Does normalizing PSA after successful treatment of chronic prostatitis with high PSA value exclude prostatic biopsy?

Objective

Evaluate male patients with diagnosed chronic prostatitis, elevated serum prostate-specific antigen (PSA) to find out whether medical treatment with antibiotics and anti-inflammatory drugs can lower serum PSA, and consequently decrease the prostate cancer detection rate in patients with post-treatment PSA<4 ng/mL.

Materials and methods

This prospective study evaluated 142 male patients aged 40-73 years whose presented with elevated serum PSA>4 ng/mL and were consequently diagnosed with chronic prostatitis as expressed prostatic excretions examination revealed more than 10 white blood cells per high power field. The Patients underwent treatment with antibiotics and nonsteroidal anti-inflammatory agents for 6-weeks. Subsequently, all patients are Followed-up by serum PSA and performed transrectal ultrasonography-guided prostate biopsy within 2 months of treatment.

Results

Mean patient age was (54.4±13.5) years. The mean PSA pretreatment was (8.11±3.7) ng/mL and after treatment, the mean PSA denoted a significant decrease to (4.7±3.5) ng/mL (P=0.002). The percent of changes in mean PSA was 41.9%. Prostatic biopsy after treatment showed that, cancer prostate in 31 patients (21.8%), chronic prostatitis in 71 patients (50.7%), chronic prostatitis plus benign prostatic hyperplasia (BPH) in 31 (21.8%) and BPH in 9 patients (6.3%) With regard to PSA values, cancer prostate patients were 3/25 (12%) if PSA<2.5 ng/mL, 6/47 (12.7%) if 4.0>PSA≥2.5 and 21/70 (30%) if PSA≥4.0. The numbers of cancer prostate detected patients were 30 (21.1%).

Conclusions

Chronic prostatitis is one of the causes that elevate serum PSA levels. Treatment of chronic prostatitis with elevated PSA by antibiotics and anti-inflammatory agents can decrease the elevated PSA to the normal levels. Nevertheless, the opportunities of potential prostate cancer still exist in patients with a decreased PSA level even also if PSA<2.5 ng/mL.     

The 20-core prostate biopsy as an initial strategy: impact on the detection of prostatic cancer

Introduction:

To increase the detection rate of prostate cancer in recent years, we examined the increase in the number of cores taken at initial prostate biopsy. We hypothesized that an increasing number of cores may undermine the accuracy of models predicting the presence of prostate cancer at initial biopsy in patients submitted to 20-core initial biopsy.

Methods:

A total of 232 consecutive patients with prostate-specific antigen (PSA) between 4 and 20 ng/mL and/or abnormal digital rectal examination (DRE) underwent 12-core prostate biopsy protocol (group 1) or 20-core prostate biopsy protocol (group 2). The patients were divided into subgroups according to the results of their serum PSA and prostate volume. We evaluated the cancer detection rate overall and in each subgroup. Clinical data were analyzed using chi-square analysis and the unpaired t-test or 1-way ANOVA with significance considered at 0.05.

Results:

The 2 groups of patients were not significantly different with regard to parameters (age, abnormal DRE and serum PSA), although median prostate volume in group 1 (57.76 ± 26.94 cc) were slighter greater than in group 2. Cancer detection rate for patients submitted to 20 prostate biopsy was higher than patients submitted to 12 prostate biopsy (35.2% vs. 25%, p = 0.095). Breakdown to PSA level showed a benefit to 20 prostate biopsy for PSA <6 ng/mL (37.1% vs. 12.9%, p = 0.005). Stratifying results by prostate volume, we found that the improvement of cancer detection rate with 20 prostate biopsy was significant in patients with a prostate volume greater than 60 cc (55% in 20 prostate biopsy vs. 11.3% p < 0.05). Morbidity rates were identical in groups 1 and 2 with no statistically significant difference. There appeared to be no greater risk of infection and bleeding with 20 prostate biopsy protocol.

Conclusion:

The 20-core biopsy protocol was more efficient than the 12-core biopsy protocol, especially in patients with prostate specific antigen <6 ng/mL and prostate volume greater than 60 cc.     

