Detection of prostatic carcinoma: the role of TRUS, TRUS guided biopsy, digital rectal examination, PSA and PSA density

The purpose of this study was to evaluate the efficacy of various diagnostic tests including transrectal ultrasound (TRUS), TRUS guided biopsy, digital rectal examination (DRE), prostate specific antigen (PSA), and prostate specific antigen density (PSAD) in detecting prostatic carcinomas. One hundred and thirty-four men underwent TRUS guided random, or directed and random sonographic biopsies of the prostate. The mean age was 64.67 (range, 31- 88) years. Indications for biopsy were abnormal findings suggesting prostatic carcinoma on DRE or increased levels of PSA, defined as 4.0 ng/ml or greater in a monoclonal antibody assay. PSAD was calculated by dividing the serum PSA in ng/ml to the volume of the entire prostate in cm3. The biopsy results were grouped as benign, malign and, prostatitis. The patients were also divided into three groups according to their PSA values. Of the 134 patients evaluated, 31 (23.1%) had prostate adenocarcinoma, 89 (66.4%) had benign prostatic tissue, hyperplasia or prostatic intraepithelial neoplasia, and 14 (10.4%) had prostatitis. The mean PSA and PSAD of the carcinoma group were significantly higher than those of the noncancer group. In the group of patients with PSA levels between 4 and 10 ng/ml, abnormal TRUS or DRE increased cancer detection rate, where neither PSA nor PSAD was capable of discriminating the patients with and without cancer. PSAD did not prove to be superior to the other diagnostic tests in this study. We recommend biopsy when either TRUS or DRE is abnormal in patients with PSA levels between 4 and 10 ng/ml. In the patients with PSA levels greater than 10 ng/ml, biopsy is indicated whatever the findings on TRUS or DRE are, since cancer detection rate is high.     

Clinical usefulness of free PSA in early detection of prostate cancer.

OBJECTIVE: Measurement of serum prostate-specific antigen (PSA) is widely used as an aid in early detection of prostate cancer. Most patients with prostate cancer and a PSA level less than 10.0 ng/ml have early-stage disease. Thus, the detection of prostate cancer in its potentially curable stages requires the use of low PSA cutoffs, inevitably leading to many unnecessary biopsies. The combined use of free PSA and total PSA increases specificity of early detection. To develop risk assessment guidelines and a cutoff value of ratio of free (f) to total (t) PSA with a high predictive value for prostate cancer in men to whom the test would be applied in real life practice, a multicenter early detection trial was initiated. PATIENTS AND METHODS: In one week in November 1997, 963 urologists prospectively examined 11,644 men between 45 and 75 years by digital rectal examination (DRE) and prostate-specific antigen with 4.0 ng/ml as cutoff. Data of physical examination were collected by questionnaire. At this time participants were not aware of their PSA values. Suspicious findings were further investigated with sextant biopsy. Prostate volume was determined with transrectal ultrasound (TRUS). Different cutoff levels were correlated to age and detection rate. RESULTS: From1,115 biopsied men, the data of 633 men fulfilled the criteria DRE-negative, TRUS-estimated volume, and PSA 4.0-10.0 ng/ml. In that cohort 91 cancers were detected. Percentage of fPSA was significantly more predictive of cancer than tPSA (p < 0.001). The area under the ROC curve was 0.72 for percent fPSA (% fPSA) and 0.62 for total PSA. The cancer risk nearly doubled using a cutoff of 10% fPSA, the median %PSA level of the detected cancers. A better discrimination of cancer and noncancer especially in the age group above 70 years is possible. Using a cutoff of 16% fPSA increases positive predictive value (PPV) to 25% missing only 4% of cancers. Nearly 45% of the biopsies could be avoided. In the age group 45-69 years, a cutoff of 20% fPSA leads to PPV of 15%, missing 6% of cancers. Unnecessary biopsies could be avoided in 12%. CONCLUSIONS: Using % fPSA in early detection of prostate cancer reduces the number of unnecessary biopsies, especially in men with negative rectal examination in the PSA range of 4.0-10.0 ng/ml. In order to diminish biopsy rate in men 70 years or older a cutoff of 16% fPSA should be used. A cutoff of 20% fPSA in men younger than 70 years is recommended to increase sensitivity in that age group.     

