Hypofractionation for clinically localized prostate cancer
- PMID: 31476800
- PMCID: PMC6718288
- DOI: 10.1002/14651858.CD011462.pub2
Hypofractionation for clinically localized prostate cancer
Abstract
Background: Using hypofractionation (fewer, larger doses of daily radiation) to treat localized prostate cancer may improve convenience and resource use. For hypofractionation to be feasible, it must be at least as effective for cancer-related outcomes and have comparable toxicity and quality of life outcomes as conventionally fractionated radiation therapy.
Objectives: To assess the effects of hypofractionated external beam radiation therapy compared to conventionally fractionated external beam radiation therapy for men with clinically localized prostate cancer.
Search methods: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and trials registries from 1946 to 15 March 2019 with reference checking, citation searching and contact with study authors. Searches were not limited by language or publication status. We reran all searches within three months (15th March 2019) prior to publication.
Selection criteria: Randomized controlled comparisons which included men with clinically localized prostate adenocarcinoma where hypofractionated radiation therapy (external beam radiation therapy) to the prostate using hypofractionation (greater than 2 Gy per fraction) compared with conventionally fractionated radiation therapy to the prostate delivered using standard fractionation (1.8 Gy to 2 Gy per fraction).
Data collection and analysis: We used standard Cochrane methodology. Two authors independently assessed trial quality and extracted data. We used Review Manager 5 for data analysis and meta-analysis. We used the inverse variance method and random-effects model for data synthesis of time-to-event data with hazard ratios (HR) and 95% confidence intervals (CI) reported. For dichotomous data, we used the Mantel-Haenzel method and random-effects model to present risk ratios (RR) and 95% CI. We used GRADE to assess evidence quality for each outcome.
Main results: We included 10 studies with 8278 men in our analysis comparing hypofractionation with conventional fractionation to treat prostate cancer.Primary outcomesHypofractionation may result in little or no difference in prostate cancer-specific survival [PC-SS] (HR 1.00, 95% CI 0.72 to 1.39; studies = 8, participants = 7946; median follow-up 72 months; low-certainty evidence). For men in the intermediate-risk group undergoing conventional fractionation this corresponds to 976 per 1000 men alive after 6 years and 0 more (44 fewer to 18 more) alive per 1000 men undergoing hypofractionation.We are uncertain about the effect of hypofractionation on late radiation therapy gastrointestinal (GI) toxicity (RR 1.10, 95% CI 0.68 to 1.78; studies = 4, participants = 3843; very low-certainty evidence).Hypofractionation probably results in little or no difference to late radiation therapy genitourinary (GU) toxicity (RR 1.05, 95% CI 0.93 to 1.18; studies = 4, participants = 3843; moderate-certainty evidence). This corresponds to 262 per 1000 late GU radiation therapy toxicity events with conventional fractionation and 13 more (18 fewer to 47 more) per 1000 men when undergoing hypofractionation.Secondary outcomesHypofractionation results in little or no difference in overall survival (HR 0.94, 95% CI 0.83 to 1.07; 10 studies, 8243 participants; high-certainty evidence). For men in the intermediate-risk group undergoing conventional fractionation this corresponds to 869 per 1000 men alive after 6 years and 17 fewer (54 fewer to 17 more) participants alive per 1000 men when undergoing hypofractionation.Hypofractionation may result in little to no difference in metastasis-free survival (HR 1.07, 95% CI 0.65 to 1.76; 5 studies, 4985 participants; low-certainty evidence). This corresponds to 981 men per 1000 men metastasis-free at 6 years when undergoing conventional fractionation and 5 more (58 fewer to 19 more) metastasis-free per 1000 when undergoing hypofractionation.Hypofractionation likely results in a small, possibly unimportant reduction in biochemical recurrence-free survival based on Phoenix criteria (HR 0.88, 95% CI 0.68 to 1.13; studies = 5, participants = 2889; median follow-up 90 months to 108 months; moderate-certainty evidence). In men of the intermediate-risk group, this corresponds to 804 biochemical-recurrence free men per 1000 participants at six years with conventional fractionation and 42 fewer (134 fewer to 37 more) recurrence-free men per 1000 participants with hypofractionationHypofractionation likely results in little to no difference to acute GU radiation therapy toxicity (RR 1.03, 95% CI 0.95 to 1.11; 4 studies, 4174 participants at 12 to 18 weeks' follow-up; moderate-certainty evidence). This corresponds to 360 episodes of toxicity per 1000 participants with conventional fractionation and 11 more (18 fewer to 40 more) per 1000 when undergoing hypofractionation.
Authors' conclusions: These findings suggest that moderate hypofractionation (up to a fraction size of 3.4 Gy) results in similar oncologic outcomes in terms of disease-specific, metastasis-free and overall survival. There appears to be little to no increase in both acute and late toxicity.
Conflict of interest statement
BH: received financial support from the Princess Alexandra Cancer Collaborative Group (PAH CCG), which funded a research assistant for handsearching and data management.
MLJ: none.
TD: none.
FYS: none.
MJ: none.
