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The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer—Quo Vadimus?

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Abstract

Purpose

Stereotactic body radiotherapy (SBRT) is an emerging treatment option for localized prostate cancer. There is increasing interest to reduce the number of fractions for prostate SBRT.

Methods

We provide a narrative review and summary of prospective trials of different fractionation schedules for prostate SBRT, focusing on efficacy, toxicities, and quality of life outcomes.

Results

There are two randomized phase 3 trials comparing standard external beam radiotherapy with ultra-hypofractionated radiotherapy. HYPO-RT-PC compared 78 Gy in 39 fractions vs 42.7 Gy in 7 fractions (3D-CRT or IMRT) showing non-inferiority in 5-year biochemical recurrence-free survival and equivalent tolerability. PACE-B trial compared 78 Gy in 39-fraction or 62 Gy in 20-fraction vs 36.25 Gy in 5-fraction prostate SBRT, with no significant differences in toxicity outcomes at 2 years. Five-year efficacy data for PACE-B are expected in 2024. Five-fraction prostate SBRT is currently the most common and well-established fractionation schedule with multiple prospective phase 2 trials published to date. There is more limited data on 1–4 fraction prostate SBRT. All fractionation schedules had acceptable toxicity outcomes. Experience from a high-dose-rate brachytherapy randomized trial showed inferior efficacy with single-fraction compared to two-fraction brachytherapy. Hence, caution should be applied in adopting single-fraction prostate SBRT.

Conclusion

Two-fraction SBRT is likely the shortest fractionation schedule that maintains the therapeutic ratio. Several randomized trials currently recruiting will likely provide us with more definite answers about whether two-fraction prostate SBRT should become a standard-of-care option. Enrollment of eligible patients into these trials should be encouraged.

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References

  1. Brenner DJ, Hall EJ (1999) Fractionation and protraction for radiotherapy of prostate carcinoma. Int J Radiat Oncol Biol Phys 43(5):1095–1101

    Article  CAS  PubMed  Google Scholar 

  2. Vogelius IR, Bentzen SM (2020) Diminishing returns from ultrahypofractionated radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys 107(2):299–304

    Article  PubMed  PubMed Central  Google Scholar 

  3. Brenner DJ (2004) Fractionation and late rectal toxicity. Int J Radiat Oncol Biol Phys 60(4):1013–1015

    Article  PubMed  Google Scholar 

  4. Tucker SL et al (2011) Estimation of alpha/beta for late rectal toxicity based on RTOG 94-06. Int J Radiat Oncol Biol Phys 81(2):600–605

    Article  PubMed  PubMed Central  Google Scholar 

  5. Dearnaley D et al (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

    Article  PubMed  PubMed Central  Google Scholar 

  6. Catton CN et al (2017) Randomized trial of a hypofractionated radiation regimen for the treatment of localized prostate cancer. J Clin Oncol 35(17):1884–1890

    Article  CAS  PubMed  Google Scholar 

  7. Lee WR et al (2016) Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer. J Clin Oncol 34(20):2325–2332

    Article  PubMed  PubMed Central  Google Scholar 

  8. Morgan SC et al (2018) Hypofractionated radiation therapy for localized prostate cancer: an ASTRO, ASCO, and AUA evidence-based guideline. J Clin Oncol 36(34):JCO1801097

    Article  PubMed  Google Scholar 

  9. Widmark A et al (2019) Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet 394(10196):385–395

    Article  PubMed  Google Scholar 

  10. Fransson P et al (2021) Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial. Lancet Oncol 22(2):235–245

    Article  PubMed  Google Scholar 

  11. Madsen BL et al (2007) 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 67(4):1099

    Article  PubMed  Google Scholar 

  12. King CR et al (2012) Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. Int J Radiat Oncol Biol Phys 82(2):877–882

    Article  PubMed  Google Scholar 

  13. Katz A, Formenti SC, Kang J (2016) Predicting biochemical disease-free survival after prostate stereotactic body radiotherapy: risk-stratification and patterns of failure. Front Oncol 6:168

    Article  PubMed  PubMed Central  Google Scholar 

  14. Musunuru HB et al (2016) Dose-escalation of five-fraction SABR in prostate cancer: toxicity comparison of two prospective trials. Radiother Oncol 118(1):112–117

    Article  PubMed  Google Scholar 

  15. Alayed Y et al (2018) Dose escalation for prostate stereotactic ablative radiotherapy (SABR): late outcomes from two prospective clinical trials. Radiother Oncol 127(2):213–218

