Moderate versus extreme hypofractionated radiotherapy: a toxicity comparative analysis in low- and favorable intermediate-risk prostate cancer patients
External beam radiotherapy (EBRT) is an effective treatment option for low- and favorable intermediate-risk prostate cancer (PCa) and it is usually delivered in conventional fractionation or with moderate hypofractionation (hRT), with comparable results. In the last years, a new treatment approach with stereotactic body radiotherapy (SBRT) has shown promising results. The aim of the present study was to directly compare the toxicity and outcome between hRT and SBRT in low and favorable intermediate PCa patients.
Materials and methods
The hRT schedules were: 71.4 Gy or 74.2 Gy in 28 fractions for low- or favorable intermediate-risk PCa, respectively, while the SBRT schedules were: 35 Gy or 37.5 Gy in five fractions, for low or favorable intermediate risk, respectively. Toxicity assessment was performed according to CTCAE v5.0 grading. The International Prostatic Symptoms Score (IPSS) was also recorded.
One hundred forty-nine patients were analyzed, overall 81 (54.36%) patients were low risk and 68 (45.64%) were favorable intermediate risk. Sixty-nine (46.3%) patients were treated with hypo-RT and 80 (53.7%) with SBRT. Median follow-up was 33 months (range 11–58 months). The actuarial survival rate was 98.66%. The 3-years BFS rates were 95.5% and 100% for hRT and SBRT, respectively (p = 0.051). One case (0.6%) of acute grade 3 urinary toxicity occurred in a patient with favorable intermediate risk treated with hRT. He initially suffered gross hematuria and acute urinary retention not treatable with urinary catheter, therefore a suprapubic catheter was placed and steroids were administered. No differences in acute, late or severe toxicity were detected.
Stereotactic body radiotherapy reported a good clinical outcome and safe toxicity profile. Results are comparable to hRT, but a longer follow-up is needed to assess the late effectiveness and toxicity.
KeywordsProstate cancer Low risk Favorable intermediate risk Hypofractionated radiotherapy SBRT Stereotactic body radiotherapy
The authors would like to thank Prof. Brian Hawkins for his help in the final revision of the manuscript.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
- Alongi F, Cozzi L, Arcangeli S, Iftode C, Comito T, Villa E, Lobefalo F, Navarria P, Reggiori G, Mancosu P, Clerici E, Fogliata A, Tomatis S, Taverna G, Graziotti P, Scorsetti M (2013) Linac based SBRT for prostate cancer in 5 fractions with VMAT and flattening filter free beams: preliminary report of a phase II study. Radiat Oncol 8(8):171. https://doi.org/10.1186/1748-717X-8-171 CrossRefPubMedPubMedCentralGoogle Scholar
- Alongi F, Mazzola R, Fiorentino A, Corradini S, Aiello D, Figlia V, Gregucci F, Ballario R, Cavalleri S, Ruggieri R (2019) Phase II study of accelerated Linac-based SBRT in five consecutive fractions for localized prostate cancer. Strahlenther Onkol 195(2):113–120. https://doi.org/10.1007/s00066-018-1338-7 CrossRefPubMedGoogle Scholar
- De Bari B, Arcangeli S, Ciardo D, Mazzola R, Alongi F, Russi EG, Santoni R, Magrini SM, Jereczek-Fossa BA, on the behalf of the Italian Association of Radiation Oncology (AIRO) (2016) Extreme hypofractionation for early prostate cancer: Biology meets technology. Cancer Treat Rev. 50:48–60. https://doi.org/10.1016/j.ctrv.2016.08.005 CrossRefPubMedGoogle Scholar
- Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, Graham J, Kirkbride P, Logue J, Malik Z, Money-Kyrle J, O’Sullivan JM, Panades M, Parker C, Patterson H, Scrase C, Staffurth J, Stockdale A, Tremlett J, Bidmead M, Mayles H, Naismith O, South C, Gao A, Cruickshank C, Hassan S, Pugh J, Griffin C, Hall E, CHHiP Investigators (2016) 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 17(8):1047–1060. https://doi.org/10.1016/s1470-2045(16)30102-4 CrossRefPubMedPubMedCentralGoogle Scholar
