Use Of Prostate Specific Antigen Density Research Articles

Oncological outcomes in robot-assisted radical prostatectomy: the value of PSA density as a preoperative predictive factor

Background: Pretreatment assessment of patients diagnosed with localized prostate cancer (PCa) is essential for therapeutic decision-making. Currently available staging systems based on prostate-specific antigen (PSA), Gleason score, and clinical stage allow for determining the prognostic characteristics of these patients. Several studies have evaluated the preoperative use of prostate-specific antigen density (PSAD) as a prognostic factor for further risk stratification. To date, the role of PSAD in this setting is still an object of debate. Objectives: The present analysis aimed to assess the predictive potential of PSAD for adverse oncological outcomes after robot-assisted radical prostatectomy (RARP) and to compare its accuracy to preoperative PSA (pPSA). Design and methods: We retrospectively reviewed 427 patients diagnosed with localized PCa who underwent RARP at a single institution between January 2015 and January 2020. Generating receiver operator characteristic (ROC) curves, calculating areas under the curves (AUCs), and using a linear regression model, we analyzed the association of PSAD and pPSA with postoperative positive surgical margins (PSM), Gleason score ⩾ 7, persistent PSA, and biochemical recurrence (BCR), with a median follow-up of 47 months. Results: PSAD showed a significant association with PSM ( p < 0.0001), PSA persistence ( p < 0.0001), and Gleason ⩾ 7 ( p < 0.0001), without being statistically significant in predicting BCR ( p = 0.098). The predictive value of PSAD was comparable to pPSA for outcomes of PSA persistence (AUC 0.727 versus 0.771) and Gleason ⩾ 7 (AUC 0.683 versus 0.649). Conclusion: PSAD is a predictive factor for postoperative oncological outcomes of PSM, Gleason score ⩾ 7, and persistence of PSA. Despite the need for further studies, PSAD could be useful as a prognostic parameter in conjunction with established staging systems.

Determination of Whether Apex or Non-Apex Prostate Cancer Is the Best Candidate for the Use of Prostate-Specific Antigen Density to Predict Pathological Grade Group Upgrading and Upstaging after Radical Prostatectomy

Objective: Previous studies have demonstrated that prostate-specific antigen density (PSAD) may aid in predicting Gleason grade group (GG) upgrading and pathological upstaging in patients with prostate cancer (PCa). However, the differences and associations between patients with apex prostate cancer (APCa) and non-apex prostate cancer (NAPCa) have not been described. The aim of this study was to explore the different roles of PSAD in predicting GG upgrading and pathological upstaging between APCa and NAPCa. Patients and Methods: Five hundred and thirty-five patients who underwent prostate biopsy followed by radical prostatectomy (RP) were enrolled. All patients were diagnosed with PCa and classified as either APCa or NAPCa. Clinical and pathological variables were collected. Univariate, multivariate, and receiver operating characteristic (ROC) analyses were performed. Results: Of the entire cohort, 245 patients (45.8%) had GG upgrading. Multivariate analysis revealed that only PSAD (odds ratio [OR]: 4.149, p < 0.001) was an independent, significant predictor of upgrading. A total of 262 patients (49.0%) had pathological upstaging. Both PSAD (OR: 4.750, p < 0.001) and percentage of positive cores (OR: 5.108, p = 0.002) were independently significant predictors of upstaging. Of the 374 patients with NAPCa, 168 (44.9%) displayed GG upgrading. Multivariate analysis also showed PSAD (OR: 8.176, p < 0.001) was an independent predictor of upgrading. Upstaging occurred in 159 (42.5%) patients with NAPCa, and PSAD (OR: 4.973, p < 0.001) and percentage of positive cores (OR: 3.994, p = 0.034) were independently predictive of pathological upstaging. Conversely, of the 161 patients with APCa, 77 (47.8%) were identified with GG upgrading, and 103 (64.0%) patients with pathological upstaging. Multivariate analysis demonstrated that there were no significant predictors, including PSAD, for predicting GG upgrading (p = 0.462) and pathological upstaging (p = 0.100). Conclusions: PSAD may aid in the prediction of GG upgrading and pathological upstaging in patients with PCa. However, this may only be practical in patients with NAPCa but not with APCa. Additional biopsy cores taken from the prostatic apex region may help improve the accuracy of PSAD in predicting GG upgrading and pathological upstaging after RP.

