Treatment of patients with high risk localized prostate cancer: results from cancer of the prostate strategic urological research endeavor (CaPSURE)

PURPOSE: Pretreatment risk assessment models facilitate more appropriate selection of treatment for prostate cancer. However, men with high risk disease remain a challenge with significant potential for primary treatment failure. We characterize patterns of treatment for high risk prostate cancer in a community based cohort. MATERIALS AND METHODS: In the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database, a longitudinal disease registry of men with prostate cancer, we identified those with nonmetastatic, high risk disease based on T stage, tumor grade and serum prostate specific antigen (PSA). Differences in primary treatment, and the use of neoadjuvant and adjuvant therapy in patients at low, intermediate and high risk were assessed. In the high risk cohort predictors of the type of primary treatment, and the use of neoadjuvant and adjuvant androgen therapy were identified. RESULTS: Of the cancers 34%, 40% and 26% were low, intermediate and high risk, respectively. Differences in primary treatment type among the 3 risk groups were statistically significant (p <0.0001) with increasing external beam radiation therapy and androgen deprivation, and decreased surgery, brachytherapy and surveillance in men with high risk cancers. In this group older age, higher PSA and nonprivate insurance were associated with decreased use of radical prostatectomy. More than half of the men at high risk receiving radiation therapy also received androgen deprivation, which was significantly higher than in the low and intermediate risk groups (p <0.0001). Factors associated with androgen deprivation in high risk disease were primary therapy, PSA, Gleason sum, T stage, body mass index, insurance status and ethnicity. PSA and Gleason sum were the primary determinants of adjuvant radiation after prostatectomy. CONCLUSIONS: Men with high risk but nonmetastatic prostate cancer are more likely to receive radiation therapy as well as androgen deprivation with the latter as primary therapy or in conjunction with local treatment. These data stress the importance of pretreatment risk stratification, education regarding appropriate combinations of local and systemic therapies, and the consideration of novel clinical trials in patients at higher risk.     

Identification of apoptotic and antiangiogenic activities of terazosin in human prostate cancer and endothelial cells

PURPOSE: It has been suggested that terazosin has an inhibitory effect on prostate tumor growth. We determined if terazosin action contributes to direct suppression of the angiogenic effect. MATERIALS AND METHODS: PC-3 cells and primary cultures of human benign prostatic cells were used in this study. The cytotoxic effect was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase release reaction. The in vivo angiogenic effect was determined in nude mice models, followed by histological examination and quantification by the hemoglobin detection assay. In vitro determination of cell migration, proliferation and tube formation was performed in cultured human umbilical vein endothelial cells.RESULTS Terazosin induced cytotoxicity in PC-3 and human benign prostatic cells with an IC50 of more than 100 microM. The positive terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling and lactate dehydrogenase release reaction was associated with terazosin induced cytotoxicity, indicating apoptotic and necrotic cell death. Furthermore, cytotoxicity due to terazosin action was not a common characteristic of a quinazoline based structure. Terazosin significantly inhibited vascular endothelial growth factor induced angiogenesis in nude mice with an IC50 of 7.9 microM., showing that it had a more potent anti-angiogenic than cytotoxic effect. Terazosin also effectively inhibited vascular endothelial growth factor induced proliferation and tube formation in cultured human umbilical vein endothelial cells (IC50 9.9 and 6.8 microM., respectively). CONCLUSIONS: Together our data suggest that terazosin shows direct anti-angiogenic activity through the inhibition of proliferation and tube formation in endothelial cells. This action may partly explain the in vivo antitumor potential of terazosin.     

