Stereotactic Body Radiotherapy for Low- and Intermediate-Risk Prostate Cancer

With over a decade׳s worth of clinical experience to guide stereotactic body radiotherapy (SBRT) for the treatment of clinically localized prostate cancer (PCa), sufficient data exist for robust conclusions to be made regarding its efficacy and the toxicities associated with this treatment. We briefly review the fundamental radiobiological basis of SBRT for PCa and provide a comprehensive synthesis of the medical literature to date, focusing on clinical outcomes and toxicities. When possible, we draw comparisons to comparable data for conventionally fractionated radiotherapy. Finally, a brief overview of technical considerations is presented. Although randomized clinical trials comparing SBRT with conventionally fractionated radiotherapy are underway, the current body of evidence supports the efficacy and safety of SBRT for PCa.

Introduction

Radiotherapy (RT) has long been considered as a standard treatment option for localized prostate cancer (PCa). Stereotactic body radiotherapy (SBRT)—a unique form of RT in which a small number (≤5) of fractions, each of comparatively high dose, are delivered to the target volume using highly conformal techniques to minimize dose to adjacent organs-at-risk—is primed for use in PCa, given that classical radiobiology analyses have suggested that PCa appears to be particularly sensitive to large doses of radiation per fraction. The clinical evidence supporting SBRT in the treatment of low- and intermediate-risk PCa is predominantly derived from single-institution prospective studies, multi-institutional phase I and II trials, and pooled consortium data. As a result of the promising biochemical recurrence-free survival (BCRFS) outcomes of these studies, the American Society for Therapeutic Radiology and Oncology (ASTRO) model policy update in 2013 recognized SBRT as an alternative to conventionally fractionated RT for PCa, noting “SBRT could be considered an appropriate alternative for select patients with low- to intermediate-risk disease.”¹ Since 2014, the National Comprehensive Cancer Network guidelines have stated that “extremely hypofractionated image-guided intensity-modulated radiotherapy (IMRT) or SBRT regimens (6.5 Gy per fraction or greater) are an emerging treatment modality with single institutional and pooled reports of similar efficacy and toxicity to conventionally fractionated regimens. They can be considered as a cautious alternative to conventionally fractionated regimens at clinics with appropriate technology, physics, and clinical expertise (for low- and intermediate-risk PCa).”²

In addition to the aforementioned theoretical radiobiological advantages to SBRT for PCa, economic considerations are also worthy of discussion, given the increasing incidence of PCa and the projected $18.53 billion annual cost of PCa care in 2020.3, 4 A recently published time-driven activity-based costing analysis of various treatment modalities for low-risk PCa estimated the average cost of a course of IMRT to be $23,565 vs $8978 for low-dose rate (LDR) brachytherapy and $11,665 for SBRT.⁵ A Markov decision model also found that the average cost of SBRT was substantially lower than IMRT ($22,152 vs $35,431), as did a Medicare claims analysis ($13,645 vs $21,023).6, 7

In this review, we review the basic radiobiological rationale for SBRT for PCa, as well as the evidence for its clinical efficacy in low- and intermediate-risk PCa. We also discuss the toxicity profile of SBRT in detail, and provide a sample protocol.