septiembre 2019

Adjuvant Therapy in Patients With RCC

A Gul, BI Rini
Cancer, July 2019
DOI: 10.1002/cncr.32144

Abstract

Localized renal cell carcinoma (RCC) has an associated risk of recurrence after nephrectomy. Several clinical risk models attempt to predict oncologic outcomes based on clinical and pathologic features. In addition, novel gene signatures have been developed to refine risk prediction based on tumor biology. Systemic therapies targeting angiogenic pathways that are effective in metastatic RCC failed to show an improvement in overall survival in the adjuvant setting. Immune checkpoint inhibitors have shown significant antitumor activity with prolonged and durable responses in metastatic RCC, which led to an interest in evaluating these agents in the adjuvant setting. In this review, clinical risk predictive models, novel gene signatures, major clinical trials completed in the adjuvant setting, ongoing immune checkpoint inhibitor trials, and the perspective of adjuvant treatment in RCC are discussed.

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Surgical Safety of Cytoreductive Nephrectomy Following Sunitinib: Results from the Multicentre, Randomised Controlled Trial of Immediate Versus Deferred Nephrectomy (SURTIME)

Roderick Emile De Bruijna, Peter Muldersb, Michael A. Jewett, et al
European Urology, 2019
DOI: 10.1016/j.eururo.2019.06.006

Abstract

The European Organisation for Research and Treatment of Cancer SURTIME trial explored timing of sunitinib, a tyrosine kinase inhibitor (TKI), and cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma. Previous retrospective studies suggest increased surgery-related adverse events (AEs) after presurgical TKI. We report surgical safety from a randomised comparison of CN before or after sunitinib. In-hospital mortality, 30-d readmission rate, and intraoperative and 30-d postoperative AEs according to Common Terminology Criteria for Adverse Events version 4 and Clavien-Dindo (CD) were analysed. Patients were randomised 1:1 to immediate CN followed by sunitinib versus sunitinib followed by deferred CN 24 h after the last dose of sunitinib. None of the tumours in the deferred arm became unresectable, and only two patients had a sunitinib-related delay of CN of >2 wk. AEs related to surgery (all grades) in the immediate and deferred arms occurred in 52% and 53% after CN, respectively, although the number of intraoperative surgery-related AEs was higher in the immediate arm. Postoperative AEs (CD ≥3), 30-d readmission, and in-hospital mortality rates were 6.5%, 13%, and 4.3% in the immediate arm and 2.5%, 7.5%, and 2.5% in the deferred arm, respectively. There were no differences in surgery time, blood loss, and hospital stay.

Patient summary:

Patients with metastatic kidney cancer do not have more surgical complications irrespective of whether they are treated with systemic therapy before or after surgery.

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Renal cell cancer treatment: an expert panel recommendation from the Latin American cooperative group-genitourinary and the Latin American renal cancer group: focus on surgery

Stênio de Cássio Zequi, Walter Henriques da Costa , Fernando Korkes, Rodolfo Borges dos Reis, Wilson Francisco Schreiner Busato, Wagner Eduardo Matheus, Deusdedit Cortez Vieira da Silva Neto, Felipe de Almeida e Paula, Gustavo Franco Carvalhal, Lucas Nogueira, Roni de Carvalho Fernandes, Adriano Gonçalves e Silva, André Deeke Sasse, André P. Fay, Denis Leonardo Jardim, Diogo Assed Bastos, Diogo Augusto Rodrigues da Rosa, Evanius Wierman, Fabio Kater, Fabio A. Schutz, Fernando Cotait Maluf, Fernando Nunes Galvão de Oliveira, Igor Alexandre Protzner Morbeck, José Augusto Rinck, Karine Martins da Trindade, Manuel Caitano Maia, Vinicius Carrera Souza, Fernando Sabino Marques Monteiro and Andrey Soares.

Abstract

Background:

Renal cell cancer (RCC) is one of the 10 most common cancers in the world, and its incidence is increasing, whereas mortality is declining only in developed countries. Therefore, two collaborative groups, The Latin American Oncology Cooperative GroupGenitourinary Section (LACOG-GU) and the Latin American Renal Cancer Group (LARCG), held a consensus meeting to develop this guideline.

Methods:

Issues (134) related to the treatment of RCC were previously formulated by a panel of experts. The voting panel comprised 26 specialists (urologists and medical oncologists) from the LACOG-GU/LARCG. A consensus was reached if 75% agreement was achieved. If there was less concordance, a new discussion was undertaken, and a consensus was determined by the most votes after a second voting session.

