Articles

Prognostic value of perirenal and/or sinus fat infiltration in patients with pT3a renal cell carcinoma: A multicentre cohort study. LARCG Group

García Marchiñena P, Tobia I, Abreu D, et al.
Actas Urológicas Españolas, Volume 43, Issue 9, November 2019, Pages 495-502
DOI: 10.1016/j.acuro.2019.01.005

Abstract

Introduction and objectives

The objective of this study is to evaluate overall survival (OS), cancer-specific survival (CSS), relapse-free survival, local and distant (LRFS and DRFS, respectively) rates in patients with pT3a renal cell carcinoma (RCC) considering the perirenal and/or sinus fat infiltration (FI) as prognostic factors.

Materials and methods

Retrospective cohort of patients with pT3a RCC who underwent radical or partial nephrectomy. The data were extracted from the LARCG (Latin American Renal Cancer Group) database. The demographic, clinical, pathological and surgical variables were evaluated. FI was divided into 4 groups (vein, perirenal, sinus and both fats infiltration). The Kaplan Meier and Cox regression curves were performed.

Results

293 patients were included in the study. The mean age was 61.4 years. The median follow-up was 21 months (r: 1-194). CSS, RFS, LRFS and DRFS estimated at 3 years in the group of both fats’ infiltration were 53.1, 45.1, 58.7 and 51.6 months, respectively, and always statistically lower than the rest (P˂0.005). In the multivariate analysis, the infiltration of both fats significantly increased specific mortality, overall and local relapse with respect to vein infiltration (HR: 4.5, 2.42 and 8.08, respectively). The Fuhrman grade and renal pelvis infiltration were independent predictors of CSS and RFS.

Conclusions

Infiltration of both fats increases the risk of overall and local relapse in pT3a RCC. In the same way, it is associated with a lower cancer-specific survival and should be considered as a factor of poor prognosis.

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Validation of the GRade, Age, Nodes and Tumor (GRANT) score within the Surveillance Epidemiology and End Results (SEER) database: A new tool to predict survival in surgically treated renal cell carcinoma patients

Buti S, Karakiewicz P, Bersanelli M, et al.
Scientific Reports volume 9, Article number: 13218 (2019)
DOI: 10.1038/s41598-019-49250-6

Abstract

The purpose of the present study was to validate the new GRade, Age, Nodes and Tumor (GRANT) score for renal cell carcinoma (RCC) prognostication within a large population of patients. Within the Surveillance, Epidemiology, and End Results database, we identified patients with either clear-cell or papillary RCC, who underwent nephrectomy between 2001 and 2015. Harrell’s C-Index, calibration plot and decision curve analysis were used to validate the GRANT model using a five-risk group stratification (0 vs. 1 vs. 2 vs. 3 vs. 4 risk factors). The primary endpoint was overall survival (OS) at 60 months. The analyses were repeated according to the histologic subgroup. The overall population included 73217 cases; 60900 with clear-cell RCC and 12317 with papillary histology, respectively. According to a five-risk group stratification, 23985 patients (32.8%) had no risk factor (0), 35019 (47.8%) had only one risk factor (1), 13275 (18.1%) had risk score 2854 (1.2%) had 3 risk factors and 84 (0.1%) of cases had a GRANT score of 4, respectively. At 60 months, OS rates as determined by the GRANT score were respectively 94% (score 0) vs. 86% (score 1) vs. 76% (score 2) vs. 46% (score 3) vs. 16% (score 4). In both histologic subtypes, the GRANT score yielded good calibration and high net benefit. OS C-Index values were 0.677 and 0.650 for clear-cell and papillary RCC at 60 months after surgery, respectively. In conclusion, the GRANT score was validated with a five-risk group stratification in a huge population from the SEER database, offering a further demonstration of its reliability for prognostication in RCC.

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Complete Surgical Metastasectomy for Renal Cell Carcinoma in the Post-cytokine Era

Lyon TD, Thompson RH, Shah PH, et al.
Journal of Urology, August 2019
DOI: https://doi.org/10.1097/JU.0000000000000488

Abstract

Purpose

Data supporting complete metastasectomy (CM) for metastatic renal cell carcinoma (RCC) is derived primarily from the era of cytokine therapy, and whether CM remains beneficial among patients receiving more recently approved systemic therapies has not been well studied. The objective of this study was to examine survival outcomes among patients treated with CM in the era of targeted therapy and checkpoint blockade availability.

