinib initiation and haemoglobin baseline levels were significantly associated although further validation may be required. First-line sunitinib outcomes were also correlated with prolonged response. These results might be helpful in real-life management of mRCC patients.

Serum C-reactive protein (CRP) is reportedly associated with metastatic renal cell carcinoma (mRCC) activity. However, in the era of immune checkpoint inhibitors, the predictive value of CRP is unclear. In this study, we investigated the predictive impact of pretreatment CRP levels and early changes in CRP levels for the treatment of mRCC with nivolumab plus ipilimumab (NIVO-IPI) therapy.Forty-eight patients with mRCC treated with NIVO-IPI as a first-line therapy were retrospectively analyzed. First, patients were divided into 2 groups: initial CRP ≥ 1.0 mg/dL and1.0 mg/dL. Progression-free survival (PFS) was compared between the 2 groups. Second, based on the CRP change within the first 3 months of NIVO-IPI, patients were placed in the normal group (CRP remains1.0 mg/dL), normalized group (CRP decreased1.0 mg/dL), and non-normalized group (CRP remained or increased to ≥ 1.0 mg/dL). The predictive association between CRP change and PFS was evaluated.PFS was significantly lower in the high initial CRP group (n = 24, 50%) compared to the normal CRP group (n = 24, 50%) (median: 4.3 vs. 28.1 months, P = .03). As for the early CRP change, the normal (2.7 vs. 28.1, P = .0002) and normalized (2.7 vs. 11.0, P = .0094) groups showed significantly higher PFS, compared to the non-normalized group. Meanwhile, there was no significant difference between normal, and normalized groups (P = .51). The objective response rate was higher in the normal (57.1% vs. 18.7%, P = .015) and normalized (81.8 vs. 18.7%, P = .0008) groups, compared to the non-normalized group. Multivariate Cox regression analysis showed that normal [Hazard ratio (HR) = 0.15, 95% Confidence interval (CI) = 0.02-0.70, P = .026] and normalized (HR 0.21, 95% CI = 0.05-0.73, P = .015) CRP showed significant association with PFS.In the NIVO-IPI therapy for mRCC, early changes in CRP could predict PFS. This data may be useful for the early detection of ineffective NIVO-IPI therapy and conversion to subsequent therapies.

Introduction : Recently increasing evidence has suggested that obesity is associated with the development and prognosis of renal cell carcinoma. The aim of the study was to investigate the association between different obesity measurements and overall survival in patients with surgically treated clear cell renal cell carcinoma. Patients and Methods : The data of 342 consecutive patients who underwent radical or partial nephrectomy at Peking University People's Hospital from January 2009 to November 2014 were retrospectively reviewed. Median follow-up was 82 months. The association between different obesity measurements and overall survival was evaluated using the Kaplan-Meier method and Cox regression models. Results : In univariate Cox regression analyses, perirenal fat accumulation was significantly associated with overall survival (HR: 2.271; 95%CI: 1.311-3.935; p=0.003), as well as age, sex, clinical manifestation, surgical option, tumor size and grade. The other obesity measurements, including body mass index, waist circumference, total adipose tissue, visceral adipose tissue and percentage of visceral adipose tissue, were not assessed as prognostic indicators of overall survival in this study (p>0.05). After adjusting for age, sex, clinical manifestation, surgical option, tumor size, T stage and tumor grade, perirenal fat accumulation was still identified as an independent predictor of overall survival (HR: 2.264; 95%CI: 1.305-3.926; p=0.004). The results of Kaplan-Meier model also revealing that patients with higher percentage of perirenal fat showed poorer overall survival (p=0.003). Conclusion : Higher percentage of perirenal adipose tissue is independently associated with increased mortality risk in surgically treated clear cell renal cell carcinoma. MicroAbstract : The association between obesity and the prognosis of ccRCC patients is conflicting. Herein we conducted this study to examine the association between different obesity measurements and overall survival in patients with surgically treated ccRCC. In total, 342 patients with ccRCC were enrolled. The results indicate that the percentage of perirenal adipose tissue is superior to both BMI and percentage of visceral fat surface area for predicting overall survival.