Results:

The expert meeting provided recommendations that were in line with the global literature; 75.0% of the recommendations made by the panel of experts were evidence-based level A, 22.5% of the recommendations were level B, and 2.5% of the recommendations were level D.

Conclusions:

This review suggests recommendations for the surgical treatment of RCC according to the LACOG-GU/LARCG experts.

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Clear-cell Renal Cell Carcinoma: Molecular Characterization of IMDC Risk Groups and Sarcomatoid Tumors

Verbiest A, Renders I1, Caruso S, et al.
Clinical Genitourinary Cancer, 2019
DOI: 10.1016/j.clgc.2019.05.009

Abstract

Introduction:

Recent trials have suggested predictive biomarkers in advanced clear-cell renal cell carcinoma (accRCC): International Metastatic RCC Database Consortium (IMDC) good risk or angiogenic gene signature for sunitinib and IMDC intermediate/poor risk for ipilimumab-nivolumab and T-effector cell signature or sarcomatoid dedifferentiation for atezolizumab-bevacizumab. We hypothesized that earlier described molecular subtypes, ccrcc1 to ccrcc4, could provide similar information as a single generic biomarker and molecularly characterize the heterogeneous intermediate-risk group.

Patients and Methods:

Patients with accRCC treated with systemic therapies were included. We assessed associations between the 5 biomarkers and their impact on progression-free survival (PFS) and response rate (RR) on first-line sunitinib or pazopanib. The cutoff percentage of sarcomatoid dedifferentiation with optimal discriminative value was determined.

Results:

In total, 430 patients were included (163 with molecular data). The molecular ccrcc2 subtype identified tumors with higher angiogenic gene expression across IMDC risk groups: prevalence was high in IMDC good risk and low in IMDC poor risk (P < .001). Molecular subtype, IMDC, and angiogenic gene expression had comparable C-indices to predict PFS and RR (range, 60%-66%). The ccrcc2 subtype and angiogenic gene expression were positive predictors of PFS in IMDC intermediate-risk patients (P = .006; P = .04). Immune signature did not differ between IMDC groups, but was strongly correlated with molecular subtype (P = .8 and P = .0007). A cutoff value of 25% sarcomatoid differentiation discriminated tumors with distinct molecular characteristics and therapeutic sensitivity.

Conclusion:

In accRCC, molecular subtypes can explain differences in IMDC risk group, expression of angiogenesis and immune response genes, and sarcomatoid dedifferentiation. They can identify molecularly different patient populations within the heterogeneous IMDC intermediate group and select patients for systemic therapies.

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Predicting Renal Cancer Recurrence: Defining Limitations of Existing Prognostic Models With Prospective Trial-Based Validation

Correa A, Jegede O, Haas N, et al.
Journal of Clinical Oncology, June 2019.
DOI: 10.1200/JCO.19.00107

Abstract

PURPOSE:

To validate currently used recurrence prediction models for renal cell carcinoma (RCC) by using prospective data from the ASSURE (ECOG-ACRIN E2805; Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) adjuvant trial.

PATIENTS AND METHODS:

Eight RCC recurrence models (University of California at Los Angeles Integrated Staging System [UISS]; Stage, Size, Grade, and Necrosis [SSIGN]; Leibovich; Kattan; Memorial Sloan Kettering Cancer Center [MSKCC]; Yaycioglu; Karakiewicz; and Cindolo) were selected on the basis of their use in clinical practice and clinical trial designs. These models along with the TNM staging system were validated using 1,647 patients with resected localized high-grade or locally advanced disease (≥ pT1b grade 3 and 4/pTanyN1Mo) from the ASSURE cohort. The predictive performance of the model was quantified by assessing its discriminatory and calibration abilities.

RESULTS:

Prospective validation of predictive and prognostic models for localized RCC showed a substantial decrease in each of the predictive abilities of the model compared with their original and externally validated discriminatory estimates. Among the models, the SSIGN score performed best (0.688; 95% CI, 0.686 to 0.689), and the UISS model performed worst (0.556; 95% CI, 0.555 to 0.557). Compared with the 2002 TNM staging system (C-index, 0.60), most models only marginally outperformed standard staging. Importantly, all models, including TNM, demonstrated statistically significant variability in their predictive ability over time and were most useful within the first 2 years after diagnosis.

