Digital rectal examination for detecting prostate cancer at prostate specific antigen levels of 4 ng./ml. or less

PURPOSE: We evaluated the detection rate of prostate cancer in men with suspicious digital rectal examination findings and serum prostate specific antigen (PSA) 4 ng./ml. or less. We also evaluated the stage and grade of cancers detected. MATERIALS AND METHODS: We screened 22,513 community volunteers by PSA testing and digital rectal examination at 6-month intervals. Biopsy was recommended when either test was suspicious for cancer. In the subset of 2,703 white and black men in whom PSA was 4 ng./ml. or less and digital rectal examination was suspicious for prostate cancer we compared compliance with biopsy recommendations, cancer detection rates, and stage and grade of cancers detected. We then correlated these results with patient age, race and serum PSA concentration. We performed multivariate logistic regression analysis to predict cancer based on clinical characteristics, and evaluated the positive predictive value of digital rectal examination for detecting cancer as stratified by race and PSA. RESULTS: Of the men 70% underwent biopsy with no difference in compliance according to age, race or PSA level. The 13% cancer detection rate correlated with age, race and PSA (p <0.003). The positive predictive value of a suspicious digital rectal examination was 5, 14 and 30% in men with PSA 0 to 1.0, 1.1 to 2.5 and 2.6 to 4.0 ng./ml., respectively. All cancers were clinically localized. Of the 72% of cases that were surgically staged 82% were organ confined and 78% were moderately differentiated. CONCLUSIONS: The positive predictive value of suspicious digital rectal examination was appreciable in men with low serum PSA. The majority of cancer cases detected by digital rectal examination had features of clinically important and potentially curable disease.     

Predicting radionuclide bone scan findings in patients with newly diagnosed, untreated prostate cancer: prostate specific antigen is superior to all other clinical parameters.

Presently, the standard staging evaluation of prostate cancer includes digital rectal examination, measurement of serum tumor markers and a radionuclide bone scan. To evaluate the ability of local clinical stage, tumor grade, serum acid phosphatase, serum prostatic acid phosphatase (PAP) and serum prostate specific antigen (PSA) to predict bone scan findings, a retrospective review of 521 randomly chosen patients (mean age 70 years, range 44 to 92 years) with newly diagnosed, untreated prostate cancer was performed. Local clinical stage, tumor grade, acid phosphatase, PAP and PSA all correlated positively with bone scan findings (p less than 0.0001). Using receiver operating characteristic curves, however, PSA had the best over-all correlation with bone scan results. The median serum PSA concentration in patients with a positive bone scan was 158.0 ng./ml., whereas men with a negative bone scan had a median serum PSA level of 11.3 ng./ml. (p less than 0.0001). Using multivariate logistic regression analysis, local clinical stage, tumor grade, acid phosphatase and PAP were evaluated in combination with PSA to assess whether these parameters increased the ability of PSA alone to predict bone scan findings. None of these clinical parameters, irrespective of the combination used, contributed appreciably to the predictive power of PSA alone. A probability plot with 95% confidence intervals was constructed that allows the practicing urologist to estimate on an individual basis the probability of a positive bone scan for any given serum PSA value. The most significant finding of this study, however, was the negative predictive value of a low serum PSA concentration for bone scan findings. In 306 men with a serum PSA level of 20 ng./ml. or less only 1 (PSA 18.2 ng./ml.) had a positive bone scan (negative predictive value 99.7%). This finding would suggest that a staging radionuclide bone scan in a previously untreated prostate cancer patient with a low serum PSA concentration may not be necessary.     

Percent free prostate specific antigen in the total prostate specific antigen 2 to 4 ng./ml. range does not substantially increase the number of biopsies needed to detect clinically significant prostate cancer compared to the 4 to 10 ng./ml. range