Neoadjuvant immune checkpoint blockade represents a novel approach for potentially decreasing the risk of recurrence in patients with nonmetastatic renal cell carcinoma (RCC). In this early phase clincal tiral, we evaluated the safety and tolerability of neoadjuvant treatment with the programmed cell death protein 1 (PD-1) inhibitor nivolumab in patients with nonmetastatic high-risk RCC. Nonprimary endpoints included objective radiographic tumor response rate, immune-related pathologic response rate, quality of life alterations, and metastasis-free and overall survival. In total, 17 patients were enrolled in this study and underwent surgery without a delay after receiving three every-2-wk doses of neoadjuvant nivolumab. Adverse events (AEs) of any grade occurred in 14 (82.4%) patients, with two (11.8%) experiencing grade 3 events. Ten (58.8%) patients experienced an AE of any grade potentially attributable to nivolumab (all grade 1–2), and no grade 4–5 AEs occurred regardless of treatment attribution. The most common AEs were grade 1 fatigue (41.2%), grade 1 pruritis (29.4%), and grade 1 rash (29.4%). All evaluable patients had stable disease as per established radiographic criteria, with one (6.7%) demonstrating features of an immune-related pathologic response. Quality of life remained stable during treatment, with improvements relative to baseline noted at ≥6 mo postoperatively. Metastasis-free survival and overall survival were 85.1% and 100% at 2 yr, respectively. Patient summary In this study, we evaluated the safety and tolerability of preoperative administration of three doses of the immune checkpoint inhibitor nivolumab in patients with clinically localized high-risk renal cell carcinoma. We demonstrated the safety of this approach and found that, although most patients will not experience a radiographic response to treatment, a subset may have features of an immune-related pathologic response.

Background Cabozantinib, a potent multi-tyrosine kinases inhibitor (TKI), has demonstrated overall survival (OS) benefit over everolimus in patients previously treated with VEGFR TKI for metastatic Renal Cell Carcinoma (mRCC). The efficacy of systemic treatments after cabozantinib failure has not been investigated. Methods We conducted a retrospective study on patients receiving systemic treatment after cabozantinib failure in heavily pre-treated patient with mRCC. We assessed Time to Treatment Failure (TTF), OS and objective response rate (ORR). Results Among 150 patients treated with cabozantinib in our institution, 56 (37.3%) received subsequent systemic therapy and were eligible for the analysis. IMDC prognostic group was good, intermediate and poor in 11 (19.6%), 24 (42.9%) and 11 (19.6%) patients, respectively. Cabozantinib was administered mainly as a second (41.1%), or third (33.9%) line treatment. axitinib or immune-checkpoint inhibitors were the subsequent treatment in 18 (34.8%) patients for each everolimus (n:16, 28.6%), other angiogenesis inhibitors (n:4, 7.1%) TTF and OS from subsequent systemic therapy after cabozantinib failure were 2.8 months (95%CI 1.9-3.7) and 7.7 months (95%CI 4.4-10.8), respectively. ORR was 8.7% and two patients with axitinib and two patients treated with Immune checkpoint inhibitors achieved a partial response. Conclusions Overall, activity of systemic therapies after cabozantinib was limited. Micro abstract We performed a retrospective analysis on 56 patients with metastatic renal cell carcinoma who received at least 1 systemic treatment line after cabozantinib. Median OS after cabozantinib was 7.7 months, while median TTF after cabozantinib was 2.8 months. Further investigation is needed in this clinical context

Актуальність. Серед онкоурологічних захворювань нирково-клітинний рак посідає третє місце після раку сечового міхура і передміхурової залози, а за рівнем смертності знаходиться на першому місці. За даними різних авторів, приблизно в 30–50 % пацієнтів у різні терміни після ­нефректомії з’являються метахронні метастази. Мета — аналіз віддалених результатів хірургічного лікування хворих на нирково-клітинний рак. Матеріали та методи. У дослідженні брали участь 120 пацієнтів. Серед них було 56 жінок (46,6 %) та 64 (53,4 %) чоловіки, середній вік яких становив 66,3 ± 1,8 року. До проспективного аналізу було включено пацієнтів із локальною формою нирково-клітинного раку — 95 осіб (79,1 %) та місцево-поширеною формою нирково-клітинного раку — 25 (20,9 %), до ретроспективного аналізу — 60 пацієнтів із дисемінованою формою. Результати. Віддалені результати хірургічного і комбінованого лікування 120 пацієнтів продемонстрували прогресування захворювання в 31,6 % хворих. Висновки. Медіана строку безрецидивного періоду перевищувала 9,0 ± 1,1 місяця в групі пацієнтів, яким проводилась передопераційна емболізація судинної ніжки. У групі хворих, яким була виконана типова радикальна нефректомія, безрецидивний період становив 5,3 ± 0,2 місяця. Збільшення ступеня анаплазії пухлини (GIII) призводило до зниження терміну безрецидивного періоду — середня тривалість життя становила 6–12 місяців, і лише у 12 (10 %) пацієнтів із цієї когорти вона була більше ніж 2 роки.

