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Protons Versus Photons for Prostate Cancer: An Answer That Is Long Overdue and Coming

      To discuss the controversial topic of protons versus photons in prostate cancer, let us establish some truths:
      • Approximately 70% (and growing) of all level 1 evidence in localized prostate cancer involves the use of photon-based radiation therapy. Surgery is a distant second with ∼20%, and brachytherapy and conservative management round out 99% of all randomized trials in localized prostate cancer. The last 1% is from a combination of typically small or under-accrued trials of treatments such as cryotherapy.
      • Two published dose-escalation randomized trials have used protons as a boost for prostate cancer. One demonstrated high rates of gastrointestinal (GI) toxicity (32% had rectal bleeding), and the other showed a modest increase in toxicity (12% increase in grade 2+ GI toxicity).
        • Shipley WU
        • Verhey LJ
        • Munzenrider JE
        • et al.
        Advanced prostate cancer: The results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone.
        ,
        • Zietman AL
        • Bae K
        • Slater JD
        • et al.
        Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: Long-term results from Proton Radiation Oncology Group/American College of Radiology 95-09.
        In both trials, the majority of the treatment was delivered with photons and used outdated proton and photon technologies.
      • No randomized phase 3 trials of protons versus photons in prostate cancer have been reported to date. Thus, the entirety of comparative effectiveness research to support or reject the use of protons for prostate cancer is retrospective and/or nonrandomized research.
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      References

        • Shipley WU
        • Verhey LJ
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        • et al.
        Advanced prostate cancer: The results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone.
        Int J Radiat Oncol Biol Phys. 1995; 32: 3-12
        • Zietman AL
        • Bae K
        • Slater JD
        • et al.
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      1. Kubeš J, Haas A, Vondráček V, et al. Ultra-hypofractionated proton radiotherapy in the treatment of low-and intermediate-risk prostate cancer–5-years outcomes. Int J Radiat Oncol Biol Phys.,in press.

      2. Vapiwala N, Wong JK, Handorf E, et al. A pooled toxicity analysis of moderately hypofractionated proton beam therapy and intensity-modulated radiation therapy in early stage prostate cancer patients [e-pub ahead of print]. Int J Radiat Oncol Biol Phys. doi:10.1016/j.ijrobp.2021.01.043, accessed April 5, 2021.

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