Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making

Oefelein, Michael G.; Feng, Adrian H.; Scolieri, Michael J.; Ricchiutti, Daniel; Resnick, Martin I.

doi:10.1016/s0090-4295(00)00793-7

Cited by 234 publications

(166 citation statements)

References 15 publications

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“…2 Early serum testosterone assays used double-isotope-derivative dilution with a thin-layer chromatography modification and were limited in their accuracy and sensitivity. [3][4][5] The limits of measurement imposed by these assays led to the target testosterone suppression definition of less than 1.7 nmol/L; 4,6 however, more recent studies measuring serum testosterone levels after surgical castration with the use of more modern techniques, using improved radioimmunoassay (RIA) and chemiluminescent immunoassay (CLIA) and mass spectrometry (MS) methods, have reported mean testosterone levels as low as 0.003 nmol/L. 4,[7][8][9][10][11] Several studies since the early 1990s have therefore challenged the outdated benchmark of 1.7 nmol/L and recommended revisiting the definition, with many suggesting a new benchmark of 0.7 nmol/L.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5] The limits of measurement imposed by these assays led to the target testosterone suppression definition of less than 1.7 nmol/L; 4,6 however, more recent studies measuring serum testosterone levels after surgical castration with the use of more modern techniques, using improved radioimmunoassay (RIA) and chemiluminescent immunoassay (CLIA) and mass spectrometry (MS) methods, have reported mean testosterone levels as low as 0.003 nmol/L. 4,[7][8][9][10][11] Several studies since the early 1990s have therefore challenged the outdated benchmark of 1.7 nmol/L and recommended revisiting the definition, with many suggesting a new benchmark of 0.7 nmol/L. 4,[12][13][14] In light of conflicting opinion on the ideal goal for suppression of serum testosterone in men with advanced cancer, we conducted a survey of Canadian urologists, uro-oncologists, and radiation oncologists to gain a better understanding of their testosterone monitoring practices when managing men with hormone-sensitive prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

“…4,[7][8][9][10][11] Several studies since the early 1990s have therefore challenged the outdated benchmark of 1.7 nmol/L and recommended revisiting the definition, with many suggesting a new benchmark of 0.7 nmol/L. 4,[12][13][14] In light of conflicting opinion on the ideal goal for suppression of serum testosterone in men with advanced cancer, we conducted a survey of Canadian urologists, uro-oncologists, and radiation oncologists to gain a better understanding of their testosterone monitoring practices when managing men with hormone-sensitive prostate cancer. Survey participants were selected from a private database of Canadian healthcare providers who have participated in educational, advisory, and editorial activities related to the treatment of prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

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Testosterone monitoring for men with advanced prostate cancer: Review of current practices and a survey of Canadian physicians

Shayegan

Pouliot

et al. 2017

CUAJ

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Androgen-deprivation therapy (ADT) is a standard of care in the treatment of advanced prostate cancer; however, testosterone monitoring practices for men undergoing ADT vary across Canada. Although a testosterone level of 1.7 nmol/L or lower has historically been defined as the accepted castrate level, newer assays with improved sensitivity have shown that both medical and surgical castration can suppress testosterone levels to below 0.7 nmol/L. This review explores the evidence supporting a redefinition of the castrate testosterone level as 0.7 nmol/L or lower, and presents results of a survey of testosterone monitoring practices among 153 Canadian urologists, uro-oncologists, and radiation oncologists who manage the treatment of men with hormone-sensitive prostate cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Testosterone monitoring for men with advanced prostate cancer: Review of current practices and a survey of Canadian physicians

Shayegan

Pouliot

et al. 2017

CUAJ

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“…15 This approach was limited in both accuracy and sensitivity. 16,17 The consequence was that target testosterone suppression levels were defined within the limitations of measurement, as <1.7 nmol/l. 16,18 More recent technological advancements include improved radioimmunoassay, as well as chemiluminescent and mass spectrometry methods, 19,20 which show that both surgical and medical castration can achieve levels Maximal testosterone suppression in the management of recurrent and metastatic prostate cancer…”

