Kidney Cancer - Volume 7, issue 1

Authors: Ibañez Vázquez, Laura | Abad López, Pablo | Gómez Rivas, Juan | De La Parra Sánchez, Irene | Enikeev, Dimitry | Serrano Pascual, Álvaro | Fernández Montarroso, Lorena | García Rojo, Esther | Moreno Sierra, Jesús

Article Type: Systematic Review

Abstract: BACKGROUND: Renal cysts are the most frequently occurring incidental renal lesions. They are asymptomatic, which explains why they tend to be diagnosed incidentally as a result of imaging tests. In cases where malignancy is suspected, there are various therapeutic alternatives. OBJECTIVE: The objective of this study is to review the diagnostic and therapeutic alternatives for cystic renal lesions. METHOD: A systematic search was conducted in Pubmed, Science Direct, Scopus, and Google Scholar databases between May and October 2022. The review of articles was conducted following the methodological recommendations of the Preferred Reporting Items for Systematic reviews …and Meta-Analyses (PRISMA) 2020 Statement. As a result, 25 articles were selected. RESULTS: Thirteen studies focused on diagnostic management. In five of the cases ultrasound was used, multiparametric magnetic resonance imaging (mpMRI) was considered in six articles, and computerized tomography (CT) was studied in three. Eleven papers were retrospective series, one of the studies was prospective, and one was a simulated cost-effectiveness model. Among the 12 articles on treatment, five focused on surgery and one on the results of active surveillance, while three compared active surveillance with other treatments. Four articles assessed the percutaneous approach and radiofrequency ablation. All articles were retrospective cohorts. CONCLUSIONS: CT is the most standard of the tests. In doubtful cases, mpMRI and ultrasound can serve as complementary tests. Partial nephrectomy is currently the gold standard treatment and the results are similar for both open and laparoscopic approaches. Percutaneous radiofrequency treatments produce reasonable survival rates free of local recurrence and metastasis and are recommended in patients with high surgical risk. Show more

Keywords: Kidney diseases, cystic, diagnosis, therapy, CT, nephrectomy

DOI: 10.3233/KCA-230002

Citation: Kidney Cancer, vol. 7, no. 1, pp. 95-114, 2023

Authors: Tsimafeyeu, Ilya | Musaeva, Gunel | Utyashev, Igor | Zakurdaeva, Kristina | Gerk, Ivan | Anna, Olshanskaya | Mahmudova, Samira | Otkhozoria, Nana | Volkova, Maria | Mitin, Timur

Article Type: Research Article

Abstract: Background: Introduction of immune checkpoint inhibitors in the standard of care for metastatic renal cell carcinoma (mRCC) requires robust but yet simple biomarkers to predict efficacy of immunotherapy. Objective: The aim of this study was to evaluate the association between fibrinogen levels and efficacy of second-line therapy with nivolumab in mRCC. Methods: This is a prospective multicenter biomarker study. Fibrinogen levels were measured one week prior to second-line nivolumab therapy and six times monthly. A high fibrinogen level was defined as ≥5 g/L. Patients were divided into two cohorts: high (H) and normal (N) fibrinogen levels. The …primary endpoint was overall survival (OS). Results: The median OS was 31.5 months (95% confidence interval [CI], 27.9 to 35.1) in cohort N vs. 20.9 months (95% CI, 18.1 to 23.7) in cohort H (hazard ratio [HR], 0.39; 98.5% CI, 0.21 to 0.7; P  = 0.002). The median progression-free survival was 9.4 months (95% CI, 5.5 to 14.1) in cohort N and 4.0 months (95% CI, 2.9 to 5.1) in cohort H (HR, 0.65; 95% CI, 0.51 to 0.72; P  <  0.001). The objective response rate was higher in N cohort (33% vs. 17% ; P  = 0.012). No statistically significant changes of fibrinogen concentration during nivolumab therapy were found. Conclusion: The study demonstrated an association of hyperfibrinogenemia with worse clinical outcomes of second-line nivolumab monotherapy in patients with mRCC. Further validation of fibrinogen as a predictive biomarker for immunotherapy efficacy in patients with mRCC is warranted. Show more