Contains fulltext : 249093.pdf (Publisher’s version ) (Open Access) Cabozantinib is registered in fixed 60 mg dose. However, 46% to 62% of patients in the registration studies needed a dose reduction due to toxicity. Improved clinical efficacy has been observed in renal cell carcinoma patients (RCC) with a cabozantinib exposure greater than 750 μg/L. In our study we explored the cabozantinib exposure in patients with different tumour types. We included RCC patients from routine care and salivary gland carcinoma (SGC) patients from a phase II study with ≥1 measured C(min) at steady-state. The geometric mean (GM) C(min) at the starting dose, at 40 mg and at best tolerated dose (BTD) were compared between both tumour types. Forty-seven patients were included. All SGC patients (n = 22) started with 60 mg, while 52% of RCC patients started with 40 mg. GM C(min) at the start dose was 1456 μg/L (95% CI: 1185-1789) vs 682 μg/L (95% CI: 572-812) (P

Treatment options for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC) have increased dramatically over the past decade. However, even when novel approaches have proven to be effective as monotherapy, many patients still develop progressive disease, and different strategies are needed to increase clinical response and quality of life. Strategies combining targeted therapy (TT) and immunotherapy (IO) have emerged as a way to shorten the gap between responders and nonresponders to monotherapy and have reported promising results. In this review, we discuss the current role of cabozantinib in combination with IO agents in the treatment of metastatic RCC and UC and go over future directions in the field.Lay abstract Treatment options for both advanced kidney and bladder cancers have increased significantly over the last decade. However, even when these new approaches have proven to be effective, many patients still experience disease progression. Therefore, different strategies are needed to increase the response to treatment and quality of life. Strategies combining therapies directed to reduce the tumor's blood supply (targeted therapies) and therapies that increase the ability of the body to recognize and attack tumor cells (immunotherapy) have emerged as a way to increase the effectiveness obtained when using these drugs on their own. In this review, we discuss the current role of cabozantinib, a targeted therapy, in combination with immune-based agents in the treatment of advanced kidney and bladder cancers and go over future directions in the field.

Background: For patients with nonmetastatic renal cell carcinoma (nmRCC) treated with nephrectomy, prediction of cancer-specific mortality (CSM) by T stage and substage has not been validated for the separate histological subtypes. Objective: To investigate the ability of pathological T stage and substage to predict CSM for patients with clear-cell, papillary, or chromophobe nmRCC treated with nephrectomy. Design, setting, and participants: Using the SEER database for 2004–2016, we identified 87 149 patients with T1–4 N0/X M0 nmRCC treated with nephrectomy for the clear-cell (65 715; 75.4%), papillary (14 587; 16.7%), or chromophobe (6847; 7.9%) histological subtype. Outcome measurements and statistical analysis: Kaplan-Meier plots and Cox regression models were used to estimate CSM. Results and limitations: For all three histological subtypes, patients with T1a–T3a disease exhibited more favorable CSM than patients with T3b–T4 RCC. For clear-cell RCC, there were clinically meaningful and statistically significant differences for virtually all intergroup comparisons among T1a–T3a stages. For papillary T1a–T3a RCC, clinically meaningful differences disappeared, although the statistical significance remained. For chromophobe T1a–T3a RCC, no clinically meaningful or statistically significant differences were observed. For all three histological subtypes, patients with T3b–T4 RCC exhibited virtually uniformly unfavorable CSM, with no clinically meaningful intergroup CSM differences. Conclusion: The use of T stage and substage for stratification of patients with nmRCC treated with nephrectomy revealed differences in CSM among T1a–T3a cases, but not T3b–T4. The magnitude of the CSM difference was greatest for clear-cell, intermediate for papillary, and marginal for chromophobe RCC. Patient summary: For patients with kidney cancer, the stage of their disease assessed after surgery on the affected kidney can predict how likely they are to die from their cancer. This prediction varies for different subtypes of kidney cancer. Stratification of surgically treated patients with nonmetastatic renal cell carcinoma (RCC) by T stage revealed mortality differences among T1a–T3a cases, but not T3b–T4 cases. The magnitude of the differences was greatest for the clear-cell subtype, intermediate for papillary histology, and marginal for chromophobe RCC.

To understand the influence of histologic subtypes on the survival outcomes of intermediate-high and high-risk renal cell carcinoma (RCC) following nephrectomy.This study employed data files from the SEER Program to identify patients diagnosed with intermediate-high or high risk RCC and treated with nephrectomy. Unadjusted Kaplan Meier curves, and multivariable Cox regression analyses were applied to estimate the hazards of histologic types for overall survival (OS) and cancer-specific survival (CSS).OS was higher for chromophobe (HR=0.58, 95% CI 0.47-0.70; P.0001), similar for papillary (HR=0.90, 95% CI 0.80-1.02; P=.11) and worse for sarcomatoid (HR=3.17, 95% CI 2.70-3.72; P.0001) subtypes relative to the clear cell subtype. OS was lower in the high-risk disease (HR=2.35, 95% CI 2.01-2.74; P.0001) versus intermediate-high risk disease. CSS was higher for chromophobe (HR=0.47, 95% CI 0.35-0.63; P.0001), similar for papillary (HR=0.91, 95% CI 0.77-1.08; P=.28) and worse for sarcomatoid (HR=4.19, 95% CI 3.50-5.02; P.0001) subtypes relative to the clear cell subtype. CSS was lower for the high-risk disease (HR=2.86, 95%CI 2.39-3.43; P.0001) relative to intermediate-high risk disease.

