Preface

**Section 3 Medical Management of Kidney Cancer 135**

Chapter 9 **Medical Management of Renal Cell Cancer 155**

Chapter 10 **Current Role of Adjuvant Therapy in High Risk for Recurrence**

Chapter 11 **Surgical Strategy for the Management of Renal Cell Carcinoma with Inferior Vena Cava Tumor Thrombus 197**

Fadil Hassan, Shahid Lambe, Kiran Sharma and Anil Kapoor

Cheng Peng, Liangyou Gu, Luojia Yang, Baojun Wang, Qingbo Huang, Dan Shen, Songliang Du, Xu Zhang and Xin Ma

Mohammed Kamil Quraishi, Edward Ramez Latif, Milan Thomas,

Jennifer Turner, Adrian Simoes, Albert Edwards and Rakesh Raman

Chapter 8 **Target Therapy for Kidney Cancer 137** Yang Wang and Lingxiang Liu

**VI** Contents

**Resected Kidney Cancer 173**

**Section 4 Surgical Approach to Kidney Cancer 195**

Chapter 12 **Focal Therapy in Kidney Cancer 211** Manar Malki and Amr Emara

**Approach 223**

**Techniques 235**

Chapter 13 **Robotic Surgery and Successful Set-Up: A Stepwise**

Chapter 14 **Robot-Assisted Partial Nephrectomy: Evolving**

Christopher J. Anderson and Hiten R.H. Patel

Ben Eddy, Elio Mazzone and Alexandre Mottrie

Ours is an exciting time. At no other time in history has there been such an exponential in‐ crease in our understanding of disease processes through research and innovation. Kidney cancer is no exception. The recent propulsion and coupling of technological advances and targeted drug therapy in the management of kidney cancer has ushered with it a plethora of significant advances in our current approach. However, kidney cancer continues to impose a significant cancer burden and its incidence continues to rise globally. Mortality in ad‐ vanced kidney cancer remains high despite oncological, surgical and multimodal optimisa‐ tion. Genetic associations, heterogeneity and limitations in early diagnosis through lack of optimal biomarkers and early detection tools add to the challenges.

This book is the first in a series that aims to act as a primer and to provide the reader with a comprehensive and up-to-date framework to optimise understanding and stimulate further research and innovation. The chapters were written by a global faculty of leading experts in the respective fields with a multidisciplinary approach. The authorship includes scientists, pathologists, engineers, surgeons, radiologists, oncologists and innovators. The focus of the book is broad and includes genetics, immunology, virtual augmented reality, surgical simu‐ lation and robotic surgery. Some chapters explore leading edge concepts while others cap‐ ture the evolving trends and future concepts.

The Editors would like to acknowledge the respective authors and sponsors for their hard work and support in generating this book.

#### **Dr. Sashi S. Kommu**

Associate Professor in Uro-oncology and Cancer Biology School of Biosciences, University of Kent Consultant Urological and Minimally Invasive Surgeon East Kent Hospitals University NHS Foundation Trust National Institute for Health Research (NIHR) Lead for Surgery in Kent, Surrey and Sussex, UK

#### **Dr. Inderbir S. Gill**

Chair and Distinguished Professor of Urology Shirley and Donald Skinner Chair in Urologic Cancer Surgery Executive Director, USC Institute of Urology Associate Dean for Clinical Innovation University of Southern California (USC) Los Angeles, California, USA

**Section 1**

**Genetic Susceptibility and Immunotherapy**

**Genetic Susceptibility and Immunotherapy**

**Chapter 1**

**Provisional chapter**

**Genetic Susceptibility to Kidney Cancer**

According to the latest knowledge, hereditary kidney cancers may account for 5–8% of all kidney cancers, and it may be more common than previously thought. Hereditary RCC is often characterized by an early age of onset (approximately 45 years), typical histological pattern, and frequently the bilaterality and multicentricity of the primary tumor. Wilms' tumor (nephroblastoma) is the most common kidney tumor of childhood. More than 15 syndromes with inherited susceptibility to kidney cancer are known, and there are over 25 known genes associated with them. Most of these are dominantly inherited in which the offspring of the proband has a 50% chance of inheriting a gene mutation with susceptibility to kidney cancer. The aggressiveness of hereditary RCCs and recommended surgery varies depending on the syndrome and mutation type. Also, systemic therapy may be optional. Multigene next generation sequencing (NGS) panel technology allows genes of interest to be studied quickly and cost-effectively. Sequencing investigations have improved the accuracy of hereditary cancer diagnoses. Diagnostic utility has been hugely increased by multigene NGS panels. It is important to identify hereditary cancer susceptibility, because the risk of cancer in the mutation carriers can be reduced. In this review article, the latest literature on syndromes subjecting to hereditary kidney cancer and

