Incidence of prostate cancer in Sicily: results of a multicenter case-findings protocol

OBJECTIVE: To establish the incidence of prostate cancer (PCa) in Sicily in patients who entered an early detection protocol. METHODS: From February 2002 to February 2004, 16,298 subjects aged 40-75 entered the protocol. Patients with suspicious DRE, PSA>10 ng/ml, PSA相似文献   

Prostate cancer detection is also relevant in low prostate specific antigen ranges

OBJECTIVE: To address detection rates and clinical features of the cancers detected with low prostate specific antigen (PSA) levels. METHODS: In the context of a prostate cancer (PCa) screening program 1097 men attended to a new rescreen round. Sextant prostate biopsy was recommended when PSA > or =3 ng/ml. We also recommended to undergo biopsy in the range 1.0-2.99 ng/ml when free to total (f/t) PSA ratio < or =20%. Detection rate was calculated and clinical features of the cancers detected were studied. RESULTS: Mean age was 61.1 years. A total of 497 (45.3%) had total PSA <1.0 ng/ml, 439 (40%) between 1.0 and 2.99 ng/ml, and 161 (14.7%) > or =3.0 ng/ml. In the group with PSA between 1.0 and 2.99 ng/ml and f/t PSA ratio < or =20% a total of 249 biopsies were indicated (159 performed, acceptance 63.9%), and 15 cancers detected (detection rate 9.4%). Biopsy was recommended to 72 men with PSA between 3.0 and 3.99 ng/ml, performed in 56 (77.8%), and 12 tumors detected (detection rate 21.4%). All cancers in the study were clinically localized. Only 4 out of 15 cancers with PSA in the range 1.0-2.99 ng/ml (26.7%) fulfilled clinical criteria of insignificant cancer. Two were poorly differentiated and found to have patologically extracapsular disease. None of the 12 patients with PCa and PSA between 3.0 and 3.99 ng/ml had poorly differentiated features and only one complied with criteria of insignificant cancer. One out of seven who underwent RRP was found to have extracapsular disease. CONCLUSIONS: Cancer detection in low PSA ranges is lower but still relevant. The detection of potentially aggresive cancers is still of concern.     

Prevalence of prostate cancer at different levels of serum prostate-specific antigen (PSA) and different free: total PSA ratios in a consecutive series of men referred for prostate biopsies

OBJECTIVE: In this retrospective study we report on the detection rate of prostate cancer (PCa) at different levels of prostate-specific antigen in serum (s-PSA) and at different PSA ratios (free:total PSA) during a 2-year period in patients without previously known PCa. MATERIAL AND METHODS: During the years 2001 and 2002, 361 consecutive patients were examined with ultrasound-guided core needle biopsies at our department. The patients were biopsied due to an increased s-PSA level, a low PSA ratio or findings at digital rectal examination (DRE). Patients with previously known cancer (T1a/b or cancer already detected with fine-needle aspiration cytology) were excluded. We used the BioPince biopsy needle, which has a stroke length of 32 mm. In 91% of the patients, eight biopsies were taken from the apex, mid-medial, mid-lateral and base positions bilaterally. RESULTS: Of the 361 patients, 188 (52%) had PCa. Most cancers were T1c or T2 tumors (51% and 34%, respectively). Among patients with an s-PSA level of < 4 ng/ml, 8/35 (23%) had PCa. Five of 13 patients with a normal DRE (T1c) and an s-PSA level of < 4 ng/ml had PCa. In total, in the PSA ratio intervals 0.05-0.1 and 0.11-0.17, cancer was found in 71% and 51% of cases, respectively. In contrast, only 35% of patients had positive biopsies when the PSA ratio was normal (p<0.01). CONCLUSIONS: The overall cancer detection rate was high and a large proportion of patients with an s-PSA level of < 4 ng/ml had PCa. The risk of having PCa increased considerably with a low PSA ratio.     

