Emerging Technologies in Prostate Cancer Radiation Therapy: Improving the Therapeutic Window

Matthew C. Biagioli, MD, MS; Sarah E. Hoffe, MD

Disclosures

Cancer Control. 2010;17(4):223-32. 

In This Article

Abstract and Introduction

Abstract

Background: Radiation therapy is a standard of care in the treatment of prostate cancer. Relatively recent advances in technologies in the delivery of radiation therapy are altering our current approach to treatment of prostate cancer.
Methods: This review discusses the results of retrospective, prospective, and randomized clinical trials that have evaluated clinical outcomes in prostate cancer treated with newer radiation therapy technologies.
Results: Randomized trials have demonstrated that higher doses of radiation therapy improve clinical outcomes but with increased toxicity to normal tissue. The introduction of more conformal radiation therapy techniques such as intensity-modulated radiation therapy, proton therapy, stereotactic body radiotherapy, and brachytherapy have allowed for further dose escalation with simultaneous reduction in toxicity. However, use of more conformal treatments requires a better understanding of prostate motion and the ability to track prostate movements in real time.
Conclusions: Technological advancements have improved radiation dose delivery to the prostate and have reduced normal tissue toxicity. Randomized trials are warranted to ultimately evaluate clinical benefit and outcomes.

Introduction

Over the past 20 years, multiple randomized trials have demonstrated that the delivery of higher doses of radiation in the treatment of localized prostate cancer results in improved tumor control.[1–6] Standard radiation doses have been shown to be inferior to doses ≥ 76 Gy in terms of biochemical-free survival (bFS) and local control. However, conventional techniques used for dose escalation have resulted in higher toxicities to pelvic organs, especially rectal and bladder morbidity.[7–9]

In the 1980s, improvements in radiation therapy planning software, as well as the introduction of computed tomography (CT)-based planning, led to the development of three-dimensional conformal radiation therapy (3D CRT). The use of 3D CRT in prostate cancer permitted further dose escalation strategies with improved sparing of normal tissue. For the first time, radiation oncologists were able to compare different treatment plans by evaluating the doses received to 3D volumes of tissue, a relationship portrayed in a dose-volume histogram. However, even with these improvements, available technology still limited the optimal escalation of prostate dose in the setting of adjacent normal bladder and rectal tissue.

By the mid-1990s, further developments of treatment planning software, coupled with the integration of multileaf collimators (ie, mechanized radiation beam shaping devices), allowed for the introduction of a more conformal treatment modality — intensity-modulated radiation therapy (IMRT). With this technique, the radiation beam is divided into individual beamlets so that differences in position of tumor vs normal tissue can be exploited with varying doses. Planning is facilitated by assigning maximal doses to the targets at risk and assigning minimized doses to normal tissue volumes. IMRT, which has arguably become the standard of care for external beam prostate radiation therapy, has permitted not only further prostate dose escalation beyond 81 Gy[10–12] but also a better understanding of the relationship between doses to specific volumes of organs at risk and their reduced morbidity.[10,13,14]

With the introduction of more conformal radiation therapy techniques, it became apparent that daily prostate movement could result in inaccuracies with treatment delivery, thus producing geographical target misses. Prostate motion necessitated investigations into different imaging modalities for daily prostate localization now known as image-guided radiation therapy (IGRT). Most recently, all of these technologies have culminated in the recent experimentation with short courses of very conformal radiation therapy employing extremely high radiation doses per individual treatment known as stereotactic body radiation therapy (SBRT). Additionally, the development of proton acceleration for clinical use, now increasingly available to the general population, has provided an alternative to standard x-ray treatments. Furthermore, improved imaging technologies have advanced the conformal application of internally applied prostate radiation used in brachytherapy.

This review summarizes the body of literature supporting the use of dose escalation in the treatment of prostate cancer and in the use of conformal treatments such as IMRT to reduce associated toxicities. Furthermore, we review current data supporting the use of imaging technologies currently employed to account for prostate motion. Lastly, we discuss alternative forms of radiation therapy, including brachytherapy, proton therapy, and the recent emergence of prostate cancer SBRT.

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