PURPOSE: Percent free prostate specific antigen (PSA) is useful to select patients for prostate biopsy with total PSA 4 to 10 ng./ml. However, 20% of men with PSA between 2.6 and 4 ng./ml. harbor significant prostate cancer and percent free PSA has been suggested to aid in the decision to biopsy in this total PSA range as well. Concerns exist that the number of biopsies needed to detect 1 cancer in this range may be inappropriately high. In a prospective referral population we evaluated sensitivity and specificity of various percent free PSA cutoffs and determined the biopsy-per-cancer ratio in the PSA 2 to 4 ng./ml. range in men with a benign digital rectal examination, and report on the biological nature of the detected cancers based on Gleason score. Results were compared to those obtained from a reference group of patients (PSA 4 to 10 ng./ml., benign digital rectal examination) from the same prospective referral cohort. MATERIALS AND METHODS: Total PSA and free PSA were measured and percent free PSA was calculated. Of the initial 1,602 men 756 had a benign digital rectal examination and PSA 4 to 10 ng./ml., and 219 had a benign digital rectal examination and PSA 2 to 4 ng./ml. Sensitivity, specificity, the number of true positive (evidence of cancer) and false-positive (no evidence of cancer) biopsies were determined. The ratio of true positive biopsies-to-all biopsies performed was used to determine the biopsy-per-cancer ratio. Gleason score of the detected cancers was evaluated. The procedure was repeated for the PSA 4 to 10 ng./ml. range. RESULTS: In the PSA 4 to 10 ng./ml. range a sensitivity of 63.7% to 92.5% with a specificity of 57.5% to 18.7% was found when percent free PSA was 18% to 25%. On average 3 biopsies were needed to detect 1 cancer. When PSA was 2 to 4 ng./ml. sensitivity was 46.3% to 75.6% and specificity was 73.6% to 37.6% when the same percent free PSA cutoff was examined. Calculation of the biopsy-per-cancer ratio for various percent free PSA cutoffs revealed that 3 to 5 biopsies were needed to find 1 cancer. Of 41 cancers detected in the PSA 2 to 4 ng./ml. range 6 had a Gleason score 5. The majority (28 of 41) of cases had a Gleason score of 6. Gleason score was 7 in 5 patients and 8 in 1. CONCLUSIONS: In the PSA 4 to 10 ng./ml. range high sensitivity for prostate cancer detection is critical and 3 biopsies are needed to detect 1 cancer. In the PSA 2 to 4 ng./ml. range a percent free PSA cutoff of 18% to 20% detected about 50% of cancers while sparing up to 73% of unnecessary biopsies with a biopsy-to-cancer ratio of 3 to 4:1. Percent free PSA can be applied to the PSA 2 to 4 ng./ml. range to detect prostate cancer and only moderately increases the number of biopsies needed to detect 1 significant cancer compared to the greater than 4 to 10 ng./ml. range.     

Prostate cancer detection at low prostate specific antigen

PURPOSE: At low prostate specific antigen (PSA) the indication for prostate biopsy is usually an abnormal digital rectal examination. We evaluate the diagnostic value of PSA, digital rectal examination, transrectal ultrasonography and tumor characteristics at low PSA (0 to 4.0 ng./ml.). We confirm and add to recent evidence that digital rectal examination has a low predictive value and that many significant cancers at this PSA range may be missed. MATERIALS AND METHODS: From 1994 to 1997 a total of 10,523 participants 54 to 74 years old were randomized to screening in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. Of the participants 9,211 (87.5%) had PSA less than 4.0 ng./ml., and underwent digital rectal examination and transrectal ultrasonography. Expected rates of prostate cancer detection were calculated using logistic regression analysis. Radical prostatectomy was performed in about half of the 478 men diagnosed with prostate cancer. Tumors were characterized by pT category, Gleason score and cancer volume in 166 processed radical prostatectomy specimens. In 50 of these cases PSA was 0 to 4.0 ng./ml. RESULTS: The positive predictive value of digital rectal examination and transrectal ultrasonography at PSA 0 to 4.0 ng./ml. was only 9.7%. Positive predictive value strongly depended on PSA. Sensitivity was calculated by using estimates of the prevalence of sextant biopsy detectable prostate cancers. Of 760 detectable cancers 478 (67%) were diagnosed irrespective of PSA in men screened with digital rectal examination, transrectal ultrasonography and PSA. Only 127 of 348 detectable prostate cancers (36.5%) were actually diagnosed in men with PSA 2 to 4 mg./ml. The importance of these missed cancers was evaluated with parameters of tumor aggressiveness within PSA ranges. CONCLUSIONS: Approximately half of the tumors missed with PSA 0 to 4 ng./ml. had aggressive characteristics (Gleason score 7 or greater, Gleason 4-5 components) and were organ confined. These tumors should be diagnosed and treated according to the present understanding of their natural history. More sensitive and selective screening strategies are needed. Presently a wrong "window of opportunity" is used for early detection of prostate cancer.     

