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 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.     

Prostate specific antigen changes as related to the initial prostate specific antigen: data from the prostate, lung, colorectal and ovarian cancer screening trial

PURPOSE: Annual screening with PSA, although of unproven benefit, is currently used for prostate cancer early detection. A large fraction of screened men have low (less than 2 ng/ml) initial PSA. The yield over time of positive PSA screens (ie more than 4 ng/ml) in these men has not been well characterized in large cohorts in the United States. MATERIALS AND METHODS: Men in the screening arm of the PLCO received baseline PSA and annual tests for 5 years. 30,495 of these men had baseline PSA 4 ng/ml or less. We estimated the cumulative probability of converting to PSA greater than 4 at years 1 through 5 as a function of baseline PSA. RESULTS: Among men with baseline PSA less than 1 ng/ml, 1.5% converted by year 5 (95% CI 1.2-1.7). Among men with baseline PSA of 1.0 to 1.99 ng/ml, 1.2% (95% CI 0.9-1.3) and 7.4% (95% CI 6.8-8.1) converted by year 1 and 5, respectively. A total of 33.5% and 79% of men with initial PSA of 2.0 to 2.99 and 3.0 to 4.0, respectively, converted by year 5. Of men with baseline PSA less than 1 ng/ml converting to PSA more than 4 ng/ml, 8% were diagnosed with cancer within 2 years of conversion. About 10% of men with baseline PSA less than 1 ng/ml and negative baseline DRE had a positive DRE within 3 years. CONCLUSIONS: For men choosing PSA screening, screening every 5 years for baseline PSA less than 1 ng/ml and every 2 years for PSA 1 to 2 ng/ml could result in a 50% reduction in PSA tests and in less than 1.5% of men missing earlier positive screens, but with an unknown effect on prostate cancer mortality.     

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.     

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.     

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.     

Prostate specific antigen testing in men older than 75 years in the United States

PURPOSE: Although there is general agreement that men older than 75 years are unlikely to benefit from prostate specific antigen testing, patient reported testing rates in these patients exceed 30%. We examined physician reported PSA testing in elderly men, and physician and practice characteristics associated with testing. MATERIALS AND METHODS: Using the 1999 to 2002 National Ambulatory Medical Care Survey, a nationally representative sample of outpatient visits to nonfederal office based physicians, we measured rates of prostate specific antigen testing by age group in men without prostate cancer who were 40 years or older and who visited outpatient family medicine, internal medicine or urology clinics. RESULTS: An estimated 42.3 million prostate specific antigen tests were performed from 1999 to 2002, of which 5.91 million (14.0%) were performed in men older than 75 years. The population based testing rate was 6.1% in patients 40 to 49-year-old, 26.0% in patients 50 to 75-year-old and 27.8% in patients older than 75 years. Urologists performed 35.4% of prostate specific antigen tests in men older than 75 years. Controlling for sociodemographic variables physicians with a laboratory on site were more likely to perform a prostate specific antigen test (OR 1.35, 95% CI 1.07 to 1.71). In men older than 75 years the odds of prostate specific antigen testing were 1.58 times higher (95% CI 1.01 to 2.50) in practices with a laboratory on site. CONCLUSIONS: Up to a third of men older than 75 years undergo prostate specific antigen testing despite an average life expectancy of less than 10 years. Physician and practice characteristics are associated with prostate specific antigen PSA testing.     

Comparative analysis of complexed prostate specific antigen, free prostate specific antigen and their ratio in detecting prostate cancer

PURPOSE: We evaluate the diagnostic use of total, free and complexed serum prostate specific antigen (PSA), and their ratios for enhancing the specificity in detecting prostate cancer. MATERIALS AND METHODS: A total of 354 nonconsecutive men undergoing prostate biopsy were eligible for this retrospective and prospective study. Cancer was found in 122 of these 354 men (34%). Receiver operating characteristics curve analyses were used to calculate and compare the performance of total PSA (Hybritech, San Diego California and Bayer, Tarrytown, New York), complexed PSA (Bayer), percent complexed PSA and percent free PSA. In addition, sensitivity and specificity were calculated and compared. RESULTS: The area under the receiver operating characteristics curve was highest for percent free PSA, followed by percent complexed PSA, complexed PSA and the 2 total PSA assays (Hybritech and Bayer). The cutoff value of 3.45 ng./ml. for complexed PSA detected the same number of cancers and resulted in 1 additional false-positive case compared with a Hybritech total PSA threshold of 4.0 ng./ml. At sensitivities of 80% to 95%, there were no significant differences for detection comparing the corresponding specificities between Hybritech total PSA and complexed PSA for all 354 men. Complexed PSA alone did not enhance the overall diagnostic accuracy compared with percent free PSA in the Hybritech total PSA range between 4.01 and 6.00 ng./ml., between 6.01 and 10.00 ng./ml., and between 2.50 and 6.00 ng./ml. At sensitivities of 80% to 95% specificity of percent complexed PSA was almost identical to that of percent free PSA except for the Hybritech total PSA range less than or equal to 4.00 ng./ml. CONCLUSIONS: This study suggests complexed PSA is equivalent to total PSA for the early detection of prostate cancer. Percent free PSA outperforms complexed PSA and percent complexed PSA performed equivalently to percent free PSA in all total PSA ranges analyzed between 2.5 and 10 ng./ml.     

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.     

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.     

Prostate specific antigen velocity threshold for predicting prostate cancer in young men

PURPOSE: Longitudinal changes in prostate specific antigen are increasingly used to guide the recommendation for biopsy. Prostate specific antigen velocity 0.75 ng/ml yearly has been proposed to distinguish prostate cancer from benign prostate conditions. However, this threshold might be too high in young men with lower total prostate specific antigen. MATERIALS AND METHODS: In a large prostate cancer screening study 6,844 men were 60 years or younger at study entry and prostate specific antigen velocity calculation was possible. Of these men 346 (5%) were subsequently diagnosed with prostate cancer and various prostate specific antigen velocity thresholds were examined for prediction of prostate cancer risk. Multivariate analysis was performed to determine whether prostate specific antigen velocity is an independent predictor of prostate cancer in men younger than 60 years. RESULTS: Median prostate specific antigen velocity was significantly higher in men who were later diagnosed with prostate cancer than in those who were not (0.840 vs 0.094 ng/ml yearly, p<0.0001). On multivariate analysis prostate specific antigen velocity greater than 0.4 ng/ml yearly was more predictive of prostate cancer than age, total prostate specific antigen, family history or race. Multivariate analysis in the subgroup of men with total prostate specific antigen less than 2.5 ng/ml had similar results. Overall a cutoff of 0.4 ng/ml yearly was associated with 67.3% sensitivity, 81.2% specificity, 16% positive predictive value and 98% negative predictive value for prostate cancer detection in young men. CONCLUSIONS: The traditional prostate specific antigen velocity threshold of 0.75 ng/ml yearly is too high for men younger than 60 years and it misses 48% of prostate cancers. Young men with prostate specific antigen velocity greater than 0.4 ng/ml yearly are at significantly greater risk for prostate cancer and close followup is warranted.     

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.