Prostate-specific antigen 1.5-4.0 ng/mL: a diagnostic challenge and danger zone

Study Type – Prognosis (inception cohort) Level of Evidence 1b What’s known on the subject? and What does the study add? Large population screening trials like the ERSPC, PCPT and PLCO have noted that men with seemingly low PSA (even as low as 0.5 ng/dL) still can have prostate cancer. Despite these findings, PSA is still predominantly used as a current indicator for possible presence of prostate cancer rather than also serving as a prognostic marker. This study examines a larger number of men in a diverse US population to determine the prognostic value of a man’s baseline or first PSA.

OBJECTIVES

? To assess the value of a PSA threshold of 1.5 ng/mL as a predictor of increased prostate cancer risk over a four‐year period based on a man’s first PSA test, including racial differences. ? To review the risk of progression of benign prostatic hyperplasia (BPH) based on a similar PSA threshold.

PATIENTS AND METHODS

? A retrospective review involving 21 502 men from a large Midwestern health system was performed. ? Men at least 40 years old with baseline PSA values between 0 and 4.0 ng/mL and at least four years of follow‐up after initial PSA test were included. ? Optimal PSA threshold and predictive value of PSA for development of prostate cancer were calculated.

RESULTS

? Prostate cancer rates were 15‐fold higher in patients with PSA ≥1.5 ng/mL vs patients with PSA <1.5 ng/mL (7.85% vs 0.51%). ? African American patients with baseline PSA <1.5 ng/mL faced prostate cancer rates similar to the whole study population (0.54% vs 0.51%, respectively), while African American patients with PSA 1.5–4.0 ng/mL faced a 19‐fold increase in prostate cancer.

CONCLUSION

? Both Caucasian and African American men with baseline PSA values between 1.5 and 4.0 ng/mL are at increased risk for future prostate cancer compared with those who have an initial PSA value below the 1.5 ng/mL threshold. ? Based on a growing body of literature and this analysis, it is recommended that a first PSA test threshold of 1.5 ng/mL and above, or somewhere between 1.5 and 4.0 ng/mL, represent the Early‐Warning PSA Zone (EWP Zone). ? This should serve to inform patients and clinicians alike to future clinical activities with respect to prostate cancer and BPH.     

Recommendations by Canadian urologists and radiation oncologists for the treatment of clinically localized prostate cancer

Objective

Previous work has shown that urologists and radiation oncologists prefer the treatment that they themselves deliver when treating clinically localized prostate cancer. Our objective was to determine whether Canadian radiation oncologists and urologists have similar biases in favour of the treatments that they themselves deliver for localized prostate cancer.

Methods

We developed a survey to poll the beliefs that Canadian radiation oncologists and urologists held toward prostate specific antigen (PSA) screening, survival benefits of treatment, recommendations for treatment of prostate cancer and the likelihood of side effects with each therapy.

Results

Urologists were more likely to recommend routine PSA screening for men up to age 70 (p < 0.001), while radiation oncologists were more likely to recommend PSA screening for men over age 80 (p < 0.04). More urologists felt that there was “definitely” a survival advantage with radical prostatectomy (RP) (60% v. 21%, p < 0.001). More radiation oncologists recommend external beam radiation therapy (EBRT) (p < 0.01) or brachytherapy (p < 0.03) to treat low-risk prostate cancer. More urologists than radiation oncologists recommend RP for intermediate-risk patients (98% v. 70%, p < 0.001).

Conclusion

Most Canadian urologists and radiation oncologists recommend routine PSA screening for men aged 50 to 70. A significant preference was detected among both urologists and radiation oncologists for the treatment that they themselves deliver. While both urologists and radiation oncologists recommend prostatectomy for the treatment of low-risk localized prostate cancer, urologists are significantly less likely to recommend EBRT. Conversely, when patients present with intermediate-risk prostate cancer, radiation oncologists were significantly less likely than urologists to recommend a prostatectomy.     

Outcome of Transurethral Plasmakinetic Vaporization for Benign Prostatic Hyperplasia

Purpose

To assess the outcome of transurethral plasmakinetic vaporization (PKVP) in the management of benign prostatic hyperplasia (BPH).

