Top

BMC Cancer

Published in:

Open Access 01-12-2024 | Prostate Cancer | Study Protocol

SABR-Dual: a phase II/III trial of two-fraction versus five-fraction stereotactic radiotherapy for localized low- and favorable intermediate-risk prostate cancer

Authors: Elisha Fredman, Oded Icht, Assaf Moore, Dimitri Bragilovski, Jonathan Kindler, Shay Golan, Dror Limon

Published in: BMC Cancer | Issue 1/2024

Abstract

Background

Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen.

Methods

502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40 Gy in 5 fractions given every-other-day and 27 Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints.

Discussion

This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community.

Trial registration

This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.

Dearnaley DP, Jovic G, Syndikus I, Khoo V, Cowan RA, Graham JD, 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):464–73. https://doi.org/10.1016/S1470-2045(14)70040-3.CrossRefPubMed

Kuban DA, Levy LB, Cheung MR, Lee AK, Choi S, Frank S, 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):1310–7. https://doi.org/10.1016/j.ijrobp.2010.01.006.CrossRefPubMed

Michalski JM, Moughan J, Purdy J, Bosch W, Bruner DW, Bahary JP et al. Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate Cancer: The NRG Oncology RTOG 0126 Randomized Clinical Trial. JAMA Oncol. 2018; 14;4(6):e180039. https://doi.org/10.1001/jamaoncol.2018.0039.

Zietman AL, DeSilvio ML, Slater JD, Rossi CJ, Miller DW, Adams JA, et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA. 2005;294(10):1233–9. https://doi.org/10.1001/jama.294.10.1233.CrossRefPubMed

Michalski JM, Moughan J, Purdy J, Bruner DW, Amin M, Bahary JP, et al. Long-term outcomes of NRG/RTOG 0126, a Randomized Trial of High Dose (79.2 gy) vs. standard dose (70.2 gy) Radiation Therapy (RT) for men with localized prostate Cancer. Int J Radiat Oncol Biol Phys. 2023;117(2):S4–5. https://doi.org/10.1016/j.ijrobp.2023.06.210.CrossRef

Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield 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):1047–60. https://doi.org/10.1016/S1470-2045(16)30102-4.CrossRefPubMedPubMedCentral

Catton CN, Lukka H, Gu CS, Martin JM, Supiot S, Chung PWM, et al. Randomized Trial of a Hypofractionated Radiation Regimen for the treatment of localized prostate Cancer. J Clin Oncol. 2017;35(17):1884–90. https://doi.org/10.1200/JCO.2016.71.7397.CrossRefPubMed

Lee WR, Dignam JJ, Amin MB, Bruner DW, Low DL, Swanson GP, et al. Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in patients with low-risk prostate Cancer. J Clin Oncol. 2016;34(20):2325–32. https://doi.org/10.1200/JCO.2016.67.0448.CrossRefPubMedPubMedCentral

Jackson WC, Silva J, Hartman HE, Dess RT, Kishan AU, Beeler WH, et al. Stereotactic body Radiation Therapy for localized prostate Cancer: a systematic review and Meta-analysis of over 6,000 patients treated on prospective studies. Int J Radiat Oncol Biol Phys. 2019;104(4):778–89. https://doi.org/10.1016/j.ijrobp.2019.03.051.CrossRefPubMedPubMedCentral

10.

Hoffman KE, Penson DF, Zhao Z, Huang L, Conwill R, Laviana AA, et al. Patient-reported outcomes through 5 years for active surveillance, surgery, Brachytherapy, or External Beam Radiation with or without androgen deprivation therapy for localized prostate Cancer. JAMA. 2020;323(2):149–63. https://doi.org/10.1001/jama.2019.20675.CrossRefPubMedPubMedCentral

11.

Pickles T, Morris WJ, Kattan MW, Yu C, Keyes M. Comparative 5-year outcomes of brachytherapy and surgery for prostate cancer. Brachytherapy. 2011;10(1):9–14. https://doi.org/10.1016/j.brachy.2009.12.004.CrossRefPubMed

12.