Figures
Update of
- doi: 10.1002/14651858.CD011462
References
References to studies included in this review
Arcangeli 2010 {published data only}
-
- Arcangeli G, Fowler J, Gomellini S, Arcangeli S, Saracino B, Petrongari M, et al. Acute and late toxicity in a randomized trial of conventional versus hypofractionated three‐dimensional conformal radiotherapy for prostate cancer. International Journal of Radiation Oncology, Biology, Physics 2011;79(4):1013‐21. - PubMed
-
- Arcangeli G, Fowler J, Gomellini S, Arcangeli S, Saracino B, Petrongari MG, et al. A phase III randomized study of high‐dose conventional versus hypofractionated radiotherapy in patients with high‐risk prostate cancer. International Journal of Radiation Oncology, Biology, Physics 2009;75(3):S79.
-
- Arcangeli G, Saracino B, Arcangeli S, Gomellini S, Petrongari MG, Sanguinetti G, et al. Moderate hypofractionation in high‐risk, organ‐confined prostate cancer: final results of a phase III randomised controlled trial. Journal of Clinical Oncology 2017;35(17):1891‐7. [DOI: 10.1200/JCO.2016.70.4189] - DOI - PubMed
-
- Arcangeli G, Saracino B, Gomellini S, Petrongari M, Arcangeli G, Sentinelli S, et al. A prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high‐risk prostate cancer. International Journal of Radiation Oncology, Biology, Physics 2010;78(1):11‐8. - PubMed
-
- Arcangeli S, Strigari L, Gomellini S, Saracino B, Petrongari M, Pinnaro P, et al. Updated results and pattern of failure in a randomized hypofractionation trial for high‐risk prostate cancer. International Journal of Radiation Oncology, Biology, Physics 2012;84(3):S147. - PubMed
CHHiP 2016 {published data only}
-
- CHHiP Trial Management Committee. Conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer protocol version 9.2. www.thelancet.com/cms/10.1016/S1470‐2045(11)70293‐5/attachment/69c8416a‐... (accessed 10 March 2019).
-
- Dearnaley D, Griffin CL, Syndikus I, Scrase C, Thomas S, Naismith O. IGRT for prostate cancer: results from the CHHiP IGRT phase II sub‐study. Radiotherapy and Oncology 2014;19(1):S59.
-
- Dearnaley D, Syndikus E, Mossop H, Khoo V, BIrtle A, Bloomfield D, et al. Conventional versus hypo‐fractionated high‐dose intensity modulated radiotherapy for prostate cancer: 5‐year outcomes of the randomised, non‐inferiority, phase 3 CHHiP trial. Lancet Oncology 2016;17(8):1047‐60. [DOI: 10.2016/S1470-2045(16)30102-4] - DOI - PMC - PubMed
-
- Dearnaley D, Syndikus I, Mossop H, Birtle A, Bloomfield D, Cruickshank C, et al. 5 year outcomes of a phase III randomised trial of conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer (CRUK/06/016): report from the CHHiP Trial Investigators Group. European Journal of Oncology 2015;51:S712.
Fox Chase 2013 {published data only}
-
- Jean‐Pierre P, Stoyanova R, Penedo F, Antoni M, Abramowitz M, Buyyounouski M, et al. Treatment‐related side effects and quality of life among prostate cancer patients treated with conventional versus hypofractionated intensity mediated radiotherapy: a phase iii hypofractionation trial. International Journal of Radiation Oncology, Biology, Physics 2011;2:S667.
-
- Konski AA, Buyyounouski MK, Stoyanova R, Movsas B, Uzzo R, Horwitz EM, et al. Quality adjusted survival comparing standard versus hypofractionated radiation therapy in the treatment of prostate cancer. International Journal of Radiation Oncology, Biology, Physics 2015;93(3):S118‐9.
-
- NCT00062309. A phase III intensity modulated radiotherapy dose escalation trial for prostate cancer using hypofractionation. clinicaltrials.gov/ct2/show/NCT00062309 (first received 6 June 2003).
-
- Pollack A, Bae K, Khor LY, Hammond E, Al‐Saleem T Li T, et al. Stability of tumor biomarkers in archival tissue from men treated with radiotherapy for prostate cancer: an analysis of RTOG 92‐02 and Fox Chase randomized trials. International Journal of Radiation Oncology Biology, Physics. 2006; Vol. 66 3S:S365‐S366.
HYPRO Dutch 2016 {unpublished data only}
-
- Aluwini S, Pos F, Schimmel E, Krol S, Toorn PP, Jager H, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): late toxicity results from a randomised, non‐inferiority, phase 3 trial. Lancet Oncology 2016;17(4):464‐74. - PubMed
-
- Aluwini S, Pos F, Schimmel E, Lin E, Krol S, Toorn PP, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): acute toxicity results from a randomised non‐inferiority phase 3 trial. Lancet Oncology 2015;16(3):274‐83. - PubMed
-
- Aluwini S, Pos F, Lin E, Schimmel E, Krol A, Toorn P, et al. Acute toxicity of the randomized phase III Dutch Hypofractionation trial (HYPRO) for prostate cancer. Radiotherapy and Oncology 2012;103:S84‐5.
-
- Heemsbergen W, Incrocci I, Vens C, Witte M, Aluwini S, Pos F, et al. More acute proctitis symptoms with hypofractionation (3.4Gy) than 2 Gy fractions. Radiotherapy and Oncology 2016;119 S1:S155‐6.
-
- Heemsbergen W, Wortel R, Pos F, Smeenk R, Kro S, Aluwini S, et al. Patient‐reported outcome in the prostate HYPRO trial: gastrointestinal toxicity. Radiotherapy and Oncology 2017;123:S60.