Patients and methods

From August 2010 to May 2012, 60 patients with obstructive LUTS due to BPH were included in the study. All patients were evaluated by International Prostate Symptom Score (IPSS), general examination, digital rectal examination, PSA, routine laboratory examinations, pelvi-abdominal ultrasound, trans-rectal ultrasound, and uroflowmetry. Patients with Qmax of <10 mL/sec., an IPSS of >8 and a prostate volume of >40 mL underwent transurethral PKVP.

Results

Mean age of the patients was 66.8±4.5 years. The mean times of the operation, post-operative bladder irrigation, and post-operative catheterization were 63.8±13.9 minutes, 15.2±5.7 hours, and 23.9±5.2 hours, respectively. At 3 months of follow-up, there were significant reductions in the mean IPSS from 23.4±3.5 to 9.2±3.7 (P=0.4), mean PSA from 3.03±2.2 ng/mL to 1.2±1.04 ng/mL (P value=0.02), mean post voiding residual urine from 149.8±59.5 mL to 46.9±24.1 mL (P value <0.01), and mean prostate volume from 72.8±10.3 mL to 22.7±6.1 mL (P value <0.01). Also, there was a statistically significant increase in the mean Q max. from 8.7±2.4 mL/s to 19.5±3.5 mL/s (P value <0.01).

Conclusion

PKVP is an effective and safe treatment option in the management of symptomatic BPH.     

Insulin-like growth factor (IgF)-I,IgF binding protein-3, and prostate cancer: correlation with gleason score

Introduction

Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa).

Objective

This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH).

Materials and Methods

This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups.

Results

PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p<0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p<0.001) and at the inclusion in the study (p<0.001) and IGFBP3 (0.016) among patients with Gleason <7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason <7 and ≥7.

Conclusions

Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients.     

Radical prostatectomy for high-risk clinically localized prostate cancer: a prospective single institution series

Objective:

The objective of this paper is to report on the pathologic and biochemical progression-free outcomes of patients who underwent radical prostatectomy for high-risk localized prostate cancer.

Methods:

Data was collected prospectively from 299 patients who underwent radical prostatectomy for high-risk clinically localized prostate cancer by 2 surgeons at a single institution. High risk was defined as 1 or more of 3 adverse factors: prostate-specific antigen (PSA) >20, biopsy Gleason score 8 to 10 and clinical stage T3. PSA recurrence was defined as PSA >0.4 ng/mL or any salvage therapy.

Results:

Median age was 63.3 years (46.1–75.9). Median follow-up was 4.7 years (range 0.5–17.3 years). PSA at diagnosis was >20 ng/mL in 31.4%. Biopsy Gleason score was 8 to 10 in 66.9%. Clinical stage was T3 in 24.4%. 81.6% of patients had a single baseline risk factor, 15.7% had 2 risk factors and 2.7% had all 3 risk factors. Neoadjuvant therapy was administered to 184 patients (61.5%). Pathologic stage was organ-confined in 39.6%, specimen-confined in 26%, non-specimen-confined in 26.4%, and 8% had lymph node positive disease. Overall survival, cancer-specific survival and biochemical progression-free survival was 99%, 99.67% and 70.2%, respectively. Univariate analysis showed that PSA at diagnosis, percentage of cores positive and number of risk factors were predictors of PSA recurrence (p < 0.05). Multivariate analysis showed that PSA at diagnosis was an independent predictor of PSA recurrence (p < 0.05).

Conclusion:

Radical prostatectomy is associated with favourable biochemical progression-free, clinical and overall survival in selected men with high-risk localized prostate cancer, and should therefore be considered an option in these patients. Baseline PSA >20 ng/mL is a significant independent predictor of PSA recurrence.     

