Kidney Cancer - Volume 6, issue 2

Authors: Dawsey, Scott J. | Gupta, Shilpa

Article Type: Review Article

Abstract: BACKGROUND: Hereditary renal cell carcinoma (RCC) is a complex and rapidly evolving topic as there is a growing body of literature regarding inherited syndromes and mutations associated with an increased risk of RCC. OBJECTIVES: We sought to systematically review 13 hereditary syndromes associated with RCC; von Hippel-Lindau Disease associated RCC (VHLRCC), BAP-1 associated clear cell RCC (BAPccRCC), Familial non-von Hippel Lindau clear cell RCC (FccRCC), Tuberous Sclerosis Complex associated RCC (TSCRCC), Birt-Hogg-Dub e ´ Syndrome associated RCC (BHDRCC), PTEN Hamartoma Tumor Syndrome associated RCC (PHTSRCC), Microphthalmia-associated Transcription Family translocation RCC (MiTFtRCC), RCC with …Chromosome 6p Amplification (TFEBRCC), Autosomal Dominant Polycystic Kidney Disease associated RCC (ADPKDRCC), Hereditary Leiomyomatosis associated RCC (HLRCC), Succinate Dehydrogenase RCC (SDHRCC), Hereditary Papillary RCC (HPRCC), and ALK-Rearrangement RCC (ALKRCC). RESULTS: Hereditary RCC is generally associated with an early age of onset, multifocal and/or bilateral lesions, and aggressive disease course. VHLRCC, BAPccRCC, FccRCC, and certain mutations resulting in SDHRCC are associated with clear cell RCC (ccRCC). HPRCC is associated with Type 1 papillary RCC. HLRCC is associated with type 2 papillary RCC. BHDRCC is associated with Chromophobe RCC. TSCRCC, PHTSRCC, MiTFtRCC, TFEBRCC, ADPKDRCC, certain SDHRCC and ALKRCC have variable histology. CONCLUSIONS: There has been tremendous advancement in our understanding of the pathophysiology of hereditary RCC. Ongoing research will refine our understanding of hereditary RCC and its therapeutic targets. Show more

Keywords: von Hippel-Lindau disease, Birt Hogg Dubé, kidney cancer, genetic susceptibility, genetic disease, RCC

DOI: 10.3233/KCA-210008

Citation: Kidney Cancer, vol. 6, no. 2, pp. 83-93, 2022

Authors: Zondervan, Patricia J. | Bex, Axel

Article Type: Review Article

Abstract: Upfront cytoreductive nephrectomy (CN) was the standard treatment for selected patients with metastatic Renal Cell Carcinoma (RCC) in the cytokine era for many years. In the recent ‘targeted therapy era’ it has been re-challenged by both the CARMENA and SURTIME trials. As first-line therapy for treatment-naive metastatic clear-cell RCC has now changed to immune checkpoint inhibitor combination therapy (ICI), and previous studies concerning CN were built in the targeted therapy era, the role and sequence of CN needs to be revisited. Here we address what we have learnt from both trials and how future trials should be designed to investigate …CN. Show more

Keywords: Metastatic renal cell carcinoma, cytoreductive nephrectomy, targeted therapy, immune checkpoint inhibitor combination therapy

DOI: 10.3233/KCA-220004

Citation: Kidney Cancer, vol. 6, no. 2, pp. 95-103, 2022

Authors: Parikh, Mamta | Lara, Primo N.

Article Type: Article Commentary

DOI: 10.3233/KCA-229003

Citation: Kidney Cancer, vol. 6, no. 2, pp. 105-107, 2022

Authors: Ghatalia, Pooja | Shah, Aangi | Slifker, Michael

Article Type: Brief Report

Abstract: BACKGROUND: Predictive immune signatures such as the T-effector, the 26-gene “Renal 101 Immuno signature” and the 18-gene T-cell inflamed gene expression profile were developed in clinical trials enrolling predominantly Caucasians and there is a dearth of literature comparing tumor biology between African American (AA) and Caucasian patients. OBJECTIVE: To compare the immune gene signature expression in AA (n  = 55) and Caucasian (n  = 457) patients. METHODS: Raw gene expression count data were downloaded from the TCGA KIRC dataset and tumor samples from “white” and “black or AA” patients were selected. The gene expression values of the immune …signatures were VST-transformed normalized counts and compared between the groups. RESULTS: There were 457 Caucasian and 55 AA patients in the TCGA. The immune gene expression in all three signatures was significantly lower in AA patients compared to Caucasians (p  < 0.05). We validated our findings in an independent dataset using Nanostring Immune Profile Panel. Since the majority of AA tumors in TCGA were stage I (71%), we compared gene expression between stage I AA tumors (n  = 39) with stage I Caucasian tumors (n  = 220). Once again, the immune gene expression was significantly lower in AA patients compared to Caucasians (p  < 0.05), indicating differences in tumor biology between the races. CONCLUSIONS: Low expression of predictive immune gene signatures in AA compared to Caucasian patients indicates a possible difference in the biology of their tumors. Future studies are needed to validate our findings in other datasets and to study the predictive role of these signatures in AA patients. Show more

Keywords: Kidney cancer, gene expression, TCGA, African American

DOI: 10.3233/KCA-220003

Citation: Kidney Cancer, vol. 6, no. 2, pp. 109-114, 2022

Authors: Palma dos Reis, Ana Filipa | Simão, Diana | Odeny, Thomas | Rodrigues, Chiara | Fontes-Sousa, Mário | da Luz, Ricardo | Chowdry, Rajasree Pia | Welsh, Sarah J. | Paller, Channing | Barata, Pedro C.