- Fersino S, Tebano U, Mazzola R, Giaj-Levra N, Ricchetti F, Di Paola G, Fiorentino A, Sicignano G, Naccarato S, Ruggieri R, Cavalleri S, Alongi F (2017) Moderate hypofractionated postprostatectomy volumetric modulated arc therapy with daily image guidance (VMAT-IGRT): a mono-institutional report on feasibility and acute toxicity. Clin Genitourin Cancer. 15(4):e667–e673. https://doi.org/10.1016/j.clgc.2017.01.025 CrossRefPubMedGoogle Scholar
- Franzese C, D’agostino G, Di Brina L, Navarria P, De Rose F, Comito T, Franceschini D, Mancosu P, Tomatis S, Scorsetti M (2019) Linac-based stereotactic body radiation therapy vs moderate hypofractionated radiotherapy in prostate cancer propensity-score based comparison of outcome and toxicity. Br J Radiol. 13:20190021. https://doi.org/10.1259/bjr.20190021 CrossRefGoogle Scholar
- Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Neal DE, ProtecT Study Group (2016) 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 375(15):1415–1424. https://doi.org/10.1056/nejmoa1606220 CrossRefPubMedGoogle Scholar
- Incrocci L, Wortel RC, Alemayehu WG, Aluwini S, Schimmel E, Krol S, van der Toorn PP, Jager H, Heemsbergen W, Heijmen B, Pos F (2016) 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 17(8):1061–1069. https://doi.org/10.1016/S1470-2045(16)30070-5 CrossRefPubMedGoogle Scholar
- Johnson SB, Soulos PR, Shafman TD, Mantz CA, Dosoretz AP, Ross R, Finkelstein SE, Collins SP, Suy S, Brower JV, Ritter MA, King CR, Kupelian PA, Horwitz EM, Pollack A, Abramowitz MC, Hallman MA, Faria S, Gross CP, Yu JB (2016) Patient-reported quality of life after stereotactic body radiation therapy versus moderate hypofractionation for clinically localized prostate cancer. Radiother Oncol 121(2):294–298. https://doi.org/10.1016/j.radonc.2016.10.013 CrossRefPubMedGoogle Scholar
- Kim MS, Kim W, Park IH, Kim HJ, Lee E, Jung JH, Cho LC, Song CW (2015) Radiobiological mechanisms of stereotactic body radiation therapy and stereotactic radiation surgery. Radiat Oncol J. 33(4):265–275. https://doi.org/10.3857/roj.2015.33.4.265 (Epub 2015 Dec 30) CrossRefPubMedPubMedCentralGoogle Scholar
- Kishan AU, Wang PC, Upadhyaya SK, Hauswald H, Demanes DJ, Nickols NG, Kamrava M, Sadeghi A, Kupelian PA, Steinberg ML, Prionas ND, Buyyounouski MK, King CR (2016) SBRT and HDR brachytherapy produce lower PSA nadirs and different PSA decay patterns than conventionally fractionated IMRT in patients with low- or intermediate-risk prostate cancer. Pract Radiat Oncol 6(4):268–275. https://doi.org/10.1016/j.prro.2015.11.002 CrossRefPubMedGoogle Scholar
- Kishan AU, Dang A, Katz AJ, Mantz CA, Collins SP, Aghdam N, Chu FI, Kaplan ID, Appelbaum L, Fuller DB, Meier RM, Loblaw DA, Cheung P, Pham HT, Shaverdian N, Jiang N, Yuan Y, Bagshaw H, Prionas N, Buyyounouski MK, Spratt DE, Linson PW, Hong RL, Nickols NG, Steinberg ML, Kupelian PA, King CR (2019) Long-term outcomes of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. JAMA Netw Open 2(2):e188006. https://doi.org/10.1001/jamanetworkopen.2018.8006 PubMed PMID: 30735235 CrossRefPubMedPubMedCentralGoogle Scholar
- Lee WR et al (2016) Randomized phase III non-inferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer. J Clin Oncol 34:JCO670448Google Scholar
- Mantz C (2014) A phase II trial of stereotactic ablative body radiotherapy for low-risk prostate cancer using a non-robotic linear accelerator and real-time target tracking: report of toxicity, quality of life, and disease control outcomes with 5-year minimum follow-up. Front Oncol 4:279CrossRefPubMedPubMedCentralGoogle Scholar
