Early-stage Renal Cell Carcinoma Research Articles

SABR for primary renal cell carcinoma: single-fraction or multiple-fraction?

Renal cell carcinoma accounts for about 3% of all cancers in adults, and the most frequent solid cancer type of the kidney accounts for approximately 90% of all kidney malignancies.1 Early detection of renal cell carcinoma has been increasing in tandem with the use of non-invasive imaging devices such as CT, MRI, and ultrasound.1 Although the standard treatment for early-stage renal cell carcinoma is surgical resection,1,2 a substantial number of medically inoperable cases exist due to advanced age or comorbidities.

Cost Effectiveness Analysis of Radiofrequency Ablation (RFA) Versus Stereotactic Body Radiotherapy (SBRT) for Early Stage Renal Cell Carcinoma (RCC).

To conduct a cost-effectiveness analysis of stereotactic body radiotherapy (SBRT) versus radiofrequency ablation (RFA) in the non-surgical management of early stage renal cell carcinoma (RCC) according to Consolidated Health Economic Evaluation Reporting Standards (CHEERS) criteria in the Canadian healthcare system. A Markov state transition model was constructed for initial local treatment with RFA or SBRT for early stage, kidney confined, medically inoperable RCC in a hypothetical cohort. Incremental cost effectiveness ratios (ICER) were then calculated to compare the two treatments. The analysis was conducted over 5-year time horizon from the perspective of a publicly funded health system in Canada. Secondary analyses were conducted to assess the effect of small versus large size (< 4 cm vs. > 4 cm) RCC on ICERs. Multiple one-way deterministic sensitivity analysis were conducted. Discounting of 1.5% per year was applied. Over 5 years, SBRT economically dominated RFA with a gain of 4.103 quality-adjusted life years (QALYs) and a cost of $16,097, compared with 3.607 QALYs at a cost of $18,324 for RFA. The ICER was $4490 CAD less per QALY for SBRT in the base case analysis (BCE). In patients with small tumors (T1a), SBRT compared with RFA was more effective and marginally more costly, resulting in an ICER of $2207 CAD per QALY gained, while for larger tumors (T1b), SBRT was less costly and more effective than RFA, resulting in an ICER of -$22904. Sensitivity analysis demonstrated significant variability in the cost-effectiveness of SBRT versus RFA when parameters were varied, with rates of distant metastasis following RFA or SBRT having the greatest implications on ICERs. Overall, SBRT used as a primary treatment for RCC shows promising effectiveness at an overall reduction in cost compared with RFA in the Canadian healthcare system. The use of SBRT appears to be cost-effective for larger tumors as well as smaller tumors. The validity of these conclusions are highly sensitive to the accuracy of local and distant progression rates reported in previous studies, and may be adjusted as the available data on SBRT and RFA continues to evolve and mature.

Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma.

While surgical resection has remained the mainstay of treatment in early-stage renal cell carcinoma (RCC), therapeutic options in the advanced setting have remarkably expanded over the last 20 years. Tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor (VEGF-TKIs) and anti-programmed cell death 1 (PD-1)/anti-programmed death-ligand 1 (PD-L1)-based immune checkpoint inhibitors (ICIs) have become globally accepted options in the upfront metastatic setting, with different ICI-based combination strategies improving overall survival compared to single-agent Sunitinib. Although some patients benefit from long-term responses, most eventually develop disease progression. Ongoing efforts to better understand the biology of RCC and the different mechanisms of acquired resistance have led to the identification of promising therapeutic targets. Belzutifan, a novel agent targeting the angiogenic pathway involving hypoxia-inducible factors (HIFs), has already been approved for the treatment of early-stage tumors associated with VHL disease and represents a very promising therapy in advanced RCC. Other putative targets include epigenetic regulation enzymes, as well as several metabolites such as adenosine, glutaminase and tryptophan, which are critical players in cancer cell metabolism and in the tumor microenvironment. Different methods of immune regulation are also being investigated, including CAR-T cell therapy and modulation of the gut microbiome, in addition to novel agents targeting the interleukin-2 (IL-2) pathway. This review aims to highlight the emergent novel therapies for RCC and their respective completed and ongoing clinical trials.

