The Role of Hypofractionated Radiotherapy in Prostate Cancer

Linus C Benjamin, Alison C Tree, David P Dearnaley, Linus C Benjamin, Alison C Tree, David P Dearnaley

Abstract

Purpose of review: It is now accepted that prostate cancer has a low alpha/beta ratio, establishing a strong basis for hypofractionation of prostate radiotherapy. This review focuses on the rationale for hypofractionation and presents the evidence base for establishing moderate hypofractionation for localised disease as the new standard of care. The emerging evidence for extreme hypofractionation in managing localized and oligometastatic prostate cancer is reviewed.

Recent findings: The 5-year efficacy and toxicity outcomes from four phase III studies have been published within the last 12 months. These studies randomizing over 6000 patients to conventional fractionation (1.8-2.0 Gy per fraction) or moderate hypofractionation (3.0-3.4 Gy per fraction). They demonstrate hypofractionation to be non-inferior to conventional fractionation. Moderate hypofractionation for localized prostate cancer is safe and effective. There is a growing body of evidence in support of extreme hypofractionation for localized prostate cancer. Extreme hypofractionation may have a role in managing prostate oligometastases, but further studies are needed.

Keywords: CHHiP; HYPRO; Hypofractionation; Prostate cancer; Radiotherapy.

Conflict of interest statement

Conflict of Interest

Linus C. Benjamin declares that he has no conflict of interest.

Alison Tree has received support through grants from Accuray and Elekta, and has received travel assistance for meetings from Elekta.

David P. Dearnaley declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Figures

Fig. 1
Fig. 1
Treatment plan and dose statistics for prostate SBRT with a non-coplanar technique. (Acknowledgement: Dr Nicholas van As, Kirsty Morrison, Royal Marsden Hospital, UK)

