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.     

Predicting recurrence after radical prostatectomy for patients with high risk prostate cancer

PURPOSE: Previous studies have shown that patients with clinical stage T2c-T3 prostate cancer, serum prostate specific antigen (PSA) at diagnosis greater than 20 ng./ml. or a biopsy Gleason score of 8 to 10 are at high risk for disease recurrence after radical prostatectomy. We determined the most important pretreatment predictors of disease recurrence in this high risk population. MATERIALS AND METHODS: We identified 547 patients with high risk prostate cancer who underwent radical prostatectomy at University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor data base, a longitudinal disease registry of patients with prostate cancer. High risk disease was defined as 1992 American Joint Committee on Cancer clinical stage T2c-T3 disease in 411 patients, serum PSA at diagnosis greater than 20 ng./ml. in 124 and/or biopsy Gleason score 8 to 10 in 114. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment more than 6 months after surgery. The Cox proportional hazards analysis was performed to determine significant independent predictors of disease recurrence. The likelihood of disease recurrence for clinically relevant patient groups was determined using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median followup after surgery was 3.1 years. Disease recurred in 177 patients (32%). Multivariate analysis demonstrated that serum PSA at diagnosis, biopsy Gleason score, ethnicity and the percent of positive prostate biopsies were significant independent predictors of disease recurrence, while patient age and clinical tumor stage were not. Patients with a Gleason score 8 to 10 tumor and a serum PSA of 10 ng./ml. or less had a significantly higher likelihood of remaining disease-free 5 years after surgery than those with PSA greater than 10 ng./ml. (47% versus 19%, p <0.05). Patients with a serum PSA at diagnosis of greater than 20 ng./ml. and a Gleason score of less than 8 had a significantly higher likelihood of remaining disease-free 5 years after surgery than similar patients with a Gleason score of 8 or greater (45% versus 0%, p <0.05). CONCLUSIONS: PSA, Gleason score, ethnicity and the percent of positive prostate biopsies appear to be the most important pretreatment predictors of disease recurrence in men with high risk prostate cancer. Patients with high grade disease may continue to be appropriate candidates for local therapy if PSA is less than 10 ng./ml. at diagnosis or there are fewer than 66% positive prostate biopsies.     

Prognostic features in men who died of prostate cancer

PURPOSE: Since the advent of widespread prostate specific antigen (PSA) based screening in the United States, the risk of over diagnosis as well as delayed diagnosis due to existing PSA thresholds has become a concern. Treatment decision planning is generally linked to prognostic variables, most notably PSA, clinical stage and Gleason grade. We examined these and other prognostic variables in a cohort of men who ultimately died of prostate cancer. MATERIALS AND METHODS: Of 413 men with prostate cancer in a cohort in San Antonio, Texas between 1993 and 2003 who died of disease we identified 211 who died as a direct result of prostate cancer. In these cases we assessed presenting symptoms, PSA history, tumor stage and Gleason score at diagnosis. RESULTS: Of the 211 men 141 (67%) underwent screening for prostate cancer prior to diagnosis. Of 190 men with PSA data at diagnosis available 7 (3.7%) had PSA less than 4.0 ng/ml and 27 (14%) had PSA 4.0 to 10.0 ng/ml. Clinical stage distribution was cT1 in 21.1% of cases, cT2 in 50.7% and cT3 in 26.8%. Of 167 men for whom biopsy Gleason grade was available 16.8%, 16.2%, 24% and 43.1% had Gleason sum 5 or less, 6, 7 and 8 or higher, respectively. CONCLUSIONS: While most men who ultimately die of prostate cancer have poor prognostic features, a substantial number have features associated with a potentially good prognosis, including low PSA and low Gleason grade. Many men who died of prostate cancer had undergone prior screening. These data demonstrate the need for improved markers of prognosis and continued assessment of the efficacy of screening with PSA.     

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.     