Measurement of serum zinc improves prostate cancer detection efficiency in patients with PSA levels between 4 ng/mL and 10 ng/mL

Aim： To investigate whether the measurement of serum zinc may improve the detection of prostate cancer （PCa） in men who had total prostate-specific antigen （PSA） levels higher than 4.1 ng/mL. Methods： A mass screening for PCa of 3940 men over 50 years old was undertaken using total serum PSA. Of the 190 men （4.8 %） with elevated PSA, 143 （3.6 %） underwent a transrectal ultrasonography （TRUS）-guided biopsy of the prostate, and 42 men （1% of total and 29.3 % of men undergoing biopsy） were found to have cancer. The areas under the receiver operating characteristic curves （ROC-AUC） were used to compare the diagnostic power of cancer detection by means of serum zinc, and free PSA/total PSA ratio （fit）. Results： The men with levels of serum zinc that ranged from 40 ng/mL-60 ng/mL, had an age-adjusted odds ratios（OR） of 5.0. A cutoff value of 100 gg/mL for-serum zinc concentration provided a sensitivity of 90.5 % and a specificity of 32.7 % in elevated PSA range, and a sensitivity of 93.3 % and specificity of 27.1% in gray zone, respectively. In the gray zone ranges of 4.1 ng/mL-10.0 ng/mL, the ROC-AUC for zinc was 73.0 % higher than 62.7 % of f/t PSA ratio and 56.7 % of total PSA. Conclusion： PCa displays a lower serum zinc concentration. The measurement of zinc levels improves PCa detection in the gray zone compared with the f/t PSA ratio and total PSA. （Asian J Androl 2005 Sep; 7： 323-328）     

Who’s too old to screen? Prostate cancer in elderly men

Introduction:

Prostate cancer is the most common nonskin malignancy affecting men and is the second leading cause of cancer-related death in North America. The incidence of prostate cancer increases dramatically with age. However, many health authorities advocate the cessation of routine prostate cancer testing in men older than 75 because of the belief that most patients will have a clinically insignificant cancer and will not benefit from therapy. The true prevalence of clinically significant prostate cancer in elderly men is not known.

Methods:

We analyzed 1446 needle biopsies of the prostate in men aged 75 or older. All pathological reviews were conducted by the pathology department at the Methodist Hospital in Houston, Tex. Data were collected from pathology reports, hospital and clinic databases, and medical records when available. Data obtained included age at biopsy, serum prostate-specific antigen (PSA) levels, number of positive core biopsies and Gleason grade. Statistical analysis was performed using Stata. Clinically significant cancer was defined by the pathological presence of Gleason grade 6 adenocarcinoma in more than 1 biopsy core or the presence of any Gleason 4 or 5 component in the biopsy.

Results:

The median age of the patients included in the study was 78.8 and 95% of the patients were between the ages of 75 and 85. The mean serum PSA level for patients biopsied was 10.4 μg/L. Of all biopsies reviewed, 53% were positive for prostate cancer and 78% of these would be defined as clinically significant cancer. Regression analysis revealed age to be a significant (p < 0.05) factor for increased Gleason grade in positive biopsies. Logistic regression revealed age as a significant factor (p < 0.05) for clinically significant prostate cancer even when controlling for PSA. A serum PSA threshold value of 6.5 μg/L would have missed 38% of significant cancers and a threshold of 4.0 μg/L would have missed 8% of significant cancers.

Conclusion:

Our findings suggest that the prevalence of clinically significant prostate cancer in the elderly population may be higher than previously thought. As the population continues to live longer and healthier lives, it will become more common to confront prostate cancer morbidity in the eldery population. Using higher serum PSA thresholds to eliminate unnecessary biopsies in older men does not appear to help identify patients at greater risk of having clinically significant prostate cancer. Patients with prostate cancer having aggressive clinical features may benefit from treatment of their prostate cancer well into their eighth and ninth decades of life. Testing and diagnostic recommendations should reflect the potential benefit of identifying patients with aggressive prostate cancer even after age 75.     

The association between tumour density and prostate cancer recurrence following radical prostatectomy

Purpose:

Tumour density (TD) may be an independent prognostic factor in men with prostate cancer. The purpose of this study was to evaluate the association between prostate cancer TD and recurrence following radical prostatectomy.

Materials and Methods:

Between 1995 and 2007, 645 patients from The Ottawa Hospital or Memorial Sloan-Kettering Cancer Center who had cancer and prostate volumes measured from radical prostatectomy specimens. Tumour density was defined as the relative tumour to prostate volume (tumour volume/prostate volume) and recurrence was defined as a prostate-specific antigen (PSA) >0.2 ng/mL and rising, or postoperative use of radiation or hormonal therapy. Associations between TD and recurrence are adjusted for preoperative PSA, prostatectomy Gleason sum, tumour stage and margin status.