Lee 2016 {unpublished data only}
-
- Lee RW, Dignam JJ, Amin MB, Bruner DW, Low D, Swanson GP, et al. NRD Oncology RTOG 0415: a randomized phase III non‐inferiority study comparing two fractionation schedules in men with low‐risk prostate cancer. International Journal of Radiation Oncology, Biology, Physics 2016;94 1S:S3.
-
- NCT00331773. A phase III randomized study of hypofractionated 3D‐CRT/MRT versus conventionally fractionated 3D‐CRT/MRT in patients with favorable‐risk prostate cancer. clinicaltrials.gov/ct2/show/NCT00331773 (first received 31 May 2006).
-
- Watkins Bruner D, Pugh SL, Lee WR, Dignam JJ, Low D, Swanson GP, et al. NRG Oncology/RTOG 0415, Phase 3 noninferiority study comparing 2 fractionation schedules in patients with low‐risk prostate cancer: prostate‐specific quality of life results. International Journal of Radiation Oncology, Biology, Physics 2016;96(2S):S2‐3.
Lukka NCIC 2005 {published data only}
-
- Lukka H, Hayter C, Julian JA, Warde P, Morris WJ, Gospodarowicz M, et al. Randomized trial comparing two fractionation schedules for patients with localized prostate cancer. Journal of Clinical Oncology 2005;23(25):6132‐8. - PubMed
-
- Lukka H, Hayter C, Warde P, Morris J, Julian J, Gospodarowicz M, et al. on behalf of Investigators. A randomized trial comparing two fractionation schedules for patients with localized prostate cancer. International Journal of Radiation Oncology, Biology, Physics 2003;57(2):S126. - PubMed
-
- NCT00201916. A randomized trial of a shorter radiation fractionation schedule for the treatment of localized prostate cancer. clinicaltrials.gov/ct2/show/NCT00201916 (first received 20 September 2005).
MDACC 2014 {published data only}
-
- Hoffman K, Voong KR, Levy LB, Pugh TJ, Munsell MF, Choi S, et al. Randomized trial of hypofractionated dose‐escalated IMRT vs conventionally fractionated IMRT for localized prostate cancer. International Journal of Radiation Oncology, Biology, Physics 2016;96 2S:S32.
-
- Hoffman KE, Skinner H, Pugh TJ, Voong KR, Levy LB, Choi S, et al. Patient‐reported urinary, bowel, and sexual function after hypofractionated intensity‐modulated radiation therapy for prostate cancer results from a randomized trial. American Journal of Clinical Oncology 2018;41:558‐67. - PubMed
-
- Hoffman KE, Skinner H, Pugh TJ, Voong KR, Levy LB, Choi S, et al. Patient‐reported urinary, bowel, and sexual function after hypofractionated intensity‐modulated radiation therapy for prostate cancer: results from a randomized trial. journals.lww.com/amjclinicaloncology/Abstract/publishahead/Patient_repor... (accessed 24 May 2017). [DOI: 10.1097/COC.0000000000000325] - DOI - PubMed
-
- Hoffman KE, Voong KR, Levy LB, Allen PK, Choi S, Schlembach PJ, et al. Randomized trial of hypofractionated, dose‐escalated, intensity‐modulated radiation therapy (IMRT) versus conventionally fractionated IMRT for localized prostate cancer. Journal of Clinical Oncology 2018;36(29):2943‐9. - PMC - PubMed
-
- Hoffman KE, Voong KR, Pugh TJ, Skinner H, Levy LB Takair V, et al. Risk of late toxicity in men receiving dose‐escalated hypo‐fractionated intensity modulated prostate radiation therapy: results from a randomized trial. International Journal of Radiation Oncology, Biology, Physics 2014;88(5):1074‐84. - PubMed
Norkus 2009 {published data only}
-
- Norkus D, Miller A, Kurtinaitis J, Haverkamp U, Popov S, Prott FJ. A randomized trial comparing hypofractionated and conventionally fractionated three‐dimensional external‐beam radiotherapy for localized prostate adenocarcinoma: a report on acute toxicity. Strahlentherapie Onkologie 2009;185(11):715‐21. [DOI: 10.1007/s00066-009-1982-z] - DOI - PubMed
-
- Norkus D, Miller A, Plieskiene A, Janulionis E, Valuka KV. A randomized trial comparing hypofractionated and conventionally fractionated three‐dimensional conformal external beam radiotherapy for localized prostate adenocarcinoma: a report on the first‐year biochemical response. Medicina (Kaunas) 2009;45(6):469‐75. - PubMed
-
- Norkus D, Valuckas KP, Miller A, Plieskienė A, Kurtinaitis J. Safety investigation of hypofractionated prostate gland radiotherapy [Neišplitusio priešinės liaukos vėžio hipofrakcionuoto spindulinio gydymo saugumo tyrimas]. Medicina 2005;41(12):1035. - PubMed
PROFIT 2016 {unpublished data only}
-
- Catton C, on behalf of the PROFIT trial investigators. A randomized trial of a shorter radiation fractionation schedule for the treatment of localized prostate cancer. International Journal of Radiation Oncology, Biology, Physics 2016;96(2S):32‐3. [Abstract #5003]
-
- Healy B, Kron T, Frantzis J, Thompson K, Murry R, Catton C, et al. Multi‐centre Australian dosimetric inter‐comparison of prostate IMRT delivery for the OCOG PROFIT trial. Journal of Medical Imaging and Radiation Therapy 2009;53 S1:A64.