Prostate cancer risk assessment program: a 10-year update of cancer detection

PURPOSE: Guidelines for screening men at high risk for prostate cancer remain under investigation. We report our 10-year cancer detection data from the Prostate Cancer Risk Assessment Program, a longitudinal screening program for men at high risk. MATERIALS AND METHODS: Men between ages 35 and 69 years with a family history of prostate cancer, any black man regardless of family history or any patient with a known mutation in the BRCA 1 gene are eligible for the Prostate Cancer Risk Assessment Program and undergo longitudinal followup. Cancer detection, prostate cancer features and the predictive value of screening parameters were determined based on Prostate Cancer Risk Assessment Program biopsy criteria. RESULTS: A total of 609 men were accrued to the Prostate Cancer Risk Assessment Program as of the end of June 2006, of whom 61.2% were black. Of all participants 19% underwent prostate biopsies. The prostate cancer incidence was 9.0%, more than 90% of prostate cancers were Gleason score 6 or higher and 22% were Gleason score 7 or higher. The majority were organ confined. Of men diagnosed with prostate cancer 20% had a prostate specific antigen of less than 2.5 ng/ml and a free prostate specific antigen of less than 25% with a normal digital rectal examination. CONCLUSIONS: Our results support aggressive screening measures for men at high risk for prostate cancer. The majority of cancers detected were at a prostate specific antigen of less than 4.0 ng/ml with a fifth diagnosed at a prostate specific antigen of below 2.5 ng/ml. These cancers were intermediate to high grade and organ confined, indicating a greater likelihood of cure following local therapy in these men.     

Percent free prostate specific antigen and cancer detection in black and white men with total prostate specific antigen 2.5 to 9.9 ng./ml

PURPOSE: The ratio of free-to-total prostate specific antigen (PSA), or percent free PSA, is a useful adjunct to total PSA for estimating the risk of prostate cancer when total PSA is 2.5 to 9.9 ng./ml. Relationships between cancer detection and total PSA are influenced by race but to our knowledge relationships between cancer detection and percent free PSA have not been studied. MATERIALS AND METHODS: A total of 222 black and 298 white consecutive and evaluable men with total PSA 2.5 to 9.9 ng./ml. underwent prostate biopsy for suspected cancer at a Veterans Affairs Medical Center. Clinical measurements included digital rectal examination, total and free serum PSA, prostate volume, PSA density and Gleason score of malignant biopsy specimens. RESULTS: Median percent free PSA was 14.1 (range 3.6 to 49.2) in 201 men with prostate cancer and 21.9 (range 5.7 to 83.3) in 319 without detectable cancer (p <0.0001). Significant racial differences in demographic characteristics and clinical measurements were limited to total PSA, which was higher in black men (p = 0.03). Cancer was detected in 156 black (47%) and 206 white (33%) men (p = 0.001). Areas under receiver operating characteristics curves for percent free PSA and total PSA were 0.66 and 0.58, respectively, for black men (p = 0.15), and 0.76 and 0.58, respectively, for white men (p <0.00001). Percent free PSA was 35.2 in black men and 29.2 in white men, and specificity was 9.1% and 28.7%, respectively, when sensitivity for percent free PSA was set at 95%. Of 156 black and 206 white men with percent free PSA less than 25, 83 (53%) and 85 (41%), respectively, had detectable cancer (p = 0.03). Of 66 black and 92 white men with percent free PSA 25 or greater 21 (32%) and 12 (13%), respectively, had detectable cancer (p = 0.005). CONCLUSIONS: Our study demonstrates racial differences in relationships between percent free PSA and cancer detection in men with suspected prostatic carcinoma and total PSA 2.5 to 9.9 ng./ml. Clinical application of the commonly used percent free PSA cutoff of less than 25 to determine the advisability of prostate biopsy may lead to under diagnosis of early stage prostate cancer in black men, who are at greater risk of morbidity and mortality from disease than white men.     