Results:

Median follow-up was 40.8 months. Tumour density was associated with preoperative PSA, Gleason sum, tumour stage and surgical margin status (all p < 0.0001). As a continuous variable, TD predicted recurrence-free survival (adjusted HR 1.34 per 10% increase in TD; p = 0.04). As a categorical variable, the group of patients with a TD of >10% had a 2.7 times greater hazard of recurrence compared to patients with a TD <5% (95%CI 1.41, 5.19; p = 0.003). Despite the independent association between TD and recurrence, the clinical value of TD remains in question as the discriminative performance (area under the curve) of predictive models only improved from 0.865 to 0.876.

Conclusions:

Prostate cancer TD is associated with known prognostic factors and is also independently predictive of recurrence following radical prostatectomy.     

Prostate gland biopsies and prostatectomies: an Ontario community hospital experience

Objective

Transrectal ultrasound–guided core biopsies of the prostate gland and prostatectomies have become common procedures at many community hospitals in Canada, especially in the era of serum prostate-specific antigen (PSA) screening for prostate cancer. The Gleason grading of prostate cancer in biopsies and prostatectomies is a major determinant used for treatment planning. There is evidence in the literature that suggests important discordance between community hospital pathologists and urological pathologists with respect to the Gleason grading of prostate cancer. Our objective was to determine the diagnostic rates and Gleason scoring patterns for prostate gland biopsies and prostatectomies at our institution compared with the literature.

Methods

We conducted a retrospective review of all prostate gland biopsies and prostatectomies performed at the Grey Bruce Health Services from January 2005 to September 2005. We collected data from 194 biopsies and 44 prostatectomies. We obtained prebiopsy serum PSA levels and digital rectal exam results for all patients from urologists’ office records.

Results

The average age for men having biopsies was 65.8 (standard deviation [SD] 8.6) years, and the average prebiopsy serum PSA level was 8.7 (median 7.1, SD 6.2) μg/L. The rates of diagnosis from prostate gland biopsies of benign (17.6%), high-grade prostatic intraepithelial neoplasia (11.0%), atypical small acinar proliferation suspicious for invasive malignancy (13.2%) and invasive prostatic adenocarcinoma (58.2%) at our institution were significantly different than those reported in the literature (p < 0.001). We observed a significant variation in the rates of these diagnoses among the community hospital pathologists in our study (p = 0.004). There was a strong correlation between the increasing number of positive core biopsy sites and increasing Gleason scores in biopsies (p < 0.001). There was also a strong correlation between increasing pre-biopsy serum PSA levels and increasing Gleason scores in biopsies (p < 0.001). A substantial proportion (21.9%) of the biopsies given the Gleason score of 6 had a Gleason score of 7 in the prostatectomy specimen.

Conclusion

Our results showed a significant difference in prostate gland biopsy categorical diagnoses compared with the literature. There were also significant differences in categorical diagnoses of prostate gland biopsies among the community hospital pathologists in our study. The data identify a strong positive correlation between the increasing number of positive core biopsy sites and increasing Gleason scores in biopsies, as well as a strong positive correlation between increasing prebiopsy serum PSA levels and increasing Gleason scores in biopsies that revealed cancer. We would encourage other community hospital pathologists, in collaboration with their urologists, to review periodically their prostate gland pathology practices in an attempt to improve the uniformity of diagnoses.     

Dietary habits and prostate cancer detection: a case–control study

Background

Many studies have suggested that nutritional factors may affect prostate cancer development. The aim of our study was to evaluate the relationship between dietary habits and prostate cancer detection.

Methods

We studied 917 patients who planned to have transrectal ultrasonography–guided prostatic biopsy based on an elevated serum prostate-specific antigen (PSA) level, a rising serum PSA level or an abnormal digital rectal examination. Before receiving the results of their biopsy, all patients answered a self-administered food frequency questionnaire. In combination with pathology data we performed univariable and multivariable logistic regression analyses for the predictors of cancer and its aggressiveness.

