Radiation with or without antiandrogen therapy in recurrent prostate cancer

William U. Shipley, Wendy Seiferheld, Himanshu R. Lukka, Pierre P. Major, Niall M. Heney, David Grignon, Oliver Sartor, Maltibehn P. Patel, Jean Paul Bahary, Anthony L. Zietman, Thomas M. Pisansky, Kenneth L. Zeitzer, Colleen A F Lawton, Felix Y. Feng, Richard D. Lovett, Alexander G. Balogh, Luis Souhami, Seth A. Rosenthal, Kevin J. Kerlin, James J. DignamStephanie L. Pugh, Howard M. Sandler

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

BACKGROUND Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. METHODS In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival. RESULTS The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P = 0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P = 0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001). CONCLUSIONS The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-Term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo.

Original languageEnglish (US)
Pages (from-to)417-428
Number of pages12
JournalNew England Journal of Medicine
Volume376
Issue number5
DOIs
StatePublished - Feb 2 2017

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Androgen Antagonists
Prostatic Neoplasms
Radiotherapy
Placebos
Radiation
Salvage Therapy
Incidence
Prostate-Specific Antigen
Prostatectomy
Therapeutics
Survival Rate
Gynecomastia
Survival
Lymph Node Excision
Tablets
Capsules
bicalutamide
Prostate
Neoplasms
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Shipley, W. U., Seiferheld, W., Lukka, H. R., Major, P. P., Heney, N. M., Grignon, D., ... Sandler, H. M. (2017). Radiation with or without antiandrogen therapy in recurrent prostate cancer. New England Journal of Medicine, 376(5), 417-428. https://doi.org/10.1056/NEJMoa1607529

Radiation with or without antiandrogen therapy in recurrent prostate cancer. / Shipley, William U.; Seiferheld, Wendy; Lukka, Himanshu R.; Major, Pierre P.; Heney, Niall M.; Grignon, David; Sartor, Oliver; Patel, Maltibehn P.; Bahary, Jean Paul; Zietman, Anthony L.; Pisansky, Thomas M.; Zeitzer, Kenneth L.; Lawton, Colleen A F; Feng, Felix Y.; Lovett, Richard D.; Balogh, Alexander G.; Souhami, Luis; Rosenthal, Seth A.; Kerlin, Kevin J.; Dignam, James J.; Pugh, Stephanie L.; Sandler, Howard M.

In: New England Journal of Medicine, Vol. 376, No. 5, 02.02.2017, p. 417-428.

Research output: Contribution to journalArticle

Shipley, WU, Seiferheld, W, Lukka, HR, Major, PP, Heney, NM, Grignon, D, Sartor, O, Patel, MP, Bahary, JP, Zietman, AL, Pisansky, TM, Zeitzer, KL, Lawton, CAF, Feng, FY, Lovett, RD, Balogh, AG, Souhami, L, Rosenthal, SA, Kerlin, KJ, Dignam, JJ, Pugh, SL & Sandler, HM 2017, 'Radiation with or without antiandrogen therapy in recurrent prostate cancer', New England Journal of Medicine, vol. 376, no. 5, pp. 417-428. https://doi.org/10.1056/NEJMoa1607529
Shipley, William U. ; Seiferheld, Wendy ; Lukka, Himanshu R. ; Major, Pierre P. ; Heney, Niall M. ; Grignon, David ; Sartor, Oliver ; Patel, Maltibehn P. ; Bahary, Jean Paul ; Zietman, Anthony L. ; Pisansky, Thomas M. ; Zeitzer, Kenneth L. ; Lawton, Colleen A F ; Feng, Felix Y. ; Lovett, Richard D. ; Balogh, Alexander G. ; Souhami, Luis ; Rosenthal, Seth A. ; Kerlin, Kevin J. ; Dignam, James J. ; Pugh, Stephanie L. ; Sandler, Howard M. / Radiation with or without antiandrogen therapy in recurrent prostate cancer. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 5. pp. 417-428.
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abstract = "BACKGROUND Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. METHODS In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival. RESULTS The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3{\%} in the bicalutamide group, as compared with 71.3{\%} in the placebo group (hazard ratio for death, 0.77; 95{\%} confidence interval, 0.59 to 0.99; P = 0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8{\%} in the bicalutamide group, as compared with 13.4{\%} in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5{\%} in the bicalutamide group, as compared with 23.0{\%} in the placebo group (P = 0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7{\%} of the patients in the bicalutamide group, as compared with 10.9{\%} of those in the placebo group (P<0.001). CONCLUSIONS The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-Term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo.",
author = "Shipley, {William U.} and Wendy Seiferheld and Lukka, {Himanshu R.} and Major, {Pierre P.} and Heney, {Niall M.} and David Grignon and Oliver Sartor and Patel, {Maltibehn P.} and Bahary, {Jean Paul} and Zietman, {Anthony L.} and Pisansky, {Thomas M.} and Zeitzer, {Kenneth L.} and Lawton, {Colleen A F} and Feng, {Felix Y.} and Lovett, {Richard D.} and Balogh, {Alexander G.} and Luis Souhami and Rosenthal, {Seth A.} and Kerlin, {Kevin J.} and Dignam, {James J.} and Pugh, {Stephanie L.} and Sandler, {Howard M.}",
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TY - JOUR

T1 - Radiation with or without antiandrogen therapy in recurrent prostate cancer

AU - Shipley, William U.

AU - Seiferheld, Wendy

AU - Lukka, Himanshu R.

AU - Major, Pierre P.

AU - Heney, Niall M.

AU - Grignon, David

AU - Sartor, Oliver

AU - Patel, Maltibehn P.

AU - Bahary, Jean Paul

AU - Zietman, Anthony L.

AU - Pisansky, Thomas M.

AU - Zeitzer, Kenneth L.

AU - Lawton, Colleen A F

AU - Feng, Felix Y.

AU - Lovett, Richard D.

AU - Balogh, Alexander G.

AU - Souhami, Luis

AU - Rosenthal, Seth A.

AU - Kerlin, Kevin J.

AU - Dignam, James J.

AU - Pugh, Stephanie L.

AU - Sandler, Howard M.

PY - 2017/2/2

Y1 - 2017/2/2

N2 - BACKGROUND Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. METHODS In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival. RESULTS The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P = 0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P = 0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001). CONCLUSIONS The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-Term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo.

AB - BACKGROUND Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. METHODS In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival. RESULTS The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P = 0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P = 0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001). CONCLUSIONS The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-Term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo.

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