Usefulness of Prostate-Specific Antigen Density as an Indicator for Recommending Prebiopsy Magnetic Resonance Imaging to Prevent Missed Prostate Cancer Diagnoses

Purpose: To identify the indication for recommending prebiopsy magnetic resonance imaging (MRI) to prevent prostate cancer missed diagnoses in cases without prebiopsy MRI.Materials and Methods: Between January 2017 and September 2020, 585 patients suspected with prostate cancer underwent prostate biopsy after MRI. For patients with visible lesions, MRI-targeted biopsy using an image-based fusion program was performed in addition to the 12- core systematic biopsy. Patients for whom MRI was performed in other institutions (n=4) and patients who underwent target biopsy alone (n=7) were excluded.Results: Of 574 patients (median prostate-specific antigen [PSA] level, 6.88 ng/mL; mean age, 68.2 years), 342 (59.6%) were diagnosed with prostate cancer (visible lesions=312/449 [69.5%]; nonvisible lesions=30/123 [24.0%]). The detection rates of visible lesions stratified using the Prostate Imaging Reporting and Data System score (3 vs. 4 vs. 5) were 30.9% (54 of 175), 61.2% (150 of 245), and 90.1% (127 of 141), respectively. Multivariate analysis showed that PSA density was a significant factor for presence of visible lesions, prostate cancer, and significant prostate cancer diagnosis. Among patients with positive lesions, 27 (8.2%) were diagnosed with prostate cancer concomitant with negative systematic biopsy results. A PSA density of 0.15 ng/mL/cm&lt;sup&gt;3&lt;/sup&gt; was identified as the significant cutoff value for predicting positive target biopsy in groups with negative systematic biopsy. Sixty of the negative target lesions (26.1%) were diagnosed using systematic biopsy.Conclusions: To maximize cancer detection rates, both targeted and systematic biopsies should be implemented. PSA density was identified as a useful factor for recommending prebiopsy MRI to patients suspected with prostate cancer.

Combined Use of Prostate-specific Antigen Density and Magnetic Resonance Imaging for Prostate Biopsy Decision Planning: A Retrospective Multi-institutional Study Using the Prostate Magnetic Resonance Imaging Outcome Database (PROMOD)

BackgroundPrevious studies suggested that prostate-specific antigen (PSA) density (PSAd) combined with magnetic resonance imaging (MRI) may help avoid unnecessary prostate biopsy (PB) with a limited risk of missing clinically significant prostate cancer (csPCa; Gleason grade group [GGG] >1). ObjectiveTo define optimal diagnostic strategies based on the combined use of PSAd and MRI in patients at risk of prostate cancer (PCa). Design, setting, and participantsA retrospective analysis of the international multicenter Prostate MRI Outcome Database (PROMOD), including 2512 men having undergone PSAd and prostate MRI before PB between 2013 and 2019, was performed. Outcome measurements and statistical analysisRates of avoided PB, missed GGG 1, and csPCa according to 10 strategies based on PSAd values and MRI reporting scores (Prostate Imaging Reporting and Data System [PI-RADS]/Likert/IMPROD biparametric prostate MRI Likert). Decision curve analysis (DCA) was used to statistically compare the net benefit of each strategy. Combined systematic and targeted biopsies were used for reference. Results and limitationsAccording to DCA, the best strategy in biopsy-naive patients was #7 (PI-RADS/Likert 4–5 or PI-RADS/Likert 3 if PSAd >0.2), which avoided 41.2% PBs while missed 44% of GGG 1 and 10.9% of csPCa cases. From a clinical standpoint, however, strategies with a lower risk of missing csPCa included #10 (PI-RADS/Likert 4–5 or PI-RADS 3 if PSAd >0.10 or PSAd >0.2), which avoided 27% PBs while missing 24.4% GGG 1 and 4% csPCa cases, or #5 (PI-RADS/Likert 3-5 or PSAd>0.15), which avoided 14.7% PBs while missing 9.3% GGG 1 and 1.7% csPCa cases. Similar results were found in patients with a previous negative biopsy. This study is limited by its retrospective nature, and no central review of MRI and histopathological findings. ConclusionsCombined PSAd and MRI findings allows individualization of the decision to perform PB on the basis of the risk of missing PCa that both patients and clinicians are ready to accept to avoid this procedure. Patient summaryWe compared several biopsy strategies based on a combination of prostate magnetic resonance imaging findings and prostate-specific antigen density, providing a readily available tool for each center and practicing urologist to counsel patients about their individual risk of significant prostate cancer.