Characteristics of prostatic cancer in men with a serum prostate-specific antigen level of < or =4.0 ng/ml

Fifteen out of 140 men (median age 67 years, range 62-75) had a serum prostate-specific antigen (PSA) level of < or = 4 ng/ml before radical prostatectomy which was performed without preoperative neoadjuvant hormonal therapy between 2001 January and 2004 September. Demographic and clinical data were analyzed. Pathological specimens were evaluated by routine hematoxylin and eosine staining and immunohistochemistry with anti-PSA antibody, for both pathological staging and grading, and for the presence of PSA production. Pathological data were compared between patients with PSA < or = 4 ng/ml and those with 4 < PSA < or = 10 ng/ml. Clinically insignificant cancer was defined as a cancer volume of < 0.5 ml and the Gleason score < or = 6. The median PSA level was 3.0 ng/ml (range 1.4-3.9). Thirteen tumors (87%) were pT2. One tumor had a Gleason score of 7 and 14 tumors had a final Gleason score of < or = 6. Nine (60%) tumors were clinically insignificant. Comparison of pathological variables, PSA < or = 4 ng/ml cancer had a significantly lower Gleason score (p = 0.0029), and a smaller cancer volume (p = 0.0451) than 4 < PSA < or = 10 ng/ml cancer. All tumors were stained strongly for PSA. During a median follow-up of 24 (9-36) months, no patient showed elevated PSA (PSA > or = 0.1 ng/ml). Most prostate cancers in men with a PSA level of < or = 4 ng/ml were pT2, and about half of them were clinically insignificant. All cancers produced PSA.     

Advanced prostate cancer is associated with a decrease in serum luteinizing hormone

OBJECTIVE: Depletion of serum LH by LHRH agonists is used as a therapeutic treatment in hormone-sensitive prostate cancer (PCa). However, little information on serum LH in different patient groups is available. METHODS: Patients with biopsy-proven PCa, men with BPH (biopsy-proven absence of PCa), two subgroups (serum PSA <4 ng/ml; PCa and BPH), and a PCa cohort before and after radical prostatectomy were analyzed for serum LH, testosterone (T), dihydrotestosterone (DHT), total and free PSA by immunological procedures. RESULTS: PCa patients with cancer volumes >10 cm(3), or with advanced Gleason scores, had significantly lower LH values than men in a cancer-free control group (PSA <4 ng/ml). Eight weeks after radical prostatectomy, LH levels had returned to the level of the control group (p<0.0001). These alterations were not accompanied by corresponding changes of serum androgens. Introduction of a PSA/LH ratio appeared to increase the differences between BPH and PCA groups ranked according to Gleason scores, versus PSA or LH alone. However, the calculation of ROC curves indicated that PSA/LH ratios may not improve the discrimination of malignant and benign forms of the disease, compared to presently used parameters. CONCLUSIONS: A significant reduction of circulating LH is observed in the most advanced forms of PCa. The effect does not come about by T- or DHT-mediated feedback inhibition. Since LH values after prostatectomy returned to practically the same levels as seen in the control group (BPH with <4 ng/ml PSA), it appears that the healthy prostate has no marked influence on serum LH while advanced PCa induces a decrease in serum LH.     

Outcomes in patients with Gleason score 8-10 prostate cancer: relation to preoperative PSA level

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High‐grade prostate cancers are associated with poor disease‐specific outcomes. A proportion of these tumours produce little PSA. This study demonstrates that among Gleason 8–10 prostate cancers, some of the worst survival outcomes are associated with the lowest PSA levels.

OBJECTIVE

• ? To assess outcomes of patients with Gleason score 8–10 prostate cancer (CaP) with a low (≤2.5 ng/mL) vs higher preoperative serum PSA levels.

PATIENTS AND METHODS

• ? From 1983 to 2003, 5544 patients underwent open radical prostatectomy, of whom 354 had a Gleason 8–10 tumour in the prostatectomy specimen.
• ? Patients were stratified according to preoperative PSA level into four strata: ≤2.5 ng/mL (n= 31), 2.6–4 ng/mL (n= 31), 4.1–10 ng/mL (n= 174), and >10 ng/mL (n= 118).
• ? We compared biochemical progression‐free survival (PFS), metastasis‐free survival (MFS), and cancer‐specific survival (CSS) as a function of preoperative PSA level.

RESULTS

• ? Patients with PSA level ≤2.5 ng/mL were more likely to have seminal vesicle invasion (P= 0.003).
• ? On Kaplan–Meier survival analysis, patients with a PSA level ≤2.5 ng/mL had proportionately worse outcomes than their counterparts with higher PSA levels.
• ? The 7‐year PFS in the PSA ≤2.5 ng/mL stratum was lower than those of the PSA 2.6–4 ng/mL and 4–10 ng/mL strata (36% vs 50 and 42%, respectively); however, the lowest 7‐year PFS was found in those with a PSA level >10 ng/mL (32%, P= 0.02).
• ? Gleason score 8–10 tumours with a PSA level ≤2.5 ng/mL also tended to have the lowest 7‐year MFS (75, 93, 89 and 92% for PSA level ≤2.5, 2.6–4, 4.1–10 and >10 ng/mL, respectively, P= 0.2) and CSS (81, 100, 94 and 90% for PSA level ≤2.5, 2.6–4, 4.1–10 and >10 ng/mL, respectively, P= 0.3), although these differences were not statistically significant.
• ? In the subset with palpable disease, Gleason grade 8–10 disease with PSA level ≤2.5 ng/mL also was associated with a worse prognosis.