Model of screening for prostatic cancer among patients with prostate specific antigen concentration of 4-10 ng/ml in blood

Screening based on the measurement of prostate specific antigen (PSA) in the blood is the basic method for early detection of prostatic cancer. However the specificity of this method even in combination with the digital rectal examination (DRE) or with PSA derivatives remains disputable in cases when PSA concentrations in the blood vary between 4 and 10 ng/ml. We evaluated the efficiency of different diagnostic methods in order to create an effective diagnostic method in patients with PSA concentrations of 4-10 ng/ml. The study was carried out in 176 patients divided into 2 groups. Group 1 consisted of 120 patients. The efficiency of DRE, PSA density, PSA transition zone density (PSAT), free to total PSA ratio, and repeated PSA (measured after antibiotic therapy in patients with prostatic inflammations) were assessed. Diagnostic methods with the highest predictive values were identified. Positive predictive values of PSAT (cut-point 0.25 ng/ml/cc), nodule and induration (revealed by DRE) were estimated as 100, 100, and 75%, respectively. Negative predictive value of repeated PSA measurement (after antibiotic therapy) was 100% with the threshold value of 4 ng/ml. Using these diagnostic methods, a model of prostatic cancer screening was created. Group 2 consisted of 56 cases. A screening model representing a combination of the above diagnostic methods with the highest predictive value was clinically tried in this group. The sensitivity of the model was 80%, specificity 94%, positive predictive value 89%, and negative predictive value 89%. Use of this model makes biopsies unnecessary in 64% cases, with the risk of undetected cancer cases no higher than 20%. Hence, the screening model based on the use of diagnostic methods with the highest predictive value effectively detects prostatic cancer among patients with PSA concentrations of 4-10 ng/ml.     

Predictive Value of Neutrophil to Lymphocyte Ratio in the Diagnosis of Significant Prostate Cancer at Initial Biopsy: A Comparison with Free Percent Prostate Specific Antigen,Prostate Specific Antigen Density and Primary Circulating Prostate Cells

Introduction: An elevated serum PSA is the only biomarker routinely used in screening for prostate cancer to indicate a prostate biopsy. However, it is not specific for prostate cancer and the neutrophil/lymphocyte ratio has been suggested as an alternative. We present a prospective study of men with an elevated PSA and compare the neutrophil/lymphocyte ratio, free percent PSA, PSA density and the presence of circulating prostate cells to detect clinically significant prostate cancer at first biopsy. Patients and Methods: Prospective study of consecutive men with a PSA 4-10 ng/ml referred for initial prostate biopsy, the results were compared with the neutrophil/lymphocyte ratio, free percent PSA and PSA density. Circulating prostate cells (CPCs) were detected using immunocytochemistry. The blood sample was taken immediately before the prostate biopsy. Results: 1,223 men participated, 38% (467) of whom had prostate cancer detected, of these 322 were clinically significant. The area under the curves were for neutrophil/lymphocyte ratio, free percent PSA, PSA density and CPC detection were 0.570, 0.785, 0,620 and 0.844 respectively. Sensitivity/specificity were 0.388/0.685, 0.419/0.897, 0.598/0.624 and 0.966/0.786 respectively. The neutrophil/lymphocyte ratio did not differentiate between benign and malignant disease. Conclusions: The neutrophil/lymphocyte ratio did not discriminate between benign and malignant prostatic disease in patients with a PSA between 4-10ng/ml.     

Utility of Digital Rectal Examination,Serum Prostate Specific Antigen,and Transrectal Ultrasound in the Detection of Prostate Cancer: A Developing Country Perspective

Purpose: To determine the utility of digital rectal examination (DRE), serum total prostate specific antigen(tPSA) estimation, and transrectal ultrasound (TRUS) for the detection of prostate cancer (PCa) in men withlower urinary tract symptoms (LUTS). Materials and Methods: All patients with abnormal DRE, TRUS, or serumtPSA >4ng/ml, in any combination, underwent TRUS-guided needle biopsy. Eight cores of prostatic tissue wereobtained from different areas of the peripheral prostate and examined histopathologically for the nature of thepathology. Results: PCa was detected in 151 (50.3%) patients, remaining 149 (49.7%) showed benign changeswith or without active prostatitis. PCa was detected in 13 (56.5%), 9 (19.1%), 26 (28.3%), and 103 (74.6%) ofpatients with tPSA <4 ng/ml, 4-10 ng/ml, 10-20 ng/ml and >20 ng/ml respectively. Only 13 patients with PCahad abnormal DRE and TRUS with serum PSA <4 ng/ml. The detection rate was highest in patients with tPSA>20 ng/ml. The association between tPSA level and cancer detection was statistically significant (p<0.01). Among209 patients with abnormal DRE and raised serum PSA, PCa was detected in 128 (61.2%). Conclusions: Theincidence of PCa increases with increasing serum level of tPSA. The overall screening and detection rate can befurther improved by using DRE, TRUS and TRUS-guided prostate needle biopsies.     