EDITORIAL COMMENT

Racial disparities in the diagnosis and treatment of urological malignancies are well known. In SEER-Medicare, black patients were less likely to undergo initial surgical management for early-stage renal cell carcinoma with a greater rather than reduced disparity among healthy patients.1 For patients with muscle-invasive bladder cancer in the National Cancer Data Base, differences in access and treatment rather than tumor characteristics accounted for most of the racial disparity in overall survival.

DNA methylation profiling reveals new potential subtype‐specific gene markers for early‐stage renal cell carcinoma in Caucasian population

BackgroundRenal cell carcinoma (RCC) is among the top adult cancers worldwide, with a challenging management due to lack of early diagnosis, therapy resistance, and diverse molecular background. Aberrant DNA methylation has been associated with RCC development due to transcription deregulation. We discovered potential DNA methylation‐based biomarkers for stage I RCC in Caucasian population from The Cancer Genome Atlas (TCGA) database.MethodsPatients’ clinical, methylation beta‐value, and mRNA expression data were retrieved. Differential methylation and expression analysis were conducted to obtain differentially methylated CpG‐gene pairs. Inversely correlated CpG‐gene pairs between their expression and methylation levels were selected using Pearson’s correlation test and then screened for any recorded somatic mutations. Their biomarker capacities were analyzed using the Kaplan‐Meier and receiver operating characteristic analysis, followed by protein network and functional enrichment analysis.ResultsWe obtained differentially methylated CpGs in clear cell (KIRC) and papillary RCC (KIRP) but not chromophobe RCC (KICH). Six inversely correlated CpG‐gene pairs with no reported cancer‐associated mutations were selected. Prognostic values were found in ATXN1 and RFTN1 for KIRC, along with GRAMD1B and TM4SF19 for KIRP, while diagnostic values were found in VIM and RFTN1 for KIRC, along with TNFAIP6 and TM4SF19 for KIRP. Both subtypes showed enrichment of immune and metabolism‐related pathways.ConclusionWe discovered novel potential DNA methylation‐based prognostic and diagnostic markers for early‐stage RCC in Caucasian population. Validation by wet laboratory analysis and adjustments for confounding variables might be needed, considering our study limitation to specific race.

TIMP1 Indicates Poor Prognosis of Renal Cell Carcinoma and Accelerates Tumorigenesis via EMT Signaling Pathway.

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. The mortality of advanced RCC remains high despite advances in systemic therapy of RCC. Considering the misdiagnosis of early-stage RCC, the identification of effective biomarkers is of great importance. Tissue inhibitor matrix metalloproteinase 1 (TIMP1), which belongs to TIMP gene family, is a natural inhibitor of the matrix metalloproteinases (MMPs). In this study, we found TIMP1 was significantly up-regulated in cell lines and RCC tissues. Kaplan-Meier analysis revealed that high expression of TIMP1 indicated a poor prognosis. Multivariate analysis further indicated that TIMP1 overexpression was an independent prognostic factor of RCC patients. Furthermore, knockdown of TIMP1 in vitro suppressed the proliferation, migration, and invasion of RCC cells, while upregulating TIMP1 accelerated the proliferation, migration, and invasion of RCC cells. In addition, we also found that TIMP1 prompted the progression of RCC via epithelial-to-mesenchymal transition (EMT) signaling pathway. In conclusion, the present results suggested that TIMP1 indicated poor prognosis of renal cell carcinoma and could serve as a potential diagnostic and prognostic biomarker for RCC.

A web-based prediction model for overall survival of elderly patients with early renal cell carcinoma: a population-based study