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.     

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.     

前列腺系统10点穿刺活检术的临床价值

目的探讨前列腺系统10点穿刺活检术的临床价值。方法对214例直肠指诊阳性或PSA>4.0 ng/ml及B超提示有异常回声结节的病例行经直肠B超引导下前列腺穿刺活检术(采用前列腺系统10点穿刺活检术,同时对可疑回声区随机增加穿刺点)。结果共检出前列腺癌76例,占35.51%,良性前列腺增生126例,占58.88%。慢性前列腺炎13例,占6.07%。前列腺囊肿3例,占1.40%。随机增加穿刺点检出32例,占15%。术后血尿者58例,占27.10%,血便6例,占2.80%,无一例出现前列腺脓肿、高热、败血症等严重并发症。结论前列腺穿刺活检是诊断前腺癌的重要手段,经直肠B超定位下系统10点穿刺法可以提高检出率,无严重并发症。     

前列腺特异性抗原升高的组织病理学基础

目的 探讨前列腺特异性抗原(PSA)与前列腺结节增生、Ⅳ型前列腺炎及前列腺癌之间的关系,探讨PSA升高的病理学基础.方法 有完整临床病理资料的前列腺疾病504例患者,均无前列腺癌和穿刺活检史,均行PSA、全身骨扫描、MRI和前列腺穿刺活检.直肠B超引导下以18G自动穿刺活检枪行双侧叶6-13点法前列腺穿刺活检.对患者穿刺的病理标本按前列腺结节增生、前列腺癌以及Ⅳ型前列腺炎病理诊断标准进行评价.结果 504例患者经病理证实前列腺癌185例(37%),Ⅳ型前列腺炎109例(21%),前列腺增生210例(42%).3组总PSA(t-PSA)分别为27.6(0.4～7116)、10.6(0.2～168)和9.2(0.3～60)ng/ml,3组间比较差异有统计学意义(P＜0.01);f-PSA分别为3.5(0.1～3356)、1.7(0.1～42)和1.5(0.06～15.8)ng/ml,3组间比较差异有统计学意义(P＜0.001);f/t-PSA分别为0.14(0＜0.94)、0.17(0.04～0.91)和0.16(0.02～0.75).3组间比较差异有统计学意义(P=0.019);3组间年龄、B超、直肠指诊结果比较差异无统计学意义(P＞0.05).前列腺癌分级与f-PSA(r=0.33,P＜0.001)、t-PSA(r=0.27,P＜0.001),f/t-PSA(r=0.22,P=0.003)具有显著相关性;多元线性回归分析发现前列腺癌分级与f-PSA(t=-2.34,P=0.02),t-PSA(t=2.77,P=0.006),f/t-PSA(t=3.97,P＜0.001)具有显著相关性.前列腺癌临床分期间f-PSA和t-PSA差异有统计学意义(P＜0.001).210例前列腺增生患者若按腺体增生为主和间质增生为主2类比较,t-PSA和f-PSA差异均有统计学意义(P＜0.05).多元线性回归分析发现t-PSA足前列腺增生病理结节类型最相关的指标,t-PSA≥2.5 ng/ml,确定腺体增生为主型前列腺增生的敏感性为96%,特异性为20%(P＜0.05).Ⅳ型前列腺炎109例和前列腺增生210例,2组间比较f-PSA,t-PSA,f/t-PSA差异有统计学意义(P＜0.05).通过ROC曲线确定前列腺癌敏感指标的界值:f-PSA≥0.85 ng/ml,t-PSA≥4 ng/ml和f/t-PSA≤0.16(P＜0.05).结论 血清PSA升高的病理基础为任何破坏前列腺上皮血屏障的病变;任何形成前列腺上皮增生,分泌更多PSA的病变;其中以破坏前列腺上皮血屏障最重要.     