Clinical features and treatment outcome of Hispanic men with prostate cancer following external beam radiotherapy

PURPOSE: We retrospectively analyzed the clinical characteristics and outcomes of Hispanic men compared with other groups who underwent radiotherapy alone for localized or locally advanced prostate cancer. MATERIALS AND METHODS: Between April 1987 and January 1998, 964 men who underwent full dose external beam radiotherapy alone for localized or locally advanced prostate cancer were included in the study. Patient medical records were reviewed for pertinent information. RESULTS: Of the 964 men 810 were non-Hispanic white, 54 were Hispanic and 86 were black Americans. The most significant difference among the groups was in the proportion of patients who presented with initial prostate specific antigen (PSA) greater than 20 ng/ml (22% of Hispanic vs 11% of white men, p = 0.0012). In addition, 17% of Hispanic men had a Gleason score of 8 or greater compared with 11% of white men (p = 0.0265). A greater proportion of Hispanic patients also had a less favorable posttreatment PSA nadir of greater than 1 ng/ml compared with white patients, (44% vs 26%, p = 0.0214), which may have translated into a trend toward a lower 5-year disease-free survival rate in Hispanics vs white men (52% vs 65%, p = 0.07). CONCLUSIONS: Hispanic men presented with higher PSA and higher grade prostate cancer than white men. Furthermore, a higher percent of Hispanic men had a PSA nadir of 1 ng/ml or greater after radiotherapy, which may have been responsible for their trend toward a decreased 5-year disease-free survival rate compared with white men. Improved screening and early detection may improve disease-free survival in Hispanic men with localized prostate cancer.     

Results of compliance with prostate cancer screening guidelines

PURPOSE: Current guidelines of the American Cancer Society and the National Comprehensive Cancer Network recommend offering annual prostate cancer screening with prostate specific antigen (PSA) and digital rectal examination (DRE) beginning at age 50 (age 45 in high risk men). There are limited data concerning outcomes if all men followed screening guidelines. We report early outcome data on men who entered a prostate cancer screening study, complied with the screening guidelines and were subsequently diagnosed with prostate cancer. MATERIALS AND METHODS: We reviewed records of men 45 to 59 years old at study entry with a PSA less than 2.6 ng/ml and benign DRE who underwent annual DRE and PSA testing in a screening study between 1991 and 2001. Of 10,174 men with these characteristics, 232 (2.3%) were subsequently diagnosed with prostate cancer. We evaluated PSA, Gleason score, clinical and pathological tumor stage, and treatment outcomes in these men. RESULTS: Median PSA at diagnosis was 3.1 ng/ml (range 0.4 to 9.6). Gleason scores ranged from 4 to 9. All patients had clinically localized disease. Management included predominantly radical prostatectomy (87%) and radiation therapy (10%). Of cancers in which tumor volume was assessed 13% were considered possibly harmless tumors by previously published criteria and 2% were considered possibly rapidly progressive tumors by criteria we set in this study. CONCLUSIONS: Prostate cancer screening using some current guidelines results in the detection of cancers that are organ confined in 79% of patients, possibly harmless in less than 15% and possibly rapidly progressive in 2%.     

Delays in cancer detection using 2 and 4-year screening intervals for prostate cancer screening with initial prostate specific antigen less than 2 ng/ml

Purpose:The American Urological Association and American Cancer Society advocate annual screening with serum prostate specific antigen (PSA) and digital rectal examination starting at age 50 years in the general population and earlier in men at high risk. Some groups have suggested that screening at 2 or 4-year intervals may be sufficient in men with initial PSA 2 ng/ml or less. We reviewed the records of men enrolled in a PSA and digital rectal examination based prostate cancer screening study to determine the extent to which the diagnosis of cancer would have been delayed using a 2 or 4-year screening interval.Materials and Methods:We evaluated 18,140 volunteers in a prostate cancer screening study in whom PSA was less than 2 ng/ml at initial screening and who were screened at 6-month to 1-year intervals for up to 8 years. We evaluated the cancers detected in these intervals to determine the possible delay in cancer diagnosis that would occur using prolonged screening intervals. We report the overall cancer detection rate, clinical and pathological tumor stage, and Gleason grade of the cancers detected.Results:Excluding 70 men in whom prostate cancer was detected at initial evaluation 2.0% had prostate cancer detected during the next 8 years (mean 21.6 cancers per 6 months, median 20, range 12 to 33). Using a hypothetical 2-year screening interval cancer detection 62% would have been delayed by 4 to 20 months. Using a hypothetical 4-year screening interval cancer detection would have been delayed in 77% of men by 4 to 44 months. Of the tumors detected 100% were clinically localized, 77% were pathologically organ confined and 29% had a Gleason score of 7 or greater.Conclusions:The 2 or 4-year PSA screening interval in men with initial serum PSA less than 2 ng/ml would result in substantial delays in prostate cancer detection. To our knowledge the extent to which these delays would affect treatment outcomes is undetermined.     

