Emerging Technologies in Prostate Cancer Radiation Therapy: Improving the Therapeutic Window

Matthew C. Biagioli, MD, MS; Sarah E. Hoffe, MD


Cancer Control. 2010;17(4):223-32. 

In This Article

Proton Therapy

Standard radiation therapy techniques such as 3D CRT and IMRT use accelerated photons to deliver radiation dose to the prostate. The development of particle accelerators resulted from the technological advancements in particle physics in the 1950s. This could accelerate heavier particles that could be employed for clinical use in the treatment of cancer. Among the first particles used for this purpose were protons. The Cyclotron Laboratory at Harvard University began treating patients with protons in 1961 and treated approximately 9,000 patients before its closing in 2002 and subsequent replacement by the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital. Proton therapy is an attractive alternative to photon therapy since the behavior of a proton beam has three distinct physical differences in its behavior as it interacts with tissue: (1) In contrast to photon beam, a single proton beam deposits very low amounts of dose as it enters the body, (2) the proton beam has a maximal peak dose delivery (known as a Bragg's peak) that can be defined at a specific depth in tissue by a user depending on the energy of the protons, and (3) there is no exit dose behind the peak of a proton beam. These characteristics offer a possible advantage over standard photon therapy in that theoretically, they make it possible to substantially reduce the dose delivered to normal tissue. Despite the theoretical advantages of proton therapy, it has the major disadvantage of cost. Building a hospital-based proton accelerator is prohibitively expensive. The cost of building a proton facility is estimated to be up to $150 million (US). Construction costs at two recently built facilities at the University of Pennsylvania in Philadelphia and the University of Florida in Jacksonville were $140 million and $125 million, respectively. This expense equates into a price of treatment delivery for an individual prostate patient that is greater than twice that of a standard IMRT prostate treatment. This is supported by analysis by Konski et al,[31] who demonstrated that at 15 years, the expected mean costs of proton beam therapy and IMRT are $63,511 and $36,808, respectively, for a 70-year-old man and $64,989 and $39,355 for a 60-year-old man. The quality-adjusted survival is 8.54 and 8.12, respectively, and 9.91 and 9.45 quality-adjusted life-years.

Currently, the only tumors for which there is any evidence for the superiority of protons on the basis of clinical results are in the treatment of base of skull cordomas and ocular tumors.[32] Despite the fact that protons have been in clinical use for half a century, published clinical results for prostate cancer are limited. Investigators at Loma Linda Medical Center, who began treating prostate cancer patients with proton therapy in 1991, published their initial experience of 1,255 men.[33] In their study, 731 patients were treated with 45 Gy using photons followed by a 30-Gy equivalent (GyE) dose boost with protons, while the other 524 patients were treated with protons only to a dose of 74 GyE. Though the risk factors of these patients were heterogeneous, the majority of patients had pretreatment PSA levels of < 10 ng/mL and Gleason scores of ≤ 7. The 8-year bFS rate for the entire group was 73%. When stratified based on initial PSA, the 5-year bFS rates for PSA levels of < 4, 4–10, 10–20, and > 20 ng/mL were 90%, 84%, 65%, and 48%, respectively. Zietman et al[5] published results from a randomized trial in which 393 patients were randomized to receive a proton boost of either 19.8 GyE or 28.8 GyE after receiving 50.4 Gy via traditional photons. The bFS rate at 5 years was 61.4% for conventional-dose therapy and 80.4% for high-dose therapy (P = .001), a 49% reduction in the risk of failure. The advantage to high-dose therapy was observed in both the low-risk and the higher-risk subgroups. In the high-dose arm, grade 2 or higher acute GU and GI toxicity rates were 51% and 57%, respectively. Additionally, late grade 2 or higher GU and GI toxicity rates were 21% and 18% in the high-dose arm. A pilot protocol at the Massachusetts General Hospital and Loma Linda University Medical Center has been completed that delivered 82 GyE at 2 GyE per fraction, but the results have not yet been published. More importantly, currently there is no randomized data comparing IMRT and proton therapy for prostate cancer; thus, questions on whether the theoretical benefit results into any real clinical benefit — and whether the benefit justifies the cost — remain unanswered.


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