CONCLUSIONS

• ? In patients with Gleason grade 8–10 disease, a proportion of these tumours are so poorly differentiated that they produce relatively little PSA.
• ? Patients with high‐grade, low‐PSA tumours had less favourable outcomes than many of those with higher PSA levels.

     

Effect of NIH-IV prostatitis on free and free-to-total PSA

OBJECTIVE: To examine the effect of asymptomatic prostatic inflammation (NIH category IV prostatitis) on total PSA (tPSA), free serum PSA (fPSA) and the ratio of free-to-total prostate specific antigen (%fPSA). The role of free and %fPSA as a diagnostic tool for distinguishing between cancer and non-malignant diseases of the prostate was also investigated. MATERIAL AND METHODS: In a retrospective study 1090 prostate biopsies performed between January 2000 and September 2003 were evaluated and the levels of serum total and free PSA as well as the f/tPSA ratio were determined in samples obtained immediately before biopsy. 404 patients with full clinical and histological records were included in the study. All patients underwent 6 or 8 core primary prostate needle biopsies. RESULTS: A total of 404 patients were included in the analysis. 100 prostate cancer (PCa) (24.8%), 137 NIH-IV prostatitis (33.9%) and 143 patients with benign prostatic hyperplasias (BPH) (35.4%) were identified. 24 (5.9%) patients presented with both PCa and prostatitis on histology and were excluded from further analysis. The mean (median) levels of tPSA, fPSA and %fPSA were 11.94 ng/ml (8.0), 1.31 ng/ml (1.07) and 0.15 (0.14) for NIH-IV prostatitis; 11.94 ng/ml (8.35), 1.54 ng/ml and 0.13 (0.11) for prostate cancer; and 8.19 ng/ml (7.0), 1.48 ng/ml (1.03) and 0.18 (0.15) for BPH. No significant difference was found in tPSA levels between PCa and prostatitis (p = 0.32), while the difference in tPSA levels between PCa and BPH was significant (p = 0.007). Free PSA alone had no diagnostic power in distinguishing PCa from prostatitis (p = 0. 37) and BPH (p = 0. 61). By contrast, the f/tPSA ratio showed significant between-group differences (PCa versus prostatitis (p = 0. 011), PCa versus BPH (p = 0.0001). CONCLUSIONS: Chronic asymptomatic prostatitis NIH category IV has similar effects on total PSA and free PSA levels in serum as PCa. fPSA alone cannot distinguish prostate cancer from non-malignant inflammatory disease of the prostate. The ratio of free-to-total PSA is significantly different in PCa and NIH category IV prostatitis.     

年龄≤50岁非前列腺癌男性初始PSA及PSA速度的分布特点分析

目的 探讨年龄≤50岁非前列腺癌男性初始PSA及PSA速度的分布特点.方法回顾性分析2001年1月至2009年11月初始PSA检测年龄≤50岁的非前列腺癌患者的PSA值,计算PSA检测≥2次者的PSA速度.研究不同年龄段初始PSA及PSA速度的分布范围,分析初始PSA、初始PSA年龄及PSA速度之间的相关性.用生存分析和log-rank检验比较初始PSA高于和低于中位数2组患者将来PSA≥2.5 ng/ml风险的差异.结果 4206例非前列腺癌者,初始PSA中位数为0.6 ng/ml,其中≥1.0、≥2.5和≥4.0 ng/ml者分别1026例(24.4%)、177例(4.2%)和90例(2.1%).417例PSA检测≥2次者PSA速度的中位数为0.03 ng·ml-1·y-1,其中≥0.35、≥0.75和≥2.00 ng·ml-1·y-1者分别为25例(6.0%)、13例(3.1%)和8例(1.9%).年龄与PSA、年龄与PSA速度、PSA与PSA速度之间均无明显相关性(r值分别为0.019、-0.015和-0.006,P值分别为0.218、0.754和0.897).395例PSA检测≥2次且初始PSA＜2.5 ng/ml者随访3个月～7.1年,中位时间2.0年,初始PSA高于和低于中位数2组患者将来PSA超过2.5 ng/ml的风险差异有统计学意义(P＜0.01).结论年龄≤50岁非前列腺癌男性的中位初始PSA和PSA速度分别为0.6 ng/ml 和0.03 ng·ml-1·y-1.初始PSA高于中位数的患者将来PSA超过2.5 ng/ml的风险明显增高.