Hereditary prostate cancer: clinical aspects

PURPOSE: We review the current epidemiological and genetic knowledge regarding hereditary prostate cancer, and outline its clinical implications. MATERIALS AND METHODS: Published articles on hereditary prostate cancer were identified using the MEDLINE data base. RESULTS: A risk of prostate cancer, particularly early onset disease, is strongly affected by family history (number of relatives with prostate cancer and their age at diagnosis). A family history of prostate cancer increases the positive predictive value of prostate specific antigen testing and, hence, heredity should always be assessed when deciding whether to perform biopsies in a man with a prostate specific antigen level of 3 to 10 ng./ml. Epidemiological studies indicate that dominantly inherited susceptibility genes with high penetrance cause 5% to 10% of all prostate cancer cases, and as much as 30% to 40% of early onset disease. More than a half dozen chromosome loci that may comprise such genes have been mapped, but as of May 2002 no prostate cancer susceptibility gene of major importance had been cloned. Most likely, environmental factors and comparatively common variants of several other genes affect prostate cancer risk in families with or without multiple cases of the disease. On average, hereditary prostate cancer is diagnosed 6 to 7 years earlier than sporadic prostate cancer, but does not otherwise differ clinically from the sporadic form. As a consequence of the earlier onset, a greater proportion of men with hereditary prostate cancer die of the disease than those with nonhereditary prostate cancer. At present, the only clinically applicable measure to reduce prostate cancer mortality in families with hereditary disease is screening, with the aim of diagnosing the disease when it is still in a curable stage. CONCLUSIONS: Hereditary susceptibility is now considered the strongest risk factor for prostate cancer and has profound clinical importance. The genetic mechanism behind such susceptibility has turned out to be more complex than initially thought, and will probably not be completely understood for many years to come.     

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.     

Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review

PURPOSE: Several new extended prostate biopsy schemes (greater than 6 cores) have been proposed. We compared the cancer detection rates and complications of different extended prostate biopsy schemes for diagnostic evaluation in men scheduled for biopsy to identify the optimal scheme. MATERIALS AND METHODS: In a systematic review we searched 13 electronic databases, screened relevant urological journals and the reference lists of included studies, and contacted experts. We included studies that compared different systematic prostate biopsy methods using sequential sampling or a randomized design in men scheduled for biopsy due to suspected prostate cancer. We pooled data using a random effects model when appropriate. RESULTS: We analyzed 87 studies with a total of 20,698 patients. We pooled data from 68 studies comparing a total of 94 extended schemes with the standard sextant scheme. An increasing number of cores were significantly associated with the cancer yield. Laterally directed cores increased the yield significantly (p = 0.003), whereas centrally directed cores did not. Schemes with 12 cores that took additional laterally directed cores detected 31% more cancers (95% CI 25 to 37) than the sextant scheme. Schemes with 18 to 24 cores did not detect significantly more cancers. Adverse events for schemes up to 12 cores were similar to those for the sextant pattern. Adverse event reporting was poor for schemes with 18 to 24 cores. CONCLUSIONS: Prostate biopsy schemes consisting of 12 cores that add laterally directed cores to the standard sextant scheme strike the balance between the cancer detection rate and adverse events. Taking more than 12 cores added no significant benefit.     

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.     

Screening behavior in brothers and sons of men with prostate cancer

PURPOSE: We identified factors associated with screening behavior in the brothers and sons of men with prostate cancer. MATERIALS AND METHODS: We contacted 837 men with prostate cancer to invite their 40 to 70-year-old brothers or sons to participate in this study. We mailed the brothers and sons who contacted us a survey to explore sociodemographic and medical characteristics, prostate cancer family history, prostate cancer knowledge, self-efficacy, barriers to screening, perceived benefits, perceived vulnerability and medical support. RESULTS: Of the 138 candidates who participated in the study 86 (62%) had undergone prostate specific antigen and digital rectal examination within the last 2 years. Men older than 50 years, those who had discussed prostate cancer screening with their physician, those with good knowledge of recommended screening frequency and those with no co-morbidity had undergone screening more often than others. CONCLUSIONS: Physician support and prostate cancer screening knowledge were positively associated with previous screening. Effective interventions to increase screening in families at risk should target physicians.     