A novel serum marker, total prostate secretory protein of 94 amino acids, improves prostate cancer detection and helps identify high grade cancers at diagnosis

PURPOSE: New biomarkers for prostate cancer are needed. We determined whether a novel serum marker, total PSP94 can be used to accomplish these goals. MATERIALS AND METHODS: We conducted a case-control study of 1,212 men with no previous history of prostate cancer and who underwent a prostate biopsy from 1998 to 2000 because of an increased PSA or an abnormal DRE. Serum PSP94 levels were assessed using a sandwich enzyme-linked immunosorbent assay technique. Cases were patients with prostate cancer, and controls were patients who had no evidence of cancer. Multivariate logistic regression analysis was used to determine whether or not PSP94 levels improved the predictive value for prostate cancer. RESULTS: Of the 1,212 men 596 (49.2%) had cancer detected. The median PSP94 level was significantly lower among cases (2.60 ng/ml) than among controls (3.40 ng/ml, p <0.0001). The adjusted odds ratios for the presence of prostate cancer for patients with the lowest quartile of PSP94, compared to patients in the highest quartile was 2.70 (95% CI 1.8 - 4.0, p <0.0001). Among a subgroup of 649 men in whom PSA had a low predictive value (PSA less than 20 ng/ml, normal DRE and less than 70 years), 260 (40.1%) were found to have cancer. In this subgroup total PSP94 levels helped discriminate between patients with high grade disease (Gleason score 8 or more, median 1.90 ng/ml), moderate grade disease (Gleason score 7, median 2.34 ng/ml) and low grade disease (Gleason score 6 or less, median 2.60 ng/ml, p = 0.007). PSA and the FTPSA were not able to distinguish between patients with different grades in this group. CONCLUSIONS: Patients with low total PSP94 levels had a high probability for having prostate cancer detected at biopsy. The total PSP94 level was able to help identify patients with high grade disease among a subset of patients in whom PSA and FTPSA are least informative.     

前列腺特异性抗原密度的测定在诊断前列腺癌中的价值

对１０例非转移性前列腺癌和２０例前列腺增生的前列腺特异性抗原密度（ＰＳＡＤ）进行研究。前列腺癌平均ＰＳＡＤ值为０．７１１，而前列腺增生为０．０７５；两者有极显著性差异（Ｐ＜０．００１）。９例ＰＳＡＤ＞０．２者，８例为前列腺癌。１６例ＰＳＡＤ＜０．１者，无１例前列腺癌。８例前列腺癌患者中有３例前列腺特异性抗原（ＰＳＡ）＜１０ｎｇ／ｍｌ，１例＜２．８ｎｇ／ｍｌ。１６例前列腺增生患者中７例ＰＳＡ＞２．８ｎｇ／ｍｌ，３例＞１０ｎｇ／ｍｌ。表明血清ＰＳＡ轻中度增高或正常时，ＰＳＡＤ可作为前列腺癌早期筛选诊断的有效指标之一。     