Viani GA, Arruda CV, Pellizzon ACA, De Fendi LI. HDR brachytherapy as monotherapy for prostate cancer: a systematic review with meta-analysis. Brachytherapy. 2021;20(2):307–14. https://doi.org/10.1016/j.brachy.2020.10.009.CrossRefPubMed

13.

Morton G, McGuffin M, Chung HT, Tseng CL, Helou J, Ravi A, et al. Prostate high dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: efficacy results from a randomized phase II clinical trial of one fraction of 19 gy or two fractions of 13.5 gy. Radiother Oncol. 2020;146:90–6. https://doi.org/10.1016/j.radonc.2020.02.009.CrossRefPubMed

14.

Greco C, Pares O, Pimentel N, Louro V, Santiago I, Vieira S, et al. Safety and Efficacy of virtual prostatectomy with single-dose radiotherapy in patients with intermediate-risk prostate Cancer: results from the PROSINT phase 2 Randomized Clinical Trial. JAMA Oncol. 2021;7(5):700–8. https://doi.org/10.1001/jamaoncol.2021.0039.CrossRefPubMed

15.

Magli A, Farneti A, Faiella A, Ferriero M, Landoni V, Giannarelli D, et al. Toxicity at 1 year after stereotactic body Radiation Therapy in 3 fractions for localized prostate Cancer. Int J Radiat Oncol Biol Phys. 2021;111(1):93–100. https://doi.org/10.1016/j.ijrobp.2021.03.027.CrossRefPubMed

16.

Alayed Y, Cheung P, Chu W, Chung H, Davidson M, Ravi A, et al. Two StereoTactic ablative radiotherapy treatments for localized prostate cancer (2STAR): results from a prospective clinical trial. Radiother Oncol. 2019;135:86–90. https://doi.org/10.1016/j.radonc.2019.03.002.CrossRefPubMed

17.

Kim DWN, Cho LC, Straka C, Christie A, Lotan Y, Pistenmaa D, 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):509–17. https://doi.org/10.1016/j.ijrobp.2014.03.012.CrossRefPubMed

18.

Folkert MR, Zelefsky MJ, Hannan R, Desai NB, Lotan Y, Laine AMA, Multi-Institutional. Phase 2 trial of high-dose SAbR for prostate Cancer using rectal spacer. Int J Radiat Oncol Biol Phys. 2021;111(1):101–9. https://doi.org/10.1016/j.ijrobp.2021.03.025.CrossRefPubMed

19.

Marcello M, Denham JW, Kennedy A, Haworth A, Steigler A, Greer PB, et al. Reduced dose posterior to prostate correlates with increased PSA Progression in Voxel-Based analysis of 3 Randomized phase 3 trials. Int J Radiat Oncol Biol Phys. 2020;108(5):1304–18. https://doi.org/10.1016/j.ijrobp.2020.07.030.CrossRefPubMed

20.

Abramowitz MC, Li T, Buyyounouski MK, et al. The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer. Cancer. 2008;112(1):55–60. https://doi.org/10.1002/cncr.23139.CrossRefPubMed

21.

Gharzai LA, Jiang R, Wallington D, Jones G, Birer S, Jairath N, et al. Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis. Lancet Oncol. 2021;22(3):402–10. https://doi.org/10.1016/S1470-2045(20)30730-0.CrossRefPubMedPubMedCentral

22.

Yahya S, Zarkar A, Southgate E, Nightingale P, Webster G. Which bowel preparation is best? Comparison of a high-fibre diet leaflet, daily microenema and no preparation in prostate cancer patients treated with radical radiotherapy to assess the effect on planned target volume shifts due to rectal distension. Br J Radiol. 2013;86(1031):20130457. https://doi.org/10.1259/bjr.20130457.CrossRefPubMedPubMedCentral

23.

Achard V, Zilli T, Lamanna G, Jorcano S, Bral S, Rubio C et al. Urethra-Sparing Prostate Cancer Stereotactic Body Radiation Therapy: Sexual Function and Radiation Dose to the Penile Bulb, the Crura, and the Internal Pudendal Arteries From a Randomized Phase 2 Trial. Int J Radiat Oncol Biol Phys. 2023:S0360-3016(23)08307-4. https://doi.org/10.1016/j.ijrobp.2023.12.037.