An artificial neural network considerably improves the diagnostic power of percent free prostate-specific antigen in prostate cancer diagnosis: results of a 5-year investigation

Our study was performed to evaluate the diagnostic usefulness of %fPSA alone and combined with an ANN at different PSA concentration ranges, including the low range 2-4 ng/ml, to improve the risk assessment of prostate cancer. A total of 928 men with prostate cancer and BPH without any pretreatment of the prostate in the PSA range 2-20 ng/ml were enrolled in the study between 1996 and 2001. An ANN with input data of PSA, %fPSA, patient's age, prostate volume and DRE status was developed to calculate the individual's risk before performing a prostate biopsy within the different PSA ranges 2-4, 4.1-10 and 10.1-20 ng/ml. ROC analysis and cut-off calculations were used to estimate the diagnostic improvement of %fPSA and ANN in comparison to PSA. At the 90% sensitivity level, %fPSA and ANN performed better than PSA in all ranges, enhancing the specificity by 15-28% and 32-44%, respectively. For the low PSA range 2-4 ng/mL, we recommend a first-time biopsy at an ANN specificity level of 90%. For PSA 4-10 ng/mL, we recommend a first-time biopsy based on the ANN at the 90% sensitivity level. Use of an ANN enhances the %fPSA performance to further reduce the number of unnecessary biopsies within the PSA range 2-10 ng/ml.     

Rationale for using serum prostate-specific antigen (PSA) level and PSA density (PSAD) to detect prostatic malignancy in a country with low prostate cancer incidence

Prostate-specific antigen (PSA) and PSA density (PSAD) values in Indonesia had been found uniquely much higher than the normal accepted values in western countries. However, PSA more than 10 ng/ml and PSAD above 0.15 in intermediate PSA of 4-10 ng/ml are still indicative of a prostate biopsy. This condition had led to unnecessary biopsies in view of the low incidence of prostatic carcinoma in our country. Our objective is to find alternative serum PSA levels and PSAD cutoff points that enhance the specificity and sensitivity of prostate cancer detection. This retrospective cross-sectional study included 805 consecutive patients from 40 to 95 years old in Sumber Waras Hospital (SWH) and Cipto Mangunkusumo Hospital (CMH) from 1994 to 1997. All patients underwent digital rectal examination (DRE) and transrectal ultrasonography (TRUS) to measure prostate volume. After the serum PSA level was determined and PSAD was calculated, prostate biopsies were performed if the PSA level was greater than 10 ng/ml or PSAD more than 0.15 at intermediate PSA levels of 4-10 ng/ml. The ability of PSA, intermediate PSA level, and PSAD to improve the accuracy of prostate cancer detection was evaluated using univariate analysis. Among 805 patients, 240 patients had PSA level < 4 ng/ml, 230 patients had PSA level 4-10 ng/ml, and 335 had PSA level > 10 ng/ml. Of the 230 patients with intermediate PSA level, 108 had PSAD > 0.15. Thirty-five patients had histologically confirmed prostatic carcinoma, i.e., 3 of 108 patients with PSA 4-10 ng/ml and PSAD > 0.15, and 32 of 335 patients with PSA > 10 ng/ml. There were 105 and 303 unnecessary biopsies in those groups. With a PSA cutoff level of > or = 8 ng/ml, we found 100% sensitivity to prostate cancer. PSAD > or = 0.20 within a PSA level of 8-30 ng/ml gave 100% sensitivity to prostate cancer. Using these new cutoffs there would be 148 biopsies (33.4%) saved. We concluded from this study that the commonly accepted values of serum PSA level and PSAD resulted in many unnecessary biopsies in our patients. Instead, the most sensitive cutoff points to perform prostate biopsy are serum PSA level greater than 8.0 ng/ml, and PSAD of more than 0.20 at an intermediate serum PSA level of 8-30 ng/ml.     