Abstract：

Objective To explore the distribution and characteristics of initial PSA and PSA velocity in men younger than years without prostate cancer. Methods PSA in men younger than 50 years without prostate cancer from January 2001 to November 2009 were retrieved retrospectively from our computer center. PSA velocity was calculated if their PSA was measured twice or more. The distributions of initial PSA and PSA velocity were analyzed. The correlations between initial PSA, initial PSA age, and PSA velo-city were also analyzed. Kaplan-meier and log-rank tests were used to estimate the significant difference at the risk of PSA≥ 2.5 ng/ml after initial PSA measurement, stratified by median initial PSA (0.6 ng/ml). Results A total of 4206 men without prostate cancer were included. The median initial PSA value in these men was 0.6 ng/ml. Of these men, 1026 (24.4%), 177 (4.2%), and 90 (2.1%) had an initial PSA≥1.0, ≥2.5, and ≥4.0 ng/ml, respectively. A total of 417 men had their PSA measured these men, 25 (6.0%), 13 (3.1%), and 8 (1.9%) had a PSA velocity≥0.35, ≥0.75, initial PSA age and initial PSA, initial PSA age and PSA velocity, and initial PSA and PSA velocity (correlation coefficient r=0.019, -0.015, and -0.006, respectively; P=0.218, 0.754, and 0.897, respectively). After a follow-up of up to 7.1 years from baseline PSA measurement, the risk of PSA≥2.5 ng/ml, stratified by median initial PSA (0.6 ng/ml) was significantly different (log-rank test, P＜0.001). Conclusions The median baseline PSA and PSA velocity in men younger than 50 years old without prostate cancer are 0.6 ng/ml and 0.03 cancer with an initial PSA higher than median (0.6 ng/ml) have a subsequently higher risk of PSA value ≥2.5 ng/ml.     

Prediction of pathological stage is inaccurate in men with PSA values above 20 ng/mL

INTRODUCTION: We hypothesized that either very low (0-2.5 ng/mL) or very high (>20 ng/mL) PSA values may limit the accuracy of pathological stage predictions. To test this hypothesis, we examined 5193 consecutive patients subjected to radical prostatectomy (RP) for localized prostate cancer (PCa). MATERIAL AND METHODS: Patients were divided into three cohorts according to their pre-treatment PSA value: 20 ng/mL (n=317). Subsequently in each cohort, the ability of PSA, clinical stage and biopsy Gleason sum was tested in multivariable logistic regression models predicting three separate endpoints: extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph node invasion (LNI). Predictive accuracy represented the performance benchmark. All models were adjusted for year of surgery and subjected to 200 bootstrap resamples to reduce overfit bias. RESULTS: For PSA 20 ng/mL, predictive accuracy was 63.6%, 63.7% and 70.6%. CONCLUSIONS: The ability to predict pathological stage in patients with PSA values in excess of 20 ng/mL significantly decreased, compared to patients with lower PSA values. Therefore, accurate staging of these patients may require alternative markers or staging schemes.     

IGF-II serum levels increase discrimination between benign prostatic hyperplasia and prostate cancer and improve the predictive value of PSA in clinical staging

