Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: A randomised, phase 3 trial

Padraig Warde, Malcolm Mason, Keyue Ding, Peter Kirkbride, Michael Brundage, Richard Cowan, Mary Gospodarowicz, Karen Sanders, Edmund Kostashuk, Gregory P Swanson, Jim Barber, Andrea Hiltz, Mahesh Kb Parmar, Jinka Sathya, John Anderson, Charles Hayter, John Hetherington, Matthew R. Sydes, Wendy Parulekar

Research output: Contribution to journalArticle

356 Citations (Scopus)

Abstract

Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65-69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4-8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74, 95 CI 70-78 vs 66, 60-70; hazard ratio [HR] 0·77, 95 CI 0·61-0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5) in the ADT only group, two (0·3) in the ADT and RT group; diarrhoea grade >3, four patients (0·7) vs eight (1·3); urinary toxicity grade >3, 14 patients (2·3) in both groups). The benefits of combined modality treatment - ADT and RT - should be discussed with all patients with locally advanced prostate cancer. Canadian Cancer Society Research Institute, US National Cancer Institute, and UK Medical Research Council.

Original languageEnglish (US)
Pages (from-to)2104-2111
Number of pages8
JournalThe Lancet
Volume378
Issue number9809
DOIs
StatePublished - Dec 17 2011

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Androgens
Prostatic Neoplasms
Radiotherapy
Group Psychotherapy
Therapeutics
Prostate-Specific Antigen
Survival
National Cancer Institute (U.S.)
Neoplasm Grading
Seminal Vesicles
Biomedical Research
Prostate
Diarrhea
Quality of Life
Hemorrhage

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Warde, P., Mason, M., Ding, K., Kirkbride, P., Brundage, M., Cowan, R., ... Parulekar, W. (2011). Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: A randomised, phase 3 trial. The Lancet, 378(9809), 2104-2111. https://doi.org/10.1016/S0140-6736(11)61095-7

Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer : A randomised, phase 3 trial. / Warde, Padraig; Mason, Malcolm; Ding, Keyue; Kirkbride, Peter; Brundage, Michael; Cowan, Richard; Gospodarowicz, Mary; Sanders, Karen; Kostashuk, Edmund; Swanson, Gregory P; Barber, Jim; Hiltz, Andrea; Parmar, Mahesh Kb; Sathya, Jinka; Anderson, John; Hayter, Charles; Hetherington, John; Sydes, Matthew R.; Parulekar, Wendy.

In: The Lancet, Vol. 378, No. 9809, 17.12.2011, p. 2104-2111.

Research output: Contribution to journalArticle

Warde, P, Mason, M, Ding, K, Kirkbride, P, Brundage, M, Cowan, R, Gospodarowicz, M, Sanders, K, Kostashuk, E, Swanson, GP, Barber, J, Hiltz, A, Parmar, MK, Sathya, J, Anderson, J, Hayter, C, Hetherington, J, Sydes, MR & Parulekar, W 2011, 'Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: A randomised, phase 3 trial', The Lancet, vol. 378, no. 9809, pp. 2104-2111. https://doi.org/10.1016/S0140-6736(11)61095-7
Warde, Padraig ; Mason, Malcolm ; Ding, Keyue ; Kirkbride, Peter ; Brundage, Michael ; Cowan, Richard ; Gospodarowicz, Mary ; Sanders, Karen ; Kostashuk, Edmund ; Swanson, Gregory P ; Barber, Jim ; Hiltz, Andrea ; Parmar, Mahesh Kb ; Sathya, Jinka ; Anderson, John ; Hayter, Charles ; Hetherington, John ; Sydes, Matthew R. ; Parulekar, Wendy. / Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer : A randomised, phase 3 trial. In: The Lancet. 2011 ; Vol. 378, No. 9809. pp. 2104-2111.
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AU - Warde, Padraig

AU - Mason, Malcolm

AU - Ding, Keyue

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AU - Brundage, Michael

AU - Cowan, Richard

AU - Gospodarowicz, Mary

AU - Sanders, Karen

AU - Kostashuk, Edmund

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AU - Barber, Jim

AU - Hiltz, Andrea

AU - Parmar, Mahesh Kb

AU - Sathya, Jinka

AU - Anderson, John

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AU - Sydes, Matthew R.

AU - Parulekar, Wendy

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N2 - Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65-69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4-8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74, 95 CI 70-78 vs 66, 60-70; hazard ratio [HR] 0·77, 95 CI 0·61-0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5) in the ADT only group, two (0·3) in the ADT and RT group; diarrhoea grade >3, four patients (0·7) vs eight (1·3); urinary toxicity grade >3, 14 patients (2·3) in both groups). The benefits of combined modality treatment - ADT and RT - should be discussed with all patients with locally advanced prostate cancer. Canadian Cancer Society Research Institute, US National Cancer Institute, and UK Medical Research Council.

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