Results

Prostate cancer was found in 42% (386/917) of patients. The mean patient age was 64.5 (standard deviation [SD] 8.3) years and the mean serum PSA level for prostate cancer and benign cases, respectively, was 13.4 (SD 28.2) μg/L and 7.3 (SD 4.9) μg/L. Multivariable analysis revealed that a meat diet (e.g., red meat, ham, sausages) was associated with an increased risk of prostate cancer (odds ratio [OR] 2.91, 95% confidence interval [CI] 1.55–4.87, p = 0.027) and a fish diet was associated with less prostate cancer (OR 0.54, 95% CI 0.32–0.89, p = 0.017). Aggressive tumours were defined by Gleason score (≥ 7), serum PSA level (≥ 10 μg/L) and the number of positive cancer cores (≥ 3). None of the tested dietary components were found to be associated with prostate cancer aggressivity.

Conclusion

Fish diets appear to be associated with less risk of prostate cancer detection, and meat diets appear to be associated with a 3-fold increased risk of prostate cancer. These observations add to the growing body of evidence suggesting a relationship between diet and prostate cancer risk.     

游离PSA与总PSA比值在前列腺癌鉴别诊断中的意义

目的　探讨游离前列腺特异性抗原 (fPSA)与总前列腺特异性抗原 (tPSA)比值 (f tPSA)在tPSA为 4～ 10ng ml时对前列腺癌和良性前列腺增生 (BPH)鉴别的意义及其局限性。方法　对1998年 10月至 2 0 0 2年 10月接受诊治的 180例血清tPSA为 4～ 10ng ml的前列腺癌和BPH患者进行回顾性分析。经组织学证实 ,36例 (2 0 % )是前列腺癌 ,14 4例 (80 % )是BPH。血清中tPSA和fPSA通过酶免微粒子捕捉法测定。前列腺体积通过经腹壁超声测定。前列腺癌与BPH组间比较用t检验。采用Pearson相关系数分析前列腺体积与f tPSA之间的相关性。结果　前列腺癌患者的tPSA、f tPSA平均值分别是 6 75ng ml与 0 17;BPH患者则是 6 4 8ng ml和 0 2 5。两组患者的tPSA差异无显著意义 (P >0 0 5 ) ,而前列腺癌患者的f tPSA值显著低于BPH患者 (P <0 0 1)。此外 ,两组患者的前列腺体积与f tPSA均呈显著正相关 (前列腺癌组相关系数r=0 5 0 ,P <0 0 1;BPH组r=0 2 4 ,P <0 0 1)。在前列腺体积小于 4 0cm3,两组患者的f tPSA差异有显著意义 (P <0 0 5 ) ,当体积超过 4 0cm3,则差异无显著意义 (P >0 0 5 )。结论　f tPSA对tPSA在 4～ 10ng ml之间的前列腺癌和BPH的鉴别诊断有重要意义 ,但由于受前列腺体积的影响 ,只有在     

Annual PSA tests are not necessary for men with a PSA level below 2 ng/mL: Findings of the Imari prostate cancer screening program

BACKGROUND: Annual changes in prostate specific antigen (PSA) levels detected by the Imari prostate cancer screening program were evaluated to establish a more efficient and cost-saving screening system, especially for men with low PSA levels. METHODS: Prostate specific antigen-based annual mass screenings for prostate cancer were conducted for men aged 60-69 in the Imari district, Saga, Japan. Between 1992 and 2000, 1822 men had their PSA levels tested. A total of 4661 PSA tests were conducted. Changes in PSA levels over the following 1 to 5 years were analyzed in men with PSA levels of 3 ng/mL or less, a range in which the detection rate of prostate cancer would seem to be negligibly low. RESULTS: The overall detection rate of prostate cancer between 1992 and 2000 was 0.73%. The detection rate in men with a PSA level between 3.1 and 3.9 ng/mL, and between 4 and 9.9 ng/mL was 1.6% and 8.3%, respectively. Of 4661 determinations of PSA, 2553 (54.8%) were found to be < or = 1 ng/mL, 1273 (27.3%) were between 1.1 and 2 ng/mL, and 401 (8.6%) were between 2.1 and 3 ng/mL. Four hundred and thirty-four men (9.3%) had PSA levels > or = 3.1 ng/mL, with possible indications for prostate biopsy. Of the men tested, 1.4% with an initial PSA level of < or = 2 ng/mL and 22.3% with an initial level between 2.1 and 3 ng/mL had a PSA level of > or = 3.1 ng/mL after 1 year. Almost the same rate of PSA increase was observed between the two PSA tests conducted at 2 to 5-year intervals. Of the men tested, 2.2% with an initial PSA level of < or = 2 ng/mL, and 21.9% with an initial level between 2.1 and 3 ng/mL, had a level of > or = 3.1 ng/mL after 5 years. CONCLUSION: Levels of PSA in men with an initial level below 2 ng/mL remained stable for up to 5 years. Levels of PSA in 97.8- 98.8% of men remained below 3 ng/mL after 1 to 5 years. In contrast, 18-35.3% of men with an initial PSA level between 2.1 and 3 ng/mL showed PSA progression to 3.1 ng/mL or more within 5 years. Our present data suggest that annual PSA testing is not necessary for men with a PSA level below 2 ng/mL. Prostate specific antigen testing could therefore be conducted at longer intervals in such individuals.     