Histological diagnosis of prostate cancer in Korean men aged 70-79 years

BACKGROUND: The objective of this study was to evaluate the value of the prostate-specific antigen (PSA) in the diagnosis of prostate cancer in elderly Korean men, aged 70-79 years. METHODS: Patients with an abnormal digital rectal examination (DRE) and/or a serum PSA level greater than 2.0 ng/ml underwent a biopsy. A total of 344 men (median age 73 years) constituted the study cohort. RESULTS: Of 344 men, 163 (47.4%) were diagnosed with prostate cancer upon initial biopsy. The positive predictive value (PPV) for cancer was 48.4% for a PSA cutoff of 4 ng/ml, 65.3% for a cutoff of 10 ng/ml, and 87.0% for a cutoff of 20 ng/ml. When combined with an abnormal DRE, the predictive values for these PSA cutoffs increased to 79.3, 87.3 and 100%, respectively. When 10 ng/ml was chosen as a PSA cutoff level, about 50% of patients were found to have a Gleason score of 7 or higher. When 4 ng/ml was chosen as a PSA cutoff level, more than 50% of patients with an abnormal DRE were found to have a Gleason score of 7 or higher. CONCLUSIONS: In elderly men, more than 50% of patients are found to have cancers with a Gleason score of 7 or higher when their PSA level is greater than 10 ng/ml. This threshold may be lowered to 4 ng/ml in the presence of an abnormal DRE. Our findings provide a rationale for recommending a prostate biopsy in elderly patients with an abnormal DRE and/or an elevated serum PSA level. However, at present, it is not clear whether elderly men have better outcomes when they undergo cancer screening.     

Prostate cancer screening in the Tyrol, Austria: experience and results

This article summarises the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) and per cent free PSA as the initial test. Of the 21078 volunteers 1618 (8%) had elevated PSA levels. Of these men 778 (48%) underwent biopsies; 197 (25%) biopsies were positive for prostate carcinoma and 135 (17%) underwent radical prostatectomy. 95 were found to be organ-confined. A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. 284/2272 men (13%) had elevated PSA levels and prostate carcinoma was detected in 62 men (3%). All patients underwent radical prostatectomy and histological examination revealed organ-confined tumour in all but 8 men. 98/340 men (29%) had biopsies positive for carcinoma; 28 of these patients (29%) had carcinoma that originated in the transition zone only. In the retrospective study, receiver operating characteristic curve analysis showed that by using a per cent free PSA of less than 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106/158 men (67%) with elevated PSA levels below 10.0 ng/ml were further evaluated and 37 (35%) prostate carcinomas were detected. By using a per cent free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120/465 men (26%) with total PSA levels between 1.25 and 6.49 ng/ml and a per cent free PSA<18% were further evaluated and 27 (23%) were found to have prostate carcinomas. Receiver operating characteristic curve analysis for PSA transition zone (TZ) density showed that by using a PSA transition zone density of >22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a and T1b Grade 3 carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. The rate of organ-confined tumours increased from 28.7% in 1993 to 65.7% in 1997. In this evaluation a new approach, to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cut-off point was developed. High total PSA levels, PSA density and PSA transition zone density correlated significantly with high Gleason scores, capsular penetration, a high percentage of cancer in the prostatectomy specimen and a high cancer volume. In this evaluation all of the 95 patients with PSA levels below 3.99 ng/ml who underwent radical prostatectomy showed clinically significant, organ-confined prostate cancer with negative surgical margins. The results of this evaluation suggest that older men have larger tumour volumes compared with younger men with the same PSA levels. These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Per cent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA.     

The role of prostate-specific antigen as part of the diagnostic triad and as a guide when to perform a biopsy.

The authors reviewed the results and relationship of prebiopsy prostate-specific antigen (PSA) assay, digital rectal examination (DRE), and transrectal ultrasound (TRUS) in 124 consecutive patients who underwent a prostate biopsy because of abnormal results of either DRE or TRUS. Results of the three tests (PSA, DRE, and TRUS) showed abnormalities in 54%, 75%, and 84.6% of patients, respectively; biopsy results were positive for cancer in 45.2%. Cancer detection rate increased as the PSA value increased from less than or equal to 4 ng/ml (17.5%) to more than 4 ng/ml (68.7%) to more than 20 ng/ml (83.3%), and as the number of positive tests increased (6.9% for one, 32.7% for two, and 82.6% for three). The PSA assay was the most important parameter of the diagnostic triad. These results suggested that regardless of DRE and TRUS findings, PSA less than or equal to 4 ng/ml confers a low prostate cancer risk, PSA more than 4 ng/ml but less than or equal to 10 ng/ml confers an intermediate prostate cancer risk, and PSA more than 10 ng/ml confers a high prostate cancer risk. Regardless of other findings, all patients with a PSA value more than 10 ng/ml require biopsy because of the high likelihood of cancer. All patients with abnormal DRE or TRUS results still require biopsy despite a low index of suspicion of prostate cancer when the PSA value is less than or equal to 4 ng/ml.     

