Prostate Specific Antigen is Metabolized in the Liver

Purpose

The site of metabolism of prostate specific antigen (PSA) was determined.

Materials and Methods

In a prospective study, during clinically indicated left and right heart catheterizations for various cardiac diseases in 12 men (mean age 62.5 plus/minus 8.3 years, standard deviation), selective blood samples were obtained from the infra-renal, infra-hepatic and supra-hepatic inferior vena cava, renal vein, superior vena cava, pulmonary artery and femoral artery. Mean PSA concentration was calculated for all vascular sites. Using a paired Student t test, the mean difference between the afferent and efferent PSA concentrations across the renal, hepatic, pulmonary and pelvic circulation was calculated.

Results

The hepatic gradient between the infra-hepatic and suprahepatic inferior vena cava showed the greatest decrease (0.11 plus/minus 0.16 ng./ml. or 8.3 percent) in PSA concentration and was statistically significant (p = 0.04). A smaller decrease across the pulmonary circulation was statistically insignificant. No decrease in the PSA concentration was noted across the renal circulation. The PSA concentration increased significantly (0.19 plus/minus 0.18 ng./ml. or 16.3 percent, p = 0.003) across the pelvic circulation, confirming the release of PSA from the prostate.

Conclusions

PSA is released from the prostate. The kidneys and lungs do not have a significant role in elimination of PSA, and the liver appears to be the most likely site of its metabolism. Although our sample size is small and the PSA range is narrow, our results strongly support these conclusions.     

Serum Prostate Specific Antigen and Prostate Specific Antigen Density in Patients Receiving Radical Prostatectomy

Objective: To study the significance of prostate specific antigen (PSA) and prostate specific antigen density (PSAD) for predicting the risk of occult metastatic disease and extra-prostatic invasion of prostate cancer in patients receiving radical prostatectomy.
Patients and methods: The cases of 41 consecutive patients who underwent radical prostatectomy were reviewed. Relations of PSA and PSAD using Market M PA^1M assay for grade, preopvrative clinical stage, postoperative pathological stage, capsular penetration, seminal vesicle invasion, resection margins and lymphnode metastasis are discussed.
Results: Although serum PSA was correlated with PSAD and PSA was correlated with preoperative prostate volume, PSAO was not influenced by prostate volume. PSA correlated only with the grade, while PSAD was correlated with grade, preoperative clinical Stage, postoperative pathological stage, capsular penetration, seminal vesicle invasion, resection margins and lymphnode metastasis. In addition, sixty-two percent (8/13) of margin positive patients showed a PSAD value of more than 0.4, while 93% (26/28) of margin negative patients showed less than 0.4. Sixty-seven percent (6/9) of lymphnode positive patients showed a PSAD of more than 0.4, while 91% (29/32) of lymphnode negative patients showed less than 0.4.
Conclusion: We concluded that PSAD was useful for predicting extraprostatic involvement of prostatic cancer.     

The Clinical Value of the Ratio of Free Prostate Specific Antigen to Total Prostate Specific Antigen

Objective: To examine the usefulness of the ratio of free prostate specific antigen (FPSA) to total prostate specific antigen (TPSA) in men with serum TPSA concentration of 4 to 10 ng/mL by using the cut off value of 0.15 for avoiding unnecessary biopsies. Patients and methods: Two hundred thirty-six men aged between 52 and 91 with symptoms of prostatism were evaluated with digital rectal examination (DRE), FPSA and TPSA measurements. Patients with TPSA values under 4 ng/mL were biopsied if they had positive DRE and/or a FPSA/TPSA ratio lower than 0.15. All patients with TPSA values higher than 4 ng/mL were also biopsied. The predictive value and sensitivity of FPSA/TPSA ratio and TPSA alone were calculated. Results: Eleven patients out of 170 with a TPSA value lower than 4 ng/mL were biopsied. Fifty-five patients had a value between 4.1 and 10 ng/mL. We performed transrectal ultrasound (TRUS) and prostate biopsy in these men except one patient. Biopsy proven prostate cancer was detected only in 12 patients. In this group of patients the predictive value of TPSA was 21%, but the predictive value of FPSA/TPSA ratio of 0.15 was 78% maintaining at least 90% sensitivity. Eleven of the patients had a prostate specific antigen (PSA) value higher than 10 ng/mL. In 6 of these patients the biopsy result was prostate cancer and 10 of these patients had a FPSA/TPSA ratio lower than 0.15. Conclusion: In patients with TPSA values between 4–10 ng/mL the cut off value of FPSA/TPSA ratio of 0.15 can be used to eliminate unnecessary biopsies with minimal loss of cancer patients.     