DOI: 10.5772/intechopen.91933

**Keywords:** von Hippel-Lindau, hereditary papillary RCC, hereditary leiomyomatosis and RCC, Birt-Hogg-Dubé, Wilms' tumor, hereditary kidney cancer syndromes,

Kidney cancer is the 16th most common cancer worldwide with over 400,000 cases in 2018 representing approximately 2.2% of all diagnosed malignancies worldwide [1]. The majority of primary renal malignancies are renal cell carcinomas (RCCs) with most of the remaining comprising upper tract urothelial carcinoma (UTUC). The mean age of onset of RCC is

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

**Genetic Susceptibility to Kidney Cancer**

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

recommended follow-up is summarized.

genetic susceptibility

**1. Introduction**

Minna Kankuri-Tammilehto

Minna Kankuri-Tammilehto

**Abstract**

http://dx.doi.org/10.5772/intechopen.91933

#### **Genetic Susceptibility to Kidney Cancer Genetic Susceptibility to Kidney Cancer**

#### Minna Kankuri-Tammilehto Minna Kankuri-Tammilehto

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.91933

#### **Abstract**

According to the latest knowledge, hereditary kidney cancers may account for 5–8% of all kidney cancers, and it may be more common than previously thought. Hereditary RCC is often characterized by an early age of onset (approximately 45 years), typical histological pattern, and frequently the bilaterality and multicentricity of the primary tumor. Wilms' tumor (nephroblastoma) is the most common kidney tumor of childhood. More than 15 syndromes with inherited susceptibility to kidney cancer are known, and there are over 25 known genes associated with them. Most of these are dominantly inherited in which the offspring of the proband has a 50% chance of inheriting a gene mutation with susceptibility to kidney cancer. The aggressiveness of hereditary RCCs and recommended surgery varies depending on the syndrome and mutation type. Also, systemic therapy may be optional. Multigene next generation sequencing (NGS) panel technology allows genes of interest to be studied quickly and cost-effectively. Sequencing investigations have improved the accuracy of hereditary cancer diagnoses. Diagnostic utility has been hugely increased by multigene NGS panels. It is important to identify hereditary cancer susceptibility, because the risk of cancer in the mutation carriers can be reduced. In this review article, the latest literature on syndromes subjecting to hereditary kidney cancer and recommended follow-up is summarized.

DOI: 10.5772/intechopen.91933

**Keywords:** von Hippel-Lindau, hereditary papillary RCC, hereditary leiomyomatosis and RCC, Birt-Hogg-Dubé, Wilms' tumor, hereditary kidney cancer syndromes, genetic susceptibility

## **1. Introduction**

Kidney cancer is the 16th most common cancer worldwide with over 400,000 cases in 2018 representing approximately 2.2% of all diagnosed malignancies worldwide [1]. The majority of primary renal malignancies are renal cell carcinomas (RCCs) with most of the remaining comprising upper tract urothelial carcinoma (UTUC). The mean age of onset of RCC is

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited. © 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

approximately 60–70 years. The most common kidney tumor of childhood is Wilms' tumor (nephroblastoma). In the European Union, the estimated annual number of new kidney cancers is approximately 46,000 [2]. Etiologic risk factors for kidney cancer development are male sex, obesity, and tobacco, in addition to hypertension [3–5], acquired cystic kidney disease [6], and inherited susceptibility. Prognostic factors of different protein and gene expressions in RCC have been studied [7, 8].

According to the latest knowledge, hereditary kidney cancers may account for 5–8% of all kidney cancers [9], and it may be more common than previously thought [10]. In those RCC patients without clear cell RCC (ccRCC) subtype, the amount of germline high-risk mutations is greater, 12% [11]. Susceptibility to kidney cancer may be caused by high-risk, moderate-risk, or low-risk gene mutation [12]. Even the carriership of high-risk gene mutation does not always lead to kidney cancer. The risk for kidney cancer (penetrance) varies in different syndromes. In some cases, the predisposed genetic factor to kidney cancer is chromosomal aberration, for example, as in constitutional chromosomal 3 translocation with 6 or 8 of family (**Table 2**). In hereditary cancer, the impact of environmental factors is small.

More than 15 syndromes with inherited susceptibility to kidney cancer are known, and there are over 25 known genes associated with them. Most of these are dominantly inherited in which the offspring of the proband has a 50% chance of inheriting a gene mutation with susceptibility to kidney cancer.