The optimal cutoff point for evaluating the prognosis of localized renal cell carcinoma (LRCC) remains unclear. This study aimed to verify the efficacy of tumor diameter in the 2010 American Joint Committee on Cancer (AJCC) TNM staging system and contribute to the modification of TNM staging on the prognosis of this disease. A total of 3748 patients with LRCC were enrolled and grouped according to the 2010 AJCC TNM staging system. COX analysis was used to stratify the prognosis. The optimal cutoff point of the tumor diameter in the T1 and T2 prognosis was explored. There were 3330 (88.9%) patients in stage T1 and 418 (11.1%) in stage T2. The cancer-specific mortality rate was 2.7% (100/3748). The mean follow-up was 49.8 months. A tumor diameter of 7 cm can determine the prognosis of patients at stages T1 and T2; however, 4.5 cm and 11 cm as the cutoff points for T1 and T2 sub-classification of patients with LRCC might show better recognition ability than 4 cm and 10 cm, respectively. The 2010 AJCC TNM stage can predict the prognosis of LRCC in stages T1 and T2. In addition, a tumor diameter of 4.5 cm and 11 cm might be the optimal cutoff points for the sub-classification of stages T1 and T2.

Background Life expectancy (LE) is an important consideration in the clinical decision-making for T1aN0M0 renal cell cancer (RCC) patients. Objective To test the effect of race/ethnicity (Caucasian, African American, Hispanic/Latino, and Asian) on LE predictions from Social Security Administration (SSA) life tables in male and female T1aN0M0 RCC patients. Design, setting, and participants We relied on the Surveillance, Epidemiology, and End Results database. Intervention Radical nephrectomy (RN) and partial nephrectomy (PN). Outcome measurements and statistical analysis Five-year and 10-yr observed overall survival (OS) of pT1aN0M0 RCC patients treated between 2004 and 2006 were compared with the LE predicted from SSA life tables. We repeated the comparison in a more contemporary cohort (2009–2011), with 5-yr follow-up and higher PN rates. Results and limitations In the 2004–2006 cohort, PN rate was 40.7%. OS followed the predicted LE in Caucasians, Hispanics/Latinos, and Asians, but not in African Americans, in whom 5-yr OS rates were 5.0% (male) and 8.7% (female) and 10-yr rates were 4.2% (male) and 11.1% (female) lower than predicted. In the 2009–2011 cohort, PN rate was 59.4%. Same observations were made for OS versus predicted LE in Caucasians, Hispanics/Latinos, and Asians. In African Americans, 5-yr OS rates were 1.5% (male) and 4.9% (female) lower than predicted. Conclusions In RN- or PN-treated pT1aN0M0 RCC patients, LE predictions closely approximated OS of Caucasians, Hispanics/Latinos, and Asians. In African-American patients, SSA life tables overestimated LE, more in females than in males. The limitations of our study are its retrospective nature, its validity for US patients only, and the under-representation of racial/ethnic minorities. Patient summary Social Security Administration life tables can be used to estimate long-term life expectancy in patients who are surgically treated for renal cancer (≤4 cm). However, while for Caucasians, Hispanics/Latinos, and Asians, the prediction performs well, life expectancy of African Americans is generally overestimated by life table predictions. Take Home Message In the clinical decision-making process for T1aN0M0 renal cell cancer patients eligible for radical or partial nephrectomy, the important influence of patient sex and race/ethnicity on life expectancy should be taken into account, when using Social Security Administration life tables.

