Progress in the treatment of localized prostate cancer with external beam irradiation

The efficacy of the conventional 2D technique of radiation treatment planning and delivery is limited by toxicity of normal tissue surrounding the target, such that the radiation dose that can be safely delivered to the prostate by external beam radiotherapy cannot exceed 70-72 Gy. Recent technological advances in radiation treatment planning and delivery have allowed higher doses of radiation (>72 Gy) to be safely delivered to the prostate with corresponding improved outcomes. Over the past decades, high-energy (≥4MV) linear accelerators have gradually replaced Cobalt machines in external-beam radiation therapy delivery. 2D radiation therapy treatment systems have changed to 3D conformal radiation therapy and intensity-modulated radiation therapy computed tomography-based systems, allowing tighter tumor margins and decreasing normal tissue toxicities. By switching to computed tomography-based planning, 3D-conformal radiation therapy provides better relative conformality of dose than conventional external beam irradiation therapy. Intensity-modulated radiation therapy has further refined dose conformality by spreading the low-dose region to a larger volume. Parallel with the development and implementation of 3D-conformal radiation therapy and intensity-modulated radiation therapy, improved precision of both target definition and treatment verification can be accomplished by image guidance systems to correct for interfraction and intrafraction movement of the prostate in real time. However, the potential long-term risks of larger volumes of normal tissues receiving low doses of radiation in intensity-modulated radiation therapy are unknown. Particle beam radiation therapy (PBRT) offers unique dose distributions and characteristics with higher relative biological effect and linear energy transfer. PBRT is believed to be more effective in controlling slowly proliferating tumors such as prostate carcinoma. However, the availability of PBRT is limited and the development of economically operable particle beam radiation therapy facilities in the USA is still in progress. Finally, the addition of hormonal therapy to radiation therapy has been shown to improve outcome in selected patients. Androgen deprivation causes cytoreduction of the prostate cancer (smaller volume treated to high doses), better local control and disease-free survival. Long-term adjuvant androgen deprivation has also been shown to improve overall survival, especially in more advanced tumors.