Prevalence of prostate specific antigen testing for prostate cancer in elderly men

PURPOSE: We investigated the prevalence and outcome of PSA testing for prostate cancer screening or diagnosis in elderly men 75 years or older at our academic medical center. MATERIALS AND METHODS: A cross-sectional study design was used to identify all men 75 years or older who underwent a PSA test through the family medicine or internal medicine service at our institution between January 1, 1998 and June 30, 2004. All patients with a suspected (PSA less than 0.1 ng/ml) or confirmed prior diagnosis of prostate cancer were excluded. The prevalence of PSA testing was then compared to that in younger age groups (45 to 54, 55 to 64 and 65 to 74 years). We then examined the frequency and nature of further evaluation and treatment performed in men following the PSA test. RESULTS: The 8,787 male patients who were 75 years or older generated a total of 82,672 visits in the 5.5-year period. Of these patients 505 (5.7%) underwent at least 1 PSA test. The prevalence of PSA testing in the younger age groups was 10.3% (1,769 of 17,175) in patients 45 to 54 years old, 14.9% (2,052 of 13,772) in those 55 to 64 years old and 11.8% (1,258 of 10,661) in those 65 to 74 years old (chi-square test p <0.001). Of these patients 98 of 343 (28.6%) with PSA between 0.1 and 4 ng/ml were referred to a urologist at our institution and 3 underwent biopsy. None had a prostate cancer diagnosis. Of the 162 patients with PSA more than 4 ng/ml 84 (51.9%) were referred to a urologist. Only 10 of the 84 patients (11.9%) who were referred to a urologist underwent prostate biopsy. Six of the 10 men (60%) were diagnosed with prostate cancer, including 1 with a Gleason 6 tumor, 1 with a Gleason 7 tumor and 4 who were found to have tumors with a Gleason score of 8 or greater. All patients received androgen deprivation therapy, except 1 who received local external beam radiation therapy. An additional patient was diagnosed by biopsy of a vertebral lesion and he received hormone therapy. At a median followup of 51 months (range 28 to 72) 4 of 7 men (57%) were alive with disease. CONCLUSIONS: PSA testing for prostate cancer screening and diagnosis appear to decrease with advancing age. A small but significant proportion of men who are 75 years or older continue to undergo PSA testing. Abnormal PSA results do not always result in further evaluation and therapy for prostate cancer in elderly men. The establishment of firm guideline recommendations regarding PSA testing and further evaluation for prostate cancer in elderly men, perhaps based on individualized geriatric assessment, may be helpful.     

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.     

Relationship between initial prostate specific antigen level and subsequent prostate cancer detection in a longitudinal screening study

PURPOSE: Previous studies of archived blood samples from nonscreened populations have shown an association between the prostate specific antigen (PSA) and the subsequent detection of prostate cancer. In the current study we evaluated the relationship between the initial screening PSA and the subsequent risk of prostate cancer detected in a prospective, longitudinal screening study. We also examined the relationship between initial PSA and the clinicopathological features of the cancers detected. MATERIALS AND METHODS: Between May 1991 and November 2001 we enrolled 26,111 volunteers in our PSA and digital rectal examination based prostate cancer screening study. The men were followed biannually or annually depending on the results of previous screening tests. The chi-square and Kruskal-Wallis tests were used to compare the clinical stage, pathological stage and Gleason score of subsequently detected prostate cancers as well as the time to cancer detection in different initial screening PSA strata. RESULTS: The initial screening PSA stratum was strongly associated with the subsequent detection of prostate cancer as well as the clinicopathological stage and grade of the cancers detected. CONCLUSIONS: Even in the lower PSA ranges initial screening serum PSA can help identify men at increased risk for subsequent prostate cancer detected in a longitudinal screening study.     

Prostate cancer screening with prostate specific antigen in spinal cord injured men

PURPOSE: As the spinal cord injured population ages, prostate cancer becomes a more significant cause of potential mortality. Consequently due to various bladder management techniques the validity of standard prostate specific antigen (PSA) screening values in this population must be evaluated. We compared screening PSA values in a large population of spinal cord injured patients with those in age matched, nonspinal cord injured men. MATERIALS AND METHODS: Screening PSA values were obtained using the AxSYM assay (Abbott Laboratories, Abbott Park, Illinois) in 366 spinal cord injured men 40 to 79 years old. In those with PSA elevated to greater than 4 ng./ml. who consented to further evaluation standard sextant needle biopsy of the prostate were performed under transrectal ultrasound guidance. Data were compared with data on 371 randomly selected, age matched controls from the Baylor College of Medicine community screening program database of more than 19,000 patient-tests. Analysis was performed with the unpaired Student t test. RESULTS: When we divided patients 40 to 80 years old into 4 age groups by decade and compared them with normal controls by decade, there was no statistically significant difference in mean PSA in the 2 groups. Of 18 spinal cord injured patients with PSA greater than 4 ng./ml. 12 underwent transrectal ultrasound guided needle biopsy of the prostate and 6 refused further evaluation. Five of these biopsies (1.3% overall) were positive and 7 were negative for adenocarcinoma. CONCLUSIONS: As in healthy men, PSA and digital rectal examination can be performed in spinal cord injured men to screen for prostate cancer. None of the various bladder management techniques in these cases seemed to affect screening results.     

