A significant proportion of patients treated in radiation oncology centers have prostate cancer. Side effects of treatment generally include gastrointestinal (GI) and genitourinary (GU) damage. Large numbers of patients experience urinary frequency and diarrhea during treatment, and long-term, may suffer impotence, incontinence, rectal fibrosis and bleeding, and extensive bowel fibrosis. These side effects may cause a reduction in the quality of life and result in delays of a typical radiation therapy treatment course. Proton therapy may be able to deliver equivalent, highly conformal, doses to the prostate while sparing more normal tissues when compared with photon based therapy (figure 1. Trifimov A. et al., Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):444-53.). However, this remains a subject of continued study. The above mentioned study noted that IMRT had better conformality compared with 3D conformal proton therapy as well as a lower bladder dose, where as proton therapy had better dose homogeneity and greater sparing of the bladder and rectum at lower doses (30 CGE). However, other studies have suggested a potential benefit to proton therapy regarding rectal dose (table 1) and bladder dose when compared with IMRT (table 2; Vargas C. et al., Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):744-51.). Whether these differences translate into clinically meaningful decreases in side effects remains to be seen, however, early studies out of Japan suggest that acute GI toxicity is decreased with proton therapy (Mayahara H. et al., Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):434-43. Studies out of Loma Linda demonstrated similar outcomes when proton therapy was compared with historical photon based therapy data when doses of 74 CGE were used (Slater JD et al., Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):348-52.). The side effects seen compared favorably to those seen with IMRT and 3D conformal therapy per the authors.

Table 1.

Table 2.

It is also possible that if proton therapy can decrease toxicities, higher doses may be used to treat the prostate safely, which may result in improvements in outcomes. Zietman et al. have previously shown the feasibility of dose escalation with a proton boost (Zietman A. et al., JAMA. 2005 Sep 14;294(10):1233-9.). They also found a biochemical free survival benefit with the higher dose. Expanding on this, a recent Phase I/II study run jointly by Massachusetts General Hospital and Loma Linda (Zietman et al. ASTRO 2008) treated patients with opposed laterals to 80 CGE in 2 CGE fractions. Acute grade 2 GI and GU toxicity was 1% and 14 %, respectively. Acute grade 3+ GI and GU toxicity rates were 0% and 1%, respectively. Late grade 2+ GI and GU toxicity rates were 12% and 30% , respectively. Late grade 3+ GI and GU toxicity rates were 1% and 8%, respectively. There were 2 grade 4 late toxicities, both occurred in the same patient who experienced both hematuria and rectal ulceration. This patient was noted to have a very large prostate. These results were felt to be consistent with those seen with conformal photon based radiation therapy.

Links to reviews of recent abstracts and presentations regarding proton therapy for prostate cancer:

• ASTRO 2006 Opportunities in Proton Therapy - Prostate
• ASTRO 2006 Opportunities in Proton Therapy - Prostate (with Carbon)
• Changes in the Rectal Volume and Prostate Localization with Placement of a Rectum Emptying Tube
• Conformal Proton Beam Therapy of Prostate cancer — Report of Long-term PSA Based Outcomes in Over Twelve Hundred Patients
• A Prospective Phase I/II Study using Proton Beam Radiation to Deliver 82GyE to Men with Localized Prostate Cancer: Preliminary Results of ACR 0312
• Effectiveness of Rectal Balloon as an Internal Immobilization Device for Proton Therapy of Prostate Cancer
• Interfractional Variation in the Set-up of Pelvic Bony Anatomy and Soft Tissue, and Their Implications in Proton Therapy of the Prostate
• Multi-Institutional Phase II Study of Proton Beam Therapy for Organ Confined Prostate Cancer in Japan, Focusing on the Incidence of Late Rectal Toxicities
• Pelvic Proton Radiotherapy for High-Risk Prostate Cancer
• Proton Radiation Therapy for Patients with Prostate Cancer
• Proton treatment of prostate cancer in the presence of unilateral hip replacement
• Separating the Rectum from the Prostate during Proton Beam Radiotherapy of Prostate Cancer Patients Reduces Rectal Side Effects

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