Detection of prostate cancer and changes in prostate-specific antigen (PSA) six months after surgery for benign prostatic hyperplasia in patients with elevated PSA

OBJECTIVE: To evaluate early postoperative results of patients with elevated prostate-specific antigen (PSA) levels who underwent surgery due to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: 64 patients who had lower urinary tract symptoms (LUTS), normal digital rectal examinations (DRE), elevated PSA levels and prostate biopsies reported as being benign pathologically in specimens obtained by transrectal ultrasound (TRUS)-guided biopsies, were included in the study. Patients were assessed in accordance with PSA density, free/total PSA ratio and uroflowmetric studies. Patients had no cancer pre- and postoperatively (according to operative specimens). Six months postoperatively, 32 patients were accepted for re-evaluation for all PSA parameters, routine tests and prostatic biopsies. RESULTS: 64 patients with a mean age of 66.8 (SD 6.72) were included in the study. Total PSA average value was 14.38 (SD 7.49) ng/ml. Free PSA average value was 2.11 (SD 1.43) ng/ml. Average PSA density and free/total PSA ratio were 25.19 SD (14.12) ng/ml/cm(3) and 14.53% (SD 5.35%) respectively. 56 patients had BPH, 7 had chronic prostatitis and 1 had prostatic intraepithelial neoplasia (PIN) preoperatively with biopsies. Re-biopsy of the patient with PIN was reported as BPH. In pathologic examination with resected tissues postoperatively, 49 patients had BPH, 14 had chronic prostatitis and 1 had PIN. In the sixth month, average values of free/total PSA were 0.45 (SD 0.26) and 3.71 (SD 4.96) ng/ml respectively. Average PSA density and free/total PSA ratio were 12.41 (SD 13.8) ng/ml/cm(3) and 19.59% (SD 10.33%) respectively. There were significant decreases in PSA densities (p < 0.001) and increases in free/total PSA ratios (p = 0.004). Seven patients still had elevated PSA levels 6 months postoperatively. Three of 7 patients were reported as chronic prostatitis. One of them was indicated as prostatic carcinoma who was reported as PIN preoperatively. All other patients were stated as BPH at re-biopsies. CONCLUSION: If pretreatment biopsies are negative and operative specimens are also benign in patients with high PSA values, these patients can be followed up like usual BPH patients, but long-term follow-up is still unclear.     

Prevalence and Predictors of a Positive Repeat Transrectal Ultrasound Guided Needle Biopsy of the Prostate

Purpose

We determined the prevalence of and risk factors for carcinoma in patients with 1 previously negative prostate biopsy.

Materials and Methods

Transrectal ultrasound guided prostate needle biopsies were repeated in 130 men. Risk factors analyzed included age, pathological result of initial biopsy, inter-biopsy interval, prostate specific antigen (PSA), PSA density, PSA velocity, digital rectal examination, abnormal transrectal ultrasound and family history of prostate cancer.

Results

A total of 39 patients (30%) had positive biopsies for cancer. Univariate analysis revealed that PSA more than 20 ng./ml. and abnormal transrectal ultrasound were more frequent in men with positive second biopsies. Using multivariate logistic regression analysis only PSA more than 20 ng./ml. was a significant risk factor (adjusted odds ratio 4.48, 95% confidence interval 1.02 to 20.1). We determined the incidence of carcinoma in patients who represent the lowest risk group as defined by PSA less than 10 ng./ml., PSA density less than 0.15 mg./ml./cm.³, PSA velocity less than 0.75, ng./ml. per year, no prostatic intraepithelial neoplasia plus negative transrectal ultrasound, digital rectal examination and family history. Of 21 patients who fit this cohort 5 (23.8%) had carcinoma on repeat biopsy.

Conclusions

A significant false-negative rate for initial transrectal ultrasound guided prostate biopsies exists. Baseline risk in lowest risk patients is sufficiently high such that one cannot define a subset of patients for whom repeat biopsy is unnecessary. We recommend repeat biopsy in all patients who meet the criteria for a transrectal ultrasound guided biopsy and in whom the initial biopsy is negative.     

Prospective evaluation of prostate cancer detection by prostate specific antigen related parameters: comparison in serum and plasma samples.