-
- ISRCTN43853433. A randomised trial of a shorter radiation fraction schedule for the treatment of localised prostate cancer. www.isrctn.com/ISRCTN43853433 (first received 5 November 2007). [DOI: 10.1186/ISRCTN43853433] - DOI
-
- MIddleton M, Frantzis J, Healy B, Jones M, Murry R, Kron T, et al. Successful implementation of image‐guided radiation therapy quality assurance implementation in the Trans Tasman Radiation Oncology Group 08.01 PROFIT Study. International Journal of Radiation Oncology, Biology, Physics 2011;81(5):1576‐81. - PubMed
Yeoh 2011 {published data only}
-
- Yeoh EE, Botten RJ, Butters J, Matteo AC, Holloway RH, Fowler J. Anorectal dysfunction increases with time following radiation therapy for carcinoma of the prostate. International Journal of Radiation Oncology, Biology, Physics 2004;99(2):361‐9. - PubMed
-
- Yeoh EE, Botten RJ, Butters J, Matteo AC, Holloway RH, Fowler J. Hypofractionated versus conventionally fractionated radiotherapy for prostate carcinoma: final results of phase III randomized trial. International Journal of Radiation Oncology, Biology, Physics 2011;81(5):1271‐8. - PubMed
-
- Yeoh EE, Fraser RJ, McGowan RE, Botten RJ, Matteo AC, Roos DE, et al. Evidence for efficacy without increased toxicity of hypofractionated radiotherapy for prostate carcinoma: early results of a Phase III randomized trial. International Journal of Radiation Oncology, Biology, Physics 2003;55(4):943‐55. - PubMed
-
- Yeoh EE, Holloway RH, Fraser RJ, Botten RJ, Matteo AC, Butters J, et al. Hypofractionated versus conventionally fractionated radiation therapy for prostate carcinoma: updated results of a phase III randomized trial. International Journal of Radiation Oncology, Biology, Physics 2006;66(4):1072‐83. - PubMed
-
- Yeoh EK, Holloway RH, Fraser RJ, Botten R, Matteo A, Moore JW. Anorectal function after three‐ versus two‐dimensional radiation therapy for carcinoma of the prostate. International Journal of Radiation Oncology, Biology, Physics 2009;73(1):46‐52. - PubMed
References to studies excluded from this review
MRC RT01 {published data only}
-
- Dearnaley DP, Sydes AM, Langley RE, Graham JD, Huddart RA, Syndikus I, et al. The early toxicity of escalated versus standard dose conformal radiotherapy with neo‐adjuvant androgen suppression for patients with localised prostate cancer: results from the MRC RT01 trial (ISCTN47772397). Radiotherapy and Oncology 2007;83:31‐41. - PubMed
NCT01230866 {unpublished data only}
-
- NCT01230866. A phase III prospective randomized trial of standard‐fractionation vs. hypo‐fractionation with proton radiation therapy for low risk adenocarcinoma of the prostate. clinicaltrials.gov/ct2/show/NCT01230866 (first received 29 October 2010).
NCT01444820 {published data only}
-
- NCT01444820. Phase III study of hypofractionated, dose escalation radiotherapy for high risk adenocarcinoma of the prostate, using 3D‐CRT or intensity‐modulated radiotherapy. clinicaltrials.gov/ct2/show/NCT01444820 (first received 3 October 2011).
NCT01794403 {published data only}
-
- Pollack A, Abramowitz M. Radiation hypofractionation via extended versus accelerated therapy (HEAT) for prostate cancer (HEAT). clinicaltrials.gov/ct2/show/NCT01794403 (first received 18 February 2013).
NCT02303327 {unpublished data only}
-
- NCT02303327. Phase III study of hypofractionated, dose escalation radiotherapy vs. conventional pelvic radiation therapy followed by HDR brachy boost for high risk adenocarcinoma of the prostate. clinicaltrials.gov/ct2/show/NCT02303327 (first received 27 November 2014).
Norkus 2013 {published data only}
References to studies awaiting assessment
El‐Ghamrawi 2015 {published data only}
-
- El‐Ghamrawi K, El‐Haddad M, Hanna S, Kali A, Amal M. Hypofractionated simultaneous integrated boost (SIB) versus conventional fractionation in localized prostate cancer: a randomized pilot study. Gulf Journal of Oncology 2015;1(18):44‐53. - PubMed
Felix 2012 {unpublished data only}
-
- Felix AL, Huerta J, Calva A, Reyes J, Ceja F. Morbidity results in a prospective randomized trial of hypofractionation versus standard fractionation for prostate cancer using conformal radiation therapy. International Journal of Radiation Oncology, Biology, Physics 2012;84(3S):379.
ISRCTN45905321 {unpublished data only}
-
- ISRCTN45965321. Phase III study of HYPOfractionated radiotherapy of intermediate risk localised prostate cancer. www.isrctn.com/ISRCTN45905321 (first received 9 December 2008).
-
- Widmark A, Gunnlaugsson A, Beckman L, Thellenberg‐Karlsson C, Hoyer M, Lagerlund M, et al. Extreme hypofractionation versus conventionally fractionated radiotherapy for intermediate risk prostate cancer: early toxicity results from the Scandinavian randomized phase III trial "HYPO‐RT‐PC". International Journal of Radiation Oncology, Biology, Physics 2016;96(5):938.
