Gloria Encabo

Comparison of Percent Free Prostate Specific Antigen and Prostate Specific Antigen Density as Methods to Enhance Prostate Specific Antigen Specificity in Early Prostate Cancer Detection in Men With Normal Rectal Examination and Prostate Specific Antigen Between 4.1 and 10 ng./ml.

PURPOSE We analyzed the behavior of prostate specific antigen (PSA) density and percent free PSA to enhance the specificity of PSA in the early diagnosis of prostate cancer in men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml. MATERIALS AND METHODS PSA serum level, PSA density and percent free PSA were analyzed in 74 men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml. All men underwent systematic prostate biopsy, and the diagnosis was benign prostate hyperplasia in 52 and prostate cancer in 22. Furthermore, we determined the decrease in unnecessary biopsies and the cancer detection rate using 0.10 versus 0.15 as cut points for PSA density, and 20 versus 25 as cut points for percent free PSA. RESULTS In patients with benign prostatic hyperplasia and prostate cancer, respectively, the median PSA level was 6.7 and 7.0 ng./ml. (p > 0.05), median prostate volume was 50 and 37 cc (p < 0.04), median PSA density was 0.14 and 0.19 (p < 0.007) and median percent free PSA was 18.9 and 10.1 (p < 0.005). Using PSA density cut points of 0.15 and 0.10, the decrease in negative biopsies was 53.8 and 36.5% with a sensitivity of 86.4 and 90.9%, respectively. However, using percent free PSA cut points of 20 and 25, the decrease in negative biopsies was 36.5 and 26.9% with a sensitivity of 77.3 and 95.5%, respectively. CONCLUSIONS Although both methods could minimize unnecessary biopsies in men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml., the percent free PSA was more cost-effective since transrectal ultrasound was not required. In this small series of symptomatic patients a percent free PSA cut point of 25 could detect at least 95% of prostate cancers and decrease 26.9% of negative biopsies.

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.

Osteoporosis during continuous androgen deprivation: influence of the modality and length of treatment.

OBJECTIVE To analyze the prevalence of osteoporosis in patients with prostate cancer with and without androgen ablation. To know the influence of the modality and the length of androgen ablation on the prevalence of osteoporosis. To analyze the relative risk of hip fracture. MATERIAL AND METHODS In a cross-sectional study, we assessed bone densitometry at the Wards triangle of the femoral neck in 110 patients with non-metastatic prostate cancer and without biochemical relapse. A cohort of 53 patients under continuous androgen suppression during a median period of 41 months (12-191) formed the study group and 57 age-matched patients that had been submitted to a radical prostatectomy formed a control group. RESULTS Both subsets of patients had similar mean age (70.4 vs. 69.2, p=0.07). Mean bone mass was 0.70 g/cm2 in patients under androgen suppression and 0.76 g/cm2 in the control group, p=0.06. The rate of osteoporosis was 41.5% (22/53) and 28.1% (16/57) respectively, p=0.16 and the odds ratio was 1.82 (95% CI 0,82-4.03). The rate of osteoporosis was 41.4% (12/29) in patients under maximal androgen blockade and 41.7% (10/24) in patients under chemical castration, p=0.735. According to the length of the androgen suppression the rate of osteoporosis was 36.4% when it was between 12 and 36 months, 42.1% from 36 to 60 months and 50% when it was longer than 60 months. While the overall relative risk of hip fracture in the control group was 2.0, it was 2.4 when the length of androgen suppression was between 12 and 36 months, 2.9 between 36 and 60 months and 3.9 when it was longer than 60 months. CONCLUSIONS Androgen suppression increases the prevalence of osteoporosis in patients with prostate cancer. The modality of continues androgen suppression seems not to affect its prevalence. However the length of androgen suppression would be related to its development. The relative risk of hip fracture is also increasing during the androgen suppression.

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.

Circulating CA 15.3 levels in breast cancer. Our present experience.

CA 15.3 is an antigen expressed by human breast carcinoma cells, and defined by two monoclonal antibodies, 115D8 and DF3. We used IRMA to determine the circulating serum levels of CA 15.3 in 1178 subjects with breast cancer, non-breast malignancies, benign diseases and controls. A threshold level of 40 U/ml was established with 140 healthy controls and 650 patients with benign diseases (respectively 0% subjects and 1.5% patients had abnormal antigen levels). Elevated CA 15.3 was found in 12 of 184 patients with malignancies different from breast cancer (6.5%), either epithelial carcinomas with distant metastases, mainly in the liver, or primary liver tumors. Breast cancer patients (n=204) were analysed by prior therapy, UICC stage and WHO response to therapy. Eight of 134 (5.9%) patients with stage II or III breast cancer at presentation and no evidence of disease (NED) had elevated CA 15.3. All of 22 patients with stage IV breast cancer not responding to therapy (SD and PD) had antigen levels > 40 U/ml, as did 10 of 34 (29.4%) stage IV patients in objective response (CR+PR). Three of 14 pretreatment patients had abnormal marker levels, and they later proved to have distant metastases. Serum CA 15.3 values were statistically different (p < 0.01) in NED (20.6 ± 11.2 U/ml), CR+PR (33.5 ± 24.0 U/ml), stable disease (98.8 ± 50.4 U/ml) and progressive disease (> 200 U/ml) breast cancer patients. Our results suggest that circulating CA 15.3 antigen levels agree with the stage of breast cancer and with the response to therapy.