- Musunuru HB, Klotz L, Vesprini D et al (2016) Comparison of contemporary treatment options for early prostate cancer: a single institution series. Austin J Radiat Oncol Cancer 2:1018Google Scholar
- National Comprehensive Cancer Network. Prostate cancer, version 2.2019. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Accessed 18 July 2019
- Oliai C, Bernetich M, Brady L, Yang J, Hanlon A, Lamond J, Arrigo S, Good M, Mooreville M, Garber B, Lanciano R (2016) Propensity score matched comparison of SBRT versus IMRT for the treatment of localized prostate cancer. J Radiat Oncol 5:187–195 Epub 2016 Jan 23 CrossRefPubMedPubMedCentralGoogle Scholar
- Park Y, Park HJ, Jang WI, Jeong BK, Kim HJ, Chang AR (2018) Long-term results and PSA kinetics after robotic SBRT for prostate cancer: multicenter retrospective study in Korea (Korean radiation oncology group study 15-01). Radiat Oncol 13(1):230. https://doi.org/10.1186/s13014-018-1182-z CrossRefPubMedPubMedCentralGoogle Scholar
- Ray ME, Thames HD, Levy LB, Horwitz EM, Kupelian PA, Martinez AA, Michalski JM, Pisansky TM, Shipley WU, Zelefsky MJ, Zietman AL, Kuban DA (2006) PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer: a multi-institutional analysis. Int J Radiat Oncol Biol Phys 64(4):1140–1150CrossRefPubMedGoogle Scholar
- Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, Sandler H (2006) Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO phoenix consensus conference. Int J Radiat Oncol Biol Phys 65(4):965–974CrossRefPubMedGoogle Scholar
- Ruggieri R, Naccarato S, Stavrev P, Stavreva N, Fersino S, Giaj Levra N, Mazzola R, Mancosu P, Scorsetti M, Alongi F (2015) Volumetric-modulated arc stereotactic body radiotherapy for prostate cancer: dosimetric impact of an increased near-maximum target dose and of a rectal spacer. Br J Radiol 88(1054):20140736. https://doi.org/10.1259/bjr.20140736 CrossRefPubMedPubMedCentralGoogle Scholar
- Scorsetti M, Alongi F, Clerici E, Comito T, Fogliata A, Iftode C, Mancosu P, Navarria P, Reggiori G, Tomatis S, Villa E, Cozzi L (2014) Stereotactic body radiotherapy with flattening filter-free beams for prostate cancer: assessment of patient-reported quality of life. J Cancer Res Clin Oncol 140(10):1795–1800. https://doi.org/10.1007/s00432-014-1732-1 CrossRefPubMedGoogle Scholar
- Shibamoto Y, Hashizume C, Baba F, Ayakawa S, Miyakawa A, Murai T, Takaoka T, Hattori Y, Asai R (2015) Stereotactic body radiotherapy using a radiobiology-based regimen for stage I non-small-cell lung cancer: five-year mature results. J Thorac Oncol 10(6):960–964. https://doi.org/10.1097/JTO.0000000000000525 CrossRefPubMedGoogle Scholar
- Van As NJ, Brand D, Tree A, Ostler PJ, Chu W, Loblaw A, Ford D, Tolan SP, Jain S, Martin AS, Staffurth J, Brown S, Burnett SM, Duffton A, Griffin C, Hinder V, Morrison K, Naismith OF, Hall E, On behalf of the PACE investigators (2019) PACE: analysis of acute toxicity in PACE-B, an international phase III randomized controlled trial comparing stereotactic body radiotherapy (SBRT) to conventionally fractionated or moderately hypofractionated external beam radiotherapy (CFMHRT) for localized prostate cancer (LPCa). J Clin Oncol 37(7_suppl):1CrossRefGoogle Scholar
- Zemplényi AT, Kaló Z, Kovács G, Farkas R, Beöthe T, Bányai D, Sebestyén Z, Endrei D, Boncz I, Mangel L (2018) Cost-effectiveness analysis of intensity-modulated radiation therapy with normal and hypofractionated schemes for the treatment of localised prostate cancer. Eur J Cancer Care (Engl). https://doi.org/10.1111/ecc.12430 CrossRefGoogle Scholar