Enrique Trilla

Bone Mineral Density Changes in Patients With Prostate Cancer During the First 2 Years of Androgen Suppression

PURPOSE We characterized bone mineral density changes in patients with prostate cancer on androgen deprivation therapy during the first 2 years of uninterrupted therapy, and identified which location most reflects bone mass loss. MATERIALS AND METHODS Using dual energy x-ray absorptiometry, bone mineral density was prospectively assessed in patients with nonmetastatic prostate cancer at the lumbar spine and femoral neck, Wards triangle, trochanter and total hip. Measurements were performed at baseline and yearly thereafter in patients on ADT, and at baseline and 1 year in controls (age matched patients with prostate cancer, free of biochemical progression after radical prostatectomy). RESULTS A total of 62 patients were included in the study, 31 in each group. Median age (70 and 69 years, respectively), mean Gleason score and mean baseline serum testosterone did not significantly differ. Patients receiving ADT experienced a significant bone mass loss at 12 months in all locations, ranging from 2.29% to 5.55% (p <0.001). In contrast, bone mineral density did not change significantly (0.64% to 1.68%) in patients not receiving ADT. In the 20 patients on ADT after 24 months, the second year decrease was not as severe, nor was it significant compared to first year values. The major bone mass loss occurred in Wards triangle, with decreases of 5.55% at 12 months and 7.05% at 24 months. CONCLUSIONS Bone mineral density decreases during the first 24 months of androgen suppression with the most relevant effect occurring in the first year. Wards triangle is the axial skeletal site that reflects the major bone mass loss. Because the deleterious impact of long-term androgen suppression on bone mineral density is inversely related to fracture risk and indirectly related to survival in patients with prostate cancer, early diagnosis and prevention of bone mass loss are warranted in these patients.

Failure to Maintain a Suppressed Level of Serum Testosterone during Long-Acting Depot Luteinizing Hormone-Releasing Hormone Agonist Therapy in Patients with Advanced Prostate Cancer

Objectives: It was the aim of this study to analyze the failure rates in achieving or maintaining castrate levels of serum testosterone in patients with advanced prostate cancer treated with the 3-month luteinizing hormone-releasing hormone agonist (LH-RH) therapy. Methods:Total serum testosterone was determined in 234 patients with prostate cancer in a cross-sectional study. A subset of 90 patients submitted to radical prostatectomy was used as the control group (group 1), and 144 patients with advanced prostate cancer under androgen suppression therapy were included in the study group (groups 2 and 3). The study group was divided into 93 patients (group 2) treated with 50 mg daily bicalutamide and LH-RH agonist (maximal androgen blockade, MAB) and 51 patients treated with the LH-RH agonist alone (group 3). Median follow-up after androgen suppression was 42 months. The castrate testosterone level was defined below 50 ng/dl. Results: The mean serum testosterone level was 29.1 ng/dl in patients undergoing MAB (group 2) and 29.5 ng/dl in patients treated with the LH-RH agonist (group 3; p > 0.05). In group 1, the mean serum testosterone was 445.2 ng/dl (p < 0.0001). The rate of patients with a serum testosterone level higher than 50 ng/dl was 10.9% in patients undergoing androgen suppression, 10% in patients with MAB treatment and 12.5% in those with LH-RH agonist therapy (p > 0.05). In group 1, 98.9% of the patients had a serum testosterone level higher than 50 ng/dl. Conclusions: A small but clinically significant rate of patients under 3-month LH-RH agonist therapy fail to achieve or maintain castrate testosterone serum levels. This finding supports the need of monitoring testicular response during LH-RH agonist therapy.

Nadir prostate‐specific antigen best predicts the progression to androgen‐independent prostate cancer

The objective of our study was to analyze the value of prostate‐specific antigen (PSA) levels before and after androgen suppression to predict the time to androgen‐independent progression (AIP) in patients with advanced and metastatic prostate cancer. A series of 283 prostate cancer patients under androgen suppression as a single treatment was studied. The disease was locally advanced in 98 patients and metastatic in the remainder 185. AIP was defined after 2 consecutive increases of serum PSA after the nadir value. The mean follow‐up before AIP was 29.2 months (3–198). AIP was detected in 205 patients (72.4%). In 152 patients (74.1%), the event was detected within 24 months, while in 53 patients (25.9%), it was observed beyond 24 months. The multivariate analysis showed that the nadir PSA and the time to reach the nadir PSA were the most significant predictors of the time to AIP. The odds ratio of having a biochemical response greater than 24 months was 20 times higher in patients that achieved an undetectable PSA level of 0.2 ng/mL or less. Moreover in those patients whose nadir PSA reached beyond 12 months after androgen suppression the odds ratio was 18 times higher. These results show that the ability to achieve an undetectable nadir PSA and the time to reach it are the most significant predictors of the time to AIP in patients with locally advanced and metastatic prostate cancer under androgen suppression as a single therapy.

The relationship between daily calcium intake and bone mineral density in men with prostate cancer.

To analyse the relationship between daily calcium intake (DCI) and bone mineral density (BMD) in patients with prostate cancer, and to assess if DCI is a risk factor for osteoporosis in this group of patients.