Population-based screening for prostate cancer by measuring free and total serum prostate-specific antigen in Iran.

PURPOSE: To evaluate the natural background of prostate cancer in Iran a large population-based study of screening using total prostate-specific antigen (tPSA) and per cent free PSA (fPSA) as the initial test was performed. MATERIALS AND METHODS: For 9 years (1996 to 2004) in Tehran, Iran, 3670 Iranian men older than 40 years were mass checked by PSA-based screening. They were invited to have a digital rectal examination (DRE), serum PSA assay and transrectal ultrasonography (TRUS)-guided sextant prostate biopsy to see if the DRE was clinically suspicious of malignancy, the serum PSA was > or =2.1 ng/ml or free-to-total PSA (f/tPSA) ratio < or=15%. RESULTS: In 433 (11.8%) of screened males, tPSA levels exceeded the cut-off value of > or =2.1 ng/ml and 128 prostate cancers were diagnosed [positive predictive value (PPV) 29.6%] corresponding to an overall detection rate of 3.5%. Altogether 138 cancers were detected (detection rate 3.8%); none were stage M(1), three were stage N(+) and 4 stage T(3). A threshold tPSA of > or =2.1 ng/ml would have detected 128 cancers in 447 biopsied men (PPV 29%). There were 109 of 138 (79%) men with cancer who had an f/tPSA of < or =15%, while 152 of 305 (49.8%) with benign biopsies had a f/tPSA of < or =15%, which corresponds to a PPV of 30.8%. CONCLUSION: PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Further studies are warranted in order to determine the incidence and prevalence of prostate cancer in different ethnic groups.     

Detection of prostate cancer at low and intermediate serum prostate-specific antigen levels in a country with a low incidence of prostate cancer

BACKGROUND: The objective of this study was to evaluate the cancer detection rate and the pathologic findings of biopsy in men at low and intermediate prostate-specific antigen (PSA) levels in an Asian population. METHODS: Patients between 40 and 79 years were entered into a study and 755 patients with serum PSA level of 2.0-10.0 ng/ml underwent trus-guided systematic biopsy. Patients were divided to low (PSA 2.0-4.0 ng/ml, n = 144) and intermediate (PSA 4.1-10.0 ng/ml, n = 611) PSA groups. RESULTS: Patients in the low PSA group had significantly smaller prostates (P = 0.003) and lower PSA density (P < 0.001). The rate of cancer detection was 16.7% (24 of 144) in the low PSA group and 23.7% (145 of 611) in the intermediate PSA group (P = 0.067). In men with normal digital rectal examination (DRE), prostate cancer was diagnosed in 14 (13.3%) of the 105 men in the low PSA group and 99 (19.5%) of the 508 men in the intermediate PSA group (P = 0.139). In all patients and patients with normal DRE, no statistically significant differences were found in the pathologic findings of biopsy between the two groups. CONCLUSIONS: Our findings provide a rationale to recommend prostate biopsy at lower PSA threshold in this population. At present, however, it is not clear that men who are treated when their cancers are detected at lower PSA levels have better outcomes than those who are treated when the PSA is higher than 4.0 ng/ml.     

Prostate-specific antigen, digital rectal examination, and transrectal ultrasound in predicting the probability of cancer.

Over a 4 1/2 year period, 1,940 asymptomatic men were entered in a prostate cancer detection program consisting of digital rectal examination (DRE), prostate-specific antigen (PSA), and transrectal prostate ultrasound (TRUS). Four hundred and sixteen biopsies were performed resulting in the diagnosis of 79 cancers; 82% had clinically organ confined tumors. A recommendation for biopsy was made in 260 (62%) based on the TRUS alone, 55 (13%) by DRE alone, 92 (22%) when the DRE and TRUS were both abnormal, and in 9 (2.2%) cases when only PSA levels were elevated. The DRE, PSA, and TRUS were abnormal in 1,261 (65%), 989 (51%), and 1,552 (80%) of the patients with cancer, respectively. Prostate cancer detection increased as the serum PSA level increased above 4 ng/ml. The positive predictive value of both DRE and TRUS were significantly influenced by an elevated PSA, (P = .042 and P less than .00005, respectively). The results of this study support the idea that, although the prostate cancer detection rate is influenced by these three modalities and the detection rate of localized disease can be improved by early detection programs, its effect on mortality rates remains undefined at this time.     

