Is serum PSA a predictor of male hypogonadism? Testing the hypothesis

ABSTRACT Objective: Male hypogonadism (MH) is common among infertile men. Besides testosterone, limited MH biomarkers are available, while researchers have suggested the use of prostate-specific antigen (PSA) to help diagnose MH. Hence, we sought to evaluate the potential use of PSA to predict MH among relatively young men with infertility in Nigeria. Materials and methods: The study included 707 male partners (35-44 years) in infertile couples seeking infertility evaluation at a third-level care center in Nigeria. MH was diagnosed using standard guidelines. Receiver operating characteristic (ROC) and regression analyses explored the potential of serum free PSA (fPSA) and total PSA (tPSA) in predicting MH and MH-related clinical features. Results: In all, 29.7% of the patients had MH (MH+ve). The MH+ve group had lower mean values of fPSA and tPSA than the group without MH (MH-ve). The best fPSA threshold of < 0.25 μg/L compared with the best tPSA threshold of < 0.74 μg/L had higher accuracy (area under the curve [AUC] 0.908 versus 0.866, respectively), sensitivity (87% versus 83%, respectively), and specificity (42% versus 37%, respectively) for MH diagnosis. After adjustment for confounders, fPSA level ≤ 0.25 μg/L was more likely to predict MH-related decreased libido (odds ratio [OR] 2.728, p<0.001) and erectile dysfunction (OR 3.925, p<0.001) compared with tPSA ≤ 0.74 μg/L in the MH+ve group. Conclusion: For MH diagnosis, fPSA and tPSA had good sensitivity but very poor specificity, although fPSA had better potential for MH diagnosis and association with MH-related clinical features than tPSA. Hence, fPSA could complement other biomarkers for MH diagnosis in men 35-44 years, although we recommend further studies to confirm these findings.

Evaluation of Serum Prostate Specific Antigens in Breast Cancer.

Serum Prostate Specific Antigen (PSA) is an established tumor marker for prostate cancer but its “specificity” for prostatic diseases was challenged after its extra prostatic sources and its presence in female serum was detected. Various studies showed the association of Total PSA (TPSA) and Free PSA (FPSA) with breast cancer in females. The present study was conducted to evaluate the status of TPSA and FPSA as a tumor marker in breast cancer patients. 54 breast cancer cases with 36 fibroadenoma patients along with 40 controls were selected for the study. Their blood samples were analyzed for estimation of serum Testosterone, TPSA and FPSA along with routine biochemical parameters. 34 breast cancer with 20 fibroadenoma cases were reevaluated for TPSA and FPSA 6 months after tumor removal by surgery. Our observations revealed high TPSA in the patient group compared to controls and raised FPSA specifically in breast cancer cases. FPSA was also found to be the predominant molecular form in breast cancer cases. A significant positive association was documented between serum Testosterone and PSA level in the study group. Both the parameters registered a significant decline after surgery. On statistical analysis TPSA and FPSA were found to possess high specificity for breast cancer cases but were deficient in the desired sensitivity to be considered as an ideal tumor marker.

La eficiencia del índice de PSA libre en el diagnóstico de cáncer de próstata / The efficiency of free PSA index in the diagnosis of prostate cancer

Determinar la eficiencia de la prueba de índice de PSA libre en la práctica clínica hospitalaria. Diseño: Estudio retrospectivo de evaluación de la prueba de índice de PSA libre. Lugar: Hospital Nacional Edgardo Rebagliati Martins. Participantes: 371 casos de pacientes sometidos a biopsia prostática, 104 casos de cáncer de Próstata y 267 casos de Hiperplasia Benigna de Próstata. Intervenciones: Recolección de datos mediante la revisión de registros médicos hospitalarios y revisión de estudios anatomopatológicos. Principales medidas de resultados: Sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo, curva ROC (Receiver Operating Characteristic) y el área bajo la curva ROC (ABC). Resultados: El índice de PSA libre con un punto de corte de 0,20 demostró una sensibilidad de 0,85, especificidad de 0,51, valor predictivo positivo de 0,41, Valor Predictivo Negativo 0,90. El Area bajo la curva ROC fue de 0,78. Conclusiones: El incremento de la especificidad del PSA total es insuficiente para que la prueba sea considerada como optima para discriminar a los pacientes tributarios de biopsia de próstata y evitar las biopsias innecesarias. Sería recomendable elevar el punto de corte para aumentar la sensibilidad de la prueba a 95 por ciento a fin de evitar la pérdida de casos detectados de cáncer de próstata...