WHAT IS KNOWN AND OBJECTIVE Sunitinib is used as a first-line therapy for metastatic renal cell carcinoma. The primary aim of this study was to determine the optimal total sunitinib (sunitinib plus N-desethyl sunitinib) trough concentration for the alternative dosing schedule: 2-week-on and 1-week-off schedule (2/1 schedule). METHODS Patients with metastatic renal cell carcinoma treated with the 2/1 schedule of sunitinib, whose total sunitinib concentrations were available, were recruited for this study. Out of 19 patients, 17 whose sunitinib dosage was not changed until the measurement of drug concentration were eligible for the analysis of the relationship between total sunitinib concentration and clinical outcome. Individual pharmacokinetic parameters in 19 patients were estimated via the Bayesian analysis. RESULTS The onset of severe (grade ≥3) adverse effects among 17 patients during 3 weeks as a first course of sunitinib therapy was observed in 7 (41.2%) patients. The median total sunitinib concentration in patients with severe adverse effects was significantly higher compared with that in patients without severe adverse effects [median: 119 (113-131) vs. 87.8 (77.4-102) ng/mL, p = 0.01]. According to the receiver operating characteristic analysis of the onset of severe adverse effects, the cut-off value of the total sunitinib concentration was 108 ng/mL. Patients with a total sunitinib concentration lower than 108 ng/mL had a longer time to first dose reduction or withdrawal due to adverse effects compared with those with a total sunitinib concentration of 108 ng/mL or higher (p = 0.03). The probability without treatment failure was not significantly different between the two concentration groups. In addition, the estimated sunitinib apparent oral clearance (CL/F) was significantly lower in the severe adverse effects group. Our simulation demonstrated that 0.67-time dose is needed for patients with approximately 90.0 ng/mL of sunitinib concentration on day 7 to maintain the concentration at the same level as the patients with higher CL/F. WHAT IS NEW AND CONCLUSION Maintaining the total sunitinib trough concentrations of less than 108 ng/mL is safe to avoid the onset of serious adverse effects without increasing the treatment failure in patients with metastatic renal cell carcinoma treated with the 2/1 schedule of sunitinib.

Introduction Immune checkpoint inhibitors are one of the standard treatments for metastatic renal cell carcinoma. Among immune‐related adverse events, the sarcoidosis‐like reaction is frequently difficult to differentiate from cancer progression. Case presentation A 58‐year‐old man with renal cell carcinoma with multiple lung metastases was treated with ipilimumab and nivolumab after nephrectomy. Computed tomography after three courses of treatment revealed hilar/mediastinal lymphadenopathies, pleural nodules, and pulmonary interstitial lesions, whereas lung metastases were markedly regressed. Considering positive findings of Gallium scintigraphy and serological tests together, we clinically judged the new lesions as a sarcoidosis‐like reaction and continued the treatment until cessation by liver dysfunction. After discontinuation of the immunotherapy, the sarcoidosis‐like reaction was regressed without cancer relapse. Conclusion We report here the first case of a clinically diagnosed sarcoidosis‐like reaction in metastatic renal cell carcinoma following treatment with immune checkpoint inhibitors.

Percutaneous cryoablation (PCA) is increasingly recognized as a feasible minimally invasive, nephron-sparing treatment for renal cell carcinomas, with comparable efficacy to nephrectomy. The development of abdominal wall pseudohernia (AWP) is a rare complication of PCA for renal masses, which can negatively impact patients' quality of life.To retrospectively evaluate the risk factors and prognosis for AWP after PCA and, based on these results, to discuss strategies to lower the risk of AWP associated with image-guided PCA for renal masses.We retrospectively studied 117 PCAs performed for renal masses in 92 patients, between 2016 and 2019, at our hospital. We compared the following clinical characteristics (age, sex, body mass index, tumour diameter, RENAL nephrometry score, procedural details, transcatheter arterial embolization, dissection techniques, number of cryoneedles used, location of needles, and location of ice ball) between those who developed AWP and those who did not.Of the 117 PCAs (92 patients) included in our study group, AWP complications were observed in 6 (5.1%) procedures. Puncture through the erector spinae muscle (p0.01) and non-use of hydro- or pneumo-dissection (p = 0.01) were identified as risk factors for AWP.Although PCA is relatively safe to perform and the occurrence of an associated AWP is a rare and infrequent complication, the risk for AWP could be further decreased by avoiding punctures through the erector spinae muscle and using hydro- or pneumo-dissection.

Objective To evaluate the safety, efficacy, and early oncologic outcomes of pT3a renal cell carcinoma (RCC) with venous involvement treated with robotic partial nephrectomy (RPN), given that experience and outcomes in this group is limited. Methods A retrospective chart review of patients undergoing RPN from 9/2009-7/2020 was performed. Outcomes were captured from patients with pathologic T3a disease with vein involvement. Clinical characteristics were analyzed using SPSS (IBM, Armonk, NY). Local recurrence-free survival (LRFS) and metastasis-free survival (MFS) at 2 years were calculated from Kaplan-Meier survival curves. Results For 45 included patients, mean operative and warm ischemia times were 199.6 min ± 47.3 and 30.5 min ± 10.5, with mean estimated blood loss of 324.9 cc ±209.5. Rates of transfusion, embolization, re-admission, and re-operation at 30 days were 8.9% (4/45), 2.2% (1/45), 11.1% (5/45), and 6.7% (3/45; cystoscopic stent placement), respectively. All tumors were malignant on pathology, with clear cell RCC being the most common (91.0%, n=41). The positive margin rate was 6.7% (n=3). Local recurrence occurred in 4.4% (n=2) at a mean time of 5.2 months ± 2.3. Four patients (8.9%) progressed to metastatic disease at a mean of 22.2 months ± 23.0. At 2 years, LRFS was 95.4% and MFS was 95.3%. Conclusions We present the largest known series of patients RPN for pT3a renal masses with venous tumor involvement. We found it both feasible and safe in the appropriate hands. Short term oncologic outcomes for these patients appear more favorable than historic literature suggested. Sources of Funding none