Pathological correlation between needle biopsy and radical prostatectomy specimen in patients with localized prostate cancer

Objective

This study aims to evaluate the accuracy of transrectal ultrasound (TRUS) guided prostate biopsies in predicting pathological grading and tumour distribution in the final pathological specimen of patients who underwent radical prostatectomy for clinically localized prostate cancer. The study ultimately aims to gain more understanding of the pathological behaviour of prostate cancer and the limitations of the currently available diagnostic and prognostic tools.

Material and Methods

We reviewed the records of 100 patients with localized carcinoma of the prostate diagnosed by TRUS-guided prostate biopsy and treated with radical retropubic prostatectomy, comparing tumour laterality and Gleason score in core biopsies with tumour distribution and Gleason score of the surgical specimen. We then correlated both results to diagnostic and prognostic variables such as prostate specific antigen (PSA) values and surgical margins.

Results

All 44 patients with bilateral disease on needle biopsy had bilateral disease on final pathology, with 15 of these patients (34%) having positive margins. Of the 56 patients with unilateral disease on biopsy, 37 (66%) had bilateral disease on final pathology; however, only 4 of them (7%) had positive margins (p < 0.001). Median Gleason score on final pathology was upgraded to 7, compared with a median score of 6 on biopsies. Stratifying patients to 2 groups based on their PSA level (group 1: PSA < 10 ng/mL, 72 patients; group 2: PSA > 10ng/mL, 28 patients), revealed that 57 patients (79%) in group 1 and 24 patients (85%) in group 2 had bilateral disease. In addition, 13 patients (18%) in group 1 and 6 patients (21%) in group 2 had positive margins.

Conclusions

Sixty-six percent of patients with unilateral disease on needle biopsy had bilateral disease on final pathology, but this does not increase their rate of having positive margins. Gleason score is upgraded from 6 to 7. PSA did not seem to affect laterality of disease in patients selected for radical prostatectomy.     

Characterizing prostatic adenocarcinomas in men with a serum prostate specific antigen level of < 4.0 ng/mL

OBJECTIVE: To characterize prostate cancer in men undergoing radical prostatectomy who have a prostate-specific antigen (PSA) level of < 4.0 ng/mL, hypothesizing that a low PSA is not caused by diminished tumour production of PSA, nor does it signify clinically insignificant disease. PATIENTS AND METHODS: Seventy-nine men (mean age 59.3 years, range 43-77) with a PSA level of < 4.0 ng/mL were identified from 702 who had a radical prostatectomy between 1994 and 2000. Demographic and clinical data were analysed; pathological specimens were evaluated by routine haematoxylin and eosin staining and immunohistochemistry with anti-PSA antibody, for both pathological staging and grading, and for the presence of PSA production. Tumours were classified as 'clinically insignificant' if the tumour volume was < 0.5 mL and the Gleason score < 7. RESULTS: The mean (SD, range) preoperative PSA level was 3.04 (0.85, 0.8-3.8) ng/mL Indications for biopsy included an abnormal digital rectal examination (61%), a PSA velocity of > 0.75 ng/mL/year (12%), a strong family history of prostate cancer (3%), obstructive urinary symptoms (2%), or no obvious indication (23%). Thirty-eight (48%) tumours were clinically insignificant. Of 41 clinically significant cancers, 13 had a final Gleason score of > or = 7, 20 had extraprostatic extension and 11 had a tumour volume of > or = 10 mL Of the 79 prostate cancer specimens 78 stained strongly for PSA; the exception was a Gleason 9 tumour. With a mean (range) follow-up of 3.5 (0.18-6) years only one patient had a biochemical recurrence (PSA > or = 0.1 ng/mL). CONCLUSIONS: Most prostate cancers in men with a PSA level of < 4.0 ng/mL are clinically significant and PSA-producing. Many of these tumours are high-grade, high-volume and extraprostatic. We are currently exploring factors to explain why serum PSA is not elevated in these men, including tumour location, pattern of invasion and microvessel density.     