PURPOSE: We compared the usefulness of serum and plasma samples for enhancing the specificity of prostate cancer detection. MATERIALS AND METHODS: We analyzed receiver operating characteristics curves to evaluate prospectively the cancer detection performance of prostate specific antigen (PSA) related parameters derived from serum and plasma samples in 248 and 249 consecutive patients, respectively. RESULTS: Receiver operating characteristics curve analysis showed that PSA density and transition zone PSA density were more powerful predictors of prostate cancer than total or free PSA in the group overall at intermediate serum PSA 2.1 to 10 ng./ml. and in the subgroup with total PSA 4.1 to 10 ng./ml. regardless of digital rectal examination findings. Percent free PSA performed significantly better than total PSA in patients with serum total PSA 4.1 to 10 ng./ml. PSA density, transition zone PSA density and percent free PSA did not differ substantially in patients with serum total PSA 4.1 to 10 ng./ml. However, none of these parameters distinguished patients with prostate cancer from those with benign histology when PSA was in the lower range of 2.1 to 4 ng./ml. The performance of these parameters was worse when plasma sample data were used for calculation. CONCLUSIONS: The performance of percent free PSA appears at least comparable to that of PSA density and transition zone PSA density in patients in this cohort with serum total PSA 4.1 to 10 ng./ml. without regard to digital rectal examination. The poor performance of these parameters in the lower PSA range underscores the need for other parameters to improve the specificity of cancer detection in elderly Japanese males. Continued use of serum samples is justified for measuring PSA related parameters by current assay techniques.     

Efecto del tratamiento antibiótico sobre el psa y porcentaje de psa libre en pacientes con criterios bioquímicos de biopsia prostática

IntroductionPSA serum level measurement in the most important tool in the early diagnosis of prostate cancer patients. However, it is recognised it low specificity is due mainly to prostatic benign diseases. Although it is known that immflamation can contribute on this lack of specificity, there is disagreement in the effect of no symptomatic prostatic immflamatory focus on total PSA and percent free PSA serum levelsAimTo analyse the biological variability in total PSA and percent free PSA serum levels in patients with biochemical criteria of prostatic biopsy and to compare them with the antibiotic induced variability in a previous urinary infections cohort patientsPatients and methodsWe analysed 60 patients with previous urinary infections, normal digital rectal examination and PSA between 4 and 20 ng/ml. We measured total PSA and percent free PSA serum levels. Thirty were treated with 3 weeks of ofloxacin and following a new marker determination. Sextant ultrasound guided prostatic biopsy was performed in all casesResults45 patients demonstrated BPH (29 with prostatitis) and 15 prostate cancer (T1c). Significant variations were found on total PSA serum levels (6.97 ng/ml vs 5.82 ng/ml, p = 0,001) and percent free PSA (14.73% vs 17.77%, p = 0,01) only in treated patients. These differences were significant in BPH and BPH with prostatitis patients but not in prostate cancer patients. Treated patients trend was to decrease PSA (13 treated patients shown PSA < 4 ng/ml vs 2 control patients) and to increase percent free PSA. The median variation of percent free PSA was higher than total PSA and was not influenced by PSA level or prostatic volume. Taking 25 as cut-off of percent free PSA, 18.3% of prostatic biopsies could be avoided in the first determination and 20% in the second. Adding the total PSA reduction, 56% of prostates biopsies in the treated patients could be avoidedConclusionsBiochemical criteria of prostatic biopsy could be modified in patients with previous urinary infections due to higher variations on serum markers than those explained by biological variations. These variations could be induced by the antibiotic treatment. These results suggested that the immflamatory focus could influence on total PSA and percent free PSA serum levels     