Methods

We queried our institutional nephrectomy registry to identify 586 patients who underwent partial or radical nephrectomy for unilateral, sporadic RCC with a first occurrence of metastases between 2006 and 2017, including 158 treated with CM. Associations of CM with cancer-specific and overall survival were assessed using Cox proportional hazards models.

Results

Median follow-up after diagnosis of metastases was 3.9 years, during which time 403 patients died, including 345 from RCC. Of the CM patients, 147 (93%) did not receive any systemic treatment for their index metastatic lesion(s). Two-year CSS was significantly greater for patients with CM than for those without (84% vs. 54%, p<0.001). After adjusting for age, sex, and the timing, number, and location of metastases, CM was associated with a significantly reduced likelihood of death from RCC (HR 0.47, 95% CI 0.34-0.65, p<0.001).

Conclusions

Complete surgical resection of metastases from RCC is associated with improved CSS in the post-cytokine era and may be considered for appropriate patients following a process of shared decision-making.

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Pathologic response and surgical outcomes in patients undergoing nephrectomy following receipt of immune checkpoint inhibitors for renal cell carcinoma

Singla N, Elias R, Ghandour RA, et al.
Urologic Oncology, September 2019
DOI: https://doi.org/10.1016/j.urolonc.2019.08.012

Abstract

Objective

To evaluate the pathologic response, safety, and feasibility of nephrectomy following receipt of immune checkpoint inhibition (ICI) for renal cell carcinoma (RCC).

Methods

Patients who underwent nephrectomy for RCC after exposure to nivolumab monotherapy or combination ipilimumab/nivolumab were reviewed. Primary surgical outcomes included operative time (OT), estimated blood loss (EBL), length of stay (LOS), readmission rates, and complication rates. Pathologic response in the primary and metastatic sites constituted secondary outcomes.

Results

Eleven nephrectomies (10 radical, 1 partial) were performed in 10 patients after ICI with median postoperative follow-up 180 days. Six patients received 1 to 4 cycles of ipilimumab/nivolumab, while 5 received 2 to 12 infusions of nivolumab preoperatively. Five surgeries were performed laparoscopically, and 4 patients underwent concomitant thrombectomy. One patient exhibited complete response (pT0) to ICI, and 3/4 patients who underwent metastasectomy for hepatic, pulmonary, or adrenal lesions exhibited no detectable malignancy in any of the metastases resected. No patients experienced any major intraoperative complications, and all surgical margins were negative. Median OT, EBL, and LOS were 180 minutes, 100 ml, and 4 days, respectively. Four patients experienced a complication, including 3 that were addressed with interventional radiology procedures. One patient died of progressive disease >3 months after surgery, and 1 patient succumbed to pulmonary embolism complicated by sepsis. No complications or readmissions were noted in 6 patients.

Conclusions

Nephrectomy following ICI for RCC is safe and technically feasible with favorable surgical outcomes and pathologic response. Timing of the nephrectomy relative to checkpoint dosing did not seem to impact outcome. Biopsies of lesions responding radiographically to ICI may warrant attention prior to surgical excision.

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Predictors of Survival Outcomes in Non-Metastatic Renal Cell Carcinoma in Latin America and Spain: A Multicentric Analysis

Stênio de Cássio Zequi , Thiago Camelo Mourão, Max Moura de Oliveira, Maria Paula Curado, Guilhermo Gueglio, Walter Henriques da Costa, Alvaro Zuñiga, Ruben Bengió, Carlos Scorticati, Francisco Rodríguez, Ana Maria Autran, Pablo Martínez, Carlos Ameri, Pablo Mingote, Fernando Pablo Secin, Ricardo decía, Isabela Werneck da Cunha, Gustavo Cardoso Guimarães, Sidney Glina, Joan Palou and Diego Abreu.
Kidney Cancer xx (20xx) x–xx
DOI 10.3233/KCA-190068
IOS Press

Abstract

Background

Renal cell carcinoma (RCC) is a lethal neoplasia. Data from Latin America are scarce, and the distinct ethnic origins of this population could affect predictive or prognostic factors.

Objective

We aim to describe a large cohort of non-metastatic renal cell carcinoma, identifying the demographic, clinical, and pathological prognostic factors for survival.

Methods

We used a multi-institutional retrospective cohort involving 5,670 patients who underwent radical or partial nephrectomy across seven Latin American countries and Spain from 1980 to 2016. The variables were compared, and Kaplan–Meier curves were used to estimate the overall survival (OS) and cancer-specific survival (CSS).