Relationship among initial serum prostate specific antigen, prostate specific antigen progression and prostate cancer detection at repeat screening visits

PURPOSE: We evaluated the probability of positive serum PSA (3 ng/ml or greater) and CaP detection at annual followup visits in men with negative initial PSA (less than 3 ng/ml) to optimize the re-screening schedule. MATERIALS AND METHODS: Data on 5,387 men 45 to 80 years old with negative PSA and no CaP diagnosis at the first screening visit were obtained from the Laval University Prostate Cancer Screening Program database. Accelerated failure time regressions were fitted to time from baseline to positive PSA and to time from positive PSA to CaP detection. The models were combined to estimate the cumulative probability of positive PSA followed by CaP detection at re-screening. RESULTS: The 5-year cumulative probability of detecting CaP at annual visits in men with baseline PSA up to 1.5 ng/ml remained below 0.8%, while it was 1.3%, 4.8% and 8.3% in men with PSA 1.5 to less than 2, 2 to less than 2.5 and 2.5 to less than 3 ng/ml, respectively. Time to positive PSA significantly decreased with increasing baseline PSA and age, while the time between positive PSA and CaP detection depended only on age. Men with PSA below 1.0 ng/ml could wait for 4 to 5 years before being re-tested, while men with PSA between 1.0 and 1.5 ng/ml should be screened every second year and men with PSA 1.5 ng/ml or greater should be screened every year. CONCLUSIONS: The proposed retesting schedule using current PSA and age decreases the number of visits by 38.1%, while delaying the detection of only 2.4% of CaPs that would have been detected using annual PSA testing.     

Prostate specific antigen testing and digital rectal examination before and during a randomized trial of screening for prostate cancer: European randomized study of screening for prostate cancer, Rotterdam

PURPOSE: Worldwide 2 large-scale randomized screening trials for prostate cancer have been initiated. Determining prostate specific antigen (PSA) involves a simple test that may influence the outcome of these trials if frequently done in the control arm or before study enrollment. We quantified PSA and digital rectal examination before and during the screening trial in Rotterdam, The Netherlands and in the general population. MATERIALS AND METHODS: Trial participants were administered study intake questionnaires on tests done before study participation. Data on PSA from the regional general practice laboratory were correlated with participant data. Various sources were used to quantify PSA tests and digital rectal examinations in the general population. RESULTS: Of men 55 to 74 years old 45% underwent digital rectal examination at 1 time and 13% reported that PSA was tested before trial participation. Each rate increased with age. No statistically significant effect of former PSA testing or digital rectal examination on the cancer detection rate was identified. The rate of PSA determination after initial screening and/or randomization in the control arm was 2-fold that in the screening arm (76 versus 33/1,000 person-years). PSA determination initially decreased in the screening arm but increased rapidly after some time. The number of PSA determinations in the general population was estimated to be 45/1,000 person-years at ages 55 to 69 years. CONCLUSIONS: PSA testing was moderate in the control arm but if different men undergo this test each year, the contamination rate may become rather high. In the final analysis of mortality PSA testing should be considered.     