The incidence of prostate cancer in men with prostate specific antigen greater than 4.0 ng/ml: a randomized study of 6 versus 12 core transperineal prostate biopsy

PURPOSE: The prostate cancer detection rate in patients with elevated prostate specific antigen (PSA) increases with extended needle biopsy protocols. Transperineal biopsy under transrectal ultrasound guidance is rarely reported, although notable cancer diagnoses are obtained with this technique. We describe the results of 6 and 12 core transperineal biopsy. MATERIALS AND METHODS: A total of 214 patients with PSA greater than 4.0 ng/ml were prospectively randomized to undergo 6 or 12 core transperineal biopsy. Each group of 107 patients was comparable in terms of clinical characteristics. The procedure was performed on an outpatient basis using local anesthesia. Specimens were obtained with a fan technique with 2 puncture sites slightly above the rectum (1 per lobe) under transrectal ultrasound guidance. Cores were taken from all peripheral areas, including the far lateral aspect of the prostate. RESULTS: The overall cancer detection rate was 38% and 51% for 6 and 12 core biopsy, respectively. In patients with PSA between 4.1 and 10 ng/ml the cancer detection rate was 30% and 49% for 6 and 12 core biopsy, respectively. CONCLUSIONS: The 12 core transperineal prostate biopsy is superior to 6 core biopsy. The technique provides optimal prostate cancer diagnosis. About half of the patients with PSA greater than 4.0 ng/ml and a slightly lower percent with PSA between 4.1 and 10 ng/ml have prostate cancer.     

The value of γ-seminoprotein in combination with prostate specific antigen in detecting prostate cancer

BACKGROUND: The present study was undertaken to investigate the value of gamma-seminoprotein (gamma-Sm) and the gamma-Sm/prostate specific antigen (PSA) ratio in combination with serum PSA in detecting prostate cancer. METHODS: Prostate specific antigen, gamma-Sm and the gamma-Sm/PSA ratio were evaluated in 112 patients with untreated prostate cancer and 90 patients without prostate cancer who had serum PSA and gamma-Sm levels above their respective detection limits. RESULTS: When data for all of the patients were analyzed, serum PSA and gamma-Sm levels were significantly higher and the gamma-Sm/PSA ratio was significantly lower in patients with prostate cancer than patients without prostate cancer. The serum PSA and gamma-Sm levels significantly increased and the gamma-Sm/PSA ratio significantly decreased with advancing clinical stage in patients with prostate cancer. Among the patients with serum PSA levels ranging from 1.8 to 6 ng/mL, the gamma-Sm/PSA ratio was significantly lower (P < 0.05) and gamma-Sm levels were lower (P = 0.054) in the patients with prostate cancer than in those without prostate cancer, but serum PSA levels were not significantly different (P = 0.53). A receiver operating characteristic (ROC) analysis demonstrated that the areas under the ROC curves were 0.54 for PSA, 0.65 for gamma-Sm and 0.69 for the gamma-Sm/PSA ratio for prediction of prostate cancer in the PSA range from 1.8 to 6 ng/mL, although the ROC analysis suggested that the gamma-Sm/PSA ratio does not provide significant advantage over PSA in detecting prostate cancer when all of the patients were analyzed. CONCLUSIONS: These results suggest that the gamma-Sm/PSA ratio and gamma-Sm may facilitate differentiation between patients with and without prostate cancer who have intermediate PSA levels.     

Post-brachytherapy transurethral resection of the prostate in patients with localized prostate cancer

PURPOSE: We assessed the rate and results of transurethral resection of the prostate (TURP) in patients previously treated with brachytherapy as monotherapy for localized prostate cancer. MATERIALS AND METHODS: From May 1998 to May 2003, 600 patients with localized prostate cancer were treated with brachytherapy at our institution. Brachytherapy was performed as monotherapy with curative intent for clinically localized prostate cancer without adjuvant treatment in patients with clinical stages T1c (68.4%) or T2a (31.6%) disease. -Iodine and palladium implants were used in 583 and 7 patients, respectively. A real-time interactive implantation technique was used in all but the first 17 patients, who were treated using a preplanned technique. RESULTS: Of the 600 patients 19 (3.1%) underwent TURP after brachytherapy. Among the patients with acute urinary retention the median interval between prostate brachytherapy and urinary retention was 2 months (range 0.5 to 32). No TURP was done within 6 months after implant. The median interval between prostate brachytherapy and TURP was 7 months (range 6 to 41) and median prostate specific antigen (PSA) before TURP was 0.5 ng/ml (range 0.04 to 3.4). In the 19 patients the median weight of resected prostatic tissue was 8 gm (range 2 to 19) and 1 to 11 seeds were removed (median 5). The perioperative and postoperative courses were uneventful. There was no TURP related incontinence. With a median followup of 28 months after brachytherapy (range 7 to 48) no patient had clinical or biochemical evidence of disease progression, and for the group of 19 patients who underwent TURP median serum PSA at the end of followup was 0.38 ng/ml (range 0.03 to 3.4). CONCLUSIONS: After brachytherapy as monotherapy, TURP can be done safely if indicated. In our experience the resection of prostatic tissue along with a limited number of seeds at least 6 months after implantation did not impair PSA based biological and clinical results of brachy-therapy.     