CONCLUSION:

In RCC, as in many other solid malignancies, clinicians rely on retrospective prediction tools to guide patient care and clinical trial selection and largely overestimate their predictive abilities. We used prospective collected adjuvant trial data to validate existing RCC prediction models and demonstrate a sharp decrease in the predictive ability of all models compared with their previous retrospective validations. Accordingly, we recommend prospective validation of any predictive model before implementing it into clinical practice and clinical trial design.

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Safety and Efficacy of Nivolumab in Patients With Metastatic Renal Cell Carcinoma and End-stage Renal Disease at 2 Centers

Hidekazu Tachibana, Tsunenori Kondo, Hiroki Ishihara, et al.
Clinical Genitourinary Cancer, August 2019
DOI: 10.1016/j.clgc.2019.04.004

Abstract

Introduction:

There is scarce information regarding nivolumab treatment for metastatic renal cell carcinoma (mRCC) in patients with end-stage renal disease (ESRD). This study investigated the safety and efficacy of nivolumab in patients with mRCC and ESRD.

Materials and Methods:

This 2-center retrospective study evaluated 62 patients who were administered nivolumab for mRCC between June 2013 and August 2018. The ESRD group (n = 7) and non-ESRD group (n = 55) were compared in terms of their immune-related adverse events (irAEs), objective response rate, progression-free survival, and overall survival.

Results:

All 7 patients with ESRD were male (median age, 67 years; range, 52-73 years), and their median duration of nivolumab use was 6.0 months (range, 1.8-8.2 months). One patient experienced a partial response, and 4 patients had stable disease. The objective response rate was lower in the ESRD group than in the non-ESRD group (16.7% vs. 37.5%; P = .25). Relative to the non-ESRD group, the ESRD group had slightly lower rates of all irAEs (42.9% vs. 58.7%) and grade 3 or higher irAEs (14.3% vs. 21.7%). The irAEs in the ESRD group were skin rash (grade 1), diarrhea (grade 1), and severe fatigue (grade 3) after the first nivolumab infusion, which required treatment discontinuation. The Kapan-Meier curves revealed no significant differences between the ESRD and non-ESRD groups in terms of progression-free (P = .63) and overall survival (P = .62).

Conclusion:

It may be possible to safely and effectively use nivolumab for select patients with mRCC and ESRD.

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Valor pronóstico de la invasión de grasa perirrenal y/o del seno en pacientes con carcinoma de células renales pT3a: estudio de cohorte multicéntrico. Grupo LARCG

García Marchiñena P, Tobia I, Abreu D, et al.
Actas Urológicas Españolas 2019
DOI: 10.1016/j.acuro.2019.01.005

Introducción y objetivos:

El objetivo de este estudio es evaluar las tasas de sobrevida global (OS), la sobrevida específica del cáncer (CSS), la sobrevida libre de recaída global (RFS), la sobrevida tiempo libre hasta la recaída local (LRFS) y la sobrevida tiempo libre hasta la recaída a distancia (DRFS), en los pacientes con carcinoma de células renales (CCR) pT3a considerando a la infiltración de grasa (FI) perirrenal y/o sinusal como factores pronósticos.

Materiales y métodos:

Cohorte retrospectiva de pacientes con CCR pT3a sometidos a cirugía. Los datos se extrajeron de la base de datos LARCG. Se evaluaron variables demográficas, clínicas, patológicas y quirúrgicas. La FI se dividió en 4 grupos (vena, perirrenal, sinusal y ambas grasas). Se realizaron curvas de Kaplan-Meier y regresión de Cox.

Resultados:

Se incluyeron 293 pacientes. La edad media fue de 61,4 años. La mediana de seguimiento fue de 21 meses (r: 1-194). La CSS, la RFS, el LRFS y el DRFS estimadas a 3 años en el grupo de ambas grasas infiltradas fueron 53,1, 45,1, 58,7 y 51,6 meses, respectivamente, en todos los casos estadísticamente inferiores al resto (p˂0,005). En el análisis multivariable, la infiltración de ambas grasas tuvo un aumento significativo de mortalidad específica, recaída global y local con respecto a infiltración de venas (HR: 4,5, 2,42 y 8,08, respectivamente). El grado de Fuhrman y la infiltración de la pelvis renal fueron predictores independientes de la CSS y la RFS.

Conclusiones:

La infiltración de ambas grasas renales aumenta el riesgo de recaída global y local en pT3a RCC. Del mismo modo, se asocia con una menor sobrevida específica del cáncer, debiendo considerarse como un factor de mal pronóstico.

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