References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90. doi: 10.3322/caac.20107.
    1. Schröder FH, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320–1328. doi: 10.1056/NEJMoa0810084.
    1. Withers HR. Biologic basis for altered fractionation schemes. Cancer. 1985;55(S9):2086–2095. doi: 10.1002/1097-0142(19850501)55:9+<2086::AID-CNCR2820551409>;2-1.
    1. Thames HD, Withers HR, Peters LJ, Fletcher GH. Changes in early and late radiation responses with altered dose fractionation: implications for dose-survival relationships. Int J Radiat Oncol Biol Phys. 1982;8(2):219–226. doi: 10.1016/0360-3016(82)90517-X.
    1. Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989;62(740):679–694. doi: 10.1259/0007-1285-62-740-679.
    1. Kuban DA, et al. Long-term failure patterns and survival in a randomized dose-escalation trial for prostate cancer. Who dies of disease? Int J Radiat Oncol Biol Phys. 2011;79(5):1310–1317. doi: 10.1016/j.ijrobp.2010.01.006.
    1. Zietman AL, 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. J Clin Oncol. 2010;28(7):1106–1111. doi: 10.1200/JCO.2009.25.8475.
    1. Dearnaley DP, et al. Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial. Lancet Oncol. 2014;15(4):464–473. doi: 10.1016/S1470-2045(14)70040-3.
    1. Al-Mamgani A, van Putten WL, van der Wielen GJ, Levendag PC, Incrocci L. Dose escalation and quality of life in patients with localized prostate cancer treated with radiotherapy: long-term results of the Dutch randomized dose-escalation trial (CKTO 96–10 trial) Int J Radiat Oncol Biol Phys. 2011;79(4):1004–1012. doi: 10.1016/j.ijrobp.2009.12.039.
    1. Brenner DJ, Hall EJ. Fractionation and protraction for radiotherapy of prostate carcinoma. Int J Radiat Oncol Biol Phys. 1999;43(5):1095–1101. doi: 10.1016/S0360-3016(98)00438-6.
    1. Fowler J, Chappell R, Ritter M. Is α/β for prostate tumors really low? Int J Radiat Oncol Biol Phys. 2001;50(4):1021–1031. doi: 10.1016/S0360-3016(01)01607-8.
    1. Miralbell R, Roberts SA, Zubizarreta E, Hendry JH. Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: α/β = 1.4 (0.9–2.2) Gy. Int J Radiat Oncol Biol Phys. 2012;82(1):e17–e24. doi: 10.1016/j.ijrobp.2010.10.075.
    1. Proust-Lima C, et al. Confirmation of a low α/β ratio for prostate cancer treated by external beam radiation therapy alone using a post-treatment repeated-measures model for PSA dynamics. Int J Radiat Oncol Biol Phys. 2011;79(1):195–201. doi: 10.1016/j.ijrobp.2009.10.008.
    1. Vogelius IR, Bentzen SM. Meta-analysis of the alpha/beta ratio for prostate cancer in the presence of an overall time factor: bad news, good news, or no news? Int J Radiat Oncol Biol Phys. 2013;85(1):89–94. doi: 10.1016/j.ijrobp.2012.03.004.
    1. Tree AC, Alexander EJ, Van As NJ, Dearnaley DP, Khoo V. Biological dose escalation and hypofractionation: what is there to be gained and how will it best be done? Clin Oncol. 2013;25(8):483–498. doi: 10.1016/j.clon.2013.05.003.
    1. Zaorsky NG, Ohri N, Showalter TN, Dicker AP, Den RB. Systematic review of hypofractionated radiation therapy for prostate cancer. Cancer Treat Rev. 2013;39(7):728–736. doi: 10.1016/j.ctrv.2013.01.008.
    1. Koontz BF, Bossi A, Cozzarini C, Wiegel T, D’Amico A. A systematic review of hypofractionation for primary management of prostate cancer. Eur Urol. 2015;68(4):683–691. doi: 10.1016/j.eururo.2014.08.009.
    1. Dearnaley D, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. 2016;17(8):1047–1060. doi: 10.1016/S1470-2045(16)30102-4.
    1. Wilkins A, et al. Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. 2015;16(16):1605–1616. doi: 10.1016/S1470-2045(15)00280-6.
    1. Aluwini S, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): acute toxicity results from a randomised non-inferiority phase 3 trial. Lancet Oncol. 2015;16(3):274–283. doi: 10.1016/S1470-2045(14)70482-6.
    1. Aluwini S, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): late toxicity results from a randomised, non-inferiority, phase 3 trial. Lancet Oncol. 2016;17(4):464–474. doi: 10.1016/S1470-2045(15)00567-7.
    1. Incrocci L, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2016;17(8):1061–1069. doi: 10.1016/S1470-2045(16)30070-5.