BackgroundThe number of elderly patients with early renal cell carcinoma (RCC) is on the rise. However, there is still a lack of accurate prediction models for the prognosis of early RCC in elderly patients. It is necessary to establish a new nomogram to predict the prognosis of elderly patients with early RCC.MethodsThe data of patients aged above 65 years old with TNM stage I and II RCC were downloaded from the SEER database between 2010 and 2018. The patients from 2010 to 2017 were randomly assigned to the training cohort (n = 7233) and validation cohort (n = 3024). Patient data in 2018(n = 1360) was used for external validation. We used univariable and multivariable Cox regression model to evaluate independent prognostic factors and constructed a nomogram to predict the 1-, 3-, and 5-year overall survival (OS) rates of patients with early-stage RCC. Multiple parameters were used to validate the nomogram, including the consistency index (C-index), the calibration plots, the area under the receiver operator characteristics (ROC) curve, and the decision curve analysis (DCA).ResultsThe study included a total of 11,617 elderly patients with early RCC. univariable and multivariable Cox regression analysis based on predictive variables such as age, sex, histologic type, Fuhrman grade, T stage, surgery type, tumors number, tumor size, and marriage were included to establish a nomogram. The C-index of the training cohort and validation cohort were 0.748 (95% CI: 0.760–0.736) and 0.744 (95% CI: 0.762–0.726), respectively. In the external validation cohort, C-index was 0.893 (95% CI: 0.928–0.858). The calibration plots basically coincides with the diagonal, indicating that the observed OS was almost equal to the predicted OS. It was shown in DCA that the nomogram has more important clinical significance than the traditional TNM stage.ConclusionA novel nomogram was developed to assess the prognosis of an elderly patient with early RCC and to predict prognosis and formulate treatment and follow-up strategies.

Cost-effectiveness model of renal cell carcinoma (RCC) surveillance in hereditary leiomyomatosis and renal cell carcinoma (HLRCC)

PurposeTo determine the cost-effectiveness of annual renal imaging surveillance (RIS) in hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is associated with a 21% risk to age 70 years of...

How a woman’s myomectomy saved her father’s life: evidence of fumarate hydratase–deficient uterine leiomyoma and early detection of germline variants in fumarate hydratase

ObjectiveTo 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.DesignA case report of autosomal dominant hereditary leiomyomatosis and renal cell cancer syndrome where the patient underwent 2 cycles of in vitro fertilization with preimplantation genetic testing for monogenic disease/aneuploidy (PGT-MA) that resulted in 3 unaffected, euploid embryos.SettingLarge academic single-center hospital.Patient(s)A 35-year-old nulligravida woman with a personal history of an early-onset uterine leiomyomatosis and a family history of renal cell carcinoma and uterine leiomyomas, who is heterozygous for a pathogenic variant in FH and diagnosed with hereditary leiomyomatosis and renal cell cancer syndrome. Informed consent was obtained.Intervention(s)Two laparoscopic myomectomies were performed, and tissue was sent for histopathology and immunostaining. Hereditary leiomyomatosis and renal cell cancer syndrome was confirmed by germline testing, and 2 cycles of PGT-MA were performed.Main Outcome Measure(s)Through PGT-MA, the patient was able to mitigate the risk of passing a known familial variant to her future children.Result(s)After 2 cycles of in vitro fertilization with PGT-MA, 3 unaffected embryos were available for transfer. An unaffected, euploid embryo was transferred for pregnancy, and the patient is currently pregnant in her second trimester.Conclusion(s)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 to start early screening.

Racial and Ethnic Disparities in Preoperative Surgical Wait Time and Renal Cell Carcinoma Tumor Characteristics.

Racial/ethnic minority groups have a disproportionate burden of kidney cancer. The objective of this study was to assess if race/ethnicity was associated with a longer surgical wait time (SWT) and upstaging in the pre-COVID-19 pandemic time with a special focus on Hispanic Americans (HAs) and American Indian/Alaska Natives (AIs/ANs). Medical records of renal cell carcinoma (RCC) patients who underwent nephrectomy between 2010 and 2020 were retrospectively reviewed (n = 489). Patients with a prior cancer diagnosis were excluded. SWT was defined as the date of diagnostic imaging examination to date of nephrectomy. Out of a total of 363 patients included, 34.2% were HAs and 8.3% were AIs/ANs. While 49.2% of HA patients experienced a longer SWT (≥90 days), 36.1% of Non-Hispanic White (NHW) patients experienced a longer SWT. Longer SWT had no statistically significant impact on tumor characteristics. Patients with public insurance coverage had increased odds of longer SWT (OR 2.89, 95% CI: 1.53–5.45). Public insurance coverage represented 66.1% HA and 70.0% AIs/ANs compared to 56.7% in NHWs. Compared to NHWs, HAs had higher odds for longer SWT in patients with early-stage RCC (OR, 2.38; 95% CI: 1.25–4.53). HAs (OR 2.24, 95% CI: 1.07–4.66) and AIs/ANs (OR 3.79, 95% CI: 1.32–10.88) had greater odds of upstaging compared to NHWs. While a delay in surgical care for early-stage RCC is safe in a general population, it may negatively impact high-risk populations, such as HAs who have a prolonged SWT or choose active surveillance.