Results

The clear cell subtype represented 66.7% of RCC, followed by chromophobe (13.7%), papillary (5.2%), and others (14.4%). Furthermore, 72.3% of renal masses were <7.0 cm. The 5-year OS and 10-year OS rates were 86.1% and 69.5%, respectively. The 5-year and 10-year CSS rates were 89.9% and 81.8%, respectively. The demographic and clinical predicting factors for OS in the multivariate analysis were age (HR: 2.978), anemia (HR: 1.44), presence of symptoms at presentation (HR: 1.26), Karnofsky score ≤80 (HR: 2.12), and ASA score ≥ 3 (HR: 1.49). The pathological factors were nodal metastasis (HR: 2.14), peri-renal fat invasion (HR: 2.12), inferior vena cava invasion (HR: 1.61), histologic tumoral necrosis (HR: 1.69), and tumor size >7 cm (HR: 1.64).

Conclusions

Our findings agreed with those reported for some developed countries. We emphasize that ASA and peri-renal fat invasion as prognostic factors deserve further study. Information regarding microvascular invasion should be regularly incorporated in pathological reports.

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The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice

Raimondi A, Randon G, Sepe P, et al.
Int. J. Mol. Sci, 20(17), 4263; August 2019
DOI: https://doi.org/10.3390/ijms20174263

Abstract

Immunotherapy has changed the therapeutic scenario of metastatic renal cell carcinoma (mRCC), however the evaluation of disease response to immune-checkpoint inhibitors is still an open challenge. Response evaluation criteria in solid tumors (RECIST) 1.1 criteria are the cornerstone of response assessment to anti-neoplastic treatments, but the use of anti-programmed death receptor 1 (PD1) and other immunotherapeutic agents has shown atypical patterns of response such as pseudoprogression. Therefore, immune-modified criteria have been developed in order to more accurately categorize the disease response, even though their use in the everyday clinical practice is still limited. In this review we summarize the available evidence on this topic, with particular focus on the application of immune-modified criteria in the setting of mRCC.

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Cytoreductive Nephrectomy in Metastatic Papillary Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Graham J, Wells JC, Donskov F, et al.
European Urology Oncology, Volume 0, Issue 0. Articles in Press
DOI: https://doi.org/10.1016/j.euo.2019.03.007

Abstract

Background

There is evidence that cytoreductive nephrectomy (CN) may be beneficial in metastatic renal cell carcinoma (mRCC). This has been studied predominantly in clear-cell RCC, with more limited data on the role of CN in patients with papillary histology.

Objective

To determine the benefit of CN in synchronous metastatic papillary RCC.

Design, setting, and participants

Using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) database, a retrospective analysis was performed for patients with papillary mRCC treated with or without CN.

Outcome measurements and statistical analysis

Median overall survival (OS) and progression-free survival (PFS) were determined for both patient groups. Cox regression analysis was performed to control for imbalances in individual IMDC risk factors.

Results and limitations

In total, 647 patients with papillary mRCC were identified, of whom 353 had synchronous metastatic disease. Of these, 109 patients were treated with CN and 244 were not. The median follow-up was 57.1 mo (95% confidence interval [CI] 32.9–77.8) and the OS from the start of first-line targeted therapy for the entire cohort was 13.2 mo (95% CI 12.0–16.1). Median OS for patients with CN was 16.3 mo, compared to 8.6 mo (p < 0.0001) in the no-CN group. When adjusted for individual IMDC risk factors, the hazard ratio (HR) of death for CN was 0.62 (95% CI 0.45–0.85; p = 0.0031). Limitations include the retrospective nature of the analysis.

Conclusions

The use of CN in patients with mRCC and papillary histology appears to be associated with better survival compared to no CN after adjustment for risk criteria. Selection of appropriate candidates for CN is crucial. A clinical trial in this rare population may not be possible.

Patient summary

In a population of patients with advanced papillary kidney cancer, we found that surgical removal of the primary kidney tumor was associated with better overall survival.

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Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial

Rini B, Powles T, Atkins M, et al.
The Lancet, Vol 393, 10189, P2404-2415, June 2019
DOI: https://doi.org/10.1016/S0140-6736(19)30723-8

Summary

Background

A phase 2 trial showed improved progression-free survival for atezolizumab plus bevacizumab versus sunitinib in patients with metastatic renal cell carcinoma who express programmed death-ligand 1 (PD-L1). Here, we report results of IMmotion151, a phase 3 trial comparing atezolizumab plus bevacizumab versus sunitinib in first-line metastatic renal cell carcinoma.