    1. • Lee WR, et al. Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer. J Clin Oncol 2016;JCO670448. RTOG 0415 demonstrated that the efficacy of hypofractionation was non-inferior to conventional fractionation in low-risk prostate cancer. Late grade 2–3 GI/GU toxicity was higher in the hypofractionated arm. The BED to the rectum/bladder was higher in the hypofractionated arm compared to the control arm.
    1. • Catton CN, et al. A randomized trial of a shorter radiation fractionation schedule for the treatment of localized prostate cancer. J ClinOncol 2016;34(suppl; abstr 5003). The PROFIT study demonstrates no differences in efficacy and acute toxicity between moderate hypofractionation and conventionally-fractionated radiotherapy in intermediate-risk prostate cancer. Late GI/GU toxicity was lower in the hypofractionated arm.
    1. Lukka H, et al. Randomized trial comparing two fractionation schedules for patients with localized prostate cancer. J Clin Oncol. 2005;23(25):6132–6138. doi: 10.1200/JCO.2005.06.153.
    1. Yeoh EE, Botten RJ, Butters J, Di Matteo AC, Holloway RH, Fowler J. Hypofractionated versus conventionally fractionated radiotherapy for prostate carcinoma: final results of phase III randomized trial. Int J Radiat Oncol Biol Phys. 2011;81(5):1271–1278. doi: 10.1016/j.ijrobp.2010.07.1984.
    1. Dearnaley D, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial. Lancet Oncol. 2012;13(1):43–54. doi: 10.1016/S1470-2045(11)70293-5.
    1. Kuban DA, et al. Preliminary report of a randomized dose escalation trial for prostate cancer using hypofractionation. Int J Radiat Oncol Biol Phys. 2010;78(3):S58–S59. doi: 10.1016/j.ijrobp.2010.07.170.
    1. Hoffman KE, et al. Risk of late toxicity in men receiving dose-escalated hypofractionated intensity modulated prostate radiation therapy: results from a randomized trial. Int J Radiat Oncol Biol Phys. 2014;88(5):1074–1084. doi: 10.1016/j.ijrobp.2014.01.015.
    1. Arcangeli S, et al. Updated results and patterns of failure in a randomized hypofractionation trial for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2012;84(5):1172–1178. doi: 10.1016/j.ijrobp.2012.02.049.
    1. Pollack A, et al. Randomized trial of hypofractionated external-beam radiotherapy for prostate cancer. J Clin Oncol 2013;JCO–2013.
    1. Kirkpatrick JP, Meyer JJ, Marks LB. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Semin Radiat Oncol. 2008;18:240–243. doi: 10.1016/j.semradonc.2008.04.005.
    1. Brenner DJ. The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction. Semin Radiat Oncol. 2008;18:234–239. doi: 10.1016/j.semradonc.2008.04.004.
    1. Brown JM, Carlson DJ, Brenner DJ. The tumor radiobiology of SRS and SBRT: are more than the 5 Rs involved? Int J Radiat Oncol Biol Phys. 2014;88(2):254–262. doi: 10.1016/j.ijrobp.2013.07.022.
    1. Madsen BL, Hsi RA, Pham HT, Fowler JF, Esagui L, Corman J. Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results. Int J Radiat Oncol Biol Phys. 2007;67(4):1099–1105. doi: 10.1016/j.ijrobp.2006.10.050.
    1. Loblaw A, et al. Prostate stereotactic ablative body radiotherapy using a standard linear accelerator: toxicity, biochemical, and pathological outcomes. Radiother Oncol. 2013;107(2):153–158. doi: 10.1016/j.radonc.2013.03.022.
    1. Aluwini S, van Rooij P, Hoogeman M, Kirkels W, Kolkman-Deurloo I-K, Bangma C. Stereotactic body radiotherapy with a focal boost to the MRI-visible tumor as monotherapy for low-and intermediate-risk prostate cancer: early results. Radiat Oncol. 2013;8(1):1. doi: 10.1186/1748-717X-8-84.
    1. Kim DN, et al. Predictors of rectal tolerance observed in a dose-escalated phase 1–2 trial of stereotactic body radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2014;89(3):509–517. doi: 10.1016/j.ijrobp.2014.03.012.
    1. Fuller DB, Naitoh J, Mardirossian G. Virtual HDR CyberKnife SBRT for localized prostatic carcinoma: 5-year disease-free survival and toxicity observations. Front Oncol. 2014;4:321.
    1. King CR, Brooks JD, Gill H, Presti JC. Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2012;82(2):877–882. doi: 10.1016/j.ijrobp.2010.11.054.
    1. Chen LN, et al. Stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer: the Georgetown University experience. Radiat Oncol. 2013;8(1):1. doi: 10.1186/1748-717X-8-1.
