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Expert Insights: Prostate Cancer

Trends in Proton and Carbon Ion Therapy to Assist Clinical Choices and Research Pursuits

Curtis Bryant, MD, MPH

Updates in Proton Therapy for Prostate Cancer

Curtis Bryant, MD, MPH

Department of Radiation Oncology, University of Florida

UF Health Proton Therapy Institute

Delivery of proton therapy (PT) in the management of prostate cancer is controversial because it costs more than traditional photon-based radiation therapy and its comparative advantages remain unproven. In the treatment of prostate cancer, the dosimetric superiority of PT over photon radiation is that it reduces the amount of excess radiation delivered to the rectum and bladder [1-3].

A few recently published studies have provided some clarity on the role of PT in the management of prostate cancer. In 2018, Iwata and colleagues published the largest multi-institutional study documenting the efficacy of PT for localized prostate cancer [4]. Over 1,200 patients were treated with high-dose PT between 2008 and 2011. With a median follow-up of 69 months, the 5-year biochemical relapse-free survival rates were 97%, 91%, and 83% for patients with low-, intermediate-, and high-risk prostate cancer. The rates of late grade 3 gastrointestinal (GI) and genitourinary (GU) toxicity were low at 0.5% and 0.3%, respectively.  These results compare favorably to studies documenting the efficacy and safety of IMRT in the management of prostate cancer [5-7]. 

Additionally, Pan et al recently published a retrospective comparison of PT and intensity-modulated radiotherapy (IMRT) using data from the MarketScan insurance database [8]. Patients were treated with radiation therapy for localized prostate cancer between 2005 and 2015. Mean costs to payers associated with PT were higher than with IMRT. At 2 years, patients treated with PT had lower rates of GU toxicity and erectile dysfunction, but higher rates of grade 2 GI toxicity. PT was found to have a lower mean complication cost when compared to IMRT but a higher mean total healthcare cost [8].  

Finally, Deville et al published the first known results documenting toxicity following PT for salvage or adjuvant prostate bed radiation therapy. Patients received PT between 2010 and 2016 at a single institution and to a median of 70.2 Gy (RBE) delivered at 1.8 Gy (RBE) per fraction [9]. The toxicity-free survival rate was 83% at 24 months, which is favorable when compared with studies documenting the safety of IMRT [9-11]. 

Overall, the landscape of published literature documenting the efficacy and cost effectiveness of PT is slowly taking shape and recent data should help to guide patients, physicians, and insurers about PT’s efficacy and safety profile as well as its potential clinical advantages. Eventually, the current data will be bolstered by the presence of level I evidence potentially supporting its use among patients with localized prostate cancer.  

    1. Chera BS, Vargas C, Morris CG, Louis D, Flampouri S, Yeung D, Duvvuri S, Li Z, Mendenhall NP. Dosimetric study of pelvic proton radiotherapy for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2009;75:994-1002.
    2. Trofimov A, Nguyen PL, Coen JJ, Doppke KP, Schneider RJ, Adams JA, Bortfeld TR, Zietman AL, Delaney TF, Shipley WU. Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. Int J Radiat Oncol Biol Phys. 2007;69:444-53.
    3. Vargas C, Fryer A, Mahajan C, Indelicato D, Horne D, Chellini A, McKenzie C, Lawlor P, Henderson R, Li Z, Lin L, Olivier K, Keole S. Dose-volume comparison of proton therapy and intensity-modulated radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70:744-51.
    4. Iwata H, Ishikawa H, Takagi M, Okimoto T, Murayama S, Akimoto T, Wada H, Arimura T, Sato Y, Araya M, Mizoe JE, Gosho M, Nakamura K, Shirato H, Sakurai H. Long-term outcomes of proton therapy for prostate cancer in Japan: a multi-institutional survey of the Japanese Radiation Oncology Study Group. Cancer Med. 2018;7:677-89.
    5. Spratt DE, Pei X, Yamada J, Kollmeier MA, Cox B, Zelefsky MJ. Long-term survival and toxicity in patients treated with high-dose intensity modulated radiation therapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2013;85:686-92.
    6. Liauw SL, Weichselbaum RR, Rash C, Correa D, Al-Hallaq HA, Pelizzari CA, Jani AB. Biochemical control and toxicity after intensity-modulated radiation therapy for prostate cancer. Technol Cancer Res Treat. 2009;8:201-6.
    7. Vora SA, Wong WW, Schild SE, Ezzell GA, Andrews PE, Ferrigni RG, Swanson SK. Outcome and toxicity for patients treated with intensity modulated radiation therapy for localized prostate cancer. J Urol. 2013;190:521-6.
    8. Pan HY, Jiang J, Hoffman KE, Tang C, Choi SL, Nguyen QN, Frank SJ, Anscher MS, Shih YT, Smith BD. Comparative Toxicities and Cost of Intensity-Modulated Radiotherapy, Proton Radiation, and Stereotactic Body Radiotherapy Among Younger Men With Prostate Cancer. J Clin Oncol. 2018;36:1823-30.
    9. Deville C, Jr., Jain A, Hwang WT, Woodhouse KD, Both S, Wang S, Gabriel PE, Christodouleas JP, Bekelman J, Tochner Z, Vapiwala N. Initial report of the genitourinary and gastrointestinal toxicity of post-prostatectomy proton therapy for prostate cancer patients undergoing adjuvant or salvage radiotherapy. Acta Oncol. 2018;57:1506-14.
    10. Jensen L, Yuh B, Wong JYC, Schultheiss T, Cheng J, Ruel N, Twardowski P, Sampath S. Outcomes and toxicity of 313 prostate cancer patients receiving helical tomotherapy after radical prostatectomy. Adv Radiat Oncol. 2017;2:597-607.
    11. Deville C, Vapiwala N, Hwang WT, Lin H, Ad VB, Tochner Z, Both S. Comparative toxicity and dosimetric profile of whole-pelvis versus prostate bed-only intensity-modulated radiation therapy after prostatectomy. Int J Radiat Oncol Biol Phys. 2012;82:1389-96.

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