The significance of early detection for prostate cancer in mass screening

PURPOSE: In Mitaka city, mass screening for prostate cancer was conducted for 3 years from 1995 to 1997. Clinical stages were compared between patients found by screening and those diagnosed at our clinic during the same time. The significance of serum-free prostate specific antigen (PSA) in mass screening for prostate cancer was examined. MATERIAL AND METHODS: A prospective clinical trial was conducted on men aged 50 years or older. The primary examination consisted of taking the international prostate symptom score, quality of life score, PSA (Tandem-R) and digital rectal examination (DRE). If PSA was greater than 4.0 ng./ml and/or if DRE suggested cancer, transrectal ultrasound-guided sextant prostate biopsies were indicated. RESULTS: Of the men screened, 23.2% (320/1375) had serum PSA greater than 4.0 ng./ml. and/or suspicious findings on DRE. Biopsy was performed in 199 of 320 (62.1%). Cancer was detected in 21 (1.5%, 21/1375). Prostate cancer was found in one case among 154 males (0.65%, 1/154) who were screened twice or more. The cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic (Wilcoxon's rank-sum test: p = 0.0047). Receiver operating characteristics analysis showed that the optimal free PSA-to-PSA ratio was 12%. Positive predictive value increased from 18% to 50% when free PSA-to-PSA ratio was combined with PSA. CONCLUSION: 1. Cancer detection rate was 1.5% in the mass screening in Mitaka City. 2. Cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic. 3. Free PSA determination might eliminate unnecessary biopsies in men with PSA above 4.0 ng./ml with minimal loss of cancer detection.     

Longitudinal PSA changes in men with and without prostate cancer: assessment of prostate cancer risk

BACKGROUND: To determine longitudinal PSA changes over a period of 10 years in patients with and without prostate cancer. METHODS: Serial PSA measurements performed over 10 years were evaluated in 353 men who eventually developed prostate cancer and in 2.462 participants of a screening program without prostatic malignancy. RESULTS: In men with cancer, mean tPSA increased from 2.28 ng/ml at 10 years before diagnosis to 6.37 ng/ml at the time of postive biopsy (PSA velocity: 0.409 ng/ml/year). PSA velocity was significantly associated with Gleason scores and pathologic stage. In the benign group (n=2.462), mean tPSA increased from 1.18 to 1.49 ng/ml over a period of 10 years (PSA velocity of 0.03 ng/ml/year). Of the subjects with tPSA levels of 2 ng/ml or less, 2 years prior to cancer diagnosis, 11.4% had tPSA values of more than 4 ng/ml at the time of biopsy. Of the 972 men with tPSA below 1 ng/ml 2 years before the most recent measurement was obtained, 966 (99.4%) had no evidence of prostate cancer 2 years later, while six were found to have malignancies (0.6%). CONCLUSIONS: Longitudinal PSA changes in men with and without prostate cancer are significantly different. Annual testing may not be required in men with baseline tPSA levels of 1 ng/ml or below, whereas in patients with levels higher than 1 ng/ml, it seems to be indicated because of the significant percentage of men presenting with tPSA levels of more than 4 ng/ml two years later.     

Prostate specific antigen density correlates with features of prostate cancer aggressiveness