Prostate Specific Antigen Density Versus Prostate Specific Antigen Slope as Predictors of Prostate Cancer in Men with Initially Negative Prostatic Biopsies

Purpose

We determined if prostate specific antigen (PSA) density and PSA slope alone or in combination could be used to predict which men with persistently elevated serum PSA and prior negative prostate biopsies will have prostate cancer on repeat evaluation.

Materials and Methods

In our PSA-1 data base we identified 327 men 50 years old or older with an initially negative prostate biopsy who had persistent PSA elevation, and compared those who did and did not have prostate cancer on subsequent serial prostatic biopsy.

Results

Of 70 men with a PSA density of 0.15 or more and PSA slope of 0.75 ng./ml. or more annually compared to 83 with a PSA density of less than 0.15 and PSA slope of less than 0.75 ng./ml. annually 32 (46 percent) and only 11 (13 percent), respectively, had prostate cancer on subsequent prostate biopsies (p less than 0.0001). In a hierarchical logistic regression analysis PSA density and PSA slope were predictive of prostate cancer on subsequent biopsy (p = 0.001 and 0.03, respectively). PSA density of 0.15 or more alone or PSA slope of 0.75 ng./ml. or more annually alone as the indicator for repeat biopsy would have missed 35 and 40 percent of cancers, respectively.

Conclusions

In men with persistently elevated serum PSA after an initially negative prostate biopsy, PSA density and PSA slope alone or in combination provide useful predictive information about the results of repeat prostate biopsies. However, these parameters are not sufficiently sensitive to identify all patients with detectable prostate cancer.     

血清前列腺特异抗原测定的临床意义

以12例前列腺癌、102例前列腺良性增生(BPH)、16例直肠指检(DRE)异常、5例前列腺炎及30例正常男性为对象,用酶免法测定血清前列腺特异抗原(Prostate specific antigen,PSA)浓度,用放免法测定其中37例。前列腺癌的PSA浓度明显高于BPH(P<0.01),PSA对前列腺癌诊断的敏感性为91.7％。DRE异常者大于BPH(P<0.05),低于前列腺癌(P<0.01)。BPH高于正常对照(P<0.01)。前列腺切除术后一日的PSA高于术前(P<0.01),术后6～8日同术前无显著性差异(P>0.05)。70岁以上高于70岁以下(P<0.05)。PSA>10ng/ml时酶免检测值低于放免法(0.010.05)。单纯PSA升高并不能说明任何特异性病理过程,前列腺癌的诊断,应结合PSA系列测定值及DRE和经直肠B超(TRUS)来综合分析。     

Serum Pro Prostate Specific Antigen Improves Cancer Detection Compared to Free and Complexed Prostate Specific Antigen in Men With Prostate Specific Antigen 2 to 4 Ng/Ml

PurposePro prostate specific antigen (pPSA) is a precursor form of PSA enriched in tumor compared to benign prostate tissues that may be a more specific serum marker for prostate cancer. Serum pPSA was measured in the clinically relevant early detection PSA range of 2 to 10 ng/ml.Materials and MethodsResearch use immunoassays were used to measure native and truncated forms of pPSA. The subject cohort contained 1,091 serum specimens from men enrolled in prostate cancer screening studies at 2 sites who had undergone prostate biopsy and were divided into PSA ranges of 2 to 4 ng/ml (benign 320, cancer 235) and 4 to 10 ng/ml (benign 315, cancer 221).ResultsIn PSA ranges 2 to 4, 2 to 6, 4 to 10 and 2 to 10 ng/ml, pPSA in a ratio with free PSA (%pPSA) gave the highest cancer specificity. At 2 to 4 ng/ml and 90% sensitivity, %pPSA spared 19% of unnecessary biopsies compared to 10% for free PSA and 11% for complexed PSA(p <0.001). Similar results were obtained at PSA 2 to 6 ng/ml. At 90% sensitivity in the PSA 4 to 10 ng/ml range, %pPSA spared 31% of unnecessary biopsies compared to 20% for % free PSA and 19% for complexed PSA (p <0.0001). In the combined 2 to 10 ng/ml range, %pPSA spared 21% of unnecessary biopsies compared to 13% for % free PSA and 9% for complexed PSA (p <0.0001).ConclusionsThe %pPSA significantly improved specificity for cancer detection and decreased the number of unnecessary biopsies in the PSA 2 to 4 ng/ml range. This relative improvement of %pPSA compared to % free PSA and complexed PSA was maintained throughout the PSA range of 2 to 10 ng/ml.     