Multiorgan Transplant From a Donor With Solid Renal Masses: An Initial Experience and Clinical Considerations

Patients with early-stage renal cell carcinoma (RCC) are considered to be eligible donors. Although preliminary experience in using kidneys of specific pathologic types, mainly those with small renal masses (SRMs), have been established, multiorgan utilization of the same donor with SRMs is limited. One deceased donor whose left-side kidney was diagnosed with Fuhrman grade I RCC was included. The tumor mass in the kidney was removed through partial nephrectomy according to the gold standard. Then, 3 transplant surgeries were performed, in which 1 recipient accepted kidney transplant after tumor exeresis, 1 simultaneous heart-kidney (the contralateral one) transplant, and 1 liver transplant. Recipients were followed up according to our standard protocol for renal cancers. (All allografts were allocated in compliance with the Declaration of Helsinki and the Declaration of Istanbul.) RESULTS: After 32 months, no radiographic findings showed any morphologic changes of the lesion, and all patients were in good condition, with neither tumor recurrence nor allograft rejection or infection. No complaints such as pain, oliguria, dyspnea, nausea, or fatigue were recorded. To the best of knowledge, this initial work takes the lead in elaborating the organ utilization of multiorgan donors with SRMs. We hope the experience will provide support for cross discussion concerned with multiorgan transplant from tumor-affected donors in clinical practices, further expand the donor pool and address the donor shortage problem.