-
- Widmark A, Gunnlaugsson A, Beckman L, Thellenberg‐Karlsson C, Hoyer M, Lagerlund M, et al. Ultrahypofractionation for prostate cancer: outcome from the Scandinavian phase 3 HYPO‐RT‐PC trial. Radiotherapy and Oncology 2018;128:S314.
Spagnoletti 2011 {unpublished data only}
-
- Spagnoletti G, Marchese R, Rignanese R, Leo AM, Verile V, Plotino G, et al. Hypofractionation versus conventionally fractionated radiation therapy for prostate cancer: late toxicity. International Journal of Radiation Oncology, Biology, Physics 2011;31(5):1887‐8.
-
- Spagnoletti G, Rignanese R, Cocco G, Oriolo V, Piserchia M, Enfasiet M, et al. Biochemical control after radiation therapy for prostate cancer: hypofractionation versus conventional fractionation. Anticancer Research 2013;33(5):2307‐2308.
-
- Spagnoletti G, Rignanese R, Verile V, Plotino G, Oriolo V, Bove G. Hypofractionation versus conventionally fractionated radiation therapy for prostate cancer: first results. International Journal of Radiation Oncology, Biology, Physics 2010;30(4):1472‐3.
References to ongoing studies
NCT01411332 {published data only}
-
- NCT01411332. A phase III trial of hypofractionated external beam image‐guided highly targeted radiotherapy: the HEIGHT trial. www.clinicaltrials.gov/ct2/show/NCT01411332 (first received 8 August 2011).
NCT01584258 {published data only}
-
- NCT01584258. International randomised study of laparoscopic prostatectomy vs stereotactic body radiotherapy (SBRT) and conventionally fractionated radiotherapy vs SBRT for early stage organ‐confined prostate cancer. www.clinicaltrials.gov/ct2/show/NCT01584258 (first received 24 April 2012).
NCT02300389 {unpublished data only}
-
- NCT02300389. Randomized, multi‐center clinical trial comparing hypofractionated radiotherapy boost to conventionally fractionated in a high risk group of prostate cancer patients. clinicaltrials.gov/ct2/show/NCT02300389 (first received 24 November 2014).
NCT02934685 {unpublished data only}
-
- NCT02934685. A phase III randomized study of hypofractionated image‐guided volumetric modulated arc radiotherapy (IG‐VMAT) versus conventionally fractionated IG‐VMAT in patients with localized prostate cancer. clinicaltrials.gov/ct2/show/NCT02934685 (first received 17 October 2016).
Additional references
Abramowitz 2008
-
- Abramowitz MC, Li T, Buyyounouski MK, Ross E, Uzzo RG, Pollack A, et al. The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer. Cancer 2008;12(1):55‐60. - PubMed
AJCC 2010
-
- American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th Edition. New York (NY): Springer, 2010.
Arcangeli 2018
-
- Arcangeli G, Arcangeli S, Pinzic V, Benassid M, Benassie M, Strigarie L. Optimal scheduling of hypofractionated radiotherapy for localized prostate cancer: a systematic review and metaanalysis of randomized clinical trials. Cancer Treatment Reviews 2018;70:22‐9. - PubMed
ASTRO 1997
-
- American Society for Therapeutic Radiology and Oncology Consensus Panel. Consensus statement: guidelines for PSA following radiation therapy. International Journal of Radiation Oncology, Biology, Physics 1997;37:1035‐41. - PubMed
Bannuru 2011
-
- Bannuru RR, Dvorak T, Obadan N, Yu WW, Patel K, Chung M, et al. Comparative evaluation of radiation treatments for clinically localized prostate cancer: an updated systematic review. Annals of Internal Medicine 2011;155(3):171‐8. - PubMed
Barry 1992
-
- Barry MH, Fowler FJ Jr, O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association index for benign prostatic hyperplasia: the measurement committee of the American Urological Association. Journal of Urology 1992;148(5):1549‐57. - PubMed
Bentzen 2005
-
- Bentzen SM, Ritter MA. The α/β ratio for prostate cancer: what is it, really?. Radiotherapy and Oncology 2005;76(1):1‐3. - PubMed
Boutron 2014
-
- Boutron I, Altman DG, Hopewell S, Vera‐Badillo F, Tannock I, Ravaud P. Impact of spin in the abstracts of articles reporting results of randomized controlled trials in the field of cancer: the SPIIN randomized controlled trial. Journal of Clinical Oncology 2014;32:4120‐6. - PubMed
Bray 2012
-
- Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008‐2030): a population‐based study. Lancet Oncology 2012;13(8):790‐801. - PubMed
Brenner 1999
-
- Brenner DJ, Hall EJ. Fractionation and protraction for radiotherapy of prostate carcinoma. International Journal of Radiation Oncology, Biology, Physics 1999;43(5):1095‐101. - PubMed
Brenner 2002
-
- Brenner DJ, Martinez AA, Edmundson GK, Mitchell C, Thames HD, Armour EP. Direct evidence that prostate tumors show high sensitivity to fractionation (low α/β ratio), similar to late‐responding normal tissue. International Journal of Radiation Oncology, Biology, Physics 2002;52(1):6‐13. - PubMed
Collins 1991
-
- Collins CD, Lloyd‐Davies RW, Swan AV. Radical external beam radiotherapy for localised carcinoma of the prostate using a hypofractionation technique. Clinical Oncology (Royal College of Radiologists (Great Britain)) 1991;3(3):127‐32. - PubMed
Corbett 2014
-
- Corbett MS, Higgins JP, Woolacott NF. Assessing baseline imbalance in randomised trials: implications for the Cochrane risk of bias tool. Research Synthesis Methods 2014;5:79‐85. - PubMed
Covidence [Computer program]
-
- Veritas Health Innovation. Covidence. Version accessed 6 June 2017. Melbourne, Australia: Veritas Health Innovation.