Identification of novel translocation between short arm of chromosome 4 and long arm of chromosome 6 in an infertile man using Interphase Chromosome Profiling (ICP)

Conventional cytogenetics has always been a favourite to detect chromosomal aberrations. Carriers of chromosomal translocation are often phenotypically normal but are infertile. Couples are often advised to go for karyotyping, but culture failure or improper metaphase spread with poor banding often makes the analysis difficult. We report here a novel translocation between short arm of chromosome 4 and long arm of chromosome 6 in an infertile man using an advanced molecular cytogenetic technique of Interphase Chromosome Profiling (ICP).     

Prostate cancer in a large prostate is associated with a decreased prostate specific antigen failure rate after brachytherapy

PURPOSE: A large prostate has been found to correlate with improved prostate cancer survival in men undergoing radical prostatectomy. In the current study we analyzed the relationship of prostate size and prostate specific antigen (PSA) failure in men undergoing brachytherapy for localized prostate cancer. MATERIALS AND METHODS: We studied data on 613 men who had undergone I radioactive seed implantation. Average patient age +/- SD was 65 +/- 7.2 years. Average prostate volume ultrasonically measured at seed insertion was 40 +/- 15 ml. All patients had a minimum of 2 years of followup. RESULTS: Men with a large prostate had increased freedom from failure compared to men with a small prostate. Failure time in men with an intermediate size prostate was between that for large and small prostates. This difference in failure rates was significant (log rank test p = 0.0002). We further analyzed our data with Cox regression. Large prostate size significantly correlated with increased time to PSA failure (p = 0.013) and it was independent of the significant effects of Gleason score, PSA, disease stage (p <0.001), minimal radiation dose covering 90% of prostate volume (p = 0.008) and hormone treatment, including androgen ablation (p = 0.001). CONCLUSIONS: Some investigators have postulated that paracrine signals acting to regulate epithelial proliferation in benign prostatic hypertrophy have beneficial influences on coexistent prostate cancer. Our finding that the effect of prostate size is independent of Gleason score, PSA and disease stage supports the paracrine signal mechanism. If a circulating substance, such as a cytokine, might be responsible for improved survival, this substance might be useful for treating prostate cancer. Moreover, since we found that prostate size is independent of PSA, Gleason score and tumor stage for predicting outcome, we hypothesize that patients with a small prostate treated with brachytherapy might benefit from hormone treatment and larger radiation doses. These measures are now generally reserved for men with more advanced tumors, higher PSA and increased Gleason scores.     

Hereditary prostate cancer: clinical characteristics and survival

PURPOSE: Hereditary prostate cancer accounts for 5% to 10% of all prostate cancer cases. We assessed clinical characteristics and survival in patients with hereditary prostate cancer MATERIALS AND METHODS: The study comprised 201 patients from 62 Swedish hereditary prostate cancer families and 402 controls with prostate cancer who were matched for age and calendar year at diagnosis, and the hospital where the diagnosis was made. Clinical data were obtained from the National Cancer Registry, Causes of Death Registry and medical records. RESULTS: Median age at the diagnosis of hereditary prostate cancer was 68 years, which was 6 years less than in patients with prostate cancer in the general population in Sweden. Distributions of tumor grade, symptoms at diagnosis and initial therapy were similar in hereditary prostate cancer cases and controls. More controls were classified with localized disease but it may have been due to methodological problems. Overall and cancer specific survival was similar in patients with hereditary prostate cancer and controls as well as in subgroup analyses including those with early onset and those diagnosed before 1990. Prostate cancer was the cause of death in 75% of patients with hereditary prostate cancer, in contrast to 55% with prostate cancer in the Swedish population. This difference was completely explained by the earlier age at the diagnosis of hereditary prostate cancer. CONCLUSIONS: Hereditary prostate cancer has an earlier onset than sporadic prostate cancer but this study did not indicate any other important difference in clinical characteristics or survival in patients with hereditary prostate cancer and those with sporadic prostate cancer. However, it cannot be excluded that individual hereditary prostate cancer genes may have specific biological characteristics.     