MP45-15 IMPACT OF PREOPERATIVE WAIT TIME ON RENAL CELL CARCINOMA TUMOR CHARACTERISTICS AND RACIAL AND ETHNIC DISPARITIES

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging/Surveillance I (MP45)1 Sep 2021MP45-15 IMPACT OF PREOPERATIVE WAIT TIME ON RENAL CELL CARCINOMA TUMOR CHARACTERISTICS AND RACIAL AND ETHNIC DISPARITIES Ken Batai, Eduardo Quinonez-Zanabria, Waheed Asif, Ava C. Wong, Alejandro Cruz, Francine C. Gachupin, Chiu-Hsieh Hsu, Juan Chipollini, and Benjamin R. Lee Ken BataiKen Batai More articles by this author , Eduardo Quinonez-ZanabriaEduardo Quinonez-Zanabria More articles by this author , Waheed AsifWaheed Asif More articles by this author , Ava C. WongAva C. Wong More articles by this author , Alejandro CruzAlejandro Cruz More articles by this author , Francine C. GachupinFrancine C. Gachupin More articles by this author , Chiu-Hsieh HsuChiu-Hsieh Hsu More articles by this author , Juan ChipolliniJuan Chipollini More articles by this author , and Benjamin R. LeeBenjamin R. Lee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002066.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Natural and human-caused disasters, such as the COVID-19 pandemic, often have bigger negative effects on health status and healthcare access of racial/ethnic minority patients. The purpose of this study was two-fold, to assess if 1) a longer surgical wait time (SWT, ≥ 90 days) affects renal cell carcinoma (RCC) tumor characteristics at nephrectomy and 2) race/ethnicity was associated with a longer SWT and upstaging in the pre-COVID-19 pandemic time with focus on Hispanic Americans (HAs) and Native Americans (NAs) who have heavier burden of RCC in Arizona. METHODS: Medical records of patients diagnosed with RCC who underwent nephrectomy between 2010 and 2020 (through March, before the COIVD-19 pandemic worsened) at Banner-University Medical Center Tucson were reviewed (n=489). Patients with a prior cancer diagnosis were excluded. SWT was defined as the date of diagnostic imaging examination (e.g., CT and MRI) to date of nephrectomy. Logistic regression analysis was performed to assess if race/ethnicity was associated with longer SWT or upstaging. RESULTS: A total of 393 patients were included, 34.2% and 8.3% of patients were HAs and NAs respectively. While 49.2% of HA patients had a longer SWT, only 36.1% of non-Hispanic White (NHW) patients had a longer SWT. Longer SWT did not have a significant impact on tumor characteristics. Tumor size increased (≥ 2cm) in 9.9% of patients with a longer SWT, while 8.9% of patients with a shorter SWT had increased tumor size. Pathologic upstaging was seen in 26.4% and 25.7% of patients with longer and shorter SWT, respectively. Patients with public insurance coverage had increased odds of longer SWT (OR, 2.89; 95% CI: 1.53-5.45). Public insurance coverage was higher among HAs and NAs, representing 66.1% and 70.0% of coverage compared to 56.7% in NHWs. Compared to NHWs, HAs had significantly increased odds of a longer SWT in patients with early-stage RCC (TNM Stage I or II) (OR 2.38, 95% CI: 1.25-4.53). HAs and NAs had increased odds of upstaging (OR 2.24, 95% CI: 1.07-4.66 for HAs and OR 3.79, 95% CI: 1.32-10.88 for NAs). Among patients with <90 days of SWT, HAs had significantly increased odds of upstaging (OR 4.19, 95% C.I.: 1.47-12.48), but not among patients with ≥90 days of SWT (OR 0.97, 95% C.I.: 0.26-3.64). CONCLUSIONS: While delay in surgical care for early-stage RCC is safe in a general population, it may negatively impact high risk populations, such as HAs who may choose an active surveillance of small kidney mass. Source of Funding: National Cancer Institute (1R21CA248361-01) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e809-e809 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ken Batai More articles by this author Eduardo Quinonez-Zanabria More articles by this author Waheed Asif More articles by this author Ava C. Wong More articles by this author Alejandro Cruz More articles by this author Francine C. Gachupin More articles by this author Chiu-Hsieh Hsu More articles by this author Juan Chipollini More articles by this author Benjamin R. Lee More articles by this author Expand All Advertisement Loading ...

Diverse Roles of G‐Protein‐Coupled Receptor 40 (GPR40/FFA1) and GPR120 (FFA4) in the Regulation of Cell Growth and Motile Activities in Renal Cell Carcinoma (RCC)

Renal cell carcinoma (RCC) is the 16th most common cancer worldwide with roughly 400,000 new cases diagnosed annually and approximately half of those leading to mortality. Even though the 5-year survival rate for early-stage RCC is 80%-90%, it is only 5% for the patients with metastasis. Unfortunately, anticancer drugs that are used to treat RCC are proven to be useful for only a small number of patients. Therefore, it is crucial to discover the novel molecular pathways underlying RCC to develop better therapies. The G protein-coupled receptors GPR40 and GPR120, also referred to as free fatty acid receptor 1 (FFA1) and 4 (FFA4), respectively, are activated by medium- to long-chain free fatty acids. Emerging evidence suggests that GPR40 and GPR120 are implicated in the proliferation, invasiveness, and apoptosis of various tumor cells, however, the precise mechanisms of GPCRs signaling events leading to the modifications in cancer cell growth and migration are still scarce, and the roles of these receptors in RCC are unstudied to date. Here, for the first time, we reveal the effects of GPR40 and GPR120 agonism on cell proliferation and migration in metastatic tumor-derived renal cancer cells. The present study used in vitro techniques including cell proliferation assay, wound-healing assay, and transwell migration assay to investigate the functions of GPR40 and GPR120 on the proliferative and migration capacities of the RCC cell line. The human renal cancer cell line ACHN was obtained from the American Type Culture Collection (ATCC). Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was performed to confirm the presence of GPR40 and GPR120 transcripts. Cell proliferation was assessed by plating 50,000 cells per well, followed by treatment with GPR40 and GPR120 agonists and antagonists as noted for 6 days. Cells were counted every 24 hours. For the wound-healing assay, 100,000 cells were plated on a 48-well plate and a scratch-made through the center. The time to wound healing was assessed at 0, 24, 36, and 48 hours. For migration assays, cells were plated in the top chamber of a transwell plate and cells migrated was counted by crystal violet staining after 16 hr. Using selective GPR40 and GPR120 agonists and antagonists, our results demonstrate that GPR40 enhanced and GPR120 suppressed cell proliferation, suggesting that the opposite effects of GPR120 and GPR40 are involved in the cell growth activity. The wound-healing assay revealed that both GPR40 and GPR120 agonism markedly covered the wounded area compared to vehicle-controls, an effect that is blocked by a selective GPR40 and GPR120 antagonist, respectively. In transwell migration assay, GPR40 negatively and GPR120 positively affect the ability of single cells to respond to the chemoattractant; further confirming their involvement in the acquisition of migratory properties in RCC cell. Our present results suggest that GPR40/120-mediated signaling may be involved in the regulation of renal cancer tumorigenesis and progression on the cellular level, and mechanistic studies are underway to assess the cellular cascades that are influenced by GPR40 and GPR120.