OBJECTIVE To analyze predictors, extent and functional implications associated with renal parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) prior to intervention. This phenomenon is well-recognized yet not adequately studied, and, if severe, can influence management. MATERIALS AND METHODS A retrospective review was performed of partial nephrectomy (PN) and radical nephrectomy (RN) patients with available preoperative nuclear-renal-scan and imaging demonstrating solitary RCC with normal contralateral kidney. Normal renal parenchymal volume of each kidney was measured by free-hand scripting from preoperative axial images. Primary endpoint was percent PVR which was estimated assuming that the contralateral-kidney serves as a control: PVR = (volume contralateral kidney - volume ipsilateral kidney) normalized by volume contralateral kidney. Multivariable linear-regression analysis assessed factors associated with preoperative PVR. Further analysis evaluated the functional effect of PVR prior to surgery. RESULTS 146 PN and 136 RN patients with necessary studies were analyzed. For RN, the median PVR was 15% and a quarter of patients had PVR ≥27%. In contrast, PVR was negligible in PN patients for whom median preoperative parenchymal volumes were nearly identical in the ipsilateral/contralateral kidneys (179/180cc, respectively). PVR inversely correlated with preoperative renal function in the ipsilateral kidney (P

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Thyroid follicular carcinoma like renal tumour (TFCLRT) is a rare variant of primary renal epithelial tumour and was first reported in 2006. Up till now, 40 cases have been identified worldwide and alarmingly, 17 cases have been identified from China only. The condition has been included in the WHO Renal Tumours Classification 2016. We present here the first case of thyroid follicular carcinoma like renal tumour from Pakistan that was managed in our surgical unit and a literature review. Left-sided radical nephrectomy was performed through a midline incision. The left kidney was removed along with intact Gerota fascia, left adrenal gland and lymph nodes alongwith aorta.

BACKGROUND: Lymphnode metastases (LMN) in metastatic renal cell carcinoma (mRCC) has been associated with an unfavourable prognosis. However, the prognostic impact of LNM in mRCC in context of other solid organ metastases and throughout subsequent therapeutic lines is not well-defined. OBJECTIVE: This retrospective single-center analysis was designed to elucidate the impact of LNM in the context of other solid organ metastases and throughout subsequent therapeutic lines. METHODS: mRCC patients (pts) at our center were analysed (observation period, 04/00-03/16). Primary endpoint was overall survival (OS) and the impact of line of therapy as a co-variate. Pts were grouped into: with LNM [LNM(+)], without LNM [LNN(–)]. Subgroup analyses of LNM(+) was performed including the subgroup LNM(+) and other solid organ metastases [LNM(+) other] and LNM(+) without other solid organ metastases [LMN(+) only]. RESULTS: 383/401 mRCC pts were eligible. 318 (83.2%), 230 (60.1%) and 154 (40.5%) pts received 1stL, 2ndL and 3rdL medical treatment, respectively. In the overall population OS was 40.1 months (95%CI: 32.7–47.4), with superior OS in LNM(–) compared to LNM(+) pts (log rank, HR 1.7, 95%-CI 1.3-2.2, p

BACKGROUND: Lenvatinib with everolimus (“Len/Eve”) is approved for advanced/metastatic RCC following one antiangiogenic therapy. OBJECTIVE: This study evaluated patient characteristics, treatment patterns and overall survival (OS) with second-line or later (2L+) Len/Eve for advanced/metastatic RCC. METHODS: A retrospective observational study was conducted using electronic health records. Adult patients who initiated 2L+ Len/Eve for advanced/metastatic RCC from May 13, 2016 to July 31, 2019 were included. Patient characteristics and treatment patterns were assessed across the overall population and by post-immuno-oncology (IO) and post-tyrosine kinase inhibitors (TKI) groups. OS was estimated from Len/Eve initiation (i.e., index date) using Kaplan-Meier. RESULTS: Among the study population (n = 152), 44.1%received 2L/3L Len/Eve and median number of prior therapies was 3 (range:1–8). Median age was 63.2 years, 78.9%were Caucasian, 73.7%were male, and 56.6%had ECOG performance status 0/1. At initial diagnosis, 65.8%had stage IV disease. At index, 53.3%had an International Metastatic RCC Database Consortium risk score of intermediate/poor, 15.1%favorable, and 31.6%missing score. Sixty-five (42.8%) received IO-based regimens and 49.3%received TKIs directly before index. Median OS from index was 13.9 (95%CI: 9.5–16.5) months and 2L/3L and 4L+ were 12.1 (95%CI: 8.4–17.0) and 14.8 (95%CI: 8.9–22.5) months, respectively. Median OS for Len/Eve post-IO and post-TKI were 13.9 (95%CI: 8.4–21.3) and 14.8 (95%CI: 7.8–16.5) months, respectively. Conclusion: This study suggested that 2L+ Len/Eve has clinical effectiveness for advanced/metastatic RCC in a US community oncology setting. Future studies are needed to confirm the association of improved survival with 2L+ Len/Eve.

