Serum total testosterone level predicts survival of male patients with terminal cancer

다국어 초록 (Multilingual Abstract)

Cancer is a major cause of death and illness worldwide: an estimated 14.1 million new cancer cases and 8.2 million cancer deaths occurred in 2012. In Korea as well, cancer has been the leading cause of death since 1983 and has been paid much public health concern. Based on the nationwide cancer statistics, the incidence rate for all cancers showed an annual increase of 3.3% from 1999 to 2009 [1] (Figure 1). Although early detection and developed cancer treatments have led to increased survival rates, death is inevitable. With prolonged survival rates, concerns on the cancer trajectory have shifted to better quality of life from simply increased life expectancy.
Palliative care is interdisciplinary approach that focuses on improving quality of life for patients with any serious illness and for their families [2]. It aimed to provide various support to patients and their families, by managing physical, psychological, or spiritual suffering. Ideally, palliative care should be initiated at the time of diagnosis. By contrast, hospice is a formal system that provides palliative care services to the dying in the last months of life. It has been developed in oncology setting, because survival prediction of cancer patients is relatively easier than those of other terminal illnesses.
Among the end-of-life issues, estimation of remained life is one of the greatest concerns of terminally ill cancer patients and is essential in planning of palliative care. Identification of objective prognostic factors for survival will enhance the accuracy of predicted life remained, thus will improve end-of-life care.
Many clinical or laboratory factors have been studied as prognostic indicators for survival in patients with terminal cancer. Other than tumor-related factors, patient related factors such as comorbidities, performance status, presence of certain symptoms, patient-reporting quality of life were associated with survival. Compared with other prognostic factors, laboratory indicators are objective and easy to estimate. Thus, laboratory parameters including leukocytosis, lymphocytopenia, anemia, hypoalbuminemia, elevated serum acute phase reactants;c-reactive protein (CRP) or vitamin B12, or elevated serum lactate dehydrogenase (LDH) were extensively studied as prognostic parameters for survival in patients with advanced cancer, of which consistency of evidence is variable across different many studies [3]. LDH catalyzes the change of lactate to pyruvic acid and transfers a hydride between molecules.LDH may be used as a tumor marker, because many cancers can raise LDH levels: measuring LDH levels can be helpful in monitoring cancer treatment [4]. Many noncancerous conditions (i.e., encephalitis/meningitis, acute pancreatitis, HIV and lung or liver disease, heart failure, hypothyroidism, anemia, hemolysis, pre-eclampsia) can also raise LDH levels.
Clinical estimation of life span by physician was also a significant factor [5-9]. Many studies [10-13] constructed different prognostic scoring system for estimating life expectancy in these population, incorporating clinical prediction by physician, nutrition related symptoms, cognitive impairment, dyspnea, performance status or some laboratory values.
Testosterone is metabolized in two ways: i)reductive metabolism leading to dihydrotestosterone; ii)oxidative metabolism to estradiol [14] (Figure 2). The reductive metabolism takes place in target tissues like skin, prostate, and liver. The enzyme 5a-reductase is especially active in the prostate giving 5a-dihydrotestosterone. In the liver, both 5a- and 5b-reductases are active and convert testosterone and other steroids into 5a- and 5b-steroid skeletons.In male, a very small portion of the testosterone is converted into estradiol by oxidative metabolism; most of this process happens in adipose tissue.
Testosterone depletion in male adults has been suggested to be linked with decreased bone mass, muscle weakness, and sexual dysfunction [15]. Hypogonadism was also associated with poor survival in many studies. Low serum testosterone has also been associated with higher risk of cardiovascular disease, and has further been related to their poor survival [16, 17]. In aged over 50 years old, lower serum testosterone (<241 ng/dL) had higher risk of death, regardless of preexisting health conditions [18]. In men treated with hemodialysis, lower serum testosterone(≤8.1 nmol/L) was significantly related to increased all-cause mortality and cardiovascular disease mortality after adjustment for other risk factors [19].
Hypogonadism is common in cancer patients [20, 21]. The reason and clinical impact of hypogonadism in male cancer patients is unclear; hypothalamic-pituitary-gonadal axis dysfunction, chronic inflammation, chemotherapy, corticosteroids, or opioids are possible causes [22-24]. Hypogonadic or depressed serum total testosterone concentration(<12 nmol/L) was associated with greater tumor burden [25] or symptom burden [20, 21]. Only one study [21] examined testosterone and survival in cancer patients; lower total testosterone (≤200 ng/dL) was an independent poor prognostic factor for survival along with poor performance status, high CRP level, and hypoalbuminemia in male patients with advanced cancer, however, subjects were not all terminally ill patients and the timing of laboratory workup is not clear.
In this study, we aimed to investigate the association between serum total testosterone concentrations and life expectancy, focusing terminally ill cancer patients admitted in hospice care unit.

목차 (Table of Contents)

• I. INTRODUCTION
• II. MATERIALS AND METHODS
• 1. Study Design and Subjects
• 2. Data Collection
• 3. Statistical Analysis
• III. RESULTS
• 1. Patients characteristics and serum testosterone level
• 2. Survival
• 3. Cox’s proportional hazard model of prognostic factors for survival
• IV. DISCUSSION
• V. CONCLUSION
• REFERENCES