Dataset Information

Association between ischaemic bowel syndromes and androgen deprivation therapy in patients with prostate cancer: a retrospective cohort study.

ABSTRACT:

Objective

This study investigated the risk of ischaemic bowel syndrome (IBS) in androgen deprivation therapy (ADT) users to explore the long-term outcomes of patients with prostate cancer (PC) receiving ADT treatment.

Methods

We performed a population-based retrospective cohort study. All the clinical information of the study participants were acquired from the Longitudinal Health Insurance Database for Catastrophic Illness Patients in Taiwan. We extracted data for all the patients newly diagnosed with prostate malignancy (ICD-9-CM 185 or C61 in ICD-10-CM) from 2000 to 2008. The patients were then divided into two groups: 7160 male ADT cohort receiving ADT and 7160 male non-ADT comparison group frequency matched by age and index year of ADT treatment of the ADT group. Cox proportional hazard regression was used to estimate the adjusted HR and 95% CIs of the IBS risk.

Results

No significant difference was noted in the overall incidence rate for IBS between the ADT and non-ADT cohorts (0.86 and 0.89 per 1000 person-year, respectively, p=0.89). Even after adjusting for potential risk factors, a 1.06-fold risk of IBS (95% CI 0.62 to 1.82, p=0.82) was observed in the ADT cohort relative to the non-ADT cohorts. Moreover, we stratified the ADT cohort by time point of ADT treatment after PC diagnosis. Different IBS incidence rates were observed among the early ADT, late-ADT and non-ADT users at 0.77, 1.23 and 0.89 per 1000 person-years, respectively; nonetheless, the difference was not statistically significant. Moreover, no difference was found between the ADT treatment types and IBS risk, including sole orchiectomy, sole luteinising-hormone-releasing hormone and both.

Conclusions

Results showed that ADT treatment in patients with PC is not an independent factor for IBS incidence. Large sample sizes for patients with IBS with patients with PC who had received ADT treatment are needed for further study.

SUBMITTER: Chiang IN

PROVIDER: S-EPMC5337716 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

Association between ischaemic bowel syndromes and androgen deprivation therapy in patients with prostate cancer: a retrospective cohort study.

Chiang I-Ni IN Huang Chao-Yuan CY Pu Yeong-Shiau YS Chang Chao-Hsiang CH Muo Chih-Hsin CH Chung Chi-Jung CJ Wang Ruey-Yun RY Young Tai-Horng TH

BMJ open 20170228 2

<h4>Objective</h4>This study investigated the risk of ischaemic bowel syndrome (IBS) in androgen deprivation therapy (ADT) users to explore the long-term outcomes of patients with prostate cancer (PC) receiving ADT treatment.<h4>Methods</h4>We performed a population-based retrospective cohort study. All the clinical information of the study participants were acquired from the Longitudinal Health Insurance Database for Catastrophic Illness Patients in Taiwan. We extracted data for all the patient ...[more]