Changing role of 3 screening modalities in the European randomized study of screening for prostate cancer (Rotterdam).

A randomized screening trial was started in Europe to show the effect of early detection and treatment of prostate cancer on mortality (European Study on Screening of Prostate Cancer). In one centre (Rotterdam), the screening protocol initially consisted of 3 screening tests for all men: prostate-specific antigen (PSA), digital rectal examination (DRE) and transrectal ultrasonography (TRUS). A PSA value of >/=4 ng/ml and/or an abnormality on DRE and/or TRUS were taken to indicate that biopsy was required. In this study, we examined the possibilities for a more efficient screening protocol. A logistic-regression model was used to predict the number of cancers for PSA < 4 ng/ml if all men were biopsied (predictive index, PI). Effects of a change in PSA cut-off on the screening results were explored. Weights were applied to procedures and cancers to explore the possibility of expressing differences between protocols in one overall figure. Biopsies in men with PSA < 1 ng/ml and a positive DRE or TRUS were very inefficient. Applying DRE and TRUS only in the PSA ranges 1.5 to 3.9 and 2 to 3.9 ng/ml to determine whether a biopsy was required would result in a decrease of 29 to 36% in biopsies and a decrease of 5 to 8% in cancers. However, the results of DRE and TRUS could not be duplicated entirely. A protocol with only PSA >/= 3 ng/ml as a direct biopsy indicator resulted in a decrease of detected cancers by 7.6% and of biopsies by 12%, also a much simpler screening procedure. Use of the PI would give more efficient protocols, but this should be viewed as a preliminary finding, with the disadvantage of necessitating many additional screening visits. Since the results of DRE and TRUS could not be duplicated, a change in protocol towards PSA >/= 3 ng/ml appears acceptable. If this proves effective, a final judgement about the optimal combination of screening tests may be made. Int. J. Cancer (Pred. Oncol.) 84:437-441, 1999.     

Prostate Cancer Screening in the Fit Chilean Elderly: a Head to Head Comparison of Total Serum PSA versus Age Adjusted PSA versus Primary Circulating Prostate Cells to Detect Prostate Cancer at Initial Biopsy

Background: Prostate cancer is predominately a disease of older men, with a median age of diagnosis of 68years and 71% of cancer deaths occurring in those over 75 years of age. While prostate cancer screening is notrecommended for men >70 years, fit elderly men with controlled comorbidities may have a relatively long lifeexpectancy. We compare the use of age related PSA with the detection of primary malignant circulating prostatecells mCPCs to detect clinically significant PC in this population. Materials and Methods: All men undergoing PCscreening with a PSA >4.0ng/ml underwent TRUS 12 core prostate biopsy (PB). Age, PSA, PB results defined ascancer/no-cancer, Gleason, number of positive cores and percentage infiltration were registered. Men had an 8mlblood sample taken for mCPC detection; mononuclear cells were obtained using differential gel centrifugationand mCPCs were identified using immunocytochemistry with anti-PSA and anti-P504S. A mCPC was definedas a cell expressing PSA and P504S; a positive test as at least one mCPC detected/sample. Diagnostic yieldsfor subgroups were calculated and the number of avoided PBs registered. Esptein criteria were used to definesmall grade tumours. Results: A total of 610 men underwent PB, 398 of whom were aged <70yrs. Men over 70yrs had: a higher median PSA, 6.24ng/ml versus 5.59ng/ml (p=0.04); and a higher frequency of cancer detected90/212 (43%) versus 134/398 (34%) (p=0.032). Some 34/134 cancers in men <70yrs versus 22/90 (24%) of men>70yrs complied with criteria for active surveillance. CPC detection: 154/398 (39%) men <70yrs were CPC (+),specificity for cancer 86%, sensitivity 88%, 14/16 with a false (-) result had a small low grade PC. In men >70years, 88/212 (42%) were CPC (+); specificity 92%, sensitivity 87%, 10/12 with a false (-) had small low gradetumours. False (+) results were more common in younger men 36/154 versus 10/88 (p<0.02). With a PSA cutoffof 6.5ng/ml, in men <70yrs, 108 PB would be avoided, missing 56 cancers of which 48 were clinically significant.Using CPC detection, 124 biopsies would be avoided, missing only 2 clinically significant cancers. In men >70yrs using a PSA >6.5ng/ml would have resulted in 108 PB with 34 PC detected, of which 14(41%) were smalllow grade tumours. Conclusions: The use of CPC detection in the fit elderly significantly decreases the numberof PBs without missing clinically significant cancers, indicating superiority to the use of age-related PSA.     