Comparison of biopsy strategies for prostate biopsy according to lesion size and PSA density in MRI-directed biopsy pathway.

To investigate whether the detection of clinically significant prostate cancer (csPCa) and the added value of focal saturation biopsy and systematic biopsy (SBx) differ according to index lesion size, and to compare the current guidelines for csPCa detection. This retrospective study included consecutive men who underwent MRI and subsequent SBx and MRI-targeted biopsy (TBx) for a suspicious lesion between April 2019 and February 2020. Lesion visibility on transrectal ultrasound (US) and added value of focal saturation biopsy and SBx were compared according to index lesion size using chi-square and McNemar tests. csPCa detection rates and the proportion of biopsy-indicated men were compared among four biopsy strategies based on current guidelines. Of 313 men evaluated (median age, 65; interquartile range 60‒71), csPCa was detected in 110 (35%). In lesions < 10mm, greater US invisibility (42.7% of lesions < 10mm versus 20.0% of lesions ≥ 10mm; p < 0.001) and higher added value of focal saturation biopsy and SBx (11.1% and 17.1% in lesions < 10mm versus 4.2% and 6.3% in lesions ≥ 10mm) were observed, compared with lesions ≥ 10mm. Consideration of prostate-specific antigen (PSA) density > 0.15ng/mL/mL as a cutoff in unsuspicious MRI led to a 14% reduction (44/313) in men who needed biopsy. Determination of the biopsy strategy in terms of the need for focal saturation biopsy or SBx should be made considering lesion size. The use of PSA density in non-suspicious MRI can lead to a reduction in biopsy-indicated men.

Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer.

Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines. We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7. The median PSA-density was 0.10 ng/ml2 (IQR 0.075-0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05-1.07 and OR 1.07, 95% CI 1.06-1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml2 would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml2 and 0.15 ng/ml2 resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors. PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.

Prostate‐specific antigen vs prostate‐specific antigen density as a predictor of upgrading in men diagnosed with Gleason 6 prostate cancer by contemporary multicore prostate biopsy