Treatment of chronic prostatitis lowers serum prostate specific antigen

PURPOSE: We evaluated men with documented chronic prostatitis and elevated serum prostate specific antigen (PSA) to determine whether treatment with antibiotics and anti-inflammatory drugs lowers serum PSA. MATERIALS AND METHODS: We retrospectively reviewed the records of 95 men who presented with serum PSA greater than 4 ng./ml. and were subsequently diagnosed with chronic prostatitis with greater than 10 white blood cells per high power field in expressed prostatic excretions. Patients meeting these criteria were treated with a 4-week course of antibiotics and a nonsteroidal anti-inflammatory agent. In all patients followup PSA was determined within 2 months of treatment. RESULTS: Mean PSA decreased 36.4% from 8.48 ng./ml. before to 5.39 after treatment (p <0.001). In 44 patients (46.3%) serum PSA decreased to below 4 ng./ml. (mean 2.48) and these patients no longer had an indication for biopsy. In the remaining 51 patients serum PSA remained elevated at greater than 4 ng./ml. and they underwent double sextant transrectal ultrasound guided biopsy. Pathological study showed prostate cancer in 13 cases (25.5%), chronic inflammation in 37 (72.5%) and only benign prostatic hypertrophy in 1 (1.05%). PSA in the 13 patients with prostate cancer decreased with treatment only 4.8% from 8.32 to 7.92 ng./ml. (p >0.05). Followup PSA at a mean of 11.4 months was determined in 19 of the 44 men who responded to treatment. Mean PSA increased only 4.5% from 2.35 to 2.46 ng./ml. (p >0.05) during this followup interval. CONCLUSIONS: In almost half of the patients diagnosed with elevated PSA and chronic prostatitis serum PSA normalized with treatment and there was no longer an indication for transrectal ultrasound guided biopsy. Our study suggests that chronic prostatitis is an important cause of elevated PSA and when it is identified, treatment can decrease the percent of negative biopsies.     

Prostate cancer detection in Black and White men with abnormal digital rectal examination and prostate specific antigen less then 4 ng./ml

PURPOSE: Prostate cancer is more common in black than in white American men. Experience in a longitudinal prostate cancer screening program implies that cancer detection is greater in black than in white men with an abnormal digital rectal examination and prostate specific antigen (PSA) less than 4 ng./ml. We investigated potential racial differences in cancer detection in men treated in clinical practice who had an abnormal digital rectal examination and PSA less than 4 ng./ml. MATERIALS AND METHODS: Between January 1992 and December 1999 prostate biopsy was done at a Veterans Affairs Medical Center in 179 black and 357 white men with an abnormal digital rectal examination, PSA less than 4 ng./ml. and no history of prostate surgery. Significant racial differences in demographic and clinical parameters were limited to PSA, which was higher in black men (p = 0.01). RESULTS: Cancer was detected in 38 black (21%) and 65 white (18%) men (p = 0.42). There were no significant racial differences in the PSA adjusted cancer detection rate or in the Gleason score of detected disease. In men with PSA less than 1.0, 1.0 to 1.9, 2.0 to 2.9 and 3.0 to 3.9 ng./ml. the detection rate was 4%, 15%, 27% and 29%, respectively. CONCLUSIONS: In clinical practice prostate cancer detection appears to be equivalent in black and white men when an abnormal digital rectal examination is the only indication of malignancy.     

Intraindividual variations of total and percent free serum prostatic-specific antigen levels in patients with normal digital rectal examination.

PURPOSE: To analyze intraindividual variations of total and percent free serum prostate-specific antigen (PSA) in patients with normal digital rectal examination. MATERIAL AND METHODS: Total and free serum PSA were determined in two blood samples corresponding to 107 nonconsecutive patients. The period between both determinations ranged from 23 to 60 days. Prostatic biopsy was done after both determinations in all except 17 patients because the two serum PSA concentrations were <4 ng/ml. Total and free PSA were determined using double monoclonal antibody immunoassay Tandem and Tandem free (Hybritech Inc.). The diagnosis was benign prostatic hyperplasia (BPH) in 63 patients and prostate cancer (PCA) in 44. RESULTS: The variations of PSA ranged between -6.8 and +3.2 ng/ml in BPH patients and between -2.8 and +9.0 in patients with PCA. The median coefficients of variation were 15.4 and 15.7% respectively. The variations in the percent free PSA were between -30.7 and +40.9 in the BPH group and between -17.9 and +15.8 in the PCA group. The median coefficients of variation were 32.2 and 32.3% respectively. If prostatic biopsy had been indicated when percent free PSA had been 相似文献   