PURPOSE: IGF-I serum levels have been demonstrated as being associated with prostate cancer (PCa) and can serve as a predictive factor for the risk of PCa development. However, the role of IGF-II in PCa and its importance as a predictive marker is still unclear. Our aim was to determine PSA and IGF-II serum levels in patients with PCa and benign prostatic hyperplasia (BPH) and to analyse the value of IGF-II as an additional predictive factor in the diagnostics of PCa. METHODS: 112 patients who underwent surgery for BPH or PCa (no hormonal treatment, no further malignancies) were included in this study ((I) 38 PCa, PSA < or = 15 ng/ml; (II) 34 PCa, PSA > 15 ng/ml; (III) 40 BPH). Preoperative serum levels of total PSA and total IGF-II were determined by ELFA and ELISA, respectively. RESULTS: PSA levels were (I) 5.7+/-1.9 ng/ml; (II) 25.0+/-11.5 ng/ml and (III) 4.0+/-2.8 ng/ml. (II) was statistically associated with a high grading (2b/3; p = 0.0182), a high Gleason sum score (7-10; p = 0.0049) and a non-organ confined tumor (T3/4; p = 0.0009) compared to (I), all Chi2 test. IGF-II levels were significantly higher in PCa (I+II) compared to BPH (833.8+/-238.9 ng/ml vs. 633.3+/-141.4 ng/ml, p < 0.0001, t-test). Both PSA and IGF-II were associated with tumor staging (p = 0.0097, p = 0.0308; t-test). No significant correlation was observed between PSA and IGF-II levels. Logistic regression analysis revealed that the combination of PSA and IGF-II improves the prediction of tumor staging in PCa (p = 0.0175 and p = 0.0459, Wald test). Additionally, the combination of PSA and IGF-II can significantly increase discrimination between BPH and PCa; each p < 0.0001, Wald test. CONCLUSIONS: This study provides evidence that IGF-II serum levels may serve as an additional parameter for (a) improved determination of tumor staging and (b) better discrimination between BPH and PCa.     

Standard Versus Age-Specific Prostate Specific Antigen Reference Ranges Among Men With Clinically Localized Prostate Cancer: A Pathological Analysis

Purpose

Age-specific prostate specific antigen (PSA) reference ranges have been suggested to account for the age-dependent nature of the serum PSA concentration. It has been hypothesized that reference ranges of 0 to 2.5 ng./ml. serum PSA (40 to 49 years), 0 to 3.5 ng./ml. (50 to 59 years), 0 to 4.5 ng./ml. (60 to 69 years) and 0 to 6.5 ng./ml. (70 to 79 years) would detect fewer (potentially insignificant) prostate cancers in older men and more (potentially curable) cancers in younger men.

Materials and Methods

To investigate the pathological stage of tumors that would be affected by the use of age-specific PSA reference ranges, we reviewed the medical records for 4,597 men with clinically localized (stage T1c, T2 or T3a) prostate cancer, with an average age of 62 plus/minus 7 years (range 38 to 76), who underwent radical prostatectomy between 1984 and 1994 at our institutions. Favorable pathological results were defined as organ-confined disease or capsular perforation with a Gleason score of less than 7, and unfavorable pathological results were defined as capsular perforation with a Gleason score of 7 or more, seminal vesicle invasion or lymph node involvement.

Results

Overall, 18 percent of the men had PSA levels less than the standard PSA reference range (4.0 ng./ml.) compared to 22 percent when using the age-specific ranges. There were 74 more cancers detected in men younger than 60 years with the use of age-specific ranges, of which 81 percent had favorable pathological results. Among the men 60 years or older, 191 of 252 cancers (76 percent) not detected by using age-specific ranges were of favorable pathological status. Of those cancers not detected in older men with the age-specific ranges less than 3 percent were also stage T1c and 95 percent of these undetected T1c cancers were of favorable pathological status. Age-specific PSA reference ranges increased the potential for detection of prostate cancer by 18 percent in the younger men and decreased the detection by 22 percent in the older men.

Conclusions

Among these men with clinically localized prostate cancer, age-specific PSA reference ranges increased the detection of more potentially curable tumors in young men and decreased the detection of less advanced tumors in the older men compared to the standard reference range of 4.0 ng./ml. Among older men with nonpalpable (stage T1c) tumors age-specific PSA reference ranges would have detected fewer tumors. However, 95 percent of these “missed” tumors would have had favorable pathological findings.     

Study of free to total prostate specific antigen ratio in the detection of patients with prostate cancer

BACKGROUND: We investigated the clinical usefulness of free to total serum prostate specific antigen (PSA) ratio (F/T ratio) in order to improve the specificity of total PSA measurement for detecting prostate cancer. METHOD: In this study 129 patients with total PSA level 4-20 ng/ml underwent transrectal ultrasound guided sextant biopsy. Serum samples were assessed for total PSA, free PSA and the F/T ratio calculated. All patients were pathologically diagnosed as benign prostatic hyperplasia or prostate cancer. RESULTS: Of 129 patients 21 had prostate carcinoma (PCa) and 108 had benign prostatic hyperplasia (BPH) from the results of prostate biopsies. The mean of total PSA were not significantly different between men with PCa and with BPH. The mean of free PSA for PCa was significantly lower than that for BPH (p = 0.043). Furthermore, the mean of F/T ratio was significantly different between PCa and BPH group (p = 0.0014). The F/T ratio had a higher specificity than total PSA at all levels of sensitivity in detecting prostate cancers. Sensitivity, specificity and accuracy for cancer detection at a cut off 0.12 was 90.4%, 51.8% and 58.1%, respectively. Also, free PSA was as useful as F/T ratio for cancer detection when analyzed in receiver operating characteristic curves analysis. When determined the cut off number of free PSA at 0.78 ng/ml, the sensitivity, specificity and accuracy for cancer detection were 61.9%, 66.7% and 65.9%, respectively. CONCLUSION: This study indicated that the F/T ratio and free PSA could improve the specificity without impairing the sensitivity for detecting PCa in patients with 4-20 ng/ml of total PSA.     