What's known on the subject? and What does the study add? Previously, it has been reported that PSA may not perform as accurately as PSA density (PSAD) in predicting outcomes after radical prostatectomy among patients with Gleason score 6 prostate cancer. However, there have been few studies comparing the usefulness of PSA and PSAD in predicting upgrading after surgery. Also, most published studies on the prediction of upgrading included significant proportions of subjects who did not undergo contemporary multicore prostate biopsy. Moreover, most studies from major academic centres on the potential usefulness of PSAD as a preoperative predictor of pathological and/or biochemical outcomes after surgery have not included detailed biopsy core-related data. Even when accounting for detailed biopsy core data, this study found that PSAD may be a significantly more accurate preoperative predictor of upgrading than PSA in the current era of extended prostate biopsies. This finding supports the inclusion of PSAD into the risk stratification system for patients with prostate cancer seeking less invasive treatment, such as active surveillance. • To compare the accuracies of prostate-specific antigen (PSA) and PSA density (PSAD) in predicting Gleason score upgrading after radical prostatectomy (RP) in men who have undergone contemporary multicore prostate biopsy and for whom detailed biopsy core data are available. • We analysed prospectively collected data on 505 patients who were diagnosed with Gleason 6 prostate cancer after multicore (≥ 12 cores) biopsy and who underwent RP without neoadjuvant treatment. • Receiver operating characteristic curves were used to analyse the predictive accuracies of multivariate logistic regression models. • When multivariate models were constructed incorporating either PSA or PSAD along with other upgrading predictors, including biopsy core, both PSA and PSAD were observed to be independent predictors of upgrading in all versions of models (all P < 0.05). • When predictive accuracies of multivariate models including PSA and PSAD were compared, the PSAD model was found to have significantly higher accuracy than the PSA model in three out of four versions of models analysed (model 1, P= 0.048; model 2, P= 0.002; model 3, P= 0.201; model 4, P= 0.044). • According to our analysis of prospectively collected data, PSAD may be a significantly more accurate preoperative predictor of upgrading than PSA, even when accounting for detailed biopsy core data in the current era of extended prostate biopsies. • Our findings would support the inclusion of PSAD, rather than PSA, into the risk stratification system for patients seeking less invasive treatment for prostate cancer.

Value of prostate-specific antigen and prostate-specific antigen density in detection of prostate cancer in an Iranian population of men.

The objective of this study was to evaluate the value of serum prostate-specific antigen (PSA) and prostate-specific antigen density (PSAD) in the diagnosis of prostate cancer. A total of 330 consecutive patients suspected of having prostate cancer due to either abnormal digital rectal examination or elevated serum PSA levels underwent transrectal ultrasonography-guided sextant biopsy of the prostate. The PSA and PSAD values were assessed based on the biopsy results. One hundred and twenty-one patients (36.7%) had prostate cancer. In this group, the mean PSA was 31.60 +/- 30.85 ng/mL (range, 1.9 ng/mL to 166.0 ng/mL) and the mean PSAD was 0.83 +/- 1.01 (range, 0.04 ng/mL/cm3 to 6.38 ng/mL/cm3). In those without prostate cancer the mean PSA and PSAD levels were 13.80 +/- 18.72 ng/mL (range, 0.4 ng/mL to 130.0 ng/mL; P < .001) and 0.24 +/- 0.32 (range of 0.01 ng/mL/cm3 to 2.29 ng/mL/cm3; P < .001). The receiver operating characteristic curve analysis revealed that the discriminating power of serum PSA for detecting prostate cancer, as estimated by the area under the curve, was 0.74 while that for PSAD was 0.81 (P < .001). For the PSA range of 3.5 ng/mL to 41 ng/mL (gray zone) the areas under the curve was 0.68 for PSA, while it was 0.78 for PSAD (P < .001). The use of PSAD instead of PSA in the diagnosis of prostatic cancer improves the diagnostic accuracy.

Ten year trend in prostate cancer screening with high prostate‐specific antigen exposure rate in Japan

The tendency of the results and quality control of prostate cancer screening serially performed for 10 years in an area of Japan were evaluated. A total of 39 213 men over 55 years of age have participated in the mass screening of prostate cancer in the Otokuni District, since 1995. Men whose prostate-specific antigen (PSA) levels were more than 4.1 ng/mL were indicated for the second screening. In the second screening, prostate-specific antigen density (PSAD) was calculated in men whose PSA levels ranged from 4.1 to 10.0 ng/mL. Secondary screening was indicated in a total of 2428 subjects, of whom 1633 underwent it. Prostate cancer was diagnosed in 267 men. As a result of the evaluation of the indication of prostate biopsy according to the PSAD in 894 who underwent secondary screening for the first time, the procedure was judged to be unnecessary in 269 (35%) of 765 cases. Of these 269 subjects, 23 (8.5%) were found to have cancer. Clinically localized prostate cancer increased by 17%, and locally advanced and metastatic cancers decreased by 12% in the second compared with the first five years of the ten-year period. The exposure rate of PSA screening in the Otokuni District was 65% with the application for the rate of screenees whose PSA level was 4.1 ng/mL or above. The Japanese basic health screening system allows the determination of high-PSA exposure areas. Serial prostate cancer screening showed a tendency of stage migration in the screened cancer patients. The use of PSAD in secondary screening substantially reduces the necessity of prostate biopsy; however, the encouragement of PSA-positive individuals to periodically receive prostate cancer screening is essential to maintain the quality of the screening system.