PURPOSE: An increased prostate specific antigen density (serum prostate specific antigen divided by prostate volume) is an established parameter to help determine the need to perform prostate biopsies. A man with a high prostate specific antigen and a normal size prostate gland is more likely to have cancer than a man with the same prostate specific antigen and a large gland. Prostate specific antigen in relation to prostate size should also reflect the volume of cancer in the gland. One group defined clinically unimportant prostate cancer as tumor volume less than 0.5 cc, organ confined disease and Gleason less than 7. Another group noted that at the time of biopsy, a prostate specific antigen density less than 0.15 ng/ml/cc combined with low risk clinical tumor features predicted insignificant cancer. There are limited published validating data on the association of prostate specific antigen density with the criteria for prostate cancer aggressiveness. We tested the association of prostate specific antigen density with features of tumor aggressiveness in a screened and in a nonscreened cohort of patients with clinically localized prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: The screened patient cohort included 1,280 patients with screen detected prostate cancer treated from 1990 to 2002 at Washington University, and the nonscreened cohort included 382 patients treated from 2003 to 2004 at Northwestern University. We recorded the clinical and pathological tumor parameters in a prospective database. Parameters evaluated were pathological tumor stage, Gleason sum, tumor volume, biochemical progression and the previously mentioned 2 criteria for clinically unimportant cancers. We grouped patients into 4 prostate specific antigen density categories of less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc. RESULTS: There was a significant trend for worsening clinicopathological prognostic features as prostate specific antigen density increased. There were 357 (82%), 283 (75%), 171 (75%) and 192 (55%) men with organ confined disease with clear surgical margins if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively (p <0.001). There were 86 (20%), 102 (27%), 64 (28%) and 157 (45%) men with a Gleason sum greater than 7 when grouped into each increasing PSA density category, respectively (p <0.001). There were 91 (21%), 91 (25%), 74 (33%) and 157 (46%) men with a total cancer volume greater than 0.5 cc when grouped into each increasing PSA density category, respectively (p <0.001). Prostate specific antigen velocity was greater than 2 ng/ml per year in 11%, 30%, 27% and 46% of men if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively (p <0.001). CONCLUSIONS: Prostate specific antigen density measurements are useful in helping to determine the aggressiveness of clinically localized prostate cancer, and can be used as an adjunct in predicting insignificant cancer and outcomes after local therapy.     

Screening for prostate cancer using prostate-specific antigen testing in Japanese men on hemodialysis

Objectives The objectives of this study were to evaluate the usefulness of serum prostate-specific antigen (PSA) screening in detecting prostate cancer in Japanese men on hemodialysis, and to analyze features of prostate cancer detected in these patients. Materials and methods This study included 115 male hemodialysis patients aged >55 years who agreed to the measurement of serum PSA value (group A) and 7529 men aged >55 years participating in a PSA mass screening test in Kobe City (group B) between April 2005 and March 2006. Prostate biopsy was recommended in men with serum PSA > 4.0 ng/ml in both groups. Seventy-eight patients with normal renal function aged >55 years diagnosed as having prostate cancer during the same time period as groups A and B were also included as a comparison group (group C). Results There was no significant difference in the distribution of serum PSA values between groups A and B. Prostate biopsy was performed in 8 and 205 men in groups A and B, respectively, and prostate cancer was detected in 5 and 68 in groups A and B, respectively; that is, there was no significant difference in the rate of positive prostate biopsy between these two groups (group A, 62.5%; group B, 33.2%), while the cancer detection rate in group A (4.3%) was significantly greater than that in group B (0.90%). In addition, there was no evident metastasis in five patients on hemodialysis who were diagnosed as having prostate cancer, and their serum PSA, clinical T stage and biopsy Gleason score were similar to those in group C. However, the percent of positive biopsy cores in these five was significantly greater than that in group C. All five were treated by maximal androgen blockade therapy, and all are currently alive without emergence of hormone-refractory diseases. Conclusions These findings indicate that hemodialysis patients may have an increased risk of prostate cancer, and that prostate cancer detected in such patients tends to be relatively advanced. Therefore, it would be recommended for hemodialysis patients to undergo PSA testing to screen for prostate cancer.     