24.

Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. In: Kotz S, Johnson NL, editors. Breakthroughs in statistics. Springer Series in statistics (perspectives in statistics). New York, NY: Springer; 1992. https://doi.org/10.1007/978-1-4612-4380-9_25.CrossRef

25.

Skolarus TA, Dunn RL, Sanda MG, Chang P, Greenfield TK, Litwin MS, et al. Minimally important difference for the expanded prostate Cancer Index Composite Short Form. Urology. 2015;85(1):101–5. https://doi.org/10.1016/j.urology.2014.08.044.CrossRefPubMed

26.

Kawakami S, Tsumura H, Satoh T, Tabata K, Sekiguchi A, Kainuma T, et al. A phase II trial of stereotactic body radiotherapy in 4 fractions for patients with localized prostate cancer. Radiat Oncol. 2022;17(1):67. https://doi.org/10.1186/s13014-022-02037-y.CrossRefPubMedPubMedCentral

27.

Zilli T, Franzese C, Guckenberger M, Giaj-Levra N, Mach N, Koutsouvelis N, et al. ONE SHOT - single shot radiotherapy for localized prostate cancer: 18-month results of a single arm, multicenter phase I/II trial. Radiother Oncol. 2024;194:110181. https://doi.org/10.1016/j.radonc.2024.110181.CrossRefPubMed

28.

Kishan AU, Ma TM, Lamb JM, Casado M, Wilhalme H, Low DA, et al. Magnetic resonance imaging-guided vs computed tomography-guided stereotactic body radiotherapy for prostate Cancer: the MIRAGE Randomized Clinical Trial. JAMA Oncol. 2023;9(3):365–73. https://doi.org/10.1001/jamaoncol.2022.6558.CrossRefPubMedPubMedCentral

29.

Folkert MR, Zelefsky MJ, Hannan R, Desai NB, Lotan Y, Laine AM, et al. A multi-institutional phase 2 trial of high-dose SAbR for prostate Cancer using rectal spacer. Int J Radiat Oncol Biol Phys. 2021;111(1):101–9. https://doi.org/10.1016/j.ijrobp.2021.03.025.CrossRefPubMed

30.

Armstrong N, Bahl A, Pinkawa M, Ryder S, Ahmadu C, Ross J, et al. SpaceOAR Hydrogel Spacer for reducing Radiation Toxicity during Radiotherapy for prostate Cancer. Syst Rev Urol. 2021;156:e74–85. https://doi.org/10.1016/j.urology.2021.05.013.CrossRef

Title: SABR-Dual: a phase II/III trial of two-fraction versus five-fraction stereotactic radiotherapy for localized low- and favorable intermediate-risk prostate cancer
Authors: Elisha Fredman
Oded Icht
Assaf Moore
Dimitri Bragilovski
Jonathan Kindler
Shay Golan
Dror Limon
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Prostate Cancer
Prostate Cancer
Radiotherapy
Brachytherapy
Published in: BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-024-12165-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2024

CLEC19A overexpression inhibits tumor cell proliferation/migration and promotes apoptosis concomitant suppression of PI3K/AKT/NF-κB signaling pathway in glioblastoma multiforme

MMP-11 expression in early luminal breast cancer: associations with clinical, MRI, pathological characteristics, and disease-free survival

Metabolic difference between patient-derived xenograft model of pancreatic ductal adenocarcinoma and corresponding primary tumor

A nomogram based on the quantitative and qualitative features of CT imaging for the prediction of the invasiveness of ground glass nodules in lung adenocarcinoma

Effects of physical and psychological symptoms on cancer-related fatigue among esophageal cancer patients

Oncological risk of proximal gastrectomy for proximal advanced gastric cancer after neoadjuvant chemotherapy

Keynote webinar | Spotlight on antibody–drug conjugates in cancer