Under diagnosis and over diagnosis of prostate cancer

PURPOSE: We quantified the rates of over and under diagnosis of prostate cancer in 2 large patient cohorts during the last 15 years. MATERIALS AND METHODS: A total of 2,126 men with clinical stage T1c prostate cancer were treated with radical prostatectomy during 1 of the 3 periods 1989 to 1995, 1995 to 2001 and 2001 to 2005. The respective proportions of men with a tumor that met our criteria for over diagnosis (0.5 cm3 or less, confined to the prostate with clear surgical margins and no Gleason pattern 4 or 5) and under diagnosis (nonorgan confined, pathological stage T3 or greater, or positive surgical margins) were examined. RESULTS: The proportion of men with an over diagnosed tumor was 1.3% to 7.1%. The proportion with prostate cancer that was under diagnosed was 25% to 30%. An ancillary finding was that decreasing the prostate specific antigen threshold for biopsy from 4.0 to 2.5 ng/ml in the screened population resulted in a lower rate of under diagnosis from 30% to 26%, a higher rate of over diagnosis from 1.3% to 7.1% and an increase in the 5-year progression-free survival rate from 85% to 92%. Men who were 55 years or younger were significantly more likely to meet our criteria for over diagnosed cancer. CONCLUSIONS: Under diagnosis of prostate cancer continues to occur more frequently than over diagnosis. Lowering the prostate specific antigen threshold for recommending biopsy to 2.5 ng/ml resulted in a lower rate of under diagnosis and a higher progression-free survival rate.     

Screening for prostate cancer in high risk populations

PURPOSE: Black men and men with a family history of prostate cancer are at higher risk for this disease and may have an earlier age of onset. Consequently, screening at a younger age has been recommended for high risk men, however, there are limited data on actual screening results in young, high risk populations. MATERIALS AND METHODS: In men 50 years old or older we compared screening results in 1,224 black men, 1,227 men with a positive family history and 63 men who were both with those of 15,964 nonblack men with no known family history. In high risk men in their forties we also evaluated the percent with abnormal screening tests, the positive predictive value of screening tests, cancer detection rates and the prognostic features of tumors detected. RESULTS: In men 50 years old or older prostate cancer detection rates were 6.4% for controls compared with 10.3%, 10.5% and 17.5%, respectively, for the high risk groups. Among high risk men screened in their forties 8% had suspicious screening tests and approximately 55% who underwent a biopsy had cancer detected. Of tumors detected 80% were organ confined and all but 1 were of moderate Gleason grade 5 years old or older. Only 1 tumor (7%) fulfilled the published criteria for a possibly harmless cancer. CONCLUSIONS: Black men and men with a family history of prostate cancer are at a 75% to 80% higher risk for prostate cancer. On initial screening of high risk men in their fourth decade only 8% have positive screening tests; however, approximately 55% of these men have tumors, most of which are medically important with favorable prognostic features.     

Long-term effects of finasteride on prostate specific antigen levels: results from the prostate cancer prevention trial

PURPOSE: Studies have shown that finasteride decreases prostate specific antigen (PSA) by approximately 50% during the first 12 months of use. We estimated the long-term effects of finasteride on PSA in men with and without a prostate cancer diagnosis at the end of the study. MATERIALS AND METHODS: We analyzed serial PSA in participants in the Prostate Cancer Prevention Trial who had an end of study biopsy (928 with cancer and 8,620 with negative biopsy) or an interim diagnosis of prostate cancer (671). Linear mixed effects regression models were fit to longitudinal PSA values beginning 1 year after randomization. RESULTS: In subjects with no cancer in the end of study biopsy PSA in the finasteride arm showed a median annual decrease of 2% [corrected] after year 1, while PSA in the control arm showed an annual increase of 3% (p <0.001). In end of study cases PSA increased annually by 6% (placebo) and 7% (finasteride). In those with interim diagnoses PSA increased by 11% (placebo) and 15% (finasteride) each year prior to diagnosis. Cases with high grade disease (Gleason 7 and above) had greater PSA increases than cases with low grade disease (p <0.001). CONCLUSIONS: In men who have been receiving finasteride for more than 1 year time varying adjustment factors may be needed to determine whether PSA is in the normal range. In the Prostate Cancer Prevention Trial cohort the adjustment factor required to preserve median PSA increased from 2 at 24 months to 2.5 at 7 years after the initiation of finasteride.     

血清PSA〈4．0ng/ml的人群中前列腺癌集团筛查的病理学特征

目的探讨血清PSA<4.0ng/ml的人群中前列腺癌的病理学特征。方法对长春市15192名男性进行血清前列腺特异性抗原(PSA)检测,其中46名血清PSA<4.0ng/ml伴有直肠指诊检查异常者接受了经直肠超声引导下前列腺6点活检穿刺,并应用组织病理学、免疫组织化学及统计学等方法进行系统的病理学研究和分析。结果(1)血清PSA<4.0ng/ml者有13886名,46人进行了前列腺活检穿刺,活检率为0.33%(46/13886)。(2)46名男性血清PSA值在0.03～3.84ng/ml之间,主要分布在0～1.9ng/ml间,占60.9%。(3)46例前列腺活检病理诊断:良性前列腺增生29例,占63.1%;前列腺癌10例,占21.7%;炎症性病变与肉瘤各3例,分别占6.5%;转移癌1例占2.2%。10例血清PSA<4.0ng/ml的前列腺癌中普通型腺癌5例,以中分化(3/5)、器官内癌(4/5)为主,且血清PSA值较靠近4ng/ml;特殊类型前列腺癌5例,占50%,均为进展期癌,血清PSA值相对较低。结论(1)血清PSA<4.0ng/ml的人群中有前列腺癌存在。(2)血清PSA<4.0ng/ml的人群中前列腺癌以中分化器官内腺癌和特殊类型进展期前列腺癌为主。(3)应用直肠指诊检查(DRE)能检出血清PSA<4.0ng/ml的前列腺癌,且检出率与血清PSA值成正相关,两者联合应用可以提高前列腺癌的检出率。     

