Renal Cell Carcinomas: Radiotherapy, Clinical Application, Radio-Sensitivity and Dose-Response

Abstract

Renal cell carcinoma (RCC) is traditionally considered to be a ‘‘radioresistant’’ malignancy. Surgery has been the mainstay of treatment in the management of primary RCC, from open to laparoscopic and more recently robotic radical nephrectomy. For selected patients, nephron-sparing partial nephrectomy is performed. Other local therapy options include radiofrequency ablation (RFA), cryoablation, and other ablative procedures. Adjuvant radiotherapy after nephrectomy in high-risk patients has been shown to improve local control but not overall survival. These patients have high propensity for developing distant metastases which may explain the lack of survival benefits with adjuvant radiotherapy. In addition, it is also very difficult to deliver high dose radiation with conventional technique because of the radiation tolerance of normal tissues, especially the small bowels. With the approved use of various effective targeted agents, patients with high risk and metastatic RCC are now surviving longer and the role of local therapy for both primary and metastatic RCC has also become more important. Stereotactic radiosurgery (SRS) has been shown to be very effective in the management of RCC brain metastases. Extracranially, conventional radiotherapy has played an important role in the palliation of meta static RCC associated symptoms such as pain. Stereotactic body radiation therapy (SBRT), a continuum of technological advances in SRS from intracranial to extracranial application, has now evolved to show promise in the local management primary RCC, local recurrence, and various meta static sites. In summary, due to advancements in technology that allow for the precise delivery of high-dose RT targeted at the tumor, metastasis-directed RT in mRCC has emerged as a strategy to either mitigate or delay systemic treatment, or to enhance survival when used in conjunction with TKIs and ICBs. While this review primarily discussed SABR as the form of RT for patients with mRCC, it is important to note that not only SABR, but also various RT dose-fractionation regimens delivering higher (ablative) doses, can be utilized for this purpose. In this context, the treating radiation oncologist must strike a careful balance between the tumor control probability and the normal tissue complication probability. Future studies should aim to establish the optimal RT dose fractionation and the best sequence for combining it with systemic treatments. Factors such as the probability of local and overall disease control, antitumor immunity, and the risk of toxicity should all be considered in a comprehensive manner.