Daily online adaptive magnetic resonance image (MRI) guided stereotactic body radiation therapy for primary renal cell cancer

Stereotactic body radiotherapy (SBRT) has demonstrated promising outcomes for patients with early-stage, medically inoperable, primary renal cell carcinoma (RCC) in large multi-institutional studies and prospective clinical trials. The traditional approach used in these studies consisted of a CT-based planning approach for target and organ-at-risk (OAR) volume delineation, treatment planning, and daily treatment delivery. Alternatively, MRI-based approaches using daily online adaptive radiotherapy have multiple advantages to improve treatment outcomes: (1) more accurate delineation of the target volume and OAR volumes with improved soft tissue visualization; (2) gated beam delivery with biofeedback from the patient; and (3) potential for daily plan adaptation due to changes in anatomy to improve target coverage, reduce dose to OARs, or both. The workflow, treatment planning principles, and aspects of treatment delivery specific to this technology are outlined using a case example of a patient with an early-stage RCC of the right kidney treated with MRI-guided SBRT using daily adaptive treatment to a dose of 42 Gy in 3 fractions.

Cost-Effectiveness of Radiofrequency Ablation (RFA) Versus Stereotactic Body Radiotherapy (SBRT) in the Treatment of Localized Renal Cell Carcinoma

Alternative organ preservation strategies for management of localized renal cell carcinoma (RCC) in patients unsuitable for surgery are increasingly being utilized, including radiofrequency ablation (RFA) and more recently stereotactic body radiotherapy (SBRT). We conducted a cost-effectiveness analysis of SBRT versus RFA. A Markov state transition model was constructed for initial local treatment with RFA or SBRT for early stage medically inoperable RCC, defined as node negative T1a/b (≤4 cm or 4-7 cm) lesions. In the model, hypothetical cohorts of early stage, biopsy proven, RCC patients with solitary, unilateral renal masses, and no evidence of distant metastases were created. Transition probabilities, health state utilities and costs used in the model were obtained through a comprehensive literature review of RFA and SBRT for early stage RCC. Incremental cost effectiveness ratios (ICER) were then calculated to compare the two treatments. The analysis was conducted over 5-year time horizon from the perspective of a publicly funded health system in Canada. Secondary analyses were conducted to assess effect of small versus large size (T1a versus T1b) RCC on ICERs. A one-way deterministic sensitivity analysis was conducted. Discounting of 5% was applied. Over 5 years, SBRT gained 4.2 QALYs at cost of $25,342 compared with 3.7 QALYs at cost of $27,634 for RFA. The ICER was $5,048 CAD per QALY in the base case analysis. In patients with small tumors (T1a), SBRT was $6,254 more expensive then RFA and was associated with an additional 0.42 QALYs (ICER $14,963). In patients with larger tumors (T1b), SBRT dominated RFA (i.e. $6,685 less expensive with an additional 0.54 QALYs). In the sensitivity analyses, the greatest potential influencers on cost-effectiveness were the rate of development of distant metastases (0.009-0.055 for SBRT and 0.003-0.025 for RFA) and utility values following both SBRT (0.75-0.85) and RFA (0.65-0.75). Overall, SBRT used as a primary treatment for RCC appears to be more effective at a marginal increase in cost compared with RFA. The use of SBRT appears to be cost-effective for larger tumors while for smaller tumors RFA may be more appropriate as an initial treatment strategy. Potential reasons for increased cost of RFA include equipment costs, costs for complications and admissions in comparison to SBRT> The validity of these conclusions are highly sensitive on the accuracy of local and distant progression rates reported in previous studies, and may be adjusted as the available data on SBRT and RFA continues to evolve and mature.