Prostate carcinoma staging: Clinical utility of bone alkaline phosphatase in addition to prostate specific antigen

Biochemical markers of bone disease have been of interest as part of the investigation of prostate carcinoma and the monitoring of skeletal involvement. Bone isoenzyme of the alkaline phosphatase (BAP) is an indicator of the metabolism of the osteoblasts. An immunoradioanalyses with two monoclonal antibodies in sandwich was developed, allowing an accurate measurement of BAP concentration. The goal of the current study was to compare the clinical performance of BAP and prostate specific antigen (PSA) in patients with untreated prostate carcinoma and to determine whether or not BAP can provide valuable additional information to PSA regarding the degree of skeletal extension in patients with prostate carcinoma.

Analysis of bone alkaline phosphatase as a marker for the diagnosis of osteoporosis in men under androgen ablation

The objective of this study was to evaluate the usefulness of serum determination of bone alkaline phosphatase (BAP) in the diagnosis of osteoporosis in men with prostate cancer under androgen ablation. Serum levels of BAP and bone mineral density (BMD) were assessed in 110 patients with non-metastatic, treated prostate cancer. Fifty-eight patients were under androgen deprivation during a period between two and 96 months and 52 had been submitted only to radical prostatectomy. Mean serum BAP was 11.8 ng/mL in patients with normal BMD, 16.7 ng/mL in patients with osteopenia (p. 0.058), and 19.3 ng/mL in patients with osteoporosis (p = 0.044). The correlation between serum BAP and BMD was significant (p. 0.006) but with an index of only 0.26. Receiver operating characteristic analysis for the diagnosis of osteoporosis showed an area under the curve of 0.608. None of the cutoff points that provided specificities of 75%, 90% and 95% gave significant distributions. The positive and negative predictive values as well as the odds ratios were not of any clinical usefulness. We conclude that serum BAP should not be considered a good marker for the diagnosis of osteoporosis in men with prostate cancer. Therefore, BAP serum determination cannot replace bone densitometry as a diagnostic tool.

Ca 50 Serum Levels in Patients with Liver Diseases

CA 50 is an antigenic determinant (1), defined by an Ig M monoclonal antibody, which is present in two different hydrocarbonate structures, and expressed by most (90%) carcinomas (2). It has been considered as a non-specific marker ofgeneral malignant activity (3). There are few reports in the literature that refer to the behavior of circulating CA 50 levels in patients with benign and malignant liver diseases (4). We have studied CA 50 serum levels in 180 patients with benign and malignant liver diseases. 412 patients with benign non-liver diseases and 200 normal subjects, in order to establish a threshold of tumoral activity. Circulating CA 50 serum levels were determined by a solid phase radioimmunoassay (Stena Diagnostics, Sweden). The lower limit of sensitivity was 0.2 V 1m!. Blood samples were collected between 8 and 10 a.m. All samples were frozen at -20°C until assay. Every sample was assayed by duplicate. The control group was 200 healthy blood donors (100 males and 100 females; mean age 41 years, range 18-72). The study group was 412 patients with nonliver benign pathologies (Group I); 121 patients with liver cirrhosis (Group II) and 59 patients with malignant liver diseases (Group III). In the control group, CA 50 serum levels ranged from 0.2 to 20.1 V Iml, with a mean value of 6.1 V /ml and a standard deviation of 3.7. The values of CA 50 in males (6.0 ± 3.9 V Iml, range 0.9-20.1) and females (6.2 ± 3.5, range 0.2-16.4 V 1m!) were close. 13.6V Iml (mean + 2 SD) was initially considered as the upper normal level. CA 50 serum values in the study group are shown in the table. Ninety-six (23.3 %) patients in group I had CA 50 values> 13.6 Vlml, but only 9 (2.1 %) were > 25 V /rnl (1 uterine myoma, 3 active lupus S.E., 2 pneumonias, 1 empyema and 1 agranulocytosis). In group II the mean value was 39.1 Ujml with a standard deviation of25.9; 86.7 percent of these patients had CA 50 values > 13.6 V Iml, and 66.1% of them had values > 25 V 1m!. There were no statistically significant differences related to the etiology of the cirrhosis: 25 unknown (36.6 ± 20.3 V Iml) and 26 alcoholic (35.4 ± 20.2 Vim!). Respectively 68% and 73% of them had values> 25 Ujrnl, The 18 patients with hepatocarcinoma had a mean CA 50 value of 43.3 Urml, with a standard deviation of 30.9; 83.3% of them had values> 13.6 Vlml, and 61.1% had values > 25 Vim!. CA 50 values in the 10 patients with hepatocarcinomas arising in liver cirrhosis (61.9 ± 28.0 Urrnl) and in the 8 patients with hepatocarcinoma and no prior disease (20.3 ± 14.9 Urrnl) were significantly different (p > 0.001); 100% and 90% ofpatients in the former group