Cox 1972
-
- Cox DR. Regression models and life‐tables. Journal of the Royal Statistical Society. Series B, Statistical Methodology 1972;34(2):187‐220.
Cox 1995
-
- Cox JD, Statz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organisation for Research and Treatment of Cancer (EORTC). International Journal of Radiation Oncology, Biology, Physics 1995;31:1341‐6. - PubMed
Cox 1997
-
- Cox J, Grignon D, Kaplan R, Parsons JT, Schelhammer PF. Concensus statement: guidelines for PSA following radiation therapy. International Journal of Radiation Oncology, Biology, Physics 1997;37(5):1035‐41. - PubMed
Cox 2001
-
- Cox DR, Oakes D. Analysis of Survival Data. London (UK): Chapman and Hall, 2001.
D'Amico 1998
-
- D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998;280:969. - PubMed
Datta 2017
-
- Datta NR, Stutz E, Rogers S, Bodis S. Conventional versus hypofractionated radiation therapy for localized or locally advanced prostate cancer: a systematic review and meta‐analysis along with therapeutic implications. International Journal of Radiation Oncology, Biology, Physics 2017;99(3):573‐89. - PubMed
Daşu 2012
-
- Daşu A, Toma‐Daşu I. Prostate alpha/beta revisited – an analysis of clinical results from 14168 patients. Acta Oncologica (Stockholm, Sweden) 2012;51(8):963‐74. - PubMed
Dearnaley 2014
-
- 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 Oncology 2014;15(4):464‐73. - PubMed
Deeks 2002
-
- Deeks JJ. Issues in the selection of a summary statistic for meta‐analysis of clinical trials with binary outcomes. Statistics in Medicine 2002;21(11):1575‐600. - PubMed
Deeks 2011
-
- Deeks JJ, Higgins JP, Altman DG. Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Duchesne 1999
-
- Duchesne GM, Peters LJ. What is the α/β ratio for prostate cancer? Rationale for hypofractionated high‐dose‐rate brachytherapy. International Journal of Radiation Oncology, Biology, Physics 1999;44(4):747‐8. - PubMed
Dörr 2001
-
- Dörr W, Hendry JH. Consequential late effects in normal tissues. Radiotherapy and Oncology 2001;61(3):223‐31. [PUBMED: 11730991] - PubMed
Esper 1997
-
- Esper P, Mo F, Chodak G, Sinner M, Cella D, Pienta KJ. Measuring quality of life in men with prostate cancer using the functional assessment of cancer‐therapy‐prostate instrument. Urology 1997;50:920‐8. - PubMed
Fowler 2001
-
- Fowler J, Chappell R, Ritter M. Is α/β for prostate tumors really low?. International Journal of Radiation Oncology, Biology, Physics 2001;50(4):1021‐31. - PubMed
Fowler 2005
-
- Fowler JF. The radiobiology of prostate cancer including new aspects of fractionated radiotherapy. Acta Oncologica (Stockholm, Sweden) 2005;44(3):265‐76. - PubMed
GLOBOCAN 2018
-
- International Agency for Research on Cancer. 27 – Prostate cancer fact sheet. gco.iarc.fr/today/data/factsheets/cancers/27‐Prostate‐fact‐sheet.pdf (accessed 23 February 2010).
GRADE Working Group 2004
GRADEpro GDT [Computer program]
-
- McMaster University (developed by Evidence Prime). GRADEpro GDT. Version accessed 12 May 2016. Hamilton (ON): McMaster University (developed by Evidence Prime).
Greenland 1985
-
- Greenland S, Robins JM. Estimation of a common effect parameter from sparse follow‐up data. Biometrics 1985;41(1):55‐68. - PubMed
Heemsbergen 2006
-
- Heemsbergen WD, Peeters ST, Koper PC, Hoogeman MS, Lebesque JV. Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer patients: consequential late damage. International Journal of Radiation Oncology, Biology, Physics 2006;66(1):3‐10. - PubMed
Higgins 2002
-
- Higgins JP, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Statistics in Medicine 2002;21(11):1539‐58. - PubMed
Higgins 2003
Higgins 2009
Higgins 2011
-
- Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Hou 2015
Hróbjartsson 2013
-
- Hróbjartsson A, Thomsen AS, Emanuelsson F, Tendal B, Hilden J, Boutron I, et al. Observer bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors. Canadian Medical Association Journal 2013;185(4):E201‐11. - PMC - PubMed
ICRU 1999
-
- International Commission on Radiation Units and Measurements. ICRU report 62: prescribing, recording, and reporting photon beam therapy (supplement to ICRU report 50). Bethesda (MD): International Commission on Radiation Units and Measurements, 1999.