To determine the effectiveness of the PSA test free index in Clinical Practice. Design: Retrospective evaluation of the test free PSA index. Location: Hospital National Edgardo Rebagliati Martins Participants: 371 cases of patients undergoing prostate biopsy, 104 cases of prostate cancer and 267 cases of benign prostatic hyperplasia. Interventions: Data collection through review of hospital medical records and review of pathological diagnosis. Main outcome measures: Sensitivity, specificity, positive predictive value, negative predictive value, ROC curve (Receiver Operating Characteristic) and the area under the ROC curve (AUC). Results: The index of free PSA with a cutoff of 0.20 showed a sensitivity of 0.85, specificity of 0.51, positive predictive value of 0.41, negative predictive value of 0.90. The area under the ROC curve was 0.78. Conclusions: The increased specificity of total PSA is insufficient for the test is considered optimal to discriminate against patients for prostate biopsy and avoid unnecessary biopsies. It would be advisable to raise the set point to increase the sensitivity of the test to 95 per cent in order to avoid loss of detected cases of prostate cancer...

Utilidad del APE libre en el diagnóstico de cáncer de próstata / Use of free PSA ratio in the diagnosis of prostate cancer

El Cáncer de próstata (CaP) constituye una importante causa de muerte en nuestro país. La razón Antígeno Prostático Específico libre/ Antígeno Prostático Específico total (APE-L/T) es una de las medidas descritas para mejorar la pesquisa de la enfermedad. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo analítico en el Hospital Naval de Viña del Mar entre enero 2007 a diciembre 2011 que incluyó 588 pacientes con biopsias prostáticas que presentaban APE- T entre 2-10 ng/ml. Se evaluó la edad al diagnóstico, el valor de APE-T y la razón APE-L/T en relación al resultado histológico de las biopsias. Se realizaron curvas de rendimiento diagnóstico (ROC) para APE- T y para la razón APE-L/T. Se calculó sensibilidad y especificidad para diferentes puntos de corte para la razón APE-L/T. RESULTADOS: 33 por ciento de las biopsias fueron positivas para CaP. Los valores de la razón APE-L/T fueron significativamente más bajos en pacientes con CaP (p<0.001), alcanzando un área bajo la curva ROC 0,615. El mejor punto de corte para la razón APE-L/T fue de 15 por ciento con una sensibilidad de 60 por ciento y una especificidad de 58 por ciento. Para la razón APE-L/T > 25 por ciento la sensibilidad es 20 por ciento y la especificidad 91 por ciento. En cambio, el APE-T no mostró diferencias estadísticamente significativas (p=0,1) con un AUC 0,55. CONCLUSIONES: El APE-T por sí solo no parece tener capacidad discriminante para detectar CaP cuando los valores se encuentran entre 2-10 ng/ml. La razón APE-L/T tiene una utilidad limitada frente al paciente para decidir efectuar o no una biopsia de próstata.

Prostate cancer (PCa) is one of the major causes of death in our country. The Free/Total Prostate specific antigen ratio (f/t PSA) is one of the measurements that have been used to improve the diagnosis of this disease. MATERIAL AND METHODS: A retrospective analytic study in the Almirante Nef Hospital in Viña del Mar between January 2007 and December 2011 was made, which included 588 patients with prostate biopsies that had tPSA between 2-10 ng/ml. The age at diagnosis was evaluated and the value of tPSA and the f/t PSA ratio were compared with the histological results of the biopsies. Curves were performed for the diagnostic yield (ROC) for tPSA and the f/t PSA ratio. The sensitivity and specificity for different cut-off points for the f/t PSA ratio in the diagnosis of PCa were also calculated. RESULTS: 33 percent of the biopsies were positive for PCa. The f/t PSA ratio values were significantly lower in patients with CaP (p<0.001), reaching an area under the curve of 0,615. The best cutoff for f/t PSA ratio was 15 percent with 60 percent sensitivity and 58 percent specificity. For f/t PSA ratio > 25 percent sensitivity was 20 percent and specificity was 91 percent. PSA showed no statistically significant differences (p = 0.1) with AUC: 0.55. CONCLUSIONS: tPSA alone does not seem to have discriminatory power to detect PCa in patients when values are between 2-10 ng/ml. The f/t PSA ratio has a limited utility to decide to perform a prostate biopsy or not.