Clinical use of prostate-specific antigen density in treatment decision for localized prostate cancer

4719 Background: Current treatment of localized Prostate cancer includes different options: Surgery, Radiotherapy or Watchful Waiting (WW). It is well known that surgery treatment is inappropriate when extrapostatic disease (EPD) exists. However, to date, still 25–33% of prostatectomies are shown to be EPD on pathological examination. An explanation for that might be the lack of a good imaging diagnostic test and the inaccuracy of the Gleason and prostatic specific antigen (PSA) as pathological predictors. PSA is not a good predictor mainly due to the contribution of non tumoral prostatic volume to its serum levels. On contrary, it has been suggested that PSA density (PSAD) values are not influenced by non tumoral prostatic volume, thus, becoming more useful. The purpose of the present study was to evaluate whether PSAD might have a role in the treatment decision making. Methods: The cases of 103 consecutive patients who underwent Radical Prostatectomy were reviewed. Preoperative PSA and PSAD were obtained. PSAD was calculated according to the formula: PSAD = serum PSA / prostatic volume determined by TRUS (prolate ellipse formula). Currently accepted PSA cut-off of 10 was compared with PSAD cut-off of 0.15 and 0.20 to determine its accuracy in detecting OCD. Results: The pathological examinations of the 103 prostatectomy specimens revealed EPD in 26 cases (25%). Using a PSA cut-off < 10 resulted in 59 out of 73 patients (80%) with confirmed OCD. On contrary, PSAD cut-off < 0.15 and < 0.20, resulted in 26/27 (96%) and 41/46 (89%) patients, respectively, with OCD. Conclusions: PSAD is a more accurate marker to discriminate OCD than PSA and, therefore, may lead to a more appropriate treatment decision making. No significant financial relationships to disclose.

Clinical use of prostate-specific antigen density in treatment decision for localized prostate cancer

4719 Background: Current treatment of localized Prostate cancer includes different options: Surgery, Radiotherapy or Watchful Waiting (WW). It is well known that surgery treatment is inappropriate when extrapostatic disease (EPD) exists. However, to date, still 25–33% of prostatectomies are shown to be EPD on pathological examination. An explanation for that might be the lack of a good imaging diagnostic test and the inaccuracy of the Gleason and prostatic specific antigen (PSA) as pathological predictors. PSA is not a good predictor mainly due to the contribution of non tumoral prostatic volume to its serum levels. On contrary, it has been suggested that PSA density (PSAD) values are not influenced by non tumoral prostatic volume, thus, becoming more useful. The purpose of the present study was to evaluate whether PSAD might have a role in the treatment decision making. Methods: The cases of 103 consecutive patients who underwent Radical Prostatectomy were reviewed. Preoperative PSA and PSAD were obtained. PSAD was calculated according to the formula: PSAD = serum PSA / prostatic volume determined by TRUS (prolate ellipse formula). Currently accepted PSA cut-off of 10 was compared with PSAD cut-off of 0.15 and 0.20 to determine its accuracy in detecting OCD. Results: The pathological examinations of the 103 prostatectomy specimens revealed EPD in 26 cases (25%). Using a PSA cut-off < 10 resulted in 59 out of 73 patients (80%) with confirmed OCD. On contrary, PSAD cut-off < 0.15 and < 0.20, resulted in 26/27 (96%) and 41/46 (89%) patients, respectively, with OCD. Conclusions: PSAD is a more accurate marker to discriminate OCD than PSA and, therefore, may lead to a more appropriate treatment decision making. No significant financial relationships to disclose.