Survival of patients with hormone refractory prostate cancer in the prostate specific antigen era

PURPOSE: The historically reported 12 to 18-month duration of survival of patients with hormone refractory prostate cancer is not consistent with current clinical experience. Furthermore, to our knowledge patient survival after serum prostate specific antigen (PSA) progressively increases from a nadir despite castrate testosterone has not been previously reported. For this reason we studied overall survival and the clinical variables that influence survival in patients with hormone refractory prostate cancer. MATERIALS AND METHODS: The study focused on 254 patients with prostate cancer on androgen deprivation therapy. Hormone refractory prostate cancer was defined as the first in a series of PSA elevations despite castrate levels of testosterone. The duration of survival in the hormone refractory phase was calculated from the date of the first PSA elevation to the date of death. RESULTS: Median survival after hormone refractory prostate cancer developed in patients initially staged with and without skeletal metastasis was 40 and 68 months, respectively. Six of more than 25 input variables were retained as significant in the final Cox model. Variables associated with longer survival were lower nadir PSA, younger age, higher pretreatment testosterone, no history of obstructive uropathy, no history of tobacco use (past or current) and lower alkaline phosphatase. CONCLUSIONS: Historical reports of survival in hormone refractory prostate cancer underestimate current survival observations. The likely explanations of this observation include delayed enrollment in clinical trials from which most survival data are derived, PSA lead time in staging and improved supportive care. Models predicting survival in patients with hormone refractory prostate cancer should consider multiple variables.     

Prostate saturation biopsy in the reevaluation of microfocal prostate cancer

PURPOSE: We evaluated the ability of an extended, 32-core repeat transrectal ultrasound prostate biopsy protocol to improve the characterization of low volume, well differentiated disease in men with a diagnosis of potentially insignificant microfocal prostate cancer, as defined by 1 single focus positive core of 10 with less than 5 mm of Gleason score 6 or less tumor on primary biopsy. MATERIALS AND METHODS: A total of 35 consecutive patients, who were 62 to 75 years old, had a median serum prostate specific antigen of 8 ng/ml (range 0.5 to 14) and a diagnosis of minimal prostate cancer, and were willing to consider observation with delayed treatment at progression, were offered repeat saturation prostate biopsy with a median of 32 cores (range 18 to 36) under local anesthesia. This biopsy was to determine whether more extensive prostate sampling would confirm or disprove the initial diagnosis of microfocal, well differentiated prostate cancer. RESULTS: The procedure was aborted in 1 patient because of massive rectal hemorrhage. Another patient had acute prostatitis with gram-negative sepsis. Of 34 evaluable biopsy sets 11 (32%) were negative for cancer, suggesting that tumor detected at the primary biopsy was probably of low volume and amenable to observation with delayed treatment. Of the biopsies 23 (68%) were positive, 17 were at multiple sites and 7 were upgraded to Gleason score 7 or greater. These patients were then considered to have significant tumors and were offered active treatment. CONCLUSIONS: This study is to our knowledge the first to describe the clinical use of prostate saturation biopsies for re-evaluating potentially insignificant prostate cancer. Of patients with minimal disease on standard 10-core biopsy, results show that this technique may be helpful for distinguishing the 30% who probably have minimal disease based on negative repeat saturation biopsy from the 70% who almost certainly have a significant tumor, as characterized by multiple positive cores, with or without an increased Gleason score. The latter patients should be offered active therapy.     

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.