Improved detection of prostate cancer using classification and regression tree analysis.

PURPOSE: To build a decision tree for patients suspected of having prostate cancer using classification and regression tree (CART) analysis. PATIENTS AND METHODS: Data were uniformly collected on 1,433 referred men with a serum prostate-specific antigen (PSA) levels of < or = 10 ng/mL who underwent a prostate biopsy. Factors analyzed included demographic, laboratory, and ultrasound data (ie, hypoechoic lesions and PSA density [PSAD]). Twenty percent of the data was randomly selected and reserved for study validation. CART analysis was performed in two steps, initially using PSA and digital rectal examination (DRE) alone and subsequently using the remaining variables. RESULTS: CART analysis selected a PSA cutoff of more than 1.55 ng/mL for further work-up, regardless of DRE findings. CART then selected the following subgroups at risk for a positive biopsy: (1) PSAD more than 0.165 ng/mL/cc; (2) PSAD < or = 0.165 ng/mL/cc and a hypoechoic lesion; (3) PSAD < or = 0.165 ng/mL/cc, no hypoechoic lesions, age older than 55.5 years, and prostate volume < or = 44.0 cc; and (4) PSAD < or = 0.165 ng/mL/cc, no hypoechoic lesions, age older than 55.5 years, and 50.25 cc less than prostate volume < or = 80.8 cc. In the validation data set, specificity and sensitivity were 31.3% and 96.6%, respectively. Cancers that were missed by the CART were Gleason score 6 or less in 93.4% of cases. Receiver operator characteristic curve analysis showed that CART and logistic regression models had similar accuracy (area under the curve = 0.74 v 0.72, respectively). CONCLUSION: Application of CART analysis to the prostate biopsy decision results in a significant reduction in unnecessary biopsies while retaining a high degree of sensitivity when compared with the standard of performing a biopsy of all patients with an abnormal PSA or DRE.     

Efficacy of Using Sequential Primary Circulating Prostate Cell Detection for Initial Prostate Biopsy in Men Suspected of Prostate Cancer

Background: Sequential use of circulating prostate cell (CPC) detection has been reported to potentially decrease the number of unnecessary prostate biopsies in men suspected of prostate cancer. In order to determine the real world effectiveness of the test, we present a prospective study of men referred to two hospitals from primary care physicians, one using CPC detection to determine the necessity of prostate biopsy the other not doing so. Materials and Methods: Men with a suspicion of prostate cancer because of elevated PSA >4.0ng/ml or abnormal DRE were referred to Hospitals A or B. In Hospital A all underwent 12 core TRUS biopsy, in Hospital B only men CPC (), with mononuclear cells obtained by differential gel centrifugation identified using double immunomarking with antiPSA and antiP504S, were recommended to undergo TRUS biopsy. Biopsies were classifed as cancer or nocancer. Diagnostic yields were calculated, including the number of posible biopsies that could be avoided and the number of clinically significant cancers that would be missed. Results: Totals of 649 men attended Hospital A, and 552 men attended Hospital B; there were no significant differences in age or serum PSA levels. In Hospital A, 228 (35.1%) men had prostate cancer detected, CPC detection had a sensitivity of 80.7%, a specificity of 88.6%, and a negative predictive value of 89.5%. Some 39/44 men CPC negative with a positive biopsy had low grade small volume tumors. In Hospital B, 316 (57.2%) underwent biopsy. There were no significant differences between populations in terms of CPC and biopsy results. The reduction in the number of biopsies was 40%. Conclusions: The use of sequential CPC testing in the real world gives a clear decision structure for patient management and can reduce the number of biopsies considerably.     

