Module 5: Clinical Outcomes by Disease Site - The Use of Proton Therapy in the Treatment of Cancers of the Prostate

Eric Shinohara MD, MSCI
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 15, 2009

Text Box:  Figure 1.  IMRT (a) as compared to 3D conformal radiation (b) and IMPT (c) 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.

Benefit (%)

Proton therapy IMRT p Relative Absolute
Rectum
V10 (%) 29.8 ± 5.6 72.1 ± 7.6 <0.001 58.7 42.3
V30 (%) 20.7 ± 3.9 55.4 ± 5.7 <0.001 62.7 34.7
V50 (%) 14.6 ± 3.0 31.3 ± 4.1 <0.001 53.4 16.7
V70 (%) 7.9 ± 1.8 14.0 ± 2.9 <0.001 43.6 6.1
V78 (%) 2.9 ± 1.2 5.0 ± 1.2 0.01 42.0 2.1
V80 (%) 0.1 ± 0.3 1.8 ± 1.8 0.01 94.4 1.7
Mean dose 14.2 ± 3.7 GE 34.8 ± 3.0 Gy <0.001 59.2 20.1 GE/Gy
Rectal wall
V10 (%) 27.9 ± 3.8 63.0 ± 6.0 <0.001 55.7 35.1
V30 (%) 23.8 ± 3.2 50.7 ± 4.5 <0.001 53.1 26.9
V50 (%) 19.0 ± 2.8 30.1 ± 4.9 <0.001 36.9 11.1
V70 (%) 13.2 ± 2.7 16.9 ± 2.6 0.006 21.9 3.7
V78 (%) 6.7 ± 2.5 9.3 ± 2.6 0.03 28.0 2.6
V80 (%) 0.1 ± 0.3 4.1 ± 3.3 0.004 97.6 4.0
Mean dose 16.5 ± 3.6 GE 33.2 ± 2.8 Gy <0.001 50.3 16.7 GE/Gy

Table 2.

Benefit (%)

Proton therapy IMRT p Relative Absolute
Bladder
V10 (%) 36.4 ± 13.2 60.0 ± 20.1 0.007 39.3 23.6
V20 (%) 31.4 ± 12.1 50.8 ± 18.0 0.01 38.2 19.4
V30 (%) 27.7 ± 11.1 42.8 ± 15.1 0.02 35.3 15.1
V35 (%) 26.0 ± 10.6 38.2 ± 13.2 0.04 31.9 12.2
Mean dose 18.4 ± 6.2 GE 28.4 ± 9.4 Gy 0.01 35.2 10.0
Bladder wall
V10 (%) 37.3 ± 9.9 57.3 ± 14.5 0.002 34.9 20.0
V20 (%) 33.5 ± 8.9 49.4 ± 12.8 0.005 32.2 15.9
V30 (%) 30.8 ± 8.4 42.9 ± 10.1 0.01 28.2 12.1
V35 (%) 29.7 ± 7.8 38.9 ± 8.8 0.02 23.7 9.2
Mean dose 18.4 ± 6.2 GE 28.9 ± 7.0 Gy 0.002 36.3 11.5

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:

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