A systematic review of hypofractionation for primary management of prostate cancer

Bridget F. Koontz, Alberto Bossi, Cesare Cozzarini, Thomas Wiegel, Anthony D'Amico

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Context Technological advances in radiation therapy delivery have permitted the use of high-dose-per-fraction radiation therapy (RT) for early-stage prostate cancer (PCa). Level 1 evidence supporting the safety and efficacy of hypofractionated RT is evolving as this modality becomes more widely utilized and refined. Objective To perform a systematic review of the current evidence on the safety and efficacy of hypofractionated RT for early-stage PCa and to provide in-context recommendations for current application of this technology. Evidence acquisition Embase, PubMed, and Scopus electronic databases were queried for English-language articles from January 1990 through June 2014. Prospective studies with a minimum of 50 patients were included. Separate consideration was made for studies involving moderate hypofractionation (doses of 2.5-4 Gy per fraction) and extreme hypofractionation (5-10 Gy in 4-7 fractions). Evidence synthesis Six relatively small superiority designed randomized trials of standard fractionation versus moderate hypofractionation in predominantly low- and intermediate-risk PCa have been published with follow-up ranging from 4 to 8 yr, noting similar biochemical control (5-yr freedom from biochemical failure in modern studies is >80% for low-risk and intermediate-risk patients) and late grade ≥2 genitourinary and gastrointestinal toxicities (between 2% and 20%). Noninferiority studies are pending. In prospective phase 2 studies, extreme hypofractionation has promising 2- to 5-yr biochemical control rates of >90% for low-risk patients. Results from a randomized trial are expected in 2015. Conclusions Moderate hypofractionation has 5-yr data to date establishing safety compared with standard fractionation, but 10-yr outcomes and longer follow-up are needed to establish noninferiority for clinical effectiveness. Extreme hypofractionation is promising but as yet requires reporting of randomized data prior to application outside of a clinical protocol. Patient summary Hypofractionation for prostate cancer delivers relatively high doses of radiation per treatment. Prospective studies support the safety of moderate hypofractionation, while extreme fractionation may have greater toxicity. Both show promising cancer control but long-term results of noninferiority studies of both methods are required before use in routine treatment outside of clinical protocols.

Original languageEnglish
Pages (from-to)683-691
Number of pages9
JournalEuropean Urology
Volume68
Issue number4
DOIs
Publication statusPublished - Oct 1 2015

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Prostatic Neoplasms
Radiotherapy
Safety
Clinical Protocols
Prospective Studies
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Research Design
Language
Databases
Radiation
Technology
Therapeutics
Neoplasms

Keywords

  • Gastrointestinal toxicity
  • Genitourinary toxicity
  • Hypofractionation
  • Prostate cancer
  • Prostate-specific antigen
  • Randomized trials
  • Stereotactic radiation therapy

ASJC Scopus subject areas

  • Urology

Cite this

A systematic review of hypofractionation for primary management of prostate cancer. / Koontz, Bridget F.; Bossi, Alberto; Cozzarini, Cesare; Wiegel, Thomas; D'Amico, Anthony.

In: European Urology, Vol. 68, No. 4, 01.10.2015, p. 683-691.

Research output: Contribution to journalArticle

Koontz, Bridget F. ; Bossi, Alberto ; Cozzarini, Cesare ; Wiegel, Thomas ; D'Amico, Anthony. / A systematic review of hypofractionation for primary management of prostate cancer. In: European Urology. 2015 ; Vol. 68, No. 4. pp. 683-691.
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title = "A systematic review of hypofractionation for primary management of prostate cancer",
abstract = "Context Technological advances in radiation therapy delivery have permitted the use of high-dose-per-fraction radiation therapy (RT) for early-stage prostate cancer (PCa). Level 1 evidence supporting the safety and efficacy of hypofractionated RT is evolving as this modality becomes more widely utilized and refined. Objective To perform a systematic review of the current evidence on the safety and efficacy of hypofractionated RT for early-stage PCa and to provide in-context recommendations for current application of this technology. Evidence acquisition Embase, PubMed, and Scopus electronic databases were queried for English-language articles from January 1990 through June 2014. Prospective studies with a minimum of 50 patients were included. Separate consideration was made for studies involving moderate hypofractionation (doses of 2.5-4 Gy per fraction) and extreme hypofractionation (5-10 Gy in 4-7 fractions). Evidence synthesis Six relatively small superiority designed randomized trials of standard fractionation versus moderate hypofractionation in predominantly low- and intermediate-risk PCa have been published with follow-up ranging from 4 to 8 yr, noting similar biochemical control (5-yr freedom from biochemical failure in modern studies is >80{\%} for low-risk and intermediate-risk patients) and late grade ≥2 genitourinary and gastrointestinal toxicities (between 2{\%} and 20{\%}). Noninferiority studies are pending. In prospective phase 2 studies, extreme hypofractionation has promising 2- to 5-yr biochemical control rates of >90{\%} for low-risk patients. Results from a randomized trial are expected in 2015. Conclusions Moderate hypofractionation has 5-yr data to date establishing safety compared with standard fractionation, but 10-yr outcomes and longer follow-up are needed to establish noninferiority for clinical effectiveness. Extreme hypofractionation is promising but as yet requires reporting of randomized data prior to application outside of a clinical protocol. Patient summary Hypofractionation for prostate cancer delivers relatively high doses of radiation per treatment. Prospective studies support the safety of moderate hypofractionation, while extreme fractionation may have greater toxicity. Both show promising cancer control but long-term results of noninferiority studies of both methods are required before use in routine treatment outside of clinical protocols.",
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AU - Bossi, Alberto