Renal cryoablation – a practical guide for interventional radiologists

Renal cryoablation is a treatment option for early stage renal cell carcinomas with excellent oncological outcomes and low morbidity. This review outlines the technique of renal cryoablation and provides a guide for interventional radiologists on setting up an integrated service within a renal cancer network multidisciplinary setting. Patient selection and preparation, together with the technical aspects which ensure optimal oncological outcomes and avoid collateral damage to adjacent organs are highlighted.

Serum long non‐coding RNA LINC00887 as a potential biomarker for diagnosis of renal cell carcinoma

The identification of non‐invasive biomarkers for the detection of renal cell carcinoma (RCC) in early‐stage patients may help improve disease outcome. Certain long non‐coding RNAs (lncRNAs) have been reported to be possible biomarkers for the diagnosis and prognosis of cancer. Here, we examined the suitability of the lncRNA LINC00887 as a potential biomarker for RCC because its expression has been shown to be elevated in RCC tissue versus normal tissue in the Gene Expression Profiling Interactive Analysis (GEPIA) database. We found that LINC00887 expression is significantly increased in early‐stage RCC tissues and the serum of early‐stage RCC patients compared to matched normal tissues and the serum of healthy subjects, respectively. We also demonstrated that elevated serum LINC00887 is generated from the tumor tissues of RCC patients. Moreover, a receiver operating characteristic (ROC) curve was generated to analyze the diagnostic value of serum LINC00887. The area under the ROC cure differentiating early‐stage RCC patients from healthy subjects was 0.8001, with a sensitivity of 71.05% and a specificity of 89.87%. Furthermore, we found that LINC00887 promotes RCC cell proliferation in vitro. Taken together, our findings suggest that a serum LINC00887 signature is associated with RCC cell proliferation and may be a potential biomarker for the detection of early‐stage RCC.

Treatment options for localised renal cell carcinoma of the transplanted kidney.

Currently, there is no consensus among the transplant community about the treatment of renal cell carcinoma (RCC) of the transplanted kidney. Until recently, graftectomy was universally considered the golden standard, regardless of the characteristics of the neoplasm. Due to the encouraging results observed in native kidneys, conservative options such as nephron-sparing surgery (NSS) (enucleation and partial nephrectomy) and ablative therapy (radiofrequency ablation, cryoablation, microwave ablation, high-intensity focused ultrasound, and irreversible electroporation) have been progressively used in carefully selected recipients with early-stage allograft RCC. Available reports show excellent patient survival, optimal oncological outcome, and preserved renal function with acceptable complication rates. Nevertheless, the rarity and the heterogeneity of the disease, the number of options available, and the lack of long-term follow-up data do not allow to adequately define treatment-specific advantages and limitations. The role of active surveillance and immunosuppression management remain also debated. In order to offer a better insight into this difficult topic and to help clinicians choose the best therapy for their patients, we performed and extensive review of the literature. We focused on epidemiology, clinical presentation, diagnostic work up, staging strategies, tumour characteristics, treatment modalities, and follow-up protocols. Our research confirms that both NSS and focal ablation represent a valuable alternative to graftectomy for kidney transplant recipients with American Joint Committee on Cancer stage T1aN0M0 RCC. Data on T1bN0M0 lesions are scarce but suggest extra caution. Properly designed multi-centre prospective clinical trials are warranted.

A phase III, randomized, placebo-controlled trial of nivolumab or nivolumab plus ipilimumab in patients with localized renal cell carcinoma at high-risk of relapse after radical or partial nephrectomy (CheckMate 914).