    Article  PubMed  Google Scholar 

  16. McBride SM et al (2012) Hypofractionated stereotactic body radiotherapy in low-risk prostate adenocarcinoma: preliminary results of a multi-institutional phase 1 feasibility trial. Cancer 118(15):3681–3690

    Article  PubMed  Google Scholar 

  17. 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

    Article  PubMed  PubMed Central  Google Scholar 

  18. Meier RM et al (2018) Multicenter trial of stereotactic body radiation therapy for low- and intermediate-risk prostate cancer: survival and toxicity endpoints. Int J Radiat Oncol Biol Phys 102(2):296–303

    Article  PubMed  Google Scholar 

  19. Kataria S et al (2017) Prostate-specific antigen 5 years following stereotactic body radiation therapy for low- and intermediate-risk prostate cancer: an ablative procedure? Front Oncol 7:157

    Article  PubMed  PubMed Central  Google Scholar 

  20. Alayed Y et al (2020) Accelerating prostate stereotactic ablative body radiotherapy: efficacy and toxicity of a randomized phase II study of 11 versus 29 days overall treatment time (PATRIOT). Radiother Oncol 149:8–13

    Article  CAS  PubMed  Google Scholar 

  21. Kishan AU et al (2023) Magnetic resonance imaging-guided vs computed tomography-guided stereotactic body radiotherapy for prostate cancer: the mirage randomized clinical trial. JAMA Oncol 9(3):365–373

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kishan AU et al (2019) Long-term outcomes of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. JAMA Netw Open 2(2):e188006

    Article  PubMed  PubMed Central  Google Scholar 

  23. Brand DH et al (2019) Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Lancet Oncol 20(11):1531–1543

    Article  PubMed  PubMed Central  Google Scholar 

  24. Tree AC et al (2022) Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol 23(10):1308–1320

    Article  PubMed  Google Scholar 

  25. Fuller DB et al (2018) Phase 2 multicenter trial of heterogeneous-dosing stereotactic body radiotherapy for low- and intermediate-risk prostate cancer: 5-year outcomes. Eur Urol Oncol 1(6):540–547

    Article  PubMed  Google Scholar 

  26. Aluwini S et al (2013) 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 8:84

    Article  PubMed  PubMed Central  Google Scholar 

  27. Jabbari S et al (2012) Stereotactic body radiotherapy as monotherapy or post-external beam radiotherapy boost for prostate cancer: technique, early toxicity, and PSA response. Int J Radiat Oncol Biol Phys 82(1):228–234

    Article  PubMed  Google Scholar 

  28. Pontoriero A et al (2016) High-dose robotic stereotactic body radiotherapy in the treatment of patients with prostate cancer: preliminary results in 26 patients. Technol Cancer Res Treat 15(1):179–185

    Article  CAS  PubMed  Google Scholar 

  29. Kawakami S et al (2022) A phase II trial of stereotactic body radiotherapy in 4 fractions for patients with localized prostate cancer. Radiat Oncol 17(1):67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Magli A et al (2021) Toxicity at 1 year after stereotactic body radiation therapy in 3 fractions for localized prostate cancer. Int J Radiat Oncol Biol Phys 111(1):93–100

    Article  PubMed  Google Scholar 

  31. Alayed Y et al (2019) Two StereoTactic ablative radiotherapy treatments for localized prostate cancer (2STAR): results from a prospective clinical trial. Radiother Oncol 135:86–90

    Article  PubMed  Google Scholar 

  32. Ong WL et al (2023) Two-fraction stereotactic ablative radiotherapy with simultaneous boost to MRI-defined dominant intra-prostatic lesion—results from the 2SMART phase 2 trial. Radiother Oncol 181:109503

    Article  PubMed  Google Scholar 

  33. Nicolae A et al (2015) Clinical evaluation of an endorectal immobilization system for use in prostate hypofractionated stereotactic ablative body radiotherapy (SABR). Radiat Oncol 10:122

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ong WL et al (2023) To boost or not to boost: pooled analyses from 2-fraction SABR trials for localized prostate cancer. Int J Radiat Oncol Biol Phys. https://doi.org/10.1016/j.ijrobp.2023.06.250

    Article  PubMed  Google Scholar 

  35. Alayed Y et al (2019) Two versus five stereotactic ablative radiotherapy treatments for localized prostate cancer: a quality of life analysis of two prospective clinical trials. Radiother Oncol 140:105–109

    Article  PubMed  Google Scholar 

  36. Greco C et al (2021) 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 7(5):700–708

    Article  PubMed  Google Scholar 

  37. Zilli T et al (2019) Single fraction urethra-sparing prostate cancer SBRT: Phase I results of the ONE SHOT trial. Radiother Oncol 139:83–86