Keywords: Metastatic renal cell carcinoma, nivolumab, fibrinogen, immunotherapy

DOI: 10.3233/KCA-230007

Citation: Kidney Cancer, vol. 7, no. 1, pp. 115-121, 2023

Authors: Calhoun, Shawna R. | Sharma, Manish | Lee, Chung-Han

Article Type: Systematic Review

Abstract: Background: Non-clear cell renal cell carcinoma (nccRCC) is a diverse group of cancers that occurs in approximately 25% of patients with renal cell carcinoma. In the advanced/metastatic setting, survival in all nccRCC subtypes is considered poor, due to the inherent aggressiveness of these cancers, and a lack of effective systemic treatment options. Clinical trials of immune/targeted agents have predominantly focused on patients with ccRCC. There is no globally accepted standard of care for nccRCC; however, recently clinical trials have been initiated in this population. Objective: To perform a targeted literature review of published original observational studies reporting common …real-world clinical outcomes (real-world overall response rate [rwORR], real-world progression free survival [rwPFS], real-world overall survival [rwOS]) in previously treatment naïve patients with advanced/metastatic nccRCC. Methods: A targeted search of MEDLINE and EMBASE was conducted per PRISMA guidelines to identify observational studies in previously treatment naïve patients with advanced/metastatic nccRCC. Publications with adequate information since 2010 and from select conferences since 2020 were considered. Results: 27 studies across 29 publications were identified. Sample sizes ranged from 7-1,573 across these studies with differences in nccRCC subtypes included and treatments received. Real-world ORR ranged from 0–37%, median rwPFS from 2–17 months, and median rwOS from 3–30 months, across 19, 17, and 24 studies, respectively. These outcomes also varied with receipt/type of treatment and demographic/clinical subgroups with outcomes tending to be worse in patients with papillary RCC compared to chromophobe RCC. Conclusions: Clinical outcomes varied, as patient populations, eligible histologies, treatments and methods were heterogeneous. Show more

Keywords: Renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, progression-free survival, survival rate, response evaluation criteria in solid tumors, review literature

DOI: 10.3233/KCA-230008

Citation: Kidney Cancer, vol. 7, no. 1, pp. 123-136, 2023

Authors: Tripathi, Nishita | Meza, Luis | Sayegh, Nicolas | Govindarajan, Ameish | Byron, Sara A. | Zhang, Jiaming | Chigarira, Beverly | Jo, Yeonjung | Zengin, Zeynep B. | Li, Haoran | Gebrael, Georges | Desai, Arpita | Agarwal, Neeraj | Swami, Umang | Maughan, Benjamin L. | Pal, Sumanta K.

Article Type: Research Article

Abstract: Background: Ipilimumab plus nivolumab is approved as a first-line treatment for intermediate or poor risk metastatic renal cell carcinoma (mRCC). However, ∼35% of patients progress within six months on ipilimumab plus nivolumab, and no validated genomic biomarkers predict the benefit. In this study, we explore the genomic and transcriptomic differences among patients with clear cell mRCC patients who either did or did not experience clinical benefit from first-line ipilimumab plus nivolumab therapy. Method: Patients with clear cell mRCC intermediate or poor IMDC risk scores, with available tumor whole exome with/without transcriptome sequencing before starting systemic therapy were included. …Patients who developed a complete response, partial response, or stable disease for at least six months after initiating treatment were categorized into the ‘clinical benefit’ group, whereas the rest were classified as ‘no clinical benefit.’ Genomic alteration frequencies between the groups were assessed with a chi-square test. Differentially expressed genes and gene sets were identified via DeSeq2 and GSEA v4.2.3, respectively. Result: 53 patients with clear cell mRCC (37 clinical benefit and 16 no clinical benefit) were eligible and included. No significant difference was found in the genomic alteration frequencies between these groups. Baseline tumor transcriptomic data were available for 14 patients (9 clinical benefit and 5 no clinical benefit). The apical surface and pathways downregulated by KRAS signaling were enriched in the clinical benefit group, whereas inflammatory pathways were enriched in the no clinical benefit group. Conclusion: These findings suggest that tumor specific gene expression as assessed by RNA sequencing could serve as a potential biomarker of response to ipilimumab plus nivolumab therapy. Show more

Keywords: Gene expression analysis, ipilimumab, immunotherapy, nivolumab, renal cell carcinoma

