Abstract
Purpose
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.
Results
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.
Conclusion
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.
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References
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
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
Anwar M, Weinberg V, Chang AJ, Hsu IC, Roach M 3rd, Gottschalk A (2014) Hypofractionated SBRT versus conventionally fractionated EBRT for prostate cancer: comparison of PSA slope and nadir. Radiat Oncol 2(9):42. https://doi.org/10.1186/1748-717X-9-42
Arcangeli S et al (2012) Updated results and patterns of failure in a randomized hypofractionation trial for high-risk prostate cancer. Int J Radiat Oncol Biol Phys 84(5):1172–1178
Brenner DJ, Hall EJ (1999) Fractionation and protraction for radiotherapy of prostate carcinoma. Int J Radiat Oncol Biol Phys 43(5):1095–1101
Collins CD, Lloyd-Davies RW, Swan AV (1991) Radical external beam radiotherapy for localised carcinoma of the prostate using a hypofractionation technique. Clin Oncol (R Coll Radiol) 3(3):127–132
Dasu A, Toma-Dasu I (2012) Prostate alpha/beta revisited—an analysis of clinical results from 14 168 patients. Acta Oncol 51(8):963–974. https://doi.org/10.3109/0284186X.2012.719635
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
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
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
Fowler J, Chappell R, Ritter M (2001) Is α/β for prostate tumors really low? Int J Radiat Oncol Biol Phys 50(4):1021–1031
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
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
Hannan R, Tumati V, Xie XJ et al (2016) Stereotactic body radiation therapy for low and intermediate risk prostate cancer-results from a multi-institutional clinical trial. Eur J Cancer 59:142–151
Hoffman KE et al (2014) 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 88(5):1074–1084
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
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
Katz AJ, Santoro M, Diblasio F et al (2013) Stereotactic body radiotherapy for localized prostate cancer: disease control and quality of life at 6 years. Radiat Oncol 8:118
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)
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
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
Kupelian P, Katz AJ, Freeman D et al (2013) Long-term efficacy of stereotactic body radiotherapy for localized prostate cancer: a multi-institutional pooled analysis. J Clin Oncol 31:abstr 9
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:JCO670448
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 4:279
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 2:1018
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
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
Pham HT, Song G, Badiozamani K et al (2010) Five-year outcome of stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP) for patients with low-risk prostate cancer. Int J Rad Oncol Biol Phys 78:S58
Pollack A et al (2013) Randomized trial of hypofractionated external-beam radiotherapy for prostate cancer. J Clin Oncol 31:3860 (JCO–2013)
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):1140–1150
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):965–974
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
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
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
Torre LA, Siegel RL, Ward EM, Jemal A (2016) Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol Biomark Prev 25(1):16–27. https://doi.org/10.1158/1055-9965.EPI-15-0578 (Epub 2015 Dec 14)
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):1
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
Zeng GG, McGowan TS, Larsen TM, Bruce LM, Moran NK, Tsao JR, MacPherson MS (2008) Calcifications are potential surrogates for prostate localization in image-guided radiotherapy. Int J Radiat Oncol Biol Phys 72(4):963–966. https://doi.org/10.1016/j.ijrobp.2008.07.021
Zimmermann M, Taussky D, Menkarios C et al (2016) Prospective phase II trial of once-weekly hypofractionated radiation therapy for low-risk adenocarcinoma of the prostate: late toxicities and outcomes. Clin Oncol (R Coll Radiol) 28:386–392
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The authors would like to thank Prof. Brian Hawkins for his help in the final revision of the manuscript.
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Nicosia, L., Mazzola, R., Rigo, M. et al. Moderate versus extreme hypofractionated radiotherapy: a toxicity comparative analysis in low- and favorable intermediate-risk prostate cancer patients. J Cancer Res Clin Oncol 145, 2547–2554 (2019). https://doi.org/10.1007/s00432-019-02983-3
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DOI: https://doi.org/10.1007/s00432-019-02983-3