Using PSA to guide timing of androgen deprivation in patients with T0-4 N0-2 M0 prostate cancer not suitable for local curative treatment (EORTC 30891)

OBJECTIVE: EORTC trial 30891 compared immediate versus deferred androgen-deprivation therapy (ADT) in T0-4 N0-2 M0 prostate cancer (PCa). Many patients randomly assigned to deferred ADT did not require ADT because they died before becoming symptomatic. The question arises whether serum prostate-specific antigen (PSA) levels may be used to decide when to initiate ADT in PCa not suitable for local curative treatment. METHODS: PSA data at baseline, PSA doubling time (PSADT) in patients receiving no ADT, and time to PSA relapse (>2 ng/ml) in patients whose PSA declined to <2 ng/ml within the first year after immediate ADT were analyzed in 939 eligible patients randomly assigned to immediate (n=468) or deferred ADT (n=471). RESULTS: In both arms, patients with a baseline PSA>50 ng/ml were at a>3.5-fold higher risk to die of PCa than patients with a baseline PSA12 mo. Time to PSA relapse after response to immediate ADT correlated significantly with baseline PSA, suggesting that baseline PSA may also reflect disease aggressiveness. CONCLUSIONS: Patients with a baseline PSA>50 ng/ml and/or a PSADT<12 mo were at increased risk to die from PCa and might have benefited from immediate ADT, whereas patients with a baseline PSA<50 ng/ml and a slow PSADT (>12 mo) were likely to die of causes unrelated to PCa, and thus could be spared the burden of immediate ADT.     

Early detection of prostate cancer in 2007. Part 1: PSA and PSA kinetics

OBJECTIVE: This is the first of two review papers attempting to clarify the best way to detect prostate cancer (PCa) in 2007. Screening for PCa has not yet been shown to lower PCa mortality. Still, opportunistic screening is wide spread in Europe and in most other parts of the world. METHODS: Current literature and data from screening studies are reviewed and discussed. Prostate-specific antigen (PSA) has been and remains one of the corner stones of early detection of PCa. Traditionally used cut-off values cannot be applied in an uncritical fashion after it was shown that a significant amount of overdiagnosis and that large proportions of cancers and poorly differentiated cancers are present in the low PSA ranges. The paper addresses the continued relevance of PSA cut-off values. The diagnostic value of PSA velocity is reviewed in conjunction with PSA cut-off values and as a possible replacement of total PSA. A need for more selective screening in the low PSA ranges is pointed out. RESULTS AND CONCLUSIONS: The data show that men presenting initially with PSA values below 1 do not have to be rescreened for a period of 8 yr. In the PSA range 1-2.9 ng/ml, new parameters are needed that improve specificity and are selective for screening for aggressive lesions. PSA velocity so far has not been shown to be useful in the early detection of PCa but may be useful in detecting aggressive PCa selectively. For the time being, it seems sensible to continue using PSA cut-off values such as 3.0 or 4.0 ng/ml provided overtreatment is decreased by using available nomograms.     