Joiner 1997
-
- Joiner MC, Kogel AJ. The linear‐quadratic approach to fractionation and calculation of isoeffect relationships. Basic Clinical Radiobiology. 1st Edition. New York (NY): Oxford University Press, 1997:106‐12.
Jones 2015
Kirkham 2010
-
- Kirkham JJ, Dwan KM, Altman DG, Gamble C, Dodd S, Smyth R, et al. The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews. BMJ 2010;340:c365. - PubMed
Koontz 2015
-
- Koontz BF, Bossi A, Cozzarini C, Wiegel T, D'Amico A. A systematic review of hypofractionation for primary management of prostate cancer. European Urology 2015;68:683‐91. - PubMed
Kupelian 2001
-
- Kupelian PA, Reddy CA, Klein EA, Willoughby TR. Short‐course intensity‐modulated radiotherapy (70 Gy at 2.5 Gy per fraction) for localized prostate cancer: preliminary results on late toxicity and quality of life. International Journal of Radiation Oncology, Biology, Physics 2001;51(4):988‐93. - PubMed
Leborgne 2012
-
- Leborgne F, Fowler J, Leborgne JH, Mezzera J. Later outcomes and alpha/beta estimate from hypofractionated conformal three‐dimensional radiotherapy versus standard fractionation for localized prostate cancer. International Journal of Radiation Oncology, Biology, Physics 2012;82(3):1200‐7. - PubMed
Lester 2006
Liberati 2009
Litwin 1998
-
- Litwin MS, Hays RD, Fink A, Ganz PA Leake B, Brooke RH. The UCLA Prostate Cancer Index: development, reliability, and validity of a health‐related quality of life measure. Medical Care 1998;36:1002‐12. - PubMed
Maciejewski 1986
-
- Maciejewski B, Taylor JM, Withers HR. Alpha/beta value and the importance of size of dose per fraction for late complications of the supraglottic larynx. Radiotherapy and Oncology 1986;7:323‐6. - PubMed
Mantel 1959
-
- Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. Journal of the National Cancer Institute 1959;22(4):719‐48. - PubMed
Mattieu 2009
-
- Mathieu S, Boutron I, Moher D, Altman DG, Ravaud P. Comparison of registered and published primary outcomes in randomized controlled trials. JAMA 2009;302:977‐84. - PubMed
McQuay 1999
Michalski 2013
-
- Michalski JM, Yan Y, Watkins‐Bruner D, Cosch WR, Winter K, Galvin JM, et al. Preliminary toxicity analysis of 3‐dimensional conformal radiation therapy versus intensity modulated radiation therapy on the high‐dose arm of the Radiation Therapy Oncology Group 0126 prostate cancer trial. International Journal of Radiation Oncology, Biology, Physics 2013;87(5):932‐8. - PMC - PubMed
Miralbell 2012
-
- Miralbell R, Roberts SA, Zubizarreta E, Hendry JH. Dose‐fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional data‐sets: α/β = 1.4 (0.9–2.2) Gy. International Journal of Radiation Oncology, Biology, Physics 2012;82(1):e17‐24. [PUBMED: 21324610] - PubMed
Morgan 2018
-
- Morgan SC, Hoffman K, Loblaw A, Buyyounouski MK, Caroline Patton S, Barocas D, et al. Hypofractionated radiation therapy for localized prostate cancer: executive summary of an ASTRO, ASCO, and AUA evidence‐based guideline, 2018. Practical Radiation Oncology 2018; Vol. 8, issue 6:354‐60. - PubMed
Mottett 2017
-
- Mottett N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, Santos M, et al. EAU‐ESTRO‐SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. European Urology 2017;71(4):618‐29. - PubMed
NCCN 2014
-
- National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines®): prostate cancer. Version 1.2015. www.nccn.org (accessed 23 November 2014).
NCI
-
- National Cancer Institute. Cancer statistical facts: prostate cancer. seer.cancer.gov/statfacts/html/prost.html (accessed 4 February 2019).
NCI 2006
-
- National Cancer Institute. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3... (accessed 30 September 2016).