DOI: 10.3233/KCA-230011

Citation: Kidney Cancer, vol. 7, no. 1, pp. 137-145, 2023

Authors: Dukkipati, Akasha | Li, Xiaochen | Pal, Sumanta K. | Zugman, Miguel

Article Type: Systematic Review

Abstract: Background: The nephrotoxicity profile of contemporary first-line regimens for treatment of metastatic renal cell carcinoma (mRCC) has not been systematically studied in published clinical trials. Objective: To assess the rates of nephrotoxic events of contemporary first-line regimens for treatment of mRCC in comparison to vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) mono-therapy. Methods: We performed a systematic search of the literature looking for randomized clinical trials that contemplated National Comprehensive Cancer Network (NCCN) recommended first-line regimens for treating mRCC in which the control arm was a VEGF-TKI. Selected trials could either include an experimental arm …of immune checkpoint inhibitor (ICI) plus VEGF-TKI combination or ICI-ICI combination. Nephrotoxic events were defined as proteinuria, hypertension, blood creatinine increase, acute kidney failure or nephritis, which were all described separately. Results: Five studies satisfied our inclusion criteria. Combination of ICI with VEGF-TKI showed a statistically significant higher degree of proteinuria compared to VEGF-TKI alone. There was no statistically significant difference in rates of hypertension between ICI-TKI and VEGF-TKI alone, but VEGF-TKI alone was statistically significantly more associated with hypertension than immunotherapy alone. Other renal toxicities, such as an increase in creatinine, acute kidney injury (AKI) and nephritis, were uncommon and not consistently reported in each trial. Conclusions: Contemporary regimens for first-line treatment of mRCC are associated with a higher grade of proteinuria than VEGF-TKI alone, while VEGF-TKI is more associated with hypertension than an ICI-ICI combination. Description of many renal toxicities across the studies reported have been diverse and a standardized definition across clinical trials would be helpful to reliably interpret the data regarding nephrotoxicity in the setting of treatment of renal cell carcinoma. Show more

Keywords: Renal cell carcinoma, nephrotoxicity, renal failure, immunotherapy, proteinuria, hypertension

DOI: 10.3233/KCA-230018

Citation: Kidney Cancer, vol. 7, no. 1, pp. 147-159, 2023

Authors: Gottlich, Harrison C. | Nabavizadeh, Reza | Dumbrava, Mihai | Pessoa, Rodrigo Rodrigues | Mahmoud, Ahmed M. | Garg, Ishita | Orme, Jacob | Costello, Brian A. | Cheville, John | Lucien, Fabrice

Article Type: Review Article

Abstract: Background: Approximately 30% of renal cell carcinoma (RCC) cases present with de novo metastatic disease, while 20% to 30% of those with localized disease will develop metastases following surgical resection. Various drug classes have been investigated to treat RCC, including cytokine-based therapies, small molecule Vascular Endothelial Growth Factor (VEGF) tyrosine kinase inhibitors (TKIs) and antibody-based therapies. Up to 58% of patients fail to respond to primary immune checkpoint inhibitor (ICI) therapy, and nearly all initial responders experience disease progression due to the development of secondary resistance. Consequently, novel treatment options are being investigated. Objective: Review the rapidly evolving …ADC therapeutic landscape in metastatic RCC including recent trials, emerging ADCs targets, and future directions for ADCs in the treatment of advanced RCC. Methods: Literature review using the MEDLINE database on important trials and presentations from the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO) conferences. Key words used included “renal cell carcinoma,” “RCC,” “metastatic RCC,” “advanced RCC,” “antibody-based therapies,” “immunotherapy,” “clinical trials,” and “emerging drugs.” Specifically for review of ADCs in RCC, the following search string was used with additional review of bibliographies from retrieved papers: “((antibody drug conjugate) OR (antibody-dependent cellular cytotoxicity) OR (chimeric antigen receptor)) AND ((kidney cancer) OR (renal cell carcinoma))”. Results: Several promising targets including MMP14, EGFR, MCT4, CA9, MET, CDH13, B7-H3, and PSMA were identified with relevant preclinical and clinical studies reviewed. Conclusions: While ADCs therapeutics have not shown benefit to date for renal cell carcinoma, there are ample promising candidates and targets for future research. Show more

Keywords: Renal cell carcinoma, antibody-drug conjugates, clinical trials, therapeutic targets, targeted therapies

DOI: 10.3233/KCA-230012

Citation: Kidney Cancer, vol. 7, no. 1, pp. 161-172, 2023