Determinación del punto de corte óptimo del índice PSA libre/PSA total en la indicación de biopsia de próstata / Determination of optimum cutting point between free PSA/PSA total in the indication of prostate biopsy

Determinar el mejor índice de PSAlibre / PSAtotal para la detección precoz del cáncer de próstata. Material y Métodos: Estudio retrospectivo de 496 biopsias prostáticas (2004 a 2006). Se compararon dos grupos de PSA (2.5 – 3.9 ng/dl y 4 – 9.9 ng/dl).Resultados: La detección global fue de 23.4 por ciento. En el primer grupo fue de 19.9 por ciento para el índice de 0.21, comparado con una detección del 23.6 por ciento, para el índice 0.25. Con el índice 0.21 el ahorro de biopsias es de 22 (12.5 por ciento), con una perdida de 3/22 pacientes con cáncer (13.6 por ciento). En el segundo grupo la detección fue de 22.5 para el índice 0.21, comparado con una detección del 24.4 por ciento para el índice 0.25; el índice 0,21 ahorraría 47 biopsias (14.7 por ciento), con una perdida de 6/47 canceres (12.8 por ciento). Conclusión: La perdida de detección en 9/69 pacientes (13.0 por ciento) no justifica bajar el punto de corte al índice 0,21.

To determine the best cut off point for the free PSA / total PSA index.. Material and methods: A retrospective study of 496 prostate biopsies (2004 to 2006). We compared two groups of PSA (2.5 - 3.9 ng / dl and 4 - 9.9 ng / dl). Results: The overall detection was 23.4 percent. The first group was 19.9 percent for the index of 0.21, compared with a detection of 23.6 percent for the index 0.25. With the rate 0.21 the saving is 22 biopsies (12.5 percent), with a loss of 3 / 22 cancer patients (13.6 percent). In the second group, the detection rate was 22.5 percent for the index of 0.21, compared with a detection of 24.4 percent for the index 0.25; index 0.21 saving 47 biopsies(14.7 percent), with a loss of 6 / 47 cancers (12.8 percent). Conclusions: The loss detection in 9 / 69 patients (13.0 percent) did not justify lowering the cut off point to the index 0.21.

Avaliação do valor da relação do antígeno prostático específico livre e total no diagnóstico do câncer de próstata / Evaluation of the value of the relation between free and total prostate-specific antigen in the diagnosis of prostate cancer

Introdução: Este estudo visa a determinar a importância da relação PSA livre (PSAL) / PSA total (PSA) como forma de diferenciar câncer de próstata (CAP) de hiperplasia prostática benigna (HPB) em homens com níveis séricos de PSA entre 4,1 e 10 ng/ml. Material e métodos: Entre 1999 e 2000, 140 homens consecutivos com PSA entre 4,1 e 10 ng/ml foram submetidos à biópsia prostática. Utilizou-se como ponto de corte uma RLT de 0,16, sendo valores iguais ou inferiores a este considerados sugestivos de CAP. Resultados: Em 42 homens (30%) foi detectado CAP e em 98 (70%), HPB. Entre os homens com CAP, 31 (74%) apresentaram RLT igual ou inferior a 0,16 e 11 (26%) apresentaram-na superior a este valor. Entre os homens com HPB, 25 (25,5%) apresentaram RLT igual ou inferior a 0,16 e 73 (74,5%) apresentaram-na superior a este valor. A razão de chance de CAP para os homens com RLT igual ou inferior a 0,16 foi de 8,23 (IC 95%, 3,61 ­ 18,76). A sensibilidade da RLT na detecção do CAP foi de 73,8% e a especificidade de 74,5%. Os valores preditivos positivo e negativo foram 55,4% e 86,9%, respectivamente. Conclusão: O ponto de corte igual ou inferior a 0,16 para a RLT pode ser utilizado como critério auxiliar para enfatizar indicação de biópsia prostática em homens com PSA entre 4,1 e 10 ng/ml, pelo fato de este grupo apresentar um risco maior de CAP. Entretanto, não deve ser utilizado para contra-indicar a biópsia prostática, pela possibilidade de falha diganóstica e não detecção de casos de CAP (AU)