Should prostate-specific antigen or prostate-specific antigen density be used as the determining factor when deciding which prostates should undergo biopsy during prostate ultrasound.

Prostate ultrasound has been accepted as the appropriate tool for prostate biopsy guidance to determine the presence of prostate cancer if the prostate-specific antigen (PSA) level is not normal. Prostate-specific antigen density (PSAD) has been used to determine if an increased PSA level may be because of benign enlargement of the gland or possible presence of cancer. The specific "cutoff" for PSA and PSAD to delineate which patients are at highest risk has been controversial. We attempted to assess which PSA level or PSAD level should be used. A retrospective analysis of 600 consecutive men, referred for prostate ultrasound and possible biopsy because of an abnormal DRE result or increased PSA level was undertaken. All had prostate volume determined by biplanar endorectal ultrasound. One hundred sixty-six men had cancer confirmed by biopsy. This latter group was further analyzed and was divided into PSA <4.0, PSA 4 to 10, or PSA >10.0 ng/ml. Groups were divided according to those with PSAD <0.10, <0.12, and <0.15 ng/ml. Correlation with Gleason grade of the tumor was made. Of the 166 men with cancer, 15 had PSA levels <4 ng/ml (all palpable), and 81 had PSA levels between 4.0 and 10.0 ng/ml (48 were not palpable by digital rectal examination [DRE]). There were 38 (22.8%) of 166 men with cancer who had a PSAD <0.15. Using the Gleason scoring system, 30 of 38 men had mid-grade or high-grade cancers. Twenty-one (12.6%) of 166 men with cancer had a PSAD <0.12. Of these, 17 of 21 men had mid-grade or high-grade cancers. Fifteen (9.0%) of 166 men with cancer had a PSAD <0.10. Of these, 13 of 15 had mid-grade or high-grade cancer. If the PSA level is more than 4.0 ng/ml, even if no palpable lesion is discerned by DRE, suspicion for the presence of cancer should be raised. The use of PSAD threshold of 0.15 is not inclusive enough to identify clinically important cancer, and it should not be used. Our data demonstrate that 7.9% of men with cancer had a PSAD <0.15 and mid-grade or high-grade, i.e., clinically important, cancer. Although more negative biopsy results will be obtained, we recommend the use of a lower PSAD "cutoff" than the literature has suggested. We recommend that those men with PSA levels more than 4 ng/ml and a PSAD higher than 0.10 should undergo a prostate biopsy to detect clinically important cancer.

The usefulness of prostate-specific antigen (PSA) density in patients with intermediate serum PSA level in a country with low incidence of prostate cancer

Objectives. To evaluate if a calculated PSA density (PSAD) prior to biopsy could be useful to determine the need for prostate biopsies in patients with serum PSA levels of 4.1–20.0 ng/mL in a country with low incidence of prostate cancer (PCa). Methods. A total of 185 consecutive patients aged 50–79 years who underwent prostate biopsies were evaluated by correlating the biopsy results with the results of digital rectal examination (DRE), transrectal ultrasonography (TRUS), serum PSA levels, and PSAD. Prostate volume was calculated from TRUS using prolate ellipse formula and PSAD was obtained by dividing serum PSA level by prostate volume. Results. In this study population, 27 cases (14.6%) had positive biopsies. Of 158 cases with negative biopsies, 43 (23.2%) had histologically verified prostatic inflammation. The diagnostic value of DRE and TRUS was hampered by unsatisfactory sensitivity and specificity in differentiating patients with positive biopsies from those with negative biopsies. The use of PSAD alone as an indicator for biopsy was also limited by its low specificity. A PSAD cutoff value of 0.15 resulted in a sensitivity of 100% and a specificity of only 12%. Prostatic inflammation was a confounding factor for the inadequate specificity of DRE, TRUS and PSAD. Combined use of DRE and PSAD provided the best information regarding the need for biopsies. Accordingly, if the 47 patients (25.4%) who presented with both a negative DRE and a PSAD ≤0.20 were not biopsied, the rate of positive biopsy could have increased to 19.6% (27 of 138) without missing any cancer detection. Conclusions. It is concluded from this study that for patients with serum PSA levels of 4.1–20.0 ng/mL, biopsies should only be recommended for those with abnormal DRE and/or PSAD >0.20.