    Article  PubMed  Google Scholar 

  38. King MT et al (2021) Low dose rate brachytherapy for primary treatment of localized prostate cancer: a systemic review and executive summary of an evidence-based consensus statement. Brachytherapy 20(6):1114–1129

    Article  PubMed  Google Scholar 

  39. Annede P et al (2020) Radiobiology: foundation and new insights in modeling brachytherapy effects. Semin Radiat Oncol 30(1):4–15

    Article  PubMed  Google Scholar 

  40. Morton G et al (2020) 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 146:90–96

    Article  CAS  PubMed  Google Scholar 

  41. Alayed Y et al (2019) MRI assisted focal boost integrated with HDR monotherapy study in low and intermediate risk prostate cancer (MARS): results from a phase II clinical trial. Radiother Oncol 141:144–148

    Article  PubMed  Google Scholar 

  42. Armstrong S et al (2021) Single dose high-dose-rate brachytherapy with focal dose escalation for prostate cancer: mature results of a phase 2 clinical trial. Radiother Oncol 159:67–74

    Article  CAS  PubMed  Google Scholar 

  43. Alayed Y et al (2021) Single-fraction HDR brachytherapy as monotherapy in low and intermediate risk prostate cancer: outcomes from two clinical trials with and without an MRI-guided boost. Radiother Oncol 154:29–35

    Article  PubMed  Google Scholar 

  44. Armstrong S et al (2021) Dosimetry of local failure with single dose 19 Gy high-dose-rate brachytherapy for prostate cancer. Radiother Oncol 157:93–98

    Article  CAS  PubMed  Google Scholar 

  45. Supiot S et al (2019) Reoxygenation during radiotherapy in intermediate-risk prostate cancer. Radiother Oncol 133:16–19

    Article  PubMed  Google Scholar 

  46. Correa RJM et al (2022) Two-fraction stereotactic ablative radiotherapy (SABR) versus two-fraction high dose rate (HDR) brachytherapy for localized prostate cancer: does dose heterogeneity matter? Radiother Oncol 169:51–56

    Article  PubMed  Google Scholar 

  47. Westley R, Hall E, Tree A (2022) HERMES: delivery of a speedy prostate cancer treatment. Clin Oncol (R Coll Radiol) 34(7):426–429

    Article  CAS  PubMed  Google Scholar 

  48. Hall WA et al (2022) Magnetic resonance linear accelerator technology and adaptive radiation therapy: an overview for clinicians. CA Cancer J Clin 72(1):34–56

    Article  PubMed  Google Scholar 

  49. Pathmanathan AU et al (2018) Magnetic resonance imaging-guided adaptive radiation therapy: a “game changer” for prostate treatment? Int J Radiat Oncol Biol Phys 100(2):361–373

    Article  PubMed  Google Scholar 

  50. Harvey M et al (2023) Comprehensive review of the use of hydrogel spacers prior to radiation therapy for prostate cancer. BJU Int 131(3):280–287

    Article  CAS  PubMed  Google Scholar 

  51. Mariados NF et al (2023) Hyaluronic acid spacer for hypofractionated prostate radiation therapy: a randomized clinical trial. JAMA Oncol 9(4):511–518

    Article  PubMed  PubMed Central  Google Scholar 

  52. The BS et al (2002) The use of rectal balloon during the delivery of intensity modulated radiotherapy (IMRT) for prostate cancer: more than just a prostate gland immobilization device? Cancer J 8(6):476–483

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, University of Toronto, Rm T2-161, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada

    Wee Loon Ong & Andrew Loblaw

  2. Alfred Health Radiation Oncology, Monash University, Melbourne, Australia

    Wee Loon Ong

  3. Institute of Health Policy, Measurement and Evaluation, University of Toronto, Toronto, Canada

    Andrew Loblaw

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  1. Wee Loon Ong
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  2. Andrew Loblaw
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Correspondence to Andrew Loblaw.

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Conflict of intrest

Dr Ong: no conflicts. Dr Loblaw: Grants/Research Support: TerSera, Tolmar. Honoraria/Travel: Astellas, Bayer, Janssen, Knight, Sanofi, TerSera Advisory Boards/Consulting: Astellas, Bayer, Janssen, Sanofi, TerSera. Financial Group: Sunnybrook Radiation Oncology Associates Patents/Licenses: Endorectal immobilization device (GU-Lok), Molli.

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Ong, W.L., Loblaw, A. The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer—Quo Vadimus?. World J Urol 41, 3485–3491 (2023). https://doi.org/10.1007/s00345-023-04663-x

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  • DOI: https://doi.org/10.1007/s00345-023-04663-x

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