Value of free-to-total prostate-specific antigen ratio for detection and staging of prostate cancer

Background. We aimed to evaluate the clinical usefulness of measurement of the free-to-total (F/T) ratio of prostate-specific antigen (PSA) for the differentiation of prostate cancer from benign prostate hyperplasia (BPH) and for the staging of prostate cancer. Values for PSA density (PSAD) and PSAD adjusted to the transition zone volume (PSAD-T) were also evaluated in patients with mildly elevated PSA levels (4.1–10 ng/ml). Methods. Total and free PSA and the F/T ratio were determined in 80 men with prostate cancer and 48 men BPH before treatment. PSA levels were measured with a chemiluminescent enzyme immunoassay. Results. Patients with prostate cancer had a significantly lower F/T ratio than those with BPH. A cut-off value of 14% for the F/T ratio provided a positive predictive value of 81.6% and a negative predictive value of 65.4%. The F/T ratio did not differ between patients with clinically localized and metastatic prostate cancer. In patients with a PSA value of 4.1–10 ng/ml, a cut-off value of 14% for the F/T ratio provided a sensitivity of 66.7% and a specificity of 76.2%. Sixty percent of the missed cancer in patients with an F/T value of 14% or more could be rescued using the PSAD value. Conclusion. Measurement of the F/T PSA ratio has good sensitivity and specificity in distinguishing prostate cancer from BPH, especially in patients with a PSA level of 4.1–10 ng/ml. However, compared with serum PSA level, the F/T PSA ratio is not valuable for the clinical staging of prostate cancer. Received: June 23, 1999 / Accepted: September 22, 1999     

Editorial comments

Ninety-nine of 105 consecutive men who underwent transrectal prostatic ultrasound (TRUS) at Highland Park Hospital had the results correlated with digital rectal examination (DRE), serum prostate specific antigen (PSA), and biopsy results. Ninety-six cases had evaluable ultrasound studies. Thirty-two of the 99 who underwent biopsy had primary carcinoma of the prostate. Prostate volume, predicted PSA, a ratio of observed/predicted PSA, and Gleason score were examined. There was no correlation between age and prostate volume, volume and the presence of carcinoma, or PSA and Gleason score. Thirty-one point six percent of the abnormal DREs, 36.6% of the abnormal TRUSs, and 40.6% of the elevated PSAs occurred in men with prostatic carcinoma (PCa). If PSA was normal (less than or equal to 4.0 ng/ml) and either DRE or TRUS was abnormal, then the risk of carcinoma was 2.9%. If PSA was elevated, regardless of the other two tests, the risk of finding PCa was at least 38%. If all three tests were abnormal, the risk of carcinoma was 38% in our series and 68% in a meta-analysis. Many men with PSA values between 4 and 10 ng/ml have benign biopsies. However, close future follow-up with consideration of repeat biopsy should be strongly considered. © 1994 Wiley-Liss, Inc.     

Value of Prostate Cancer Screening in a Comprehensive Community Cancer Center

Early detection of prostate cancer may help decrease cancer deaths from this disease despite the increased incidence of prostate cancer. In 1990 and 1991 we conducted one-day “screens” for prostate cancer. This analysis was undertaken to determine the value of the screening procedures for detecting prostate cancer in the community. A total of 579 men, aged 39-84 years (mean 58 years), were evaluated by digital rectal examination (DRE) by a urologist, serum prostate specific antigen (PSA) determination by monoclonal antibody assay, and completion of a detailed questionnaire. Forty-eight percent had not seen a physician in over 2 years; 17% had a 1st- or 2nd-degree relative with prostate cancer. There was a 25% “suspicious” rate including 76 (13%) men with abnormal DRE only, 48 (8%) with abnormal PSA only, and 21 (4%) with abnormal DRE and PSA. Patients with findings suspicious for cancer were recontacted by telephone at 2-month intervals for 6 months to determine outcome because subsequent diagnostic management was at the discretion of practicing physicians. By 6 months, 84% of patients with abnormal findings had seen a physician as recommended. Of the 76 with abnormal DRE only, 11 were biopsied and only one cancer was found (9%). Of 48 with an elevated PSA only, 19 were biopsied; 11 (58%) had cancer (9/9 positive transrectal ultrasound) and 8 had no cancer at biopsy (5/5 negative transrectal ultrasound). Of 21 with both tests suspicious, 11 were biopsied and 9 had cancer (82%). Thus, by 6 months after each screen there was a 3.5% overall cancer detection rate for the whole population screened, a 67% positive biopsy rate among those with an elevated PSA, a 45% positive biopsy detection rate among those with an abnormal DRE, and a 51% positive biopsy rate among all those biopsied. Eighty percent of the PSA elevations were between 4.1 and 10.0 ng/ml. This screening experience yielded several new diagnoses of prostate cancer, and the use of serum PSA levels and ultrasoundguided biopsy was associated with a high positive biopsy rate for cancer.