High-grade prostate cancer is associated with low serum testosterone levels

BACKGROUND: The aim of this study was to assess whether low serum testosterone levels in men with newly diagnosed prostate cancer have an association to the endocrine status, prostate-specific antigen (PSA) levels, Gleason score, and androgen receptor expression. METHODS: Besides a full clinical work-up, the following hormones were quantified in men with newly diagnosed prostate cancer by serum analysis: total testosterone, human luteinising hormone (hLH), human follicle stimulating hormone (hFSH), estradiol, and dehydroepiandrostendione (DHEA). In a subgroup of men, androgen receptor expression was determined immunohistochemically. RESULTS: One hundred and fifty six patients (65.7 +/- 8.5 yrs) with a mean PSA of 29.8 ng/ml (median: 7.4 ng/ml) were analysed. Fifty-two patients (33%) had a partial androgen deficiency (serum testosterone < 3.0 ng/ml). These men had lower hLH (3.3 vs. 5.9 mIU/ml), hFSH (6.2 vs. 8.4 mIU/ml), and estradiol (18.8 vs. 29.1 pg/ml) serum levels. Mean Gleason score was higher (7.4 vs. 6.2) in men with a low serum testosterone, PSA-levels were lower (25.3 vs. 31.9 ng/ml). Mean testosterone levels decreased from 4.1 +/- 1.7 ng/ml in patients with Gleason scores < or = 5 to 2.8 +/- 2.7 ng/ml with Gleason scores > or = 8. Androgen receptor expression was higher in patients with low serum testosterone. CONCLUSIONS: Patients with high Gleason score prostate cancer have lower testosterone and estradiol serum levels. The fact that gonadotropins were lower in parallel suggests a tumor-mediated suppression of the hypothalamic-pituitary-gonadal hormone axis particularly in men with high Gleason score tumours.     

Predictors of subsequent prostate cancer in men with a prostate specific antigen of 2.6 to 4.0 ng/ml and an initially negative biopsy

PURPOSE: Almost 75% of men with a prostate specific antigen (PSA) of 2.6 to 4.0 ng/ml have no evidence of prostate cancer on biopsy. Deciding whether and when to repeat the biopsy is challenging. We determined if patient specific variables might identify men at increased risk for the subsequent detection of prostate cancer. MATERIALS AND METHODS: We analyzed the records of 24,893 men from a community based prostate cancer screening study. Our study group consisted of 1,202 men with PSA 2.6 to 4.0 ng/ml and a previously negative prostate biopsy. Patient specific variables were analyzed for their value in predicting a future diagnosis of prostate cancer. RESULTS: Of 1,011 men with adequate followup 136 (13.5%) were subsequently diagnosed with prostate cancer. Mean followup +/- SD in men without prostate cancer was 72 +/- 36 months. Prostate cancer was subsequently diagnosed in 35% of men with high grade prostatic intraepithelial neoplasia (HGPIN) on initial biopsy (p <0.0001), in 18% with abnormal or suspicious digital rectal examination (DRE) (p = 0.02) and 16% with an annual PSA velocity of 0 ng/ml (p = 0.002). Multivariate analysis identified HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, family history of prostate cancer and annual PSA velocity 0 ng/ml as predictors of prostate cancer. CONCLUSIONS: Men with a PSA of 2.6 to 4.0 ng/ml and negative biopsy should be advised to undergo repeat biopsy if they have HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, a family history of prostate cancer or a PSA velocity of 0 ng/ml or greater.     

Screening for prostate cancer--how to manage in 2006?

National Societies usually recommend screening for Prostate Cancer (PC) with Serum Prostate Specific Antigen (PSA) and digital rectal examination annually beginning at age 50. In high risk population including men with a family history of PC or African population screening should start at age of 45 years. PSA has been widely used to detect PC despite the fact that PSA is not specific for PC. Over the years serum PSA level of greater than 4.0 ng/ml was considered the treshold to perform prostate biopsy, searching for PC. In 2005 the Prostate Cancer Prevention Trial (PCPT) demonstrated that the cut-off of 4.0 ng/ml for PSA is not anymore adapted due to the fact that this survey found in 15% of men with PSA < or = 4.0 ng/ml a prostate cancer on sextant biopsies. Today the value of PSA and the cut-off for Prostate biopsy is questionned suggesting that PSA level higher than 2.6 ng/ml must be the case to propose Prostate Biopsy. Catalona confirms that approximately 25% to 30% of men with PSA 2.6 to 4.0 ng/ml have prostate cancer. Schr?der and Gosselaar assert that screening for PC at low PSA levels (< 4.0 ng/ml) risks to detect clinically insignificant cancers which are no threat to man. So far in the year 2006 screening for PC demonstrates accumulating evidences of efficacy but persistent uncertainty. The major question for an urologist at work when facing a young men searching early diagnosis of PC is: at which level of PSA do we have to perform rectal biopsy?     