Article Type: Systematic Review

Abstract: BACKGROUND: Immune checkpoint inhibitors (ICI) have emerged as active therapies in the management of advanced RCC. While multiple studies have shown clinical activity of ICIs in clear cell histologies, the evidence to support their use in non-clear cell (ncc) subtypes is based on smaller prospective trials and retrospective analyses. OBJECTIVE: The objective of this review is to summarize the clinical outcomes of ICI-based therapies in ncc-subtypes and in tumors with sarcomatoid/rhabdoid features. METHODS: We performed a systematic literature search using PubMed, Google Scholar and ASCO databases. The keywords “renal cell cancer” and “immune checkpoint inhibitors” and …equivalents were used and all original publications between July 2016 and July 2021 were included. RESULTS: We included a total of 14 publications, including two clinical trials and 12 case series. The most frequent histologies were papillary (up to 75-100%), unclassified (up to 34%) and chromophobe (up to 28%). ICI monotherapy showed some activity in both 1st and 2nd line with response rates up to 27%. ICI combination regimens yielded better activity than ICI monotherapy but, overall, a heterogeneous efficacy was noted across histologies. Overall, outcomes of ICIs were superior in tumors with sarcomatoid/rhabdoid features. CONCLUSION: The observed activity of ICI-based therapies was heterogeneous. Combination regimens, papillary subtype and sarcomatoid/rhabdoid features were associated with higher responses. These findings might help treatment decisions and require further validation. Show more

Keywords: Non clear cell renal cell cancer, advanced, immunotherapy, immune checkpoint inhibitor, systematic review

DOI: 10.3233/KCA-210012

Citation: Kidney Cancer, vol. 6, no. 2, pp. 115-127, 2022

Authors: Gonçalves, Vinicius Knackfuss | Monteiro, Fernando Sabino Marques | Gazola, Antonia Angeli | Pizzolo, Felipe | Hübner, Júlia Elisa | Pellegrini, Rodrigo | Borba, Alessandra | Fay, André P.

Article Type: Systematic Review

Abstract: BACKGROUND: Immune checkpoint inhibitors (ICI) have shown clinical benefit among patients with advanced kidney cancer. Their cost burden hardens its access, especially in low- and middle-income countries. To set solutions, the impact of geographical and socioeconomic differences in the clinical outcomes and survival of renal cell carcinoma (RCC) patients needs to be explored. OBJECTIVE: This review aimed to understand if geographical differences affected the clinical outcomes of RCC patients receiving immunotherapy. METHODS: This study reviewed 45 studies that examined the OS and PFS of RCC patients undergoing ICI (2010–2020) selected from a 3028-study database search conducted …on PubMed and grey literature. The selected studies were divided into groups: Asia, multicentric studies, Europe and Anglo-America. The lethality and income of the geographical locations were measured and discussed. RESULTS: Weighted average (WAVG) of mPFS and mOS were 8,47 months, and 40,6 months in Asia. The WAVG of mOS were 12.2 months, and 20.22 months in the Anglo-American population (15 studies; 943 patients). In multicentric studies (4 studies; 1834 patients) the WAVG mPFS was 10,06. European group (13 studies; 3143 patients) had 6.1 and 20.24 months mPFS and mOS, respectively. The exploratory analysis on income and RCC lethality has shown an absolute decline of 8.7% (CI 10.1 to 7.3% - p  < 0.05) in RCC lethality, when income is raised by 100%. CONCLUSION: Clinical benefit from ICI varies across the globe. A wide access to ICI, and evaluation of biological aspects of the disease will allow a better understanding of the impact of geographic regions in the clinical outcome of patients receiving ICI and the etiology of potential differences. Show more

Keywords: Kidney neoplasms, immune checkpoint inhibitors, molecular targeted therapy, renal cell carcinoma, progression-free survival, health services accessibility, treatment outcomes, clinical trials

DOI: 10.3233/KCA-210124

Citation: Kidney Cancer, vol. 6, no. 2, pp. 129-136, 2022

Authors: Köditz, Barbara | Heidenreich, Axel | von Brandenstein, Melanie

Article Type: Systematic Review

Abstract: BACKGROUND: Renal cell carcinoma is the 9th most common malignant disease in the Western World. Typically, patients develop symptoms in a late stage of the disease and most of them are diagnosed by chance. Up to 30% of the patients at the time of diagnosis had metastatic disease. Therefore, highly specific and sensitive biomarkers for the detection and progression of kidney cancer are of great importance. Here, urine markers can be a major advantage and can have a huge clinical impact on the diagnosis, differentiation and prognosis of kidney cancer. At the moment there are several approaches to improve these …conditions.. METHODS: A systematic literature research was performed according to the PRISMA guidelines to identify studies reporting urine markers for kidney cancer between 2012 and 2021. A two-step process for the selection of the studies was initiated. In total 287 studies were considering for the final analysis. In total, 6 studies, which presented potential urinary biomarker were analyzed in depth. RESULTS: The major focus was on urinary markers for the detection, progression and differentiation of renal cell carcinoma. In total, a study population of 1099 patients were investigated in the different studies that were analyzed in depth. The median patient sample size of the different studies was 157 patients. The focus was based on the investigation of different microRNAs and proteins as urinary marker for kidney cancer detection. CONCLUSION: Overall, there are different approaches present for the detection, prognosis and differentiation of kidney cancer in urine but most of the studies are based on a small sample size and need to be validated in a greater collective. Furthermore, the standard should be improved to bring these biomarkers into routine clinical practice. Show more

Keywords: Renal cell carcinoma, detection, progression, differentiation, markers, urine

DOI: 10.3233/KCA-220005

Citation: Kidney Cancer, vol. 6, no. 2, pp. 137-142, 2022

Authors: Parikh, Mamta

Article Type: Other

DOI: 10.3233/KCA-229002

Citation: Kidney Cancer, vol. 6, no. 2, pp. 143-144, 2022