Relationship between body mass index and prostate cancer screening in the United States

PURPOSE: Obesity is associated with more advanced disease and worse outcomes in men with prostate cancer. To our knowledge the relationship between obesity and prostate cancer screening behavior in men 40 or older is unknown. Thus, we examined associations between body mass index and prostate cancer screening behavior. MATERIALS AND METHODS: We used the 2002 Behavioral Risk Factor Surveillance System to study prostate cancer screening in a representative sample of 57,827 men 40 years or older. Primary outcomes were the proportion of men ever screened and the proportion screened in the last year for prostate cancer. RESULTS: Obese men were more likely than normal weight men to have had a prostate specific antigen test (62.1% vs 56.1%, p <0.001) and to have had a prostate specific antigen test in the last year (44.2% vs 38.2%, p <0.001). After controlling for sociodemographic characteristics obese men remained more likely than normal weight men to have had a prostate specific antigen test (OR 1.46, 95% CI 1.33-1.61) and to have had a prostate specific antigen test in the last year (OR 1.42, 95% CI 1.30-1.55). Respondents reporting an ongoing relationship with a physician (OR 2.88, 95% CI 2.57-3.22) and black nonHispanic men vs white men (OR 1.58, 95% CI 1.38-1.81) were also more likely to have had a prostate specific antigen test in the last year. CONCLUSIONS: Obese men are more likely than normal weight men to be screened for prostate cancer. Associations between advanced stage, worse outcomes and obesity may not be explained by disparities in the screening of obese men for prostate cancer.     

Pretreatment predictors of time to cancer specific death after prostate specific antigen failure

PURPOSE: Whether pretreatment factors that predict for time to prostate specific antigen (PSA) failure also predict for time to prostate cancer specific death after PSA failure for patients with competing causes of mortality treated during the PSA era was the subject of this study. MATERIALS AND METHODS: Of 415 men with a median age of 73 years who underwent external beam radiation therapy between 1988 and 2001 for clinically localized prostate cancer 160 (39%) experienced PSA failure and 96 (23%) died. In 46 men (48%) the cause of death was prostate cancer. Cox regression multivariable analyses (multivariable analysis) were performed to evaluate the ability of the pretreatment PSA and centrally reviewed biopsy Gleason score to predict time to prostate cancer specific death after PSA failure. RESULTS: When analyzed as categorical variables using multivariable analysis, biopsy Gleason score 4 + 3 (p = 0.02), 8 to 10 (p = 0.02) disease and a pretreatment PSA greater than 20 ng./ml. (p = 0.03) were significant predictors of time to prostate cancer specific death after PSA failure. Estimates of prostate cancer specific death 5 years after PSA failure were 24%, 40% and 59% (p = 0.01) for patients with a biopsy Gleason score < or = 6, 3 + 4, 4 + 3 or higher and 22%, 40% and 60% (p = 0.04) for patients with a pretreatment PSA of 10 or less, greater than 10 and 20 or less, or greater than 20 ng./ml., respectively. CONCLUSIONS: Patients at high risk for PSA failure after radiation therapy based on pretreatment PSA greater than 20 ng./ml. or biopsy Gleason score 4 + 3 or greater are also at high risk for death from prostate cancer after PSA failure despite competing causes of mortality.     