Methods

In this multicentre, open-label, phase 3, randomised controlled trial, patients with a component of clear cell or sarcomatoid histology and who were previously untreated, were recruited from 152 academic medical centres and community oncology practices in 21 countries, mainly in Europe, North America, and the Asia-Pacific region, and were randomly assigned 1:1 to either atezolizumab 1200 mg plus bevacizumab 15 mg/kg intravenously once every 3 weeks or sunitinib 50 mg orally once daily for 4 weeks on, 2 weeks off. A permuted-block randomisation (block size of 4) was applied to obtain a balanced assignment to each treatment group with respect to the stratification factors. Study investigators and participants were not masked to treatment allocation. Patients, investigators, independent radiology committee members, and the sponsor were masked to PD-L1 expression status. Co-primary endpoints were investigator-assessed progression-free survival in the PD-L1 positive population and overall survival in the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, number NCT02420821.

Findings

Of 915 patients enrolled between May 20, 2015, and Oct 12, 2016, 454 were randomly assigned to the atezolizumab plus bevacizumab group and 461 to the sunitinib group. 362 (40%) of 915 patients had PD-L1 positive disease. Median follow-up was 15 months at the primary progression-free survival analysis and 24 months at the overall survival interim analysis. In the PD-L1 positive population, the median progression-free survival was 11·2 months in the atezolizumab plus bevacizumab group versus 7·7 months in the sunitinib group (hazard ratio [HR] 0·74 [95% CI 0·57–0·96]; p=0·0217). In the ITT population, median overall survival had an HR of 0·93 (0·76–1·14) and the results did not cross the significance boundary at the interim analysis. 182 (40%) of 451 patients in the atezolizumab plus bevacizumab group and 240 (54%) of 446 patients in the sunitinib group had treatment-related grade 3–4 adverse events: 24 (5%) in the atezolizumab plus bevacizumab group and 37 (8%) in the sunitinib group had treatment-related all-grade adverse events, which led to treatment-regimen discontinuation.

Interpretation

Atezolizumab plus bevacizumab prolonged progression-free survival versus sunitinib in patients with metastatic renal cell carcinoma and showed a favourable safety profile. Longer-term follow-up is necessary to establish whether a survival benefit will emerge. These study results support atezolizumab plus bevacizumab as a first-line treatment option for selected patients with advanced renal cell carcinoma.

Funding

F Hoffmann–La Roche Ltd and Genentech Inc.

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Masas Renales y Cáncer Renal Localizado: Guía de la AUA

Campbell S; Uzzo RG; Allaf ME, et al.
The Lancet, Vol 20, 10, P1332-1334, October 2019
DOI: https://doi.org/10.1016/S1470-2045(19)30510-8

Propósito

Esta Guía de la Asociación Urológica Americana (AUA, American Urological Association) se centra primariamente en la evaluación y el manejo de las masas renales esporádicas clínicamente localizadas sospechosas de ser un carcinoma de células renales (RCC, renal cell carcinoma) en los adultos, incluyendo a los tumores renales sólidos que se realzan (solid enhancing renal tumors) y las masas renales quísticas complejas de los tipos Bosniak 3 y 4. Algunos pacientes con masas renales clínicamente localizadas podrán presentarse con hallazgos sugerentes de una biología agresiva del tumor o podrán ser pasados a un estadio más avanzado en la exploración o en el estudio patológico final. También se enfocarán las consideraciones en el manejo pertinentes para los urólogos en estos pacientes. Los patrones para la práctica en referencia a tales tumores también varían considerablemente. La literatura referente a la evaluación y el manejo ha venido evolucionando con rapidez. Ejemplos notables de ello incluyen a las controversias acerca del papel de la biopsia de las masas renales y las preocupaciones referentes a la sobreutilización de la nefrectomía radical. Por favor, también revisar el algoritmo para el tratamiento de las Masas Renales y el Cáncer Renal Localizado (Renal Mass and Localized Renal Cancer).

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Renal cell carcinoma treatment after first-line combinations

Porta C, Schmidinger M.
The Lancet, Vol 20, 10, P1332-1334, October 2019
DOI: https://doi.org/10.1016/S1470-2045(19)30510-8

Treatment of metastatic renal cell carcinoma has dramatically changed in the past two decades, moving from cytokine-based immunotherapy, to vascular endothelial growth factor (VEGF) pathway inhibitors, and to combinations of these inhibitors with novel immune checkpoint inhibitors. What was once defined as an “embarassment of riches” has now reached new, unexpected heights.

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