Radiation therapy in renal cell carcinoma

https://doi.org/10.1016/j.critrevonc.2018.06.002Get rights and content

Highlights

  • Historically, the renal cell carcinoma (RCC) is considered a radioresistant tumor.

  • Radical surgery is the mainstay treatment approach.

  • Nowadays, hypofractionated radiotherapy (HRT) has gained a growing interest in RCC management.

  • Several topics, such as role, side effects and radioresponsiveness, need to be clarified.

  • Based on early clinical trials, HRT seems to be a promising option in RCC management.

Abstract

Renal cell carcinoma (RCC) is classically regarded as extremely resistant to classical fractionated radiation therapy (RT). Nowadays, there is convincing data supporting RCC radiosensitivity to high fraction doses, which may represent an ideal issue for new treatment strategies in primary and oligometastatic RCC disease. This review discusses the role of RT in RCC and its potential therapeutic scenario focusing on the most interesting clinical trials.

Introduction

Traditionally, renal cell carcinoma (RCC) has been considered a radioresistant tumor and therefore radiation therapy (RT) was mainly confined in treatment of metastasis. New advances in RT techniques, including stereotactic irradiation, have made encouraging contributions in the oncologic scenario, opening up new opportunities in RCC management.

This review provides highlights in current RCC strategies to potentially suggest a more tailored treatment approach in clinical daily practice. We firstly summarized the main RCC characteristics and presented a historical overview of RT role in RCC management. Then, we focused on the stereotactic RT and its potential value in RCC treatment. A set of queries, like definitive treatment in primary lesion and oligometastatic disease, and the radiobiological rationale, was pre-formulated as the basis for discussion.

Section snippets

Literature search strategy

All the available literature, including abstracts and full text manuscripts, regarding RT and RCC was reviewed. PubMed search was performed up to April 2018 using the following combinations of research criteria: “radiation therapy”, “radiotherapy”, “stereotactic”, “stereo body”, “ablative”, “surgery”, “nephrectomy”, “renal cell carcinoma”, “kidney cancer”, “metastatic”, “palliative therapy”. Only publications in English were retained. Reference lists of previously published consensus

Overview

Cancer of the kidney represents a rare entity, accounting for approximately 3% of all new malignancies (National Comprehensive Cancer Network, 2017). The vast majority (more than 90%) of kidney cancers are classified as renal cell carcinoma (RCC), arising from the tubular epithelium (National Comprehensive Cancer Network, 2017). The classic presenting signs, including hematuria, abdominal pain and mass, has nowadays shifted into asymptomatic lesion, due to incidental discovery on abdominal

Conventional radiation therapy

RCC has traditionally been an exclusive preserve of the surgeon. Due to the assumption that RCC is a radioresistant tumor, radiotherapy (RT) has long been considered a futile approach to manage primary disease, whereas it is mainly prescribed to treat distant metastasis, especially brain and painful bone metastasis, with a palliative intent (National Comprehensive Cancer Network, 2017).

Extent of the problem

RT does not mean an univocal strategy. At least three different fractionations are possible: i) conventional fractionation (1.8–3 Gy/fraction); ii) hyperfractionation (< 1.8 Gy/fraction); iii) hypofractionation (> 3 Gy/fraction). Nowadays, due to the advent of stereotactic radiation techniques, conventional fractionations are often supplemented by hypofractionation regimens, especially in those patients with limited metastatic disease. Hypofractionated RT refers to high dose per fraction to the

Discussion

With improving therapies for RCC patients, the life expectancies can be expected to increase over the years. Recent results from cranial and extracranial hypofractionated RT data in the palliative RCC setting have caused fresh enthusiasm for the stereotactic RT treatment of patients with oligometastatic or selected primary RCC disease. Stereotactic RT is known to increase clinical outcomes in other areas of the oncologic field and little data still exists on its real value in RCC management.

Future directions

At present, several RCC trials test the possibility of using sterotactic RT in combination with immunotherapy (Anon, 2018a; Anon, 2018b; Anon, 2018j). Details are listed in Table 3. Based on promising results achieved in other cancers, it is reasonable to expect that over the next years important advances in RCC immunotherapy will be made too (De Felice et al., 2015, 2017). There are two main potential advantages in combining sterotactic RT and immunotherapy. Firstly, sterotactic RT to small

Summary

Hypofractionated RT can be considered an efficient and safe approach in patients with oligometastatic RCC and probably in primary setting, especially in case of complex renal lesions and in those patients who refuse or are not candidates for surgery. In addition, the potential role of hypofractionated RT with concomitant immunotherapy should be investigated. This combination could produce synergistic effects, resulting in better response rate and duration, given the known immune-modulated

Funding sources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors’ contributions

Conception and design: All authors

Collection and assembly of data: All authors

Data analysis and interpretation: All authors

Manuscript writing: All authors

Final approval of manuscript: All authors

Acknowledgement

None.

Francesca De Felice was born in Rome in 1983. She graduated from the Faculty of Medicine of the University of Rome “Sapienza” in 2007. She obtained the license to practice medicine in Italy in 2008. She was specialized in Radiation Oncology at the University of Rome “Sapienza” in 2012. In 2013 she was a medical attendant at the Département de Radiothérapie, Institut de Cancérologie Gustave Roussy, Villejuif-Parigi and in 2014 she was a medical attendant at the Division of Clinical Oncology,

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    Francesca De Felice was born in Rome in 1983. She graduated from the Faculty of Medicine of the University of Rome “Sapienza” in 2007. She obtained the license to practice medicine in Italy in 2008. She was specialized in Radiation Oncology at the University of Rome “Sapienza” in 2012. In 2013 she was a medical attendant at the Département de Radiothérapie, Institut de Cancérologie Gustave Roussy, Villejuif-Parigi and in 2014 she was a medical attendant at the Division of Clinical Oncology, Guy’s and st. Thomas’ Hospital, King’s College, London, UK. From 2012 onwards she is a PhD student at the Department of Radiological Sciences, Oncology, and Pathology, University of Rome "Sapienza". She is author of several indexed papers, all in the field of clinical and experimental oncology.

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