Serial biopsy results in prostate cancer screening study

PURPOSE: We evaluated prostate biopsy results in men with elevated prostate specific antigen (PSA) levels and/or suspicious digital rectal examination whose initial biopsies did not reveal cancer. MATERIALS AND METHODS: A total of 2,526 volunteers 40 years old or older underwent 1 or more prostate biopsies for serum PSA concentrations greater than 4.0 ng./ml. (before May 1995) or greater than 2.5 ng./ml. (after May 1995), or digital rectal examination suspicious of cancer. We evaluated compliance with the biopsy recommendation and the cancer detection rate with regard to digital rectal examination results and increasing PSA levels. RESULTS: Of the men who underwent up to 10 biopsy procedures the serial cancer detection rates were 29%, 17%, 14%, 11%, 9% and 7%, respectively, on biopsy procedures 1 through 6. No significant difference in the yield of cancer on serial biopsies was observed between the groups using the greater than 4.0 ng./ml. and greater than 2.5 ng./ml. cutoff. There was a trend for more cancers detected through serial screening to be organ confined compared with those detected on initial screening (78% versus 69%, p = 0.05). Also, more cancers detected using the greater than 2.5 ng./ml. cutoff were organ confined (80% versus 66%, p = 0.004). Only approximately 1% of the cancers fulfilled the published criteria for clinically insignificant tumors. CONCLUSIONS: Nearly a quarter of prostate cancers detected in this screening study were missed by the initial biopsy. Of the 962 prostate cancers detected 77% were detected with 1, 91% with 2, 97% with 3 and 99% with 4 biopsy procedures. Serial biopsies detect more organ confined cancers without over detecting clinically unimportant tumors. Future studies are needed to determine whether obtaining more biopsy cores initially would provide earlier prostate cancer detection and avoid unnecessary repeat biopsies.     

AGE SPECIFIC PROSTATE SPECIFIC ANTIGEN REFERENCE RANGES: POPULATION SPECIFIC

Purpose

We determined whether 60 to 79-year-old men with a negative digital rectal examination and a serum prostate specific antigen (PSA) within age specific PSA reference ranges could safely forgo prostate biopsy.

Materials and Methods

We reviewed the medical records of all 60 to 79-year-old men at the Brooklyn Veterans Administration Medical Center who had a PSA assay, digital rectal examination and subsequent prostate biopsy for an abnormal rectal examination and/or PSA greater than 4.0 ng./ml. from January 1991 through August 1995. We compared our results using the standard reference range of 0 to 4.0 ng./ml. with those obtained had we used any of 4 different age specific PSA reference ranges.

Results

We performed 1,280 prostate biopsies in 1,046 men with available PSA and digital rectal examination data. Using age specific PSA reference ranges 73 of 1,280 biopsies (5.7%) would have been avoided. Of those 73 avoided biopsies 15 (20.5%) had cancer that would have gone undetected and 9 of 15 (60%) undetected cancers had unfavorable histology. Results were not statistically significantly different among the 4 age specific PSA reference ranges. Regarding race, cancer detection rates were significantly higher for black compared with white men but there was no statistically significant difference for missed cancers or missed cancers with unfavorable histology.

Conclusions

In contrast to previous reports of unfavorable histological characteristics in only 5% of missed cancers using age specific PSA reference ranges, 60% of missed cancers in our patients exhibited unfavorable histology. We conclude that age specific PSA reference ranges did not safely eliminate the need for prostate biopsy in our study population. In 60 to 79-year-old men with a negative digital rectal examination we continue to use PSA greater than 4.0 ng./ml. as an indication for prostate biopsy.     

Significance of Serum Free Prostate Specific Antigen in the Screening of Prostate Cancer

Purpose

The significance of serum free prostate specific antigen (PSA) in the screening of prostate cancer was examined.

Materials and Methods

A prospective clinical trial was conducted on 701 male volunteers 50 years old or older. Serum free PSA was determined and biopsies were performed if PSA was greater than 4 ng./ml. or if digital rectal examination was suspicious for cancer.