Introduction: The aim of this study was to evaluate the value of the relation of free PSA / to total PSA (PSA) in the differentiation of prostate cancer from benign prostatic hyperplasia (BPH) in men with PSA levels between 4.1 and 10 ng/ml. Material and Methods: Between 1999 and 2000, 140 consecutive men with PSA levels between 4.1 and 10 ng/ml were submitted to at least one transrectal ultrasound prostate biopsy. Free PSA was measured in all men, and its relation with PSA (FTR) was calculated. A FTR cutoff of 0.16 was used, and men with values at or below it were considered at risk for prostate cancer. Results: Prostate cancer was found in 42 men (30%) and BPH in 98 (70%). Of the men with prostate cancer, 31 (74%) presented with a FTR equal or below 0.16 and 11 (26%) presented with a FTR above this value. The odds ratio (OR) for prostate cancer was 8.23 (CI 95%, 3.61 ­ 18.76) in men with a FTR equal or below 0.16. FTR had a sensibility of 73.8% and a specificity of 74.5% in the detection of prostate cancer. The positive and the negative predictive values were 55.4% and 86.9%, respectively. Conclusion: The cutoff value equal or below 0.16 for the FTR may be used as an auxiliary criteria to emphasize prostate biopsy indication in men with PSA values between 4.1 and 10 ng/ml, since this group is at greater risk of harbouring prostate cancer. Nevertheless, it should not be used to contraindicate prostate biopsy because of the possibility of missing prostate cancer cases (AU)

Proper Cut-off Value of Free to Total PSA Ratio for Detection of Prostate Cancer in Korean Men

To assess whether the free-to-total prostate specific antigen (PSA) ratio (F/T PSA ratio) would enhance prostate cancer detection in Korean men with serum total PSA levels between 4 and 20 ng/ml. Methods: A total of 240 consecutive patients whose serum PSA levels were between 4 and 20 ng/ml were enrolled in this two-year study. All patients underwent ultrasound-guided transrectal biopsies of the prostate gland. The F/T PSA ratio was measured using the Roche immunoassay. Results: Of the 240 patients, 202 (84%) had benign histologies, while 38 (16%) had prostate cancer. The two patient groups were well matched for age. The mean F/T PSA ratio showed a statistically significant difference between the two groups: in the benign histology group it was 0.14 (0.04 - 0.37), and 0.10 (0.08 - 0.20) in the prostate cancer group (p< 0.05). Out of the 183 patients with a PSA level between 4-10ng/ml, the mean F/T PSA ratios were 0.14 and 0.11 in the benign histology (n=158) and prostate cancer groups (n=25), respectively (p< 0.05). From the 57 patients with a PSA level between 10 - 20 ng/ml, the mean F/T PSA ratios were 0.14 and 0.10 in the benign histology (n=44) and prostate cancer groups (n=13), respectively (p< 0.05). Overall, when the cut-off value of the F/T PSA ratio was 0.10, the sensitivity and specificity were 75.0% and 76.5%, while for the cut-off value of 0.15 they were 83.3% and 39.7% respectively. Conclusion: Our data demonstrated the usefulness of the free to total PSA ratio in distinguishing benign prostate disease and cancer disease, hence eliminating unnecessary biopsies. It is recommended that a cut-off value for the F/T PSA ratio of 0.10 be applied to Korean men which this is lower than the value used in Western countries.