BACKGROUND: Although immune checkpoint inhibitor-based therapy has improved the outcomes of many patients with metastatic renal cell carcinoma (mRCC), most eventually develop disease progression. Newer agents that modulate immune response can possibly potentiate checkpoint inhibitor therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate immunotherapy. We conducted an investigator-initiated trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC patients, particularly in those previously exposed to immune checkpoint inhibitors. METHODS: Eligible patients had mRCC of any histologic subtype, completed at least one line of prior systemic therapy which could have included prior immunotherapy, and had acceptable end-organ function with ECOG performance status of 0–2. Treatment consisted of nivolumab 240 mg intravenously every 2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade 3 or higher adverse event (AE) attributable to therapy. After identification of the recommended phase 2 dose (RP2D), up to 19 patients were enrolled to an expansion cohort to further evaluate toxicities and any early evidence of efficacy. The primary endpoints of the trial were establishment of RP2D and progression-free survival (PFS). RESULTS: A total of 31 patients were enrolled, 6 to dose level 0, 7 (of which one was not evaluable for DLT) in dose level -1, and 18 in the expansion cohort. Median age was 60 years (range, 36–90), most had clear cell histology (n = 27; 87%), and most had prior immune checkpoint inhibitor therapy (n = 28; 90%). Three patients experienced one DLT each, all in dose level 0 (all Grade 3), namely elevated lipase, hypoalbuminemia, and nausea. No DLTs were seen in dose level –1 which was declared the RP2D. The most common Grade 3 or higher AEs include anemia (n = 5), lymphocyte count decrease (4), nausea (2), and hypotension (2). Of 28 patients evaluable for response, one patient (3.6%) had a complete response, 2 (7.1%) had a partial response, and 11 (39.2%) had stable disease, for an objective response rate of 10.7%(95%CI: 3.7%–27.2%) and a disease control rate of 50%(95%CI: 32.6%–67.4%). All responders had received prior immune checkpoint inhibitor therapy. Median PFS was 2.5 months (95%CI, 1.9 –4.8) while median OS was 9.1 months (95%CI, 6.6 –19.0). CONCLUSIONS: Ibrutinib at a dose of 420 mg orally once daily in combination with nivolumab 240 mg IV every 2 weeks is feasible and tolerable in mRCC patients. No unique immune-related AEs were observed. Anti-tumor activity was seen in patients previously exposed to PD-1 targeted therapy.

Purpose: There are case reports of patients with both primary breast cancer (BC) and renal cell carcinoma (RCC). We explore the association between these two malignancies using SEER population data and our institutional records.Methods: We studied the association between BC and RCC in the 2000-2016 Surveillance, Epidemiology and End Results (SEER) database. We then reviewed our hospital records of patients with both BC and RCC and collected information including personal and family history of cancers, genetic testing, and patient outcomes.Results: Of the 813,477 females diagnosed with BC in the SEER database, 1,914 later developed RCC. The risk of developing RCC was significantly increased within the first six months, 7-12 months, and 1-5 years following BC diagnosis with standardized incidence ratios (SIRs) of 5.08 (95% CI, 4.62- 5.57), 2.09 (95% CI, 1.8-2.42), and 1.15 (95% CI, 1.06-1.24), respectively. Of 56,200 females with RCC, 1,087 later developed BC. The risk of developing BC following RCC was elevated within the first six months (SIR of 1.45 [95% CI, 1.20-1.73]). For our hospital patients, 437 had both BC and RCC. 427 (97.71%) were female, and 358 (81.92%) were white, and breast cancer was diagnosed before RCC in 246 (61.5%) patients. There were 15 germline mutations in those with genetic testing. Conclusion:Our findings suggest that BC patients are at higher risk of developing RCC and vice versa. BC tended to precede RCC, and patients frequently had personal histories of other malignancies and a family history of cancer, particularly BC.