Pitfalls in Interpreting Prostate Specific Antigen Velocity

Purpose

The concept of prostate specific antigen (PSA) velocity as an improved marker for prostate cancer detection is intriguing. However, before this concept is applied to individual patients several confounding parameters must be addressed. We determined the variability of serum PSA levels in men without prostate cancer.

Materials and Methods

We reviewed data from a prostate cancer screening program, and determined inter-assay and individual variability of the serum PSA values for a 2-year followup period in 265 men clinically free of prostate cancer.

Results

Our average inter-assay coefficient of variation was 7.5 percent. Therefore, we considered only PSA changes exceeding plus/minus 15 percent as significant. Fluctuations in serum PSA occurred in 78 percent of the men during the observation period, and 12.5 percent had at least a single PSA increase exceeding 0.75 ng./ml. per year. Fluctuations were noted throughout the entire range of serum PSA levels but became progressively larger with an increasing mean PSA.

Conclusions

The inter-assay variability must be considered when interpreting PSA velocity. Individual fluctuations in serum PSA dictate an observation period of at least 2 years before PSA velocity is considered abnormal.     

Value of the Free to Total Prostate Specific Antigen Ratio and Prostate Specific Antigen Density for Detecting Prostate Cancer in Japanese Patients

Background : This study evaluated the free to total serum prostate specific antigen (f/t PSA) ratio and prostate specific antigen density (PSAD) in detecting prostate cancer in Japanese males with a PSA level between 2.5 and 20.0 ng/mL in a community-based urology practice.
Methods : Twenty-six patients with clinically localized prostate cancer and 44 patients with histologically-proven benign prostatic hyperplasia (BPH) were studied. The serum levels of free PSA (fPSA) and total (t) PSA were determined using a chemiluminescent enzyme immunoassay. The f/t PSA ratio was calculated by dividing the fPSA value by the total PSA value and was compared with the PSA and PSAD via the receiver operating characteristic (ROC) curves.
Results: Patients with prostate cancer had a significantly lower f/t PSA ratio than patients with BPH. The PSAD was a superior diagnostic tool over PSA (P < 0.01) when analyzed by ROC curves. The f/t PSA ratio was also superior to PSA, but lacked significance (P=0.12), and similarly, the PSAD was superior, but not significant, to the f/t PSA ratio. Using a cut-off value of 0.1 9, the PSAD had a sensitivity of 81% and a specificity of 82%. With a cut-off value of 14.0%, the f/t PSA ratio had a sensitivity of 81% and a specificity of 66%.
Conclusion: This study showed that PSAD alone improved cancer detection significantly better than PSA. However, it is still unclear whether the f/t PSA ratio is superior to PSA or PSAD in the discrimination between BPH and prostate cancer in Japanese male patients.     

The Free-To-Total Prostate Specific Antigen Ratio Improves the Specificity of Prostate Specific Antigen in Screening for Prostate Cancer in the General Population

Purpose

The ratio between free and total prostate specific antigen (PSA) in serum improves the specificity of total serum PSA for the detection of prostate carcinoma in select populations. The value of the free-to-total PSA ratio for a PSA of 4.0 to 10.0 ng./ml. was analyzed in a screening population.

Materials and Methods

From 4,800 participants 55 to 76 years old 977 biopsies were obtained because of an abnormal digital rectal examination, suspicious transrectal ultrasonography and total serum PSA 4.0 ng./ml. or more. Of 191 patients with prostate carcinoma detected 101 had a serum PSA of 4.0 to 10.0 ng./ml. and 54 of them underwent radical prostatectomy. A free-to-total PSA ratio of 0.20, age specific PSA reference ranges and a PSA density of 0.12 ng./ml./cc were evaluated for the ability to increase the specificity of total serum PSA in predicting positive prostate biopsy results.

Results

Receiver operating characteristics curves for the free-to-total PSA ratio showed a significant increase in specificity compared to PSA. Retrospective application of age specific PSA reference ranges, the free-to-total PSA ratio and the PSA density decreased the number of biopsies significantly by up to 40% in our study, with a decrease in cancer detection rate of 12%. When used in combination with digital rectal examination, the pathological stage of undetected carcinomas appeared favorable.