The incidence of prostate cancer in a screening population with a serum prostate specific antigen between 2.5 and 4.0 ng/ml: relation to biopsy strategy

PURPOSE: It has recently been suggested that the diagnostic threshold for the prostate specific antigen (PSA) assay be lowered to enhance prostate cancer detection. A 22% incidence of prostate cancer has been reported in men with PSA between 2.5 and 4.0 ng/ml. We designed a study to confirm this observation. MATERIALS AND METHODS: Men who participated in our free early detection program and who had serum PSA between 2.5 and 4.0 ng/ml were asked to undergo prostate biopsy. Of 268 eligible men 151 (56%) agreed to participate in this free trial. All men underwent biopsy using an 11-core multisite directed biopsy scheme. All biopsy cores were color coded for location specificity and examined by 1 pathologist. RESULTS: Cancer was identified in 24.5% (37 of 151) of the men biopsied. The median age of men with cancer was 62 years (range 43 to 74). Conventional systematic sextant biopsies, which accounted for 6 of the 11 cores, detected 73.0% (27 of 37) of the cancers and the alternate site biopsies identified the remaining 10. Gleason score was 6 in 25 men, 3 + 4 in 5, 4 + 3 in 4 and 8 or greater in 3 (median Gleason score 6). There were 14 men who had 1 core positive for cancer, 9 had 2 and 14 had more than 2 (median number of positive cores 2). Of the 14 men with 1 positive core 11 had a less than 3 mm focus of cancer and 8 had only a positive alternate site biopsy. There were 11 cases of abnormal results on digital rectal examination, 5 of which were cancer, and 31 cases of abnormal results on ultrasonography, 13 of which were cancer. Median biological variability in PSA was +/-15% (range 0.4% to 440.0%). CONCLUSIONS: We found a significant incidence of cancer (24.5%, 37 of 51) in men with serum PSA between 2.5 and 4.0 ng/ml. In our study 67.6% of the detected cancers were significant based on the biopsy data. If the PSA threshold is lowered the conventional systematic sextant technique may be preferable to an extended strategy.     

Prostate cancer detection among men with prostate specific antigen levels of 2.5 to 4.0 ng/ml in a Japanese urological referral population

PURPOSE: Prostate cancer detection at levels of 2.5 to 4.0 ng/ml in a Japanese urological referral population has not been elucidated. The purpose of this study is to investigate the cancer detection rate and clinical relevance of prostate cancer in this PSA range. MATERIALS AND METHODS: All urological patients 70 years or younger tested for prostate cancer were studied. There were 550, 97, 112 and 52 patients with a PSA of less than 2.5, 2.5 to 4.0, 4.1 to 10.0 and more than 10.0 ng/ml, respectively. Transrectal 10-core prostate biopsy was performed in 80 (82%) of the 97 patients with a PSA of 2.5 to 4.0 ng/ml and 102 (91%) of the 112 patients with a PSA of 4.1 to 10.0 ng/ml. RESULTS: Cancer detection rates in patients who underwent biopsy were 26.3% and 34.3% at PSA levels 2.5 to 4.0 and 4.1 to 10.0 ng/ml, respectively. High grade cancers with Gleason score 7 or more were found in 19.0% and 22.9% of patients with cancer with PSA 2.5 to 4.0 and 4.1 to 10.0 ng/ml, respectively. No significant difference was found between the 2 groups in pathological findings on biopsy, including percent positive cores (16.7% vs 20.0%, p = 0.10), maximum cancer length (25.0% vs 30.0%, p = 0.28) and maximum percent cancer length (2.0 vs 3.0 mm, p = 0.17). CONCLUSIONS: Japanese urological referral patients develop prostate cancer quite commonly even if their serum PSA levels are 2.5 to 4.0 ng/ml. Since these cancer cases include high grade, clinically significant cancer, prostate biopsy might be considered at least for selected cases in this PSA range.