Nielsen 1998
-
- Nielsen OS, Bentzen SM, Sandberg E, Gadeberg CC, Timothy AR. Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases. Radiotherapy and Oncology 1998;47(3):233‐40. - PubMed
Parmar 1998
-
- Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta‐analyses of the published literature for survival endpoints. Statistics in Medicine 1998;17(24):2815‐34. - PubMed
Partin 1997
-
- Partin AW, Kattan MW, Subong EN, Walsh PC, Wojno KJ, Oesterling JE, et al. Combination of prostate‐specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multiple institutional update. JAMA 1997;277:1445‐51. - PubMed
Pavy 1995
-
- Pavy JJ, Denekamp J, Letschert J, Littbrand B, Mornex F, Bernier J, et al. Late effects toxicity scoring: the SOMA scale. International Journal of Radiation Oncology, Biology, Physics 1995;31(5):1043‐7. - PubMed
Peeters 2005
-
- Peeters ST, Heemsbergen WD, Putten WL, Slot A, Tabak H, Mens JW, et al. Acute and late complications after radiotherapy for prostate cancer: results of a multicenter randomized trial comparing 68 Gy of radiotherapy with 78 Gy. International Journal of Radiation Oncology, Biology, Physics 2005;61(4):1019‐34. - PubMed
Peeters 2006
-
- Peeters ST, Heemsbergen WD, Koper PC, Putten WL, Slot A, Dielwart MF, et al. Dose‐response in radiotherapy for localised prostate cancer treated with 3D conformal radiotherapy. Journal of Clinical Oncology 2006;24:1990‐6. - PubMed
Penson 2003
-
- Penson DF, Litwin MS. Quality of life after treatment for prostate cancer. Current Urology Reports 2003;4(3):185‐95. [PUBMED: 12756081] - PubMed
Peters 2010
-
- Peters LJ, O'Sullivan B, Giralt J, Fitzgerald TJ, Trotti A, Bernier J, et al. Critical impact of radiotherapy protocol compliance and quality in the treatment of advanced head and neck cancer: results from TROG 02.02. Journal of Clinical Oncology 2010;28(18):2996‐3001. - PubMed
Potosky 2004
-
- Potosky AL, Davis WW, Hoffman RM, Stanford JL, Stephenson RA, Penson DF, et al. Five‐year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. Journal of the National Cancer Institute 2004;96(18):1358‐67. [PUBMED: 15367568] - PubMed
Price 1986
-
- Price P, Hoskin PJ, Easton D, Austin D, Palmer SG, Yarnold JR. Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases. Radiotherapy and Oncology 1986;6(4):247‐55. - PubMed
Proust‐Lima 2011
-
- Proust‐Lima C, Taylor JM, Sécher S, Sandler H, Kestin L, Pickles T, et al. Confirmation of a low α/β ratio for prostate cancer treated by external beam radiation therapy alone using a post‐treatment repeated‐measures model for PSA dynamics. International Journal of Radiation Oncology, Biology, Physics 2011;79(1):195‐201. [PUBMED: 20381268] - PMC - PubMed
Review Manager 2014 [Computer program]
-
- The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Riley 2011
-
- Riley RD, Higgins JP, Deeks JJ. Interpretation of random effects meta‐analyses. BMJ 2011;342:d549. - PubMed
Roach 2006
-
- Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, et al. 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. International Journal of Radiation Oncology, Biology, Physics 2006;65(4):965‐74. - PubMed
Rosen 1997
-
- Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997;49:822‐30. - PubMed
Ryan 2016
-
- Ryan R, Synnot A, Hill S. Describing results: Cochrane Consumers and Communication Group, 2016. cccrg.cochrane.org/author‐resources. Version 1.0 (accessed prior to 7 July 2019).
Schünneman 2011
-
- Schünneman HJ, Oxman AD, Vist GE, Higgins JP, Deeks JT, Glaziou P, et al. Interpretation of results and drawing conclusions. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Siegel 2018
-
- Siegel RL, Miller KD, Jemal A. Cancer statistics 2018. CA Cancer Clinical Journal 2018;768:7‐30. - PubMed
START A 2008
START B 2008
Sterne 2011
-
- Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta‐analyses of randomised controlled trials. BMJ 2011;343:d4002. - PubMed
Sun 2014
-
- Sun L, Zhu S, Zhao Y, Zhang H, Shang Z, Jiang N, et al. Who benefits from hypofractionated radiotherapy for clinically localized prostate cancer: evidence from meta‐analysis. Tumor Biology 2014;35:9911‐8. - PubMed
Tierney 2007
Tucker 2011
van Andel 2008
-
- Andel G, Bottomley A, Fossa SD. An international field study of the health‐related quality of life of patients with prostate cancer. European Journal of Cancer 2008;44:2418‐24. - PubMed
Vogelius 2013
Ware 1996
-
- Ware J, Kosinski M, Keller SD. A 12‐item short‐form health survey: construction of scales and preliminary tests of reliability and validity. Medical Care 1996;34:220‐33. - PubMed
Whelan 2002
-
- Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node‐negative breast cancer. Journal of the National Cancer Institute 2002;94(15):1143‐50. - PubMed
Williamson 2002
-
- Williamson PR, Smith CT, Hutton JL, Marson AG. Aggregate data meta‐analysis with time‐to‐event outcomes. Statistics in Medicine 2002;21(22):3337‐51. - PubMed
Withers 1983
-
- Withers HR, Thames HD Jr, Peters LJ. A new isoeffect curve for change in dose per fraction. Radiotherapy and Oncology 1983;1(2):187‐91. - PubMed
Wolff 2015
-
- Wolff RF, Ryder S, Bossi A, Briganti A, Crook J, Henry A, et al. A systematic review of randomised controlled trials of radiotherapy for localised prostate cancer. European Journal of Cancer 2015;51(16):2345‐67. - PubMed
Wood 2008
Zaorsky 2013
Zumsteg 2015
-
- Zumsteg ZS, Spratt DE, Romesser PB, Pei Z, Zhang Z, Polkinghorn W, et al. The natural history and predictors of outcome following biochemical relapse in the dose escalation era for prostate cancer patients undergoing definitive external beam radiotherapy. European Urology 2015;67(6):1009. - PMC - PubMed
References to other published versions of this review
Soh 2015
-
- Soh FY, James ML, Hickey BE, Daly T, Jeffery M, See AM, et al. Altered radiation fractionation schedules for clinically localised and locally advanced prostate cancer. Cochrane Database of Systematic Reviews 2015, Issue 1. [DOI: 10.1002/14651858.CD011462] - DOI
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