Conclusions

The free-to-total PSA ratio may be used to decrease biopsies in patients with an intermediate PSA of 4.0 to 10.0 ng./ml.     

前列腺特异性膜抗原酶学特性的探讨

前列腺特异性膜抗原(PSMA)是一种前列腺上皮细胞Ⅱ型跨膜糖蛋白,表达于正常前列腺和恶变前列腺上皮细胞,其表达量并与前列腺癌恶性程度呈正相关.由于其高特异性的瘤标特性,近年来是前列腺癌治疗的热点.日前针对PSMA的中文综述范围较广,几乎涵盖PSMA各个方面,有助于读者理解,然而实用性不强,对原著的实验手段、方法阐述甚少,与实际科学研究结合不够紧密.本文着重探讨PSMA的酶学特性,务求更加细致阐述PSMA这方面功能,对深化该领域研究有所帮助.     

Prospective Evaluation of Prostate Specific Antigen and Prostate Specific Antigen Density in the Detection of Nonpalpable and Stage T1C Carcinoma of the Prostate

Purpose

We evaluated prospectively prostate specific antigen (PSA) and prostate specific antigen density in the detection of prostate cancer in patients with normal findings on digital rectal examination with and without normal transrectal ultrasound.

Materials and Methods

Consecutive patients (184) with an elevated serum PSA and normal digital rectal examination underwent transrectal ultrasound with lesion directed and systematic biopsies (6 if prostatic volume was 50 cc or less and 12 if volume was more than 50 cc). Receiver operating characteristic curves, predictive values and likelihood ratios were calculated for PSA and PSA density.

Results

Of the 184 patients 50 (27 percent) with a normal digital rectal examination had cancer compared to 30 of 112 (27 percent) with a normal digital rectal examination and transrectal ultrasound. Median PSA or PSA density did not differ between the positive and negative biopsy groups among patients with a normal digital rectal examination (8.4 versus 7.1 and 0.22 versus 0.14 ng./ml., respectively) or a normal digital rectal examination and transrectal ultrasound (8.2 versus 7.5 and 0.21 versus 0.14 ng./ml., respectively). PSA density was superior to PSA by receiver operating characteristic analysis for cancer detection when all PSA values or those between 4 and 20 ng./ml. were considered. However, the significance was lost for a PSA of 4 to 10 ng./ml. Likelihood ratios demonstrated insignificant changes in the post-test probability if PSA density was used to determine the need for biopsy and many cancers would have been missed.

Conclusions

PSA density should not be used to determine the need for biopsy in patients with a normal digital rectal examination and/or transrectal ultrasound.     

Prostate Specific Antigen Density is not an Independent Predictor of Response for Prostate Cancer Treated by Conformal Radiotherapy

Although prostate specific antigen (PSA) density appears to be an important discriminator between benign and malignant prostatic disease, conflicting data exist concerning its prognostic value. The present study was undertaken to confirm whether PSA density represents a new prognostic indicator of disease-free survival for prostate cancer treated with conformal radiotherapy. Between April 1989 and December 1992, 186 patients with organ confined prostate cancer were treated with definitive irradiation according to previously published conformal guidelines. The PSA density was defined as the ratio of the pretreatment serum PSA (ng./ml.) to the prostate volume (ml.) as determined from treatment planning computerized tomography. The median PSA density was 0.15 with a range of 0.02 to 2.12. A statistically significant advantage in actuarial freedom from biochemical relapse was noted for patients with pretreatment PSA levels less than 15 ng./ml. when compared to those with higher pretreatment PSA levels (3-year freedom from biochemical relapse 85 percent versus 28 percent, p less than 0.001). Also, patients with PSA density of 0.15 or less had statistically superior freedom from biochemical relapse compared to their counterparts with higher PSA density (3-year freedom from biochemical relapse 88 percent versus 28 percent, p less than 0.001). In a multivariate analysis only the baseline PSA (p less than 0.002) and the Gleason score (p less than 0.002) emerged as significant predictors of prolonged freedom from biochemical relapse. The PSA density had no impact on freedom from biochemical relapse whether it was entered into this multivariate model as a continuous or a dichotomous variable. In our data base baseline PSA levels remain the most powerful independent discriminant of response to conformal irradiation. PSA density is only a surrogate for baseline PSA levels and does not refine the ability to predict prolongation of freedom from biochemical relapse following conformal radiotherapy.