Screening for prostatic carcinoma: case finding is not the problem.

Prostatic cancer (CaP) is a major cause of mortality and morbidity in men. Prostate specific antigen (PSA) can be used to find cases of prostatic cancer, but at some cost. The clinical biochemistry of PSA has been comprehensively reviewed in a recent issue of this journal.' The pros and cons of using PSA as a screening tool for prostatic cancer have also been extensively reviewed.r? Screening for CaP is influenced by technical factors governing test performance, the natural history of the disease, health economic and ethical factors. Purists would argue that screening is something that is applied only to populations, while others would argue that screening is looking for disease in an asymptomatic person. There is potential for conflict in balancing population interests against individual interests. The body of informed opinion is currently against the use of PSA as a screening tool for prostatic cancer. However, the numbers of PSA tests performed in clinical laboratories are rising as evidenced by a 90% increase within the authors' laboratory over the last year. In part this reflects the ad-hoc use of PSA as a screen for CaP, a practice which generally lies outwith a formal population based screening programme and is not a planned healthcare strategy. Virtually all of the prospective trial data on the use of PSA as a screening test has been derived using the Hybritech Tandem total PSA assay. A search for greater diagnostic specificity has lead to the use of PSA density, PSA velocity and, more promisingly, 'free' PSA. However, none of these techniques have been evaluated in prospective trials. In this personal view we discuss the important issues raised by ad-hoc testing, and consider unresolved issues in relation to screening and the potential problems posed by new assays. We offer some advice to the patient or doctor who asks for a PSA test and for the laboratory worker who has to perform the 'gatekeeper' role. The incidence of prostatic cancer is increasing, partly as a result of greater ascertainment but also because of increased longevity. It is second to lung cancer as a cause of mortality and morbidity in men with malignancy. The prevalence of prostatic cancer in postmortem series is reported to be as high as 32·9% compared to the prevalence of clinical disease, which is around 1·2%.5 This implies that most prostatic cancers do not progress to clinical disease. Notwithstanding this, advocates of screening point to the need for detection of localized cancer for early curative treatment. Opponents of screening point to the costs of screening and the uncertainties about the benefits of intervention. However, they do not offer an alternative strategy for reducing the mortality and morbidity associated with this common disease. The rationale for screening for prostatic cancer as with any other screening programme are based on a management strategy in which there are three components. (1) Case finding: how effective will the test(s) be at finding the disease? (2) Prognosis: how good will it be at predicting the natural history of the disease? (3) Treatment: is there an effective and acceptable treatment for the disease?

Usefulness of Prostate-Specific Antigen Density as a Diagnostic Test of Prostate Cancer

To evaluate the diagnostic usefulness of prostate-specific antigen density (PSAD) in prostate cancer (PC) prostate-specific antigen (PSA) concentrations were measured in 175 patients with benign prostatic hypertrophy (BPH) and 50 patients with PC. Patients with BPH were classified according to the presence of complications of the disease: urinary infection or the presence of a bladder catheter. PSAD levels were observed to be greater than 0.15 in 3% of the patients with uncomplicated BPH and in 40% of the patients with complicated BPH. PSA levels were higher than 10 micrograms/l in 3 and 27% of these patients, respectively. High levels of PSAD were observed in 80% of the patients with cancer. Sixty-four percent of the patients with cancer presented PSA levels greater than 10 micrograms/l. These results indicate that PSAD is a useful parameter in the differential diagnosis of PC and BPH with the diagnostic efficacy of PSAD being greater than that of the serum determination of PSA.