PMID: 28246133

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Project description:BackgroundHSD3B1 (1245A>C) has been mechanistically linked to castration-resistant prostate cancer because it encodes an altered enzyme that augments dihydrotestosterone synthesis from non-gonadal precursors. We postulated that men inheriting the HSD3B1 (1245C) allele would exhibit resistance to androgen-deprivation therapy (ADT).MethodsIn this multicohort study, we determined HSD3B1 genotype retrospectively in men treated with ADT for post-prostatectomy biochemical failure and correlated genotype with long-term clinical outcomes. We used data and samples from prospectively maintained prostate cancer registries at the Cleveland Clinic (Cleveland, OH, USA; primary study cohort) and the Mayo Clinic (Rochester, MN, USA; post-prostatectomy and metastatic validation cohorts). In the post-prostatectomy cohorts, patients of any age were eligible if they underwent prostatectomy between Jan 1, 1996, and Dec 31, 2009 (at the Cleveland Clinic; primary cohort), or between Jan 1, 1987, and Dec 31, 2011 (at the Mayo Clinic; post-prostatectomy cohort) and were treated with ADT for biochemical failure or for non-metastatic clinical failure. In the metastatic validation cohort, patients of any age were eligible if they were enrolled at Mayo Clinic between Sept 1, 2009, and July 31, 2013, with metastatic castration-resistant prostate cancer. The primary endpoint was progression-free survival according to HSD3B1 genotype. We did prespecified multivariable analyses to assess the independent predictive value of HSD3B1 genotype on outcomes.FindingsWe included and genotyped 443 patients: 118 in the primary cohort (who underwent prostatectomy), 137 in the post-prostatectomy validation cohort, and 188 in the metastatic validation cohort. In the primary study cohort, median progression-free survival diminished as a function of the number of variant alleles inherited: 6·6 years (95% CI 3·8-not reached) in men with homozygous wild-type genotype, 4·1 years (3·0-5·5) in men with heterozygous variant genotype, and 2·5 years (0·7 to not reached) in men with homozygous variant genotype (p=0·011). Relative to the homozygous wild-type genotype, inheritance of two copies of the variant allele was predictive of decreased progression-free survival (hazard ratio [HR] 2·4 [95% CI 1·1-5·3], p=0·029), as was inheritance of one copy of the variant allele (HR 1·7 [1·0-2·9], p=0·041). Findings were similar for distant metastasis-free survival and overall survival. The effect of the HSD3B1 genotype was independently confirmed in the validation cohorts.InterpretationInheritance of the HSD3B1 (1245C) allele that enhances dihydrotestosterone synthesis is associated with prostate cancer resistance to ADT. HSD3B1 could therefore potentially be a powerful genetic biomarker capable of distinguishing men who are a priori likely to fare favourably with ADT from those who harbour disease liable to behave more aggressively, and who therefore might warrant early escalated therapy.FundingProstate Cancer Foundation, National Institutes of Health, US Department of Defense, Howard Hughes Medical Institute, American Cancer Society, Conquer Cancer Foundation of the American Society of Clinical Oncology, Cleveland Clinic Research Programs Committee and Department of Radiation Oncology, Gail and Joseph Gassner Development Funds.

Project description:ContextAndrogen deprivation therapy (ADT) for prostate cancer (PCa) represents one of the most effective systemic palliative treatments known for solid tumors. Although clinical trials have assessed the role of ADT in patients with metastatic and advanced locoregional disease, the risk-benefit ratio, especially in earlier stages, remains poorly defined. Given the mounting evidence for potentially life-threatening adverse effects with short- and long-term ADT, it is important to redefine the role of ADT for this disease.ObjectiveReview the published experience with currently available ADT approaches in various contemporary clinical settings of PCa and reported serious treatment-related adverse events. This review addresses the level of evidence associated with the use of ADT in PCa, focusing upon survival outcome measures. Furthermore, this paper discusses evolving approaches targeting androgen receptor signaling pathways and emerging evidence from clinical trials with newer compounds.Evidence acquisitionA comprehensive review of the literature was performed, focusing on data from the last 10 yr (January 2000 to July 2011) and using the terms androgen deprivation, hormone treatment, prostate cancer and adverse effects. Abstracts from trials reported at international conferences held in 2010 and 2011 were also evaluated.Evidence synthesisData from randomized controlled trials and population-based studies were analyzed in different clinical paradigms. Specifically, the role of ADT was evaluated in patients with nonmetastatic disease as the primary and sole treatment, in combination with radiation therapy (RT) or after surgery, and in patients with metastatic disease. The data suggest that in men with nonmetastatic disease, the use of primary ADT as monotherapy has not shown a benefit and is not recommended, while ADT combined with conventional-dose RT (<72Gy) for patients with high-risk disease may delay progression and prolong survival. The postoperative use of ADT remains poorly evaluated in prospective studies. Likewise, there are no trials evaluating the role of ADT in patients with biochemical relapses after surgery or RT. In patients with metastatic disease, there is a clear benefit in terms of quality of life, reduction of disease-associated morbidity, and possibly survival. Treatment with bilateral orchiectomy, luteinizing hormone-releasing hormone agonist therapy, with and without antiandrogens has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality.ConclusionsAlthough ADT is an effective treatment of PCa, consistent long-term benefits in terms of quality and quantity of life are predominantly evident in patients with advanced/metastatic disease or when ADT is used in combination with RT (<72Gy) in patients with high-risk tumors. Implementation of ADT should be evidence based, with special consideration to adverse events and the risk-benefit ratio.

Dataset Information

Association between ischaemic bowel syndromes and androgen deprivation therapy in patients with prostate cancer: a retrospective cohort study.

Objective

Methods

Results

Conclusions

Publications

Association between ischaemic bowel syndromes and androgen deprivation therapy in patients with prostate cancer: a retrospective cohort study.

Similar Datasets

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