    1. Bolzicco G, Favretto MS, Satariano N, Scremin E, Tambone C, Tasca A. A single-center study of 100 consecutive patients with localized prostate cancer treated with stereotactic body radiotherapy. BMC Urol. 2013;13(1):1. doi: 10.1186/1471-2490-13-49.
    1. Meier R, et al. Stereotactic body radiation therapy for intermediate-risk prostate cancer: five-year outcomes from a multi-institutional study. Int J Radiat Oncol Biol Phys. 2015;93:S199. doi: 10.1016/j.ijrobp.2015.07.477.
    1. Katz AJ, Kang J. Quality of life and toxicity after SBRT for organ-confined prostate cancer, a 7-year study. Front Oncol. 2014;4:301.
    1. Meier R, et al. Five-year outcomes from a multicenter trial of stereotactic body radiation therapy for low-and intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2016;96(2S):S33. doi: 10.1016/j.ijrobp.2016.06.094.
    1. Evans JR, et al. Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy. Radiother Oncol. 2015;116(2):179–184. doi: 10.1016/j.radonc.2015.07.016.
    1. Meier R. Dose-escalated robotic SBRT for Stage I–II prostate cancer. Front Oncol 2015;5.
    1. King CR, et al. Stereotactic body radiotherapy for localized prostate cancer: pooled analysis from a multi-institutional consortium of prospective phase II trials. Radiother Oncol. 2013;109(2):217–221. doi: 10.1016/j.radonc.2013.08.030.
    1. Arscott WT, et al. Obstructive voiding symptoms following stereotactic body radiation therapy for prostate cancer. Radiat Oncol Lond Engl. 2014;9:163. doi: 10.1186/1748-717X-9-163.
    1. Tree AC, et al. Prostate stereotactic body radiotherapy—first UK experience. Clin Oncol. 2014;26(12):757–761. doi: 10.1016/j.clon.2014.08.007.
    1. Quon HC, et al. PATRIOT Trial: randomized phase II study of prostate stereotactic body radiotherapy comparing 11 versus 29 days overall treatment time. J Clin Oncol. 2015;33(suppl 7):abstr 6. doi: 10.1200/jco.2015.33.7_suppl.6.
    1. Lussier YA, et al. Oligo-and polymetastatic progression in lung metastasis (es) patients is associated with specific microRNAs. PLoS One. 2012;7(12):e50141. doi: 10.1371/journal.pone.0050141.
    1. Furuya Y, Akakura K, Akimoto S, Inomiya H, Ito H. Pattern of progression and survival in hormonally treated metastatic prostate cancer. Int J Urol. 1999;6(5):240–244. doi: 10.1046/j.1442-2042.1999.00060.x.
    1. Decaestecker K, et al. Repeated stereotactic body radiotherapy for oligometastatic prostate cancer recurrence. Radiat Oncol. 2014;9(1):1. doi: 10.1186/1748-717X-9-135.
    1. Schick U, et al. Androgen deprivation and high-dose radiotherapy for oligometastatic prostate cancer patients with less than five regional and/or distant metastases. Acta Oncol. 2013;52(8):1622–1628. doi: 10.3109/0284186X.2013.764010.
    1. Jereczek-Fossa BA, et al. Robotic image-guided stereotactic radiotherapy, for isolated recurrent primary, lymph node or metastatic prostate cancer. Int J Radiat Oncol Biol Phys. 2012;82(2):889–897. doi: 10.1016/j.ijrobp.2010.11.031.
    1. Casamassima F, et al. Efficacy of eradicative radiotherapy for limited nodal metastases detected with choline PET scan in prostate cancer patients. Tumori. 2011;97(1):49.
    1. Muacevic A, Kufeld M, Rist C, Wowra B, Stief C, Staehler M. Safety and feasibility of image-guided robotic radiosurgery for patients with limited bone metastases of prostate cancer. Urol Oncol. 2013;31(4):455–460. doi: 10.1016/j.urolonc.2011.02.023.
    1. Ost P, et al. Metastasis-directed therapy of regional and distant recurrences after curative treatment of prostate cancer: a systematic review of the literature. Eur Urol. 2015;67(5):852–863. doi: 10.1016/j.eururo.2014.09.004.
    1. Ost P, et al. Pattern of progression after stereotactic body radiotherapy for oligometastatic prostate cancer nodal recurrences. Clin Oncol (R Coll Radiol) 2016;28(9):e115–120. doi: 10.1016/j.clon.2016.04.040.
    1. Ost P, et al. Progression-free survival following stereotactic body radiotherapy for oligometastatic prostate cancer treatment-naive recurrence: a multi-institutional analysis. Eur Urol. 2016;69(1):9–12. doi: 10.1016/j.eururo.2015.07.004.

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