Alendronate decreases the fracture risk in patients with prostate cancer on androgen-deprivation therapy and with severe osteopenia or osteoporosis

To evaluate changes in bone mass and fracture risk in patients with prostate cancer on androgen‐deprivation therapy (ADT) and with a basal T‐score of >−2.0, who were treated with an oral bisphosphonate, as such patients treated with ADT are at increased risk of bone loss and bone fracture.

Altered transcription factor E3 expression in unclassified adult renal cell carcinoma indicates adverse pathological features and poor outcome.

What’s known on the subject? and What does the study add?

The Percentage of Free Prostatic-Specific Antigen Is Also Useful in Men with Normal Digital Rectal Examination and Serum Prostatic-Specific Antigen between 10.1 and 20 ng/ml

OBJECTIVE The percentage of free prostatic-specific antigen (PSA) has been introduced as a tool to avoid unnecessary biopsies in men with normal digital rectal examination (DRE) and serum PSA between 4.1 and 10 ng/ml. In this series we also analyze its utility in men with normal DRE and serum PSA between 10.1 and 20 ng/ml. MATERIALS AND METHODS A series of 1149 consecutive men with normal DRE and serum PSA between 4.1 and 20 ng/ml submitted for the first ultrasound guided sextant biopsy is analyzed. In 921 (80.2%) the serum PSA was from 4.1 to 10 ng/ml and in 228 (19.8%) from 10.1 to 20 ng/ml. Total and free serum PSA determinations were done by the inmunoradiometric assays Tandem and Tandem free PSA (Hybritech Inc.). RESULTS The overall detection rate of prostate cancer was 27.9%. In the group of men which serum PSA ranged from 4.1 to 10 ng/ml the rate of detection was 25.4% and 37.7% when it was between 10.1 and 20 ng/ml. Using 25% or less of percent free PSA as a criterion for performing prostatic biopsy it would have detected 95.3% and 95.4% of the prostate cancers, respectively. The rate of unnecessary avoided biopsies would be 17.5% when serum PSA ranged from 4.1 to 10 ng/ml and 17.6% between 10.1 and 20 ng/ml. CONCLUSIONS This prospective study demonstrates that the percentage of free PSA seems to have similar utility when serum PSA levels are between 4.1 and 10 ng/ml and between 10.1 and 20 ng/ml, at the time of the first prostatic biopsy indication.

Analysis of the lipid profile and atherogenic risk during androgen deprivation therapy in prostate cancer patients.

Objective: To analyse changes in lipid profiles observed in patients receiving androgen deprivation therapy (ADT) and to evaluate differences between medical castration and maximal androgen blockade (MAB). Material and Methods: Serum levels of total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL) and triglycerides (TG) were prospectively evaluated in 33 patients with locally advanced or metastatic prostate cancer treated with ADT. The median age was 73.4 years. Serum lipids were measured at baseline and thereafter at 6 and 12 months. The modality of ADT was medical, with 3 months depot LHRH agonist, in 11 patients and MAB, by addition of 50 mg/day of bicalutamide, in 22 patients. Results: TC increased from 210 to 227 mg/dl (p < 0.05), while LDL increased from 132 to 148 mg/dl (p < 0.05) at 6 months. There were no significant changes in HDL or TG levels. There were no significant differences in any of the analysed parameters after 12 months of ADT. The comparison between the group of patients treated with LHRH agonists alone and the group treated with MAB demonstrated no significant differences in any of the analysed parameters at 6 and 12 months (p > 0.05). Conclusions: Changes observed in TC and LDL after 6 months of ADT were transitory. No significant differences were observed according to the modality of ADT.

Preoperative Prediction of Pathologically Insignificant Prostate Cancer in Radical Prostatectomy Specimens: The Role of Prostate Volume and the Number of Positive Cores

Introduction: To determine clinical and biopsy features with predictive capacity to identify pathologically insignificant prostate cancer (pIPCa). Material and Methods: pIPCa was defined as cancer volume <0.5 cm3 and a Gleason score (GS) of ≤6 in radical prostatectomy (RP) specimens. Clinical and biopsy parameters were studied as predictors of pIPCa and validated by applying them to d’Amico’s low-risk cases: T1c-T2a, prostate-specific antigen (PSA) <10 and biopsy GS ≤6. Appropriate cut-offs were selected. Results: 280 patients were evaluated; 11.8% (33) had pIPCa, increasing to 23% in low-risk cases. In patients fulfilling d’Amico’s low-risk criteria, variables significantly different in pIPCa were: volume, number of positive cylinders (NPC), percentage of positive cylinders (%PC), percentage of the most affected cylinder (%MAC) and uni/bilaterality. In these cases, volume and the NPC increased as independent variables on logistic regression and when adding a volume threshold of 45 cm3 and 1 positive core, specificity reached 95.8%. Conclusions: The incidence of pIPCa in RP specimens is relevant, especially in low-risk cases. Prostate volume and NPC are independent predictors of pIPCa. We propose a simple predictive model by adding the features of 1 positive core and volume ≧45 cm3 to d’Amico’s criteria. This allows to preoperatively distinguish between patients that most probably would benefit from radical treatment and patients that might be offered active surveillance.

Is there a relationship between prostate volume and Gleason score

To review the relationship between the Gleason grade and prostate volume in biopsy and radical prostatectomy (RP) specimens, and thus assess the hypothesis that smaller prostates have a greater incidence of high‐grade tumours.