Prognostic value of testosterone castration levels following androgen deprivation and high-dose radiotherapy in localized prostate cancer: Results from a phase III trial.

BACKGROUND/OBJECTIVE: The optimal prognostic value of testosterone following androgen deprivation therapy (ADT) is controversial. We studied the effect of serum testosterone levels on clinical outcome in localized prostate cancer (PCa) treated with ADT and high-dose radiotherapy (HRT). PATIENTS AND METHODS: The DART01/05 trial randomized 355 men with intermediate and high-risk PCa to 4 months of ADT plus HRT (STADT, N = 178) or the same treatment followed by 24 months of ADT (LTADT, N = 177). This study included patients treated with LTADT who had at least 3 determinations of testosterone during ADT (N = 154). Patients were stratified into 3 subgroups by testosterone level: minimum <20 ng/dL; median 20-49 ng/dL; and maximum ≥50 ng/dL. Kaplan-Meyer and Cox regression analysis were used for overall survival (OS) and Fine & Gray regression model for metastasis free survival (MFS), biochemical disease-free survival (bDFS) and time to TT recovery. RESULTS: There were no statistically significant differences in 10-year bDFS, MFS, or OS between the <20 ng/mL and 20-49 ng/dL subgroups. Multivariate analysis showed that a median testosterone ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95%CI 1.28-33.76, p = 0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups. CONCLUSIONS: Our results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20-49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.

Usefulness of Methotrexate in the Reduction of Relapses and Recurrences in Polymyalgia Rheumatica: An Observational Study.

OBJECTIVES: Methotrexate (MTX) has been studied with conflicting results in patients with polymyalgia rheumatica (PMR). Our objective was to evaluate the effectiveness of MTX to reduce relapses and recurrences in patients with PMR. METHODS: This observational longitudinal cohort study included 94 consecutive patients with PMR. Patients were assigned to 3 groups according to the prescribed treatment: group 1, treated with glucocorticoids (GCs) alone; group 2, treated with GCs initially plus MTX after a relapse or recurrence; and group 3, treated with GCs plus MTX since diagnosis.Factors associated with a first relapse were studied in the population. To evaluate MTX effect, patients from group 2 were evaluated comparing results from the first treatment period (GCs alone) to the second treatment period with GCs plus MTX. RESULTS: Ninety-four patients were included. The median follow-up time was 21.3 months (interquartile range [IQR], 11.7-56.2). Fifty-three patients (56.4%) were in group 1, 33 (35.1%) in group 2, and 8 (8.5%) in group 3. We found that female sex had a tendency to be associated with a first relapse (p = 0.07).In group 2, 35 relapses were identified during the first treatment period and only 8 relapses during the combined treatment period (p < 0.001). In this group, after the addition of MTX, the GCs dose at relapse was lower (5.1 vs 3 mg/d, p = 0.02) and the time to accomplish remission was shorter (22.9 vs 8.7 months, p = 0.01). There were no differences in the number of recurrences. CONCLUSIONS: The use of MTX in PMR patients who already had a relapse reduced the number of future relapses and decreased the time to achieve remission. Adding MTX allowed a reduction of GCs dose at relapse.

Increased Serum Al Levels in Hemodialysis Patients Kept Enhanced during a 2-Year Prospective Study.

The regulation of mineral homeostasis is altered in hemodialysis patients with renal insufficiency, producing increased risk for secondary diseases like cardiovascular ones. We hypothesized that risen serum aluminum (Al) concentration in hemodialysis patients kept enhanced during a 2-year longitudinal study is associated with enhanced cardiovascular risk and influenced by medical treatments. This study reports the prospective monitoring of serum Al levels in six-monthly samplings over 2 years in 116 hemodialysis patients and a control group of 50 healthy adults. The influence of other factors like sex, age, kidney transplant, disease etiology, and drug consumption was also considered. At each sampling, serum Al levels were significantly higher in the patients than in the healthy controls (P < 0.05). Levels in the patient group were statistically significantly lower at the third and fourth versus first and second samplings, which may be related to Al accumulation in tissues. Increased Al levels in patients were positively and significantly related to serum calcium (Ca) and uric acid levels. Serum Al concentrations were significantly lower in patients receiving vasodilators and diuretics. Higher serum Al levels in hemodialyzed patients administered with phosphate binders or anti-hyperkalemics are attributable to their usual Al salt content. The consumption of antianemic drugs increases Al absorption by forming more bioavailable complexes with the compounds in these drugs. In conclusion, this is the first study to indicate that cardiovascular problems associated with elevated serum Al levels in hemodialysis patients may be in part mitigated by administrating vasodilators and diuretics, which reduce these levels.