Risk of colorectal cancer in men on long-term androgen deprivation therapy for prostate cancer

Silke Gillessen, Arnoud Templeton, Giancarlo Marra, Yong Fang Kuo, Emanuele Valtorta, Vahakn B. Shahinian

Research output: Contribution to journalArticle

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Abstract

BackgroundAndrogen deprivation with gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is a common but controversial treatment for prostate cancer. Uncertainties remain about its use, particularly with increasing recognition of serious side effects. In animal studies, androgens protect against colonic carcinogenesis, suggesting that androgen deprivation may increase the risk of colorectal cancer.MethodsWe identified 107859 men in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were diagnosed with prostate cancer in 1993 through 2002, with follow-up available through 2004. The primary outcome was development of colorectal cancer, determined from SEER files on second primary cancers. Cox proportional hazards regression was used to assess the influence of androgen deprivation on the outcome, adjusted for patient and prostate cancer characteristics. All statistical tests were two-sided.ResultsMen who had orchiectomies had the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95% confidence interval [CI] = 5.3 to 7.5), followed by men who had GnRH agonist therapy (4.4 per 1000 person-years; 95% CI = 4.0 to 4.9), and men who had no androgen deprivation (3.7 per 1000 person-years; 95% CI = 3.5 to 3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose-response effect (Ptrend =. 010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (hazard ratio [HR] = 1.31, 95% CI = 1.12 to 1.53) or with orchiectomy (HR = 1.37, 95% CI = 1.14 to 1.66).ConclusionLong-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cancer.

Original languageEnglish (US)
Pages (from-to)1760-1770
Number of pages11
JournalJournal of the National Cancer Institute
Volume102
Issue number23
DOIs
StatePublished - Dec 2010

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Androgens
Colorectal Neoplasms
Prostatic Neoplasms
Orchiectomy
Confidence Intervals
Gonadotropin-Releasing Hormone
Epidemiology
Therapeutics
Second Primary Neoplasms
Medicare
Uncertainty
Carcinogenesis
Databases
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Risk of colorectal cancer in men on long-term androgen deprivation therapy for prostate cancer. / Gillessen, Silke; Templeton, Arnoud; Marra, Giancarlo; Kuo, Yong Fang; Valtorta, Emanuele; Shahinian, Vahakn B.

In: Journal of the National Cancer Institute, Vol. 102, No. 23, 12.2010, p. 1760-1770.

Research output: Contribution to journalArticle

Gillessen, Silke ; Templeton, Arnoud ; Marra, Giancarlo ; Kuo, Yong Fang ; Valtorta, Emanuele ; Shahinian, Vahakn B. / Risk of colorectal cancer in men on long-term androgen deprivation therapy for prostate cancer. In: Journal of the National Cancer Institute. 2010 ; Vol. 102, No. 23. pp. 1760-1770.
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abstract = "BackgroundAndrogen deprivation with gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is a common but controversial treatment for prostate cancer. Uncertainties remain about its use, particularly with increasing recognition of serious side effects. In animal studies, androgens protect against colonic carcinogenesis, suggesting that androgen deprivation may increase the risk of colorectal cancer.MethodsWe identified 107859 men in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were diagnosed with prostate cancer in 1993 through 2002, with follow-up available through 2004. The primary outcome was development of colorectal cancer, determined from SEER files on second primary cancers. Cox proportional hazards regression was used to assess the influence of androgen deprivation on the outcome, adjusted for patient and prostate cancer characteristics. All statistical tests were two-sided.ResultsMen who had orchiectomies had the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95{\%} confidence interval [CI] = 5.3 to 7.5), followed by men who had GnRH agonist therapy (4.4 per 1000 person-years; 95{\%} CI = 4.0 to 4.9), and men who had no androgen deprivation (3.7 per 1000 person-years; 95{\%} CI = 3.5 to 3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose-response effect (Ptrend =. 010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (hazard ratio [HR] = 1.31, 95{\%} CI = 1.12 to 1.53) or with orchiectomy (HR = 1.37, 95{\%} CI = 1.14 to 1.66).ConclusionLong-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cancer.",
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T1 - Risk of colorectal cancer in men on long-term androgen deprivation therapy for prostate cancer

AU - Gillessen, Silke

AU - Templeton, Arnoud

AU - Marra, Giancarlo

AU - Kuo, Yong Fang

AU - Valtorta, Emanuele

AU - Shahinian, Vahakn B.

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N2 - BackgroundAndrogen deprivation with gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is a common but controversial treatment for prostate cancer. Uncertainties remain about its use, particularly with increasing recognition of serious side effects. In animal studies, androgens protect against colonic carcinogenesis, suggesting that androgen deprivation may increase the risk of colorectal cancer.MethodsWe identified 107859 men in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were diagnosed with prostate cancer in 1993 through 2002, with follow-up available through 2004. The primary outcome was development of colorectal cancer, determined from SEER files on second primary cancers. Cox proportional hazards regression was used to assess the influence of androgen deprivation on the outcome, adjusted for patient and prostate cancer characteristics. All statistical tests were two-sided.ResultsMen who had orchiectomies had the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95% confidence interval [CI] = 5.3 to 7.5), followed by men who had GnRH agonist therapy (4.4 per 1000 person-years; 95% CI = 4.0 to 4.9), and men who had no androgen deprivation (3.7 per 1000 person-years; 95% CI = 3.5 to 3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose-response effect (Ptrend =. 010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (hazard ratio [HR] = 1.31, 95% CI = 1.12 to 1.53) or with orchiectomy (HR = 1.37, 95% CI = 1.14 to 1.66).ConclusionLong-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cancer.

AB - BackgroundAndrogen deprivation with gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is a common but controversial treatment for prostate cancer. Uncertainties remain about its use, particularly with increasing recognition of serious side effects. In animal studies, androgens protect against colonic carcinogenesis, suggesting that androgen deprivation may increase the risk of colorectal cancer.MethodsWe identified 107859 men in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were diagnosed with prostate cancer in 1993 through 2002, with follow-up available through 2004. The primary outcome was development of colorectal cancer, determined from SEER files on second primary cancers. Cox proportional hazards regression was used to assess the influence of androgen deprivation on the outcome, adjusted for patient and prostate cancer characteristics. All statistical tests were two-sided.ResultsMen who had orchiectomies had the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95% confidence interval [CI] = 5.3 to 7.5), followed by men who had GnRH agonist therapy (4.4 per 1000 person-years; 95% CI = 4.0 to 4.9), and men who had no androgen deprivation (3.7 per 1000 person-years; 95% CI = 3.5 to 3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose-response effect (Ptrend =. 010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (hazard ratio [HR] = 1.31, 95% CI = 1.12 to 1.53) or with orchiectomy (HR = 1.37, 95% CI = 1.14 to 1.66).ConclusionLong-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cancer.

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