The long-term data from five randomised trials published between 2005 and 2010 confirmed the advantage of high dose radiation therapy for patients with localised adenocarcinoma of the prostate (Fig. 1).¹

Dearnaley et al. (2005) published the results of a Royal Marsden NHS Trust and Institute of Cancer Research (RMH) phase III dose escalation pilot study. The total of 126 men with localised (T1–T3b) prostate cancer were randomised after an initial 3–6 month period of androgen suppression to deliver a dose of 64 Gy with or without a 10 Gy boost (64 and 74 Gy arms) between 1995 and 1997. The results showed that freedom from PSA failure was higher in the 74 Gy arm compared to the 64 Gy arm, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71 % in the 74 Gy arm vs. 59 % in the 64 Gy arm (p = 0.10). There was no difference in the time to restarting hormone therapy between the randomised groups (5-year actuarial rate 15–16 % in each group).

The following randomised Medical Research Council (MRC) RT01 trial with 843 men with localised prostate cancer (T1–T3a, PSA < 50 nag/mL), which were randomly assigned to escalated dose (74 Gy; n = 422) or standard-dose (64 Gy; n = 421) conformal radiotherapy was published by Dearnaley et al. (2007). After a median follow-up of 63 months, 5 year biochemical progression-free survival (bPFS) was a 71 % in the escalated and a 60 % in the standard group (p = 0.0007). In the subgroup analysis, no heterogeneity of effect on bPFS according to risk groups was found. Neither of these analyses showed that escalated dose treatment is more or less beneficial in either of these risk groups. The bPFS at 5 years for the standard and escalated groups were 79 and 85 % in the low-risk group, 70 and 79 % in the intermediate-risk group and 43 and 57 % in the high-risk group, respectively. No significant benefits were detected for clinical progression-free survival (p = 0.064), local control (p = 0.16), freedom from salvage androgen suppression (p = 0.12), and metastases-free survival (p = 0.21).

Al-Mamgani et al. (2008) presented the analysis of the Dutch dose escalation trial of radiotherapy for prostate cancer. A total of 669 patients with localised prostate cancer (T1–T4, PSA < 60 ng/mL) were randomly assigned 1997–2003 to receive either 68 or 78 Gy. After a median follow-up of 70 months, freedom from biochemical or clinical failure (FFF) using the ASTRO definition was significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 54 % vs. 47 %, respectively; p = 0.04). The FFF using the Phoenix definition was also significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 56 % vs. 45 %, respectively; p = 0.03). However, no difference was found between the high- and low-dose arms in freedom from clinical failure (70 % vs. 68 % at 7 years, respectively, p = 0.68).