EBRT for prostate cancer has evolved dramatically since the mid-1980s. Traditionally, bony landmarks were used to delineate field boundaries designed to encompass the pelvic lymph nodes, prostate and seminal vesicles (also known as a 4-field “box” technique). Using these fields, large volumes of normal tissue were irradiated. This limited the radiation dose that was safely deliverable to the prostate to 64 to 70 Gy and doses above these levels were associated with a significant morbidity risk, particularly with respect to the rectum and bowel (Smit et al. 1990). Newer techniques which use three-dimensional treatment planning and delivery such as 3D CRT and IMRT have refined EBRT markedly allowing more precise treatment delivery leading to more effective treatment with improved tumor control and morbidity outcomes.

Five randomized trials have been reported to date demonstrating a clear advantage to dose-escalated EBRT in terms of biochemical control and are discussed further in another section. Although there remains some controversy over which patients benefit most from dose escalation, it appears that intermediate and higher risk groups may derive a larger benefit (Kim et al. 2012; Pollack et al. 2002).

Despite improvements achieved by dose escalation with 3D CRT, increasing radiation dose came at a cost. Approximately 15–35 % of patients receiving doses ≥70 Gy developed grade ≥2 rectal toxicity (Dearnaley et al. 2007; Kuban et al. 2008; Zietman et al. 2010). In the M.D. Anderson randomized trial comparing 70 and 78 Gy, grade ≥2 gastrointestinal toxicity rates were observed in 13 and 23 % of patients, respectively (Pollack et al. 2002). Peeters et al. reported an increased rate of rectal bleeding requiring laser/transfusion (p = 0.07) in patients treated to 78 Gy compared with 68 Gy (Peeters et al. 2006). Urinary morbidity has been less consistently altered by dose escalation with some studies showing similar outcomes (Michalski et al. 2010) and some showing worse toxicity with dose escalation (Dearnaley et al. 2007).

In order to further establish the benefits of dose escalation, the Memorial Sloan-Kettering Cancer Center initiated a phase I/II protocol in 1988, whereby the prescription dose was increased from 64.8 to 86.4 Gy in successive increments of 5.4 Gy (Leibel et al. 1994; Zelefsky et al. 1998). In 1996, IMRT was introduced as a therapeutic tool to overcome the increased rectal toxicity seen with dose escalation using 3D-CRT at doses ≥75.6 Gy. The first report demonstrating the potential benefits of IMRT over 3D conformal approaches was published by Zelefsky et al. in 2000 (Zelefsky et al. 2000). In that study, 61 patients received 81 Gy with 3D-CRT and 171 patients received the same dose with IMRT. Twenty randomly selected patients were planned with both IMRT and 3D-CRT. Toxicity and dosimetric analyses comparing the two techniques demonstrated that IMRT resulted in better coverage of the CTV by the prescription dose than 3D-CRT (p < 0.01) and reduced the volumes of rectal and bladder walls receiving 75 Gy (p < 0.01). Clinically, this translated into a reduced rate of late grade 2 and 3 rectal bleeding in the IMRT group (2 vs. 10 %, p < 0.001). In 2002, Zelefsky et al. reported the safety of delivering doses of 81 Gy to the prostate using IMRT in a larger cohort of 772 patients (Zelefsky et al. 2002). In that series, the 3-year actuarial likelihood of developing grade ≥2 late genitourinary and gastrointestinal toxicity was 15 and 4 %, respectively. Although at the time follow-up was limited, IMRT resulted in at least equivalent biochemical control rates as non-IMRT approaches, quelling concerns that IMRT may result in underdosing of the target due to constricted dose distributions. In a recent update of these data with a median follow-up of 7 years, the 8-year likelihood of developing grade ≥2 late genitourinary and gastrointestinal toxicity was 15 and <2 %, confirming the long-term safety of this treatment (Cahlon et al. 2008). In addition, biochemical control rates remained excellent with 8-year actuarial PSA relapse-free survival rates for patients in favorable, intermediate, and unfavorable risk groups of 89, 78, and 67 %, respectively (p = 0.0004).

Others have found similar benefits of dose-escalated IMRT. Vora et al. reported biochemical and toxicity outcomes of dose-escalated IMRT (75.6 Gy) compared with conventional doses (68.4 Gy) in a series of 272 patients and found a 14 % improvement in 5-year biochemical control in the high dose group (Vora et al. 2007). Higher dose IMRT was well tolerated as there were no significant differences in toxicity between the two groups. In a series of 133 patients treated with 74–76 Gy using IMRT reported by De Meerleer et al., toxicity was also noted to be low with 17 and 19 % of patients experiencing late grade 2 GI and GU toxicity, respectively (De Meerleer et al. 2007). Additionally, biochemical outcome was excellent with 3-year biochemical control rates of 100, 94, and 74 % for low-, intermediate-, and high-risk patients, respectively.

The most updated analysis of the MSKCC dose escalation experience has recently been reported including over 1,000 patients treated with IMRT to a dose of 86.4 Gy (Spratt et al. 2013). With a median follow-up of 5.5 years, the 7-year biochemical relapse-free survival rates were 98.8, 85.6, and 67.9 % for low-, intermediate-, and high risk patients, respectively. Late toxicity was minimal with <1 and 2.2 % of patients experiencing late grade 2 or higher GI and GU toxicity, respectively. The rate of acute grade 2 of higher GI and GU toxicity was 4.4 and 21.1 %, respectively.

The development of three-dimensional treatment planning techniques has significantly improved the accuracy of EBRT. Dedicated treatment planning CT and MRI scanners in radiation oncology simulation suites allow the capture of complete volumetric anatomical information which can be directly imported into the treatment planning software. Radiation therapy treatment plans are generated by a careful definition of the target and normal tissues from which customized beams can be individually shaped allowing better shielding of organs at risk. The dose distributions can then be analyzed either graphically in a dose–volume histogram (DVH) or on axial, sagittal, and/or coronal CT images. By using volumetric parameters to evaluate dose, a more careful and complete analysis of target and normal tissue dose distribution is achievable.