Use of 2.6 ng/ml prostate specific antigen prompt for biopsy in men older than 60 years

PURPOSE: Since the United States Food and Drug Administration approved the prostate specific antigen (PSA) blood test as an aid to early prostate cancer detection, using a cutoff of 4.0 ng/ml in 1994, this cutoff has been widely adopted to recommend prostate biopsy. There has been recent investigation into lowering the PSA prompt for biopsy, especially in men younger than 60 years. We determined how a lower cutoff would perform in men older than 60 years. MATERIALS AND METHODS: From a prostate cancer screening study we studied 782 consecutive men who underwent prostate biopsy for PSA greater than 2.5 ng/ml or suspicious digital rectal examination. Biopsy results were evaluated as a function of patient age. RESULTS: Clinical and pathological characteristics of cancers detected in the PSA range 2.6 to 4.0 ng/ml were similar regardless of patient age. Overall PSA between 2.6 and 4.0 ng/ml was associated with a cancer detection rate of 16.2% using a sextant biopsy technique. PSA velocity was similar in men with prostate cancer in all age groups. CONCLUSIONS: More than 15% of men with PSA 2.6 to 4.0 ng/ml who are 40 years or older have prostate cancer detected with sextant needle biopsies. PSA velocity, tumor stage, Gleason grade and tumor volume were similar in all age groups.     

Influence of prostate volume and percent free prostate specific antigen on prostate cancer detection in men with a total prostate specific antigen of 2.6 to 10.0 ng/ml

PURPOSE: Percent free prostate specific antigen and prostate specific antigen density have been independently shown to increase the specificity of prostate cancer screening in men with prostate specific antigen levels between 4.1 and 10.0 ng/ml. Recent data suggest the total prostate specific antigen cutoff for performing a biopsy should be 2.6 ng/ml. We assessed the influence of percent free prostate specific antigen and prostate volume on cancer detection in men with a prostate specific antigen between 2.6 and 10.0 ng/ml. MATERIALS AND METHODS: From 1991 to 2005 all transrectal ultrasound guided prostate biopsies (5,587) for abnormal digital rectal examination and/or increased age specific prostate specific antigen were evaluated. A total of 1,072 patients with a prostate specific antigen between 2.6 and 10.0 ng/ml and any percent free prostate specific antigen were included in study. The cancer detection rate was calculated for each percent free prostate specific antigen/volume stratum. RESULTS: Prostate cancer was detected in 296 patients (27.6%). The mean age and prostate specific antigen of the patients with benign pathology and prostate cancer were similar. Mean percent free prostate specific antigen was 17.5% and 14.1% (p>0.05), and the mean volume was 62.0 and 46.0 cc (p=0.001), respectively. The strongest risk factors for a positive biopsy were percent free prostate specific antigen (odds ratio 0.004, p<0.001), volume (OR 0.977, p<0.001) and digital rectal examination (OR 1.765, p=0.007), but not total prostate specific antigen (p=0.303). When stratified by volume and percent free prostate specific antigen, distinct risk groups were identified. The probability of detecting cancer inversely correlated with prostate volume and percent free prostate specific antigen. CONCLUSIONS: In men with prostate specific antigen levels between 2.6 and 10.0 ng/ml, the probability of detecting cancer was inversely proportional to prostate volume and percent free prostate specific antigen. This table may assist in predicting patient risk for harboring prostate cancer.     

Surrogate end point for prostate cancer specific mortality in patients with nonmetastatic hormone refractory prostate cancer

PURPOSE: We determined whether prostate specific antigen (PSA) velocity can serve as surrogate end point for prostate cancer specific mortality (PCSM) in patients with nonmetastatic, hormone refractory prostate cancer. MATERIALS AND METHODS: The study cohort comprised 919 men treated from 1988 to 2002 at 1 of 44 institutions with surgery (560) or radiation therapy (359) for clinical stages T1c-4NxMo prostate cancer, followed by salvage hormonal therapy for PSA failure. All patients experienced PSA defined recurrence while on hormonal therapy. Prentice criteria require that the surrogate should be a prognostic factor and the treatment used did not alter time to PCSM following achievement of the surrogate end point. These criteria were tested using Cox regression. All statistical tests were 2-sided. RESULTS: PSA velocity greater than 1.5 ng/ml yearly was statistically significantly associated with time to PCSM and all cause mortality following PSA defined recurrence while undergoing hormonal therapy (Cox p <0.0001). While initial treatment was statistically associated with time to PCSM and all cause mortality (Cox p = 0.001 and 0.01), this association became insignificant when PSA velocity and potential confounding variables were included in the Cox model (p = 0.22 and 0.93, respectively). The adjusted HR for PCSM in patients who experienced a greater than 1.5 ng/ml increase in PSA within 1 year while on hormonal therapy was 239 (95% CI 10 to 5,549). CONCLUSIONS: These data provide evidence to support PSA velocity greater than 1.5 ng/ml yearly as a surrogate end point for PCSM in patients with nonmetastatic, hormone refractory prostate cancer. Enrolling these men onto clinical trials evaluating the impact of chemotherapy on time to bone metastases and PCSM is warranted.