Results

Of the men 187 (27 percent) had a PSA of greater than 4 ng./ml. (11 percent) and/or a suspicious digital rectal examination (19 percent). Of 116 biopsies performed in the 701 men cancer was detected in 13 (1.9 percent). PSA detected more tumors (12 of 13, 92 percent) than digital rectal examination (9, 69 percent). Receiver operating characteristic analysis showed that the optimal free PSA-to-PSA ratio (free PSA ratio) was 12 percent. The positive predictive value for cancer according to PSA with free PSA ratio (50 percent, 10 cancers in 20 biopsies) was significantly greater (p = 0.0473) than that according to PSA alone (24 percent, 12 cancers in 50 biopsies), which indicated that 30 of 50 biopsies were avoided with only 2 cancers missed when PSA and free PSA were used for biopsy indication.

Conclusions

Free PSA determination might eliminate unnecessary biopsies in men with a PSA of more than 4 ng./ml. with minimal missed cancers.     

Prostate specific antigen in hormonally treated stage D2 prostate cancer: is it always an accurate indicator of disease status?

The clinical significance of serum prostate specific antigen (PSA) values in hormonally treated prostate cancer patients and the effect of hormonal therapy on the serum PSA concentration, independent of the response observed from its antitumor activity, are not well defined. To elucidate further the influence of antiandrogen therapy on serum PSA expression, 81 randomly selected patients with stage D2 prostate cancer were evaluated with respect to serum PSA concentration. These patients were divided into 2 groups on the basis of previous hormonal therapy. Group 1 consisted of 43 patients 55 to 89 years old (mean age 71 years) who had received no prior therapy for prostate cancer. Group 2 included 38 men 58 to 84 years old (mean age 72 years) who had received only androgen deprivation therapy with either bilateral orchiectomy or diethylstilbestrol. The mean interval between initiation of antiandrogen therapy and evaluation of these patients was 14 months (range 8 to 31 months). At the time of PSA determination both groups were similar in all respects, including tumor grade, disease symptoms and bone scan findings. The median serum PSA concentration was 96.0 ng./ml. in group 1 and 16.5 ng./ml. in group 2 (p less than 0.001), despite both groups having similar symptoms and widespread metastatic disease on radionuclide bone scan. In group 1 only 1 patient (2%) had a serum PSA level less than 4.0 ng./ml., whereas 13 men (34%) in group 2 had a serum PSA concentration below 4.0 ng./ml. (p less than 0.001). Of the patients in group 1, 2% and of the men in group 2, 45% had a serum PSA concentration less than 10 ng./ml. (p less than 0.001). These findings demonstrate that the serum PSA level in prostate cancer patients treated hormonally may have a significantly different meaning than the same serum PSA value in patients without hormonal therapy. In addition, these observations suggest that PSA expression may be under hormonal regulation and that androgen deprivation therapy may have a direct effect on the serum PSA concentration, independent of the response obtained from any antitumor activity. However, the exact mechanism of this androgenic influence on PSA expression awaits further investigation at the cellular level.     

PROSTATE SPECIFIC ANTIGEN ADJUSTED FOR THE TRANSITION ZONE VOLUME AS AN INDICATOR OF PROSTATE CANCER

Purpose

We compared prostate specific antigen (PSA) adjusted for the transition zone volume with PSA and PSA density with regard to value in diagnosing prostate cancer in men with intermediate PSA levels of 4.1 to 10.0 ng./ml. in a community based urology practice.

Materials and Methods

Between October 1994 and May 1996, PSA transition zone was obtained from 92 of 94 men who underwent systematic sextant biopsies and had a PSA value between 4.1 and 10.0 ng./ml. PSA transition zone, calculated by dividing the PSA value by the volume of the transition zone of the prostate, was compared with PSA and PSA density via the receiver operating characteristic (ROC) curves.

Results

Of the 92 men 12 (13.0%) had prostate cancer. ROC curve analysis demonstrated that PSA transition zone and PSA density predicted the biopsy outcome significantly better than PSA (p <0.05 and p <0.01, respectively). In a subset of 59 men with normal digital rectal examination PSA transition zone predicted the biopsy outcome better than PSA density, although without significant difference. With a cutoff value of 0.3 PSA transition zone had a sensitivity of 75% and a specificity of 54%.

Conclusions

PSA transition zone is more specific than PSA in distinguishing benign from malignant disease in men with intermediate PSA levels of 4.1 to 10.0 ng./ml., especially in those with normal digital rectal examination. Further study is necessary to discuss whether PSA transition zone is superior to PSA density.