Screening with low PSA cutoff values results in low rates of positive surgical margins in radical prostatectomy specimens

BACKGROUND: In the literature, positive margins in radical prostatectomy specimens, the rate of which ranges between 7% and 46%, are associated with adverse patient survival. The aim of the present study was to determine the predictive value of preoperative serum prostate specific antigen (PSA) values for the rate of positive margins in radical retropubic prostatectomy. METHODS: The study included a cohort of 845 patients who underwent radical retropubic prostatectomy between October of 1993 and December of 1999. All patients were stratified in groups on the basis of their preoperative PSA values: PSA group I, 0-1.99 ng/ml; PSA group II, 2-3.99 ng/ml; PSA group III, 4-5.99 ng/ml; PSA group IV, 6-7.99 ng/ml; PSA group V, 8-9.99 ng/ml; and PSA group VI, >10 ng/ml. For each group, the pathologic stage, Gleason score, and the incidence of positive margins were analyzed. For statistical analysis, the Mann Whitney U-test was used. RESULTS: Our data show a significantly higher rate of organ-confined prostate cancers and a significantly lower rate of positive surgical margins in patients with preoperative total PSA values of less than 4 ng/ml compared with patients with higher preoperative total PSA levels. CONCLUSION: As tumor stage and surgical margin status after radical prostatectomy are important predictors of the likelihood of PSA recurrence, which necessitates additional therapy, these findings support the concept of PSA screening by using low PSA cutoff levels.     

Distribution of prostate specific antigen (PSA) and percentage free PSA in a contemporary screening cohort with no evidence of prostate cancer

OBJECTIVE: To explore the distribution of total prostate specific antigen (PSA) and percentage free/total PSA (%f/tPSA) in healthy volunteers with no clinical evidence of prostate cancer, who participated in prostate cancer screening. SUBJECTS AND METHODS: PSA and %f/tPSA values from 2323 men, who participated in one of three annual prostate cancer screening events between 2004 and 2006, were tabulated according to age strata of 40-49, 50-59, 60-69 and 70-79 years. Local regression smoothing plots provided a graphical display of the relation between age and PSA or %f/tPSA, respectively. All PSA and %f/tPSA analyses were repeated for each age category after excluding, respectively, the top and the bottom 10% of PSA and %f/tPSA values. RESULTS: Within the entire cohort, the median PSA level was 1.0 ng/mL and the median %f/tPSA was 25%. According to the age categories the PSA level and %f/tPSA medians within the entire cohort were, respectively, 0.7, 0.9, 1.3, 1.8 ng/mL and 28.0, 26.0, 24.0 and 25.0%. Of the 2323 men, 438 (18.9%) had a PSA level of >2.5 ng/mL and 1172 (50.5%) had a %f/tPSA of < or = 25%. When either a PSA level of >2.5 ng/mL or a %f/tPSA of < or = 25% were considered, 1235 (53.2%) had one or two abnormal values. Finally, if either a PSA level of >2.5 ng/mL or %f/tPSA of < or = 15% was used, 617 (26.6%) were considered abnormal. CONCLUSION: Half of men with no clinical evidence of prostate cancer should have PSA levels of <1.0 ng/mL and a %f/tPSA of >25%. A PSA level threshold of 2.5 ng/mL would require a biopsy in 20% of men and a %f/tPSA threshold of < or = 25% in half of the men. Alternatively, a %f/tPSA threshold of < or = 15% would decrease the probability to 15%.     

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

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

Prostate cancer incidence and disease-specific survival of men with initial prostate-specific antigen less than 3.0 ng/ml who are participating in ERSPC Rotterdam

Background

The European Randomised Study of Screening for Prostate Cancer (ERSPC) applies a prostate-specific antigen (PSA) cut-off value ≥3.0 ng/ml as an indication for lateralised sextant biopsy.

Objective

To analyse the incidence and disease-specific mortality for prostate cancer (PCa) in men with an initial PSA <3.0 ng/ml.

Design, setting and participants

From November 1993 to December 1999, a total of 42 376 men identified from population registries in the Rotterdam region (55–74 yr of age) were randomised to an intervention or control arm. A total of 19 950 men were screened during the first screening round.

Intervention

A PSA <3.0 ng/ml was below the biopsy threshold. PCa cases were identified at rescreens every 4 yr or as interval cancers.

Measurements

Distribution of incidence, aggressiveness, and disease-specific mortality of PCa per PSA range was measured. Causes of death were evaluated by an independent committee, and follow-up was complete until 31 December 2008.

Results and limitations

From 1993 to 2008, 915 PCa cases were diagnosed in 15 758 men (5.8%) with an initial PSA <3.0 ng/ml and a median age of 62.3 yr. Median overall follow-up was 11 yr. PCa incidence increased significantly with higher initial PSA levels. Aggressive PCa (clinical stage ≥T2c, Gleason score ≥8, PSA >20 ng/ml, positive lymph nodes, or metastases at diagnosis) was detected in 66 of 733 screen-detected PCa cases (9.0%) and 72 of 182 interval-detected PCa cases (39.6%). Twenty-three PCa deaths occurred in the total population (0.15%), with an increasing risk of PCa mortality in men with higher initial PSA values.