The Efficacy of Prostate Specific Antigen adjusted for the Transition Zone Voume (PSATZ) as a New Predictor of Prostatic Cancer / 대한비뇨기과학회지

PURPOSE: Although PSA(prostate specific antigen) is an excellent tumor marker, it is not prostate cancer-specific but organ-specific. The objective of this study is to assess the efficacy of prostate specific antigen adjusted for the transition zone voume(PSATZ) in diagnosing prostate cancer in men with intermediate PSA levels of 4.1 to 10.0 ng/ml. MATERIALS AND METHODS: Between March 1997 and September 1998, PSATZ was obtained from 67 patients who underwent ultrasound-guided systemic sextant biopsies and had a PSA of 4.1-10.0ng/ml. PSATZ was compared with PSA, PSAD(PSA density) and free-to-total PSA ratio(F/T ratio) via receiver operating characteristic(ROC) curves. RESULTS: Of 67 patients, 22(32.8%) had prostate cancer and 45(67.2%) had benign prostatic hyperplasia on pathologic examination. Mean PSA, F/T ratio, PSAD and PSATZ were 7.96+/-2.01ng/ml 0.10+/-0.06, 0.28+/-0.14ng/ml/cc and 0.70+/-0.28ng/ml/cc in patients with prostate cancer and 6.39+/-1.68ng/ml, 0.15+/-0.05, 0.16+/-0.06ng/ml/cc and 0.29+/-0.11ng/ml/cc in patients with benign prostatic hyperplasia, respectively. ROC curve analysis demonstrated that PSATZ, F/T ratio and PSAD predicted the biopsy outcome significantly better than PSA in all 67 patients(p<0.01, respectively). In a subset of 45 men with normal digital rectal examination, PSATZ predicted the biopsy outcome better than PSAD or F/T ratio significantly(p<0.01, respectively). With cutoff value of 0.35ng/ml/cc, PSATZ had a sensitivity of 86% and a specificity of 89% for predicting prostate cancer. With cutoff value of 0.12, F/T ratio had a sensitivity of 73% and a specificity of 71% for predicting prostate cancer. CONCLUSIONS: These results suggest that PSATZ is more specific and more accurate than PSA, PSAD or F/T ratio in distinguishing benign prostatic disease from prostatic cancer in men with intermediate PSA levels of 4.1 to 10 ng/ml. But large prospective studies are requested to assess the precise role of PSATZ in early prostate cancer detection.

Clinical Significance of Percent Free PSA as a Marker for Prostate Cancer / 대한비뇨기과학회지

PURPOSE: Prostate-specific antigen(PSA) exist in serum in two major immunodetectable molecular forms: free PSA, and complexed PSA(PSA- alpha-1-antichymotrypsin). Total PSA represents the sum of the free and complexedorms. Preliminary investigations have illustrated the potential benefits of using percent free PSA to enhance the utility of PSA in distinguishing benign prostate disease from prostate cancer. Our study was undertaken to define the effectiveness of precent free PSA in the early detection of prostate cancer and to determine appropriate cutoff points for percent free PSA in Korea when total PSA level is normal or mildly elevated so as to eliminate negative biopsies. MATERIALS AND METHODS: Patient samples consisted of 24 histologically confirmed primary cancer, 83 men with untreated benign prostate disease histologically confirmed by negative sextant biopsies, and 29 men with normal digital rectal examination and PSA values less than 4.0ng/ml. Total PSA and free PSA levels were determined using PSA-RIACT and FPSA-RIACT kit(Cis Bio International, France), respectively. Percent free PSA was calculated for all patients. Within the range of 2.5-20.0ng/ml, receiver operating curve(ROC) was generated and utilized to evaluate cutpoints for percent free PSA to be used in clinical practice. RESULTS: When all subjects were included, both total PSA and percent free PSA significantly discriminated patients with prostate cancer from patients with benign histologic conditions(p=0.0003 and p=0.0001, respectively). However, in men with total PSA values between 2.5 and 20.0ng/ml, the percent free PSA significantly discriminated patients with prostate cancer from patients with benign conditions(p=0.001), whereas the total PSA did not(p=0.14). Among this subgroup of patients, the analysis of sensitivity and specificity showed that the percent free PSA had a clearly higher specificity compared with that of the total PSA at the same level of sensitivity. Within the range of 2.5-20.0ng/ml, the cutoff point for percent free PSA was 20. CONCLUSIONS: Measurement of percent free PSA enhance the ability to discriminate prostate cancer from benign histologic condition while retaining high sensitivity for detecting cancer in men who present with total PSA levels between 2.5 and 20.0ng/ml.