Introduction Few studies have evaluated real-world effectiveness of lenvatinib (Len)/everolimus (Eve) for advanced/metastatic renal cell carcinoma (a/mRCC). This study evaluated patient profiles and clinical outcomes of second- and subsequent-line (≥ 2L) Len/Eve for a/mRCC. Patients and Methods A longitudinal retrospective study examined adult patients initiating ≥ 2L Len/Eve for a/mRCC from May 13, 2016, to July 31, 2019. Len/Eve clinical trial participants or those treated for other primary tumors were excluded. Outcomes included objective response rate, duration of response, progression-free survival (PFS), time to treatment discontinuation, and overall survival. Time-to-event outcomes were estimated using Kaplan-Meier methods. Results Seventy-nine patients were assessed: the median age was 64.8 years, 78.5% were Caucasian, 73.4% were male, 78.5% had an Eastern Cooperative Oncology Group performance status score of 0/1, 29.1% received 2L/3L Len/Eve, and the median number of prior lines of therapy was 3 (range, 1-8). At initial diagnosis, 55.7% had stage IV disease, 65.8% had International Metastatic risk scores of intermediate/poor, 19.0% favorable, and 15.2% with missing score. Thirty-one (39.2%) patients received immuno-oncology–based regimens, and 50.6% received tyrosine kinase inhibitors directly before Len/Eve initiation. The median time to treatment discontinuation was 5.7 months (95% CI, 3.3-6.9). The physician-assessed objective response rate was 55.7% (1.6% complete response and 54.1% with some degree of tumor shrinkage). The median duration of response was 9.7 months (95% CI, 5.8-17.1). The median PFS was 6.1 months (95% CI, 4.4-9.0). The median PFS for patients receiving Len/Eve post–immuno-oncology was 6.4 months (95% CI, 4.1-10.8) and for post–tyrosine kinase inhibitor 5.7 months (95% CI, 4.1-10.5). Median overall survival was 14.8 months (95% CI, 10.2-23.9). Conclusion In this longitudinal retrospective study, Len/Eve showed real-world effectiveness in clinical practice in a heavily pretreated a/mRCC patient population.

Recent studies have shown that immune-related adverse events (irAEs), occurring even after the discontinuation of immune checkpoint inhibitors (ICIs), may be associated with favorable disease outcomes, particularly in patients with melanoma and lung cancer. However, a few clinical cases have been described on the correlation between irAEs and ICIs efficacy in renal cell carcinoma (RCC) patients. This study reports the clinical case of a metastatic RCC patient who has experienced severe immune-related renal toxicity after 19 months of nivolumab use. Despite immunotherapy discontinuation, the patient has maintained clinical benefit and disease progression-free for 3 years. We examined the correlation between the occurrence and the severity of irAEs, treatment discontinuation and clinical benefits. The evidence on ICI retreatment following ICI discontinuation due to irAEs was also reviewed.Lay abstract Immunotherapy has profoundly changed the treatment scenario of cancer patients. However, similar to any oncological therapy, it may cause immune-related adverse events. Cancer patients experiencing immune-related adverse events have a higher probability of better survival outcomes. This correlation has been largely described in patients with melanoma and lung cancer, but only a few data have been reported for genitourinary tumor patients. Here, we report the clinical case of a metastatic renal cell carcinoma patient who has experienced a late-onset and severe immune-related renal toxicity after 19 months of immunotherapy, which led to treatment discontinuation. Despite this, the patient has maintained a clinical benefit and disease progression-free for more than 3.5 years. We reviewed the literature on the correlation between immunotherapy benefit and immune-related adverse events, considering the time of onset, the severity of the adverse events and the concepts of treatment discontinuation and retreatment.

Laryngeal metastasis is an extremely rare condition. To the best of our knowledge, there has been no previous report on a laryngeal metastasis from renal cell carcinoma, which describes on details of the CT and MR imaging findings. A male patient in his 80s. Laryngoscopy revealed reddish-colored masses in the right false vocal cord and in the subglottic larynx. CT and MR imaging of this case showed multiple hypervascularized lesions with a wash-out effect in the supra and subglottis of the larynx and in the right intervertebral foramen of the cervical spine. Angiography revealed a hypervascular tumor consistent with the subglottic lesion. The histopathology and immunohistochemistry findings were compatible with laryngeal metastasis from renal clear cell carcinoma. A history of postoperative renal clear cell carcinoma about 7 years ago was later confirmed, which was not stated at the time of the initial imaging evaluation. It is a possible differential diagnosis in cases of multiple hypervascular masses in the head and neck region with a history of renal carcinoma. In particular, if the contrast-enhancement pattern of the lesion on the dynamic CT is similar to that of renal cell carcinoma. It is also important to reconfirm the patient's medical history, including postoperative status.