AU - Cozzarini, Cesare

AU - Wiegel, Thomas

AU - D'Amico, Anthony

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Context Technological advances in radiation therapy delivery have permitted the use of high-dose-per-fraction radiation therapy (RT) for early-stage prostate cancer (PCa). Level 1 evidence supporting the safety and efficacy of hypofractionated RT is evolving as this modality becomes more widely utilized and refined. Objective To perform a systematic review of the current evidence on the safety and efficacy of hypofractionated RT for early-stage PCa and to provide in-context recommendations for current application of this technology. Evidence acquisition Embase, PubMed, and Scopus electronic databases were queried for English-language articles from January 1990 through June 2014. Prospective studies with a minimum of 50 patients were included. Separate consideration was made for studies involving moderate hypofractionation (doses of 2.5-4 Gy per fraction) and extreme hypofractionation (5-10 Gy in 4-7 fractions). Evidence synthesis Six relatively small superiority designed randomized trials of standard fractionation versus moderate hypofractionation in predominantly low- and intermediate-risk PCa have been published with follow-up ranging from 4 to 8 yr, noting similar biochemical control (5-yr freedom from biochemical failure in modern studies is >80% for low-risk and intermediate-risk patients) and late grade ≥2 genitourinary and gastrointestinal toxicities (between 2% and 20%). Noninferiority studies are pending. In prospective phase 2 studies, extreme hypofractionation has promising 2- to 5-yr biochemical control rates of >90% for low-risk patients. Results from a randomized trial are expected in 2015. Conclusions Moderate hypofractionation has 5-yr data to date establishing safety compared with standard fractionation, but 10-yr outcomes and longer follow-up are needed to establish noninferiority for clinical effectiveness. Extreme hypofractionation is promising but as yet requires reporting of randomized data prior to application outside of a clinical protocol. Patient summary Hypofractionation for prostate cancer delivers relatively high doses of radiation per treatment. Prospective studies support the safety of moderate hypofractionation, while extreme fractionation may have greater toxicity. Both show promising cancer control but long-term results of noninferiority studies of both methods are required before use in routine treatment outside of clinical protocols.

AB - Context Technological advances in radiation therapy delivery have permitted the use of high-dose-per-fraction radiation therapy (RT) for early-stage prostate cancer (PCa). Level 1 evidence supporting the safety and efficacy of hypofractionated RT is evolving as this modality becomes more widely utilized and refined. Objective To perform a systematic review of the current evidence on the safety and efficacy of hypofractionated RT for early-stage PCa and to provide in-context recommendations for current application of this technology. Evidence acquisition Embase, PubMed, and Scopus electronic databases were queried for English-language articles from January 1990 through June 2014. Prospective studies with a minimum of 50 patients were included. Separate consideration was made for studies involving moderate hypofractionation (doses of 2.5-4 Gy per fraction) and extreme hypofractionation (5-10 Gy in 4-7 fractions). Evidence synthesis Six relatively small superiority designed randomized trials of standard fractionation versus moderate hypofractionation in predominantly low- and intermediate-risk PCa have been published with follow-up ranging from 4 to 8 yr, noting similar biochemical control (5-yr freedom from biochemical failure in modern studies is >80% for low-risk and intermediate-risk patients) and late grade ≥2 genitourinary and gastrointestinal toxicities (between 2% and 20%). Noninferiority studies are pending. In prospective phase 2 studies, extreme hypofractionation has promising 2- to 5-yr biochemical control rates of >90% for low-risk patients. Results from a randomized trial are expected in 2015. Conclusions Moderate hypofractionation has 5-yr data to date establishing safety compared with standard fractionation, but 10-yr outcomes and longer follow-up are needed to establish noninferiority for clinical effectiveness. Extreme hypofractionation is promising but as yet requires reporting of randomized data prior to application outside of a clinical protocol. Patient summary Hypofractionation for prostate cancer delivers relatively high doses of radiation per treatment. Prospective studies support the safety of moderate hypofractionation, while extreme fractionation may have greater toxicity. Both show promising cancer control but long-term results of noninferiority studies of both methods are required before use in routine treatment outside of clinical protocols.

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KW - Genitourinary toxicity

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KW - Prostate cancer

KW - Prostate-specific antigen

KW - Randomized trials

KW - Stereotactic radiation therapy

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