TPS5099 Background: Surgery is standard treatment for nonmetastatic renal cell carcinoma (RCC). Unfortunately, patients (pts) with stage II or III RCC have high risk of relapse with 5-year disease-free survival rates of ~51%–56%; prevention of recurrence is an unmet need. In CheckMate 214, first-line nivolumab plus ipilimumab (NIVO+IPI) demonstrated significant overall survival improvements in pts with advanced/metastatic RCC, with a manageable safety profile. Moreover, while not yet confirmed in randomized controlled trials, evidence suggests that anti-PD-(L)1 monotherapy may provide sufficient clinical activity in some pts with advanced RCC. These findings indicate a potential for improved clinical outcomes in the early-stage adjuvant RCC setting. As such, the phase 3, double-blind CheckMate 914 study will evaluate NIVO and NIVO+IPI vs placebo in pts with high risk of relapse after nephrectomy (NCT03138512). Methods: Key inclusion criteria: radical or partial nephrectomy with negative surgical margins &gt; 4 weeks and ≤12 weeks before randomization; predominantly clear cell histology; pathologic TNM staging T2a (grade [G] 3 or 4), T2b (any G), T3 (any G), or T4 (any G) N0M0, or any T (any G) N1M0; Eastern Cooperative Oncology Group performance status ≤1; no clinical/radiological evidence of macroscopic residual disease or distant metastases post-nephrectomy; and tumor tissue obtained ≤3 months pre-enrollment. Key exclusion criteria: conditions requiring corticosteroid or immunosuppressive systemic treatment, autoimmune disease, prior treatment with drugs specifically targeting T-cell co-stimulation or checkpoint pathways, and prior systemic treatment for RCC. In part A, pts are randomized 1:1 to receive NIVO+IPI or placebo infusions; in part B, pts are randomized 1:1:2 to receive NIVO+IPI, placebo infusions, or NIVO with IPI placebo. All treatments are given for 24 weeks or until disease recurrence, unacceptable toxicity, or withdrawal of consent. Stratification factors: TNM staging and type of nephrectomy procedure. Primary endpoint: disease-free survival per blinded independent central review (part A: NIVO+IPI vs placebo; part B: NIVO vs placebo). Secondary endpoints: overall survival (part A: NIVO+IPI vs placebo; part B: NIVO vs placebo and NIVO+IPI vs NIVO), disease-free survival (part B: NIVO+IPI vs NIVO), and safety. Enrollment in the study is ongoing. Total target enrollment across parts A and B is 1600 pts. Clinical trial information: NCT03138512 .

Partial Versus Radical Nephrectomy in Patients with Renal Cell Carcinoma: A Systematic Review and Meta-analysis.

Radical nephrectomy (RN) and partial nephrectomy (PN) are widely used for early-stage renal cell carcinoma (RCC). However, the results were inconsistent while comparing the efficiency of RN and PN. This study aimed to assess the perioperative effectiveness of RN and PN for treating RCC. PubMed, Embase, and the Cochrane Library electronic database were searched for studies on adults with RCC comparing RN and PN published until September 2019. The perioperative efficacy and safety outcomes were calculated using odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals (CIs) for dichotomous and continuous data, respectively. Subgroup analysis were conducted based on tumor stage and surgery methods for evaluation of the treatment effect on specific subsets. A total of 23 studies involving 30,018 patients with RCC were included in this meta-analysis. Notably, RCC treated with PN was associated with low incidences of hospital mortality (OR: 0.58; 95% CI: 0.38-0.89; P = 0.013) and reoperation rate (OR: 0.74; 95% CI: 0.58-0.95; P = 0.016) as compared to RN. However, PN was associated with an increased risk of overall postoperative complications (OR: 1.40; 95% CI: 1.17-1.68, P < 0.001), postoperative hemorrhagic complications (OR: 1.92; 95% CI: 1.28-2.87, P = 0.002), and urinary fistula (OR: 17.65; 95% CI: 5.35-58.30, P < 0.001) as compared to RN. These findings suggested that PN was associated with lower incidences of hospital mortality and reoperation rate, whereas RN was associated with fewer complications.