Conclusions

The risk of PCa, aggressive PCa and PCa mortality in a screening population with initial PSA <3.0 ng/ml increases significantly with higher initial PSA levels. These results contribute to the risk stratification and individual management of men in PSA-based screening programmes.     

血清／尿PSA比值对血清PSA处于“灰区”中前列腺癌的诊断价值

目的探讨血清前列腺特异性抗原（sPSA）与尿前列腺特异性抗原（uPSA）比值（s／uPSA）对血清PSA处于诊断“灰区”—sPSA于4．0～10．0ng／ml（放射免疫法范围）前列腺癌的诊断价值。方法选择血清PSA（sPSA）于诊断“灰区”的共191例前列腺疾病患者，采用放射免疫方法检测其尿PSA（uPSA）水平，根据前列腺活检结果分为前列腺癌组（PCa组，n=76）和良性前列腺增生症组（BPH组，n=115），比较两组s／uPSA比值以及两组间sPSA和s／uPSA比值的受试者运算特性曲线（ROC）面积。结果BPH组与PCa组的sPSA分别为（5．20±1．09）ng／ml和（6．41±2．12）ng／ml，uPSA分别（3．57±0．97）ng／ml和（2．17±0．61）ng／ml，sPSA和uPSA在BPH组与PCa组两者间差别均无统计学意义（t=0．91，t=1．24，P〉0．05）;BPH组与PCa组的s／uPSA分别为（2．32±0．61）和（4．13±1．09），PCa组s／uPSA比值明显高于BPH组，差别具有统计学意义（t=4．17，P〈O．01）。s／uPSA比值和sPSA的ROC曲线下面积分别为0．836和0．703。在保持95％敏感性时，s／uPSA比值和sPSA的特异性分别为77．1％和39．6％。结论在血清PSA值4．0～10．0ng／ml范围内，s／uPSA比值较sPSA更好地检出前列腺癌：在保持同一敏感性时，s／uPSA较sPSA具有更高的特异性。     

Salvage radiation for a rising PSA following radical prostatectomy

The purpose of this study was to evaluate the efficacy and complications of postprostatectomy therapeutic irradiation (RT) in patients with known residual disease. Between 1991 and 2003, 170 patients received therapeutic irradiation for a rising PSA following radical prostatectomy. No patients had clinical or radiological evidence of metastatic disease. The median pre-RT PSA level was 1.2 ng/mL (range, 0.2-43 ng/mL). During irradiation, the PSA level was checked weekly (median PSA determinations: 5, range, 2-7). A patient was considered to have a rise/fall of PSA if the level changed by > or = 0.2 ng/mL. There were 149 patients who received photon irradiation (median dose, 6800 cGy) and 21 patients received a combination of photon and neutron irradiation to a median photon dose equivalent of 7800 cGy. A patient was considered to have biochemical failure if his PSA level postnadir was measured at >0.2 ng/mL. Complications were graded according to the RTOG toxicity scale. The median follow-up time was 49 months (range, 1-137 months). Sixty-four patients (38%) had evidence of biochemical failure. The 7 year overall survival was 84%. At 7 years, the actuarial biochemical relapse free survival (bRFS) was 44%. Of the 59 patients with a preradiation PSA <1 ng/mL, the 5 year bRFS was 81%. This compares with 45% for both the PSA 1-4 and PSA >4 ng/mL group (P = 0.00008). The 3-year bRFS rates for patients whose PSA levels increased, decreased, and remained the same during radiation were 20%, 65%, and 76%, respectively (P = 0.0005). Overall survival at 7 years in the decreased PSA group was 88% compared to 67% for those whose PSA level increased (P = 0.43). Thirty-three percent and 19% of the patients experienced Grade 2 genitourinary (GU) and gastrointestinal (GI) complications, respectively. Six percent and 3% of the patients had Grade 3 GU and GI complications, respectively. On univariate and multivariate analysis, the factors significantly associated with a favorable outcome were a declining PSA during RT and a pre-RT PSA <1 ng/mL (P < 0.001). Radiation therapy is an effective treatment modality for select patients with a biochemical recurrence following radical prostatectomy. Patients with a low preradiation PSA level (<1.0 ng/mL) had a significantly better outcome, which supports the early use of therapeutic radiation. The observation that patients with a rising PSA level during treatment do poorly supports the routine practice of monitoring these levels during radiotherapy.