There are currently no reported randomised clinical trials comparing photon treatments with proton or heavy ion therapy alone (De Ruysscher et al. 2012). In localised prostate cancer, multiple systematic reviews of the available clinical data have concluded that, at present, there is no evidence of benefit for proton or heavy ion therapy over photon therapy, with regard to toxicity or tumour control (Brada et al. 2007, 2009; Lodge et al. 2007; Olsen et al. 2007; Allen et al. 2012). In the light of these facts alone it is clear that strong evidence for the superiority of proton or heavy ion therapy to photon therapy is lacking.

Proponents of proton therapy feel that its potential theoretical advantages, particularly with regard to dose distribution, will translate into a reduction in treatment-related toxicity (Goitein and Cox 2008). If dose-limiting late rectal and urinary toxicity can be reduced with proton therapy, it is claimed that dose escalation could then be undertaken. There is abundant evidence from photon therapy that higher doses of radiation reduce biochemical relapse in the treatment of localised prostate cancer—although a survival benefit has not yet been demonstrated (Viani et al. 2009). Naturally, this improvement comes at the cost of increased late (urinary and rectal) toxicity, and this has limited escalation of dose above 80–90 Gy in 2 Gy fractions, although further clinical benefit is predicted.

However, from the available phase II data, there is no clinical evidence that late toxicity is reduced with proton therapy compared with photon therapy. In fact, in a recent report on the American College of Radiology 03–12 study, 26 % of patients receiving conformal proton monotherapy to a dose of 82 GyE experienced RTOG (Radiation Therapy Oncology Group) grade two or above late toxicity (Coen et al. 2011). This study looked at a cohort of 85 men with a median follow-up of just under 3 years who were treated with a parallel opposed lateral beam technique. It concluded that further proton dose escalation with a conformal technique risked unacceptable late toxicity. A collaborative phase II study by three Japanese proton institutions enrolled 151 patients to be treated with the lower dose of 74 GyE using a conformal parallel opposed beam technique. At 2 years, CTC late grade two or above toxicity was 4.1 and 2.0 % for genitourinary and gastrointestinal symptoms, respectively. These studies can be compared with the Memorial Sloane-Kettering Cancer Centre (MSKCC) review of 170 patients treated with a dose of 81 Gy using a five field IMRT technique (Alicikus et al. 2011). At 10 years of follow-up actuarial prostate-specific antigen (PSA) relapse-free survival was 81, 78, and 62 % for low-, intermediate-, and high-risk disease. Grade two or greater late genitourinary and rectal toxicity was 16 and 3 %, respectively. A further review by the same group of over 1000 patients treated with 86.4 Gy photon IMRT with a median follow-up of 7 years found that grade two or above late genitourinary and rectal toxicity was 21.1 and 4.4 %, respectively (Spratt et al. 2012). The Fox Chase Cancer Centre have also produced published results for IMRT with doses of 74–78 Gy (Eade et al. 2008). A 3 year actuarial grade two and above genitourinary and gastrointestinal toxicities were 3.5 and 2.4 %, respectively.

Turning to therapy with carbon ions, a Japanese group at Chiba University have recently reported on over 700 patients treated with hypofractionated carbon ion therapy for localised prostate cancer (Okada et al. 2012). Doses of 66–57.6 GyE in 20–16 fractions were used. Late toxicities of grade two or above for the 664 patients with at least 1 year of follow-up were 8.0 and 2.4 %, respectively, for genitourinary and gastrointestinal symptoms. A comparison can be made with patients treated in the hypofractionated arms of the multi-centre United Kingdom CHHiP study (Dearnaley et al. 2012). Patients in these arms (150 patients each) received 60 Gy in 20 fractions or 57 Gy in 19 fractions using IMRT. At 2 years RTOG grade two and above toxicity was under 3 % for bladder toxicity and less than 4 % for bowel toxicity.

In summary, although with the caveat that we are comparing between series, it must be concluded that the available phase II evidence does not show an advantage for proton or heavy ion treatments over photon therapy with regard to toxicity. Furthermore, although there are not a large quantity of mature phase II data on proton and heavy ion therapy, it appears that these treatments are at best equivalent to photon therapy in terms of tumour control (Jensen et al. 2011). These factors argue against the possibility of significant dose escalation with protons or heavy ions.