The Effect of Age, Prostate volume and Total PSA on Percent free PSA in Men with Benign Prostatic Disease / 대한비뇨기과학회지

PURPOSE: We assessed the influence of age and prostate volume on the serum total PSA and percent free PSA level, and total PSA on the percent free PSA level in men with benign prostatic disease except clinically detectable prostatic cancer. MATERIALS AND METHODS: Sera were obtained from 250 men with total PSA level of 0 to 20 ng/ml who were clinically negative for cancer. Total and free PSA levels were measured using ELSA-PSA2 and FPSA-RIACT immunoradiometry assay. Prostate volume was determined by transrectal ultrasound. RESULTS: Age and prostate volume correlated significantly with Total PSA levels (r=0.204 and 0.482, p<0.05) and free PSA levels (r=0.246 and 0.539, p<0.05) but not with percent free PSA(r=0.057 and -0.039, p=0.188 and 0.541). Total PSA levels correlated significantly with free PSA(r=0.853, p<0.05) and percent free PSA(r=-0.398, p<0.05). CONCLUSIONS: Among men with total PSA levels of 0 to 20 ng/ml and do not have clinically detectable prostatic cancer, total PSA and free PSA increases with increasing age and prostate volume. And percent free PSA decreases with increasing total PSA but it was not influenced by age and prostate volume.

Age Specific Free PSA to Total PSA Ratio in Normal Korean Men / 대한비뇨기과학회지

Prostate specific antigen (PSA) is known as the most sensitive marker for detecting prostate carcinoma (CaP). Nevertheless, PSA testing lacks sufficient sensitivity and specificity to be considered the perfect tumor marker for the detection of early prostate cancer. PSA exists in the serum in several molecular forms; free PSA and complexed PSA (PSA complexed to alpha-1-antichymotrypsin or a-2-macrogloburin or inter-alpha -trypsin inhibitor). It has been suggested that analysis of level of free to total PSA ratio improves specificily of PSA assays in the early detection of prostate carcinoma. We measured free PSA and total PSA of 367 healthy men aged from 30 to 79 years old using radioimmunoassay (PSA-RIACT and FPSA-RIACT kit) in order to know the normal range of PSA, free PSA and free PSA to total PSA ratio. The mean free to total PSA ratio in normal Korean men is 0.31+/-0.14 and there is no correlation with patient age.

The Role of Free/Total PSA in the Differential Diagnosis of the Prostate Cancer and Benign Prostatic Hyperplasia / 대한비뇨기과학회지

OBJECTIVES: This study examined the role of free/total prostate specific antigen (PSA) in the differentiation between prostate cancer and benign prostatic hyperplasia (BPH) in patients with total PSA higher than 4.0 ng/ml. MATERIALS AND METHODS: Fourteen untreated patients with prostate Cancer and 63 patients with BPH were included in this study. All patients were pathologically diagnosed by sextant transrectal biopsy before treatment. The level of total PSA and free PSA were determined by immunoradiometric assay (Cis bio international). The median values of total PSA and F/T (free/ total PSA) were compared between prostate cancer and BPH in the three different ranges of total PSA (PSA>4.0ng/ml, 4.0 ng/ml Characteristic (ROC) curves were obtained using sensitivity and specificity of total PSA and F/T at each cutoff level. RESULTS: In the range of PSA between 4.0 and 10.0 ng/ml, the median value of F/T was significantly different between prostate cancer and BPH (p<0.05), while that of total PSA was not. In other ranges of PSA, both total PSA and F/T were significantly different between prostate cancer and BPH. The area under the F/T ROC curve was significantly larger than that of total PSA ROC curve only in the range of PSA between 4.0 and 10.0 ng/ml.. In the mean time, F/T was more specific than total PSA (52% vs 32%) at the identical sensitivity (93%) of F/T and total PSA cutoff values (F/T cutoff, 0.2; total PSA cutoff, 6.0 ng/ml). CONCLUSIONS: Free/Total PSA might provide us more reliable information on the differential diagnosis of the prostate cancer, especially in patients with PSA range between 4.0 and 10.0 ng/ml.