The value of screening tests in the detection of prostate cancer. Part II: Retrospective analysis of free/total prostate-specific analysis ratio, age-specific reference ranges, and PSA density

Objectives The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the specificity of total serum PSA for the detection of prostate carcinoma in selected populations. In this study, the value of the F/T ratio for screening of prostate cancer was compared with that of age-specific reference ranges for PSA and PSA density (PSAD) by a simulation experiment. Methods In 1726 men between 55 and 76 years old, 67 prostate carcinomas were detected by application of digital rectal examination (DRE), transrectal ultrasonography (TRUS), and total serum PSA. A serum PSA of 4.0 ng/mL or more, an abnormal DRE, or an abnormal TRUS were the indications to perform 308 biopsies. A simulation was performed in which an F/T ratio of 0.20 (ProStatus PSA Free/Total), age-specific PSA reference ranges, and a PSAD of 0.12 ng/mL/cc were used to study their capability to increase the specificity of total serum PSA in predicting prostate biopsy results. Results Using age-specific PSA reference ranges and DRE as indicators for biopsy, a reduction of 37% (113) of biopsies would have been obtained with a loss of detected cancers of 12% (11). For the use of PSAD and DRE, these numbers were 28% (96) and 11% (7), respectively. Application of a serum PSA of 4.0 ng/mL or more and an F/T ratio of 0.20 or less and an abnormal DRE as indicators for biopsy would reduce the number of biopsies by 37% (112) and the number of detected cancers by 11% (7). The biopsy to prostate cancer ratio of these simulations varied between 3.3 and 3.6. Minimal loss of cancer detection of 3% (2) with a reduction in the number of biopsies of 17% (53) is obtained when TRUS is omitted from the screening protocol. Selecting men by a total serum PSA value of 2.0 ng/mL for further diagnostic workup by TRUS and DRE would have reduced the number of biopsies by 30% (102), and the number of cancers detected by 6% (4). Conclusions The most cost-effective protocol for screening prostate carcinoma appears to be prescreening by total serum PSA. The F/T ratio might be used to detect carcinomas in the PSA range below 4.0 ng/mL, but the best threshold remains to be assessed.

Relative performance characteristics of prostate specific antigen and prostatic specific antigen density for the diagnosis of carcinoma of the prostate

Prostate specific antigen (PSA) has become an important method for early detection of prostate cancer. It has been suggested that prostate specific antigen density (PSAD) may be a more efficient test for early detection than PSA alone. A series of 327 men undergoing prostate biopsy were evaluated by PSA and PSAD. When the receiver operating characteristic curves of both tests were compared, they demonstrated little improvement in the efficiency of detection with the use of PSAD. The five-fold increase in the cost of PSAD over PSA alone does not justify its inclusion in a plan for early detection for carcinoma of the prostate.

Clinical Usefulness of Prostate Specific Antigen and Prostate Specific Antigen Density to Distinguish Benign from Malignant Prostate Diseases

The possibility of distinguishing prostate cancer from BPH with the prostate specific antigen (PSA) determination is particularly poor when PSA levels are between 4.1 and 10 ng/ml. In these cases the quotient of serum PSA and prostate volume, defined as prostate specific antigen density (PSAD), seems to enhance the accuracy of PSA alone. In this study we evaluated retrospectively the preoperative PSA levels in 139 patients with BPH and in 26 patients with prostate cancer who underwent surgical treatment at our Department. We calculated the prostate volume with the following formula: length x width x depth x 0.52. The three dimensions were obtained from the surgical specimen in the patients with prostate cancer and using transrectal ultrasound in the cases of BPH. In patients with a serum PSA level of 4.1 to 10 ng/ml, PSA alone was not able to distinguish benign from malignant prostate disease; the PSAD values, on the contrary, provided a statistically significant (p &lt; 0.003) stratification between BPH and prostate cancer (mean PSAD of 0.0088 and 0.191 respectively). Only 6% of patients with BPH had a PSAD greater than 0.15 compared to 76% of patients with prostate cancer. These results suggest the usefulness of PSAD in predicting the presence of prostate cancer in patients with intermediate levels of serum PSA.