Section: Introductionmentioning

confidence: 99%

“…16,18 Despite these advances in detection accuracy, the clinical relevance of lower testosterone levels remains controversial. This evidence-based review assesses the clinical importance of prospective and retrospective data characterizing the association between testosterone levels during ADT and outcomes in patients with hormone-sensitive, recurrent, and/or metastatic PCa.…”

Section: Introductionmentioning

confidence: 99%

Maximal testosterone suppression in the management of recurrent and metastatic prostate cancer

Klotz

Breau

Collins³

et al. 2017

CUAJ

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Introduction: Testosterone suppression, or androgen-deprivation therapy (ADT), is an established treatment for recurrent and metastatic prostate cancer (PCa). Based on the accuracy and sensitivity of early assays (c. 1960-1970), the castrate testosterone level was set at ≤1.7 nmol/l. Improved sensitivity of testosterone assays shows that both surgical and medical castration can achieve levels <0.7 nmol/l. However, the clinical implications and importance of maximum testosterone suppression remains a subject of controversy. This evidence-based review assesses prospective and retrospective clinical data, linking maximum suppression of testosterone with improved outcomes from ADT. Methods: PubMed and conference proceedings were searched for studies assessing the impact of low testosterone on clinical outcomes from ADT. The key search terms included combinations of prostate cancer and testosterone, predictive/prognostic, and androgen deprivation. Results were limited to studies investigating the relationship between testosterone levels and clinical outcomes. Results: Both prospective and retrospective data support a relationship between testosterone levels below the historical standard of 1.7 nmol/l and improved outcomes. Eight studies showed significant improvements in survival-related outcomes, with the majority of data supporting a testosterone level cutoff of ≤0.7 nmol/l. Conclusions: Tracking both testosterone and prostate-specific antigen (PSA) levels has significant clinical benefits, and the serum testosterone threshold of ≤0.7 nmol/l is a practical goal. The relative levels of testosterone and PSA may indicate continued hormone responsiveness or progression toward castration-resistant prostate cancer (CRPC) and should, therefore, inform treatment strategy. Standardization of assay methods and clinical coordination to facilitate widespread access to state-of the art laboratory equipment is necessary to ensure accurate decision-making.

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Androgen Deprivation Therapy for Prostate Cancer

Sharifi

Gulley

Dahut

2005

JAMA

916

612

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cal castration) is the cornerstone treatment of advanced prostate cancer. In 1941, Huggins and Hodges 1 first noted the beneficial effects of castration and injection of estrogens in patients with metastatic prostate cancer. The biological basis of the effect of ADT, the almost ubiquitous expression of the androgen receptor in prostate cancer, and growth dependence on the androgen receptor later became clear.Today, in addition to its wellestablished role in treating patients with metastatic disease, ADT is sometimes used to treat patients with increasing prostate-specific antigen (PSA) levels after local treatment, even without radiographic or other evidence of metastatic disease. Androgen deprivation therapy is also used as adjunct therapy for men undergoing radiation therapy for high-risk localized disease (TABLE 1). Despite frequently dramatic and sustained responses of many patients to ADT, treatment exposes patients to a host of important adverse effects (TABLE 2). We sought to systematically review existing evidence regarding the benefits and risks of ADT in contemporary management of local and metastatic prostate cancer. EVIDENCE ACQUISITIONWe performed MEDLINE searches of the English-language literature (1966 to March 2005) using the terms androgen deprivation therapy, hormone treatment, and prostate cancer. Relevant bibliographies of literature were manually reviewed for additional material. In evaluating the benefits of ADT, phase 3 randomized trial data were emphasized. On review of clinical trials, clinical end points of focus, in decreasing order of importance, were survival benefit, radiographic progression-free survival, and rising PSA level. Further information was obtained in oral and abstract form at the 2005 Prostate Cancer Symposium meeting, Orlando, Fla, and the 2005 American Society of Clini-cal Oncology meeting, Orlando, Fla. Published guidelines from the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology were also reviewed.

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Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making

Cited by 234 publications

References 15 publications

Testosterone monitoring for men with advanced prostate cancer: Review of current practices and a survey of Canadian physicians

Testosterone monitoring for men with advanced prostate cancer: Review of current practices and a survey of Canadian physicians

Maximal testosterone suppression in the management of recurrent and metastatic prostate cancer

Androgen Deprivation Therapy for Prostate Cancer

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