Prostate-specific antigen (PSA) isoform p2PSA significantly improves the prediction of prostate cancer at initial extended prostate biopsies in patients with total PSA between 2.0 and 10 ng/ml: results of a prospective study in a clinical setting

Background

Total prostate-specific antigen (tPSA), ratio of free PSA (fPSA) to tPSA (%fPSA), and PSA density (PSAD) testing have a very low accuracy in the detection of prostate cancer (PCa). There is an urgent need for more accurate biomarkers.

Objective

To compare the diagnostic accuracy of PSA isoform p2PSA and its derivatives in determining the presence of PCa at initial biopsy with the accuracy of other predictors in patients with tPSA 2.0-10 ng/ml.

Design, setting, and participants

We conducted an observational prospective study in a real clinical setting of consecutive men with tPSA 2.0-10 ng/ml and negative digital rectal examination who were scheduled for prostate biopsy at a tertiary academic center.

Intervention

Outpatient transrectal ultrasound-guided prostate biopsies were performed according to a standardized institutional saturation scheme (18-22 cores).

Measurements

We determined the diagnostic accuracy of serum tPSA, %fPSA, PSAD, p2PSA, %p2PSA [(p2PSA/fPSA) × 100] and the Beckman Coulter Prostate Health Index (phi; [p2PSA/fPSA × √tPSA]).

Results and limitations

Overall, 107 of 268 patients (39.9%) were diagnosed with PCa at extended prostate biopsies. Statistically significant differences between patients with and without PCa were observed for age, prostate and transition zone volume, PSAD, %p2PSA, and phi (all p values < 0.05). In univariate accuracy analysis, phi and %p2PSA were the most accurate predictors of PCa (area under the curve: 75.6% and 75.7%, respectively), followed by transition zone volume (66%), prostate volume (65%), patient age (63%), PSAD (61%), %fPSA (58%), and tPSA (53%). In multivariate accuracy analyses, both phi (+11%) and %p2PSA (+10%) significantly improved the accuracy of established predictors in determining the presence of PCa at biopsy (p < 0.001). Although %p2PSA and phi were significantly associated with Gleason score (Spearman ρ: 0.303 and 0.387, respectively; p ≤ 0.002), they did not improve the prediction of Gleason score ≥7 PCa in multivariable accuracy analyses (p > 0.05).

Conclusions

In patients with a tPSA between 2.0 and 10 ng/ml, %p2PSA and phi are the strongest predictors of PCa at initial extended biopsies and are significantly more accurate than the currently used tests (tPSA, %fPSA, and PSAD) in determining the presence of PCa at biopsy.     

Detection of residual prostate cancer after radical prostatectomy with the Abbott IMx PSA assay

Objectives

This analysis was performed to define the level of serum prostate-specific antigen (PSA) measured with the Abbott IMx assay that indicates residual or progressive prostate cancer after radical retropubic prostatectomy (RRP).

Methods

Since March 1992, we have used the Abbott IMx assay to determine PSA levels. Between March 1992 and June 1994, 102 of those patients having RRPs were found to have pathologic Stage C prostate cancer. Fifty-one of these patients had at least one serum PSA measurement of 0.1 ng/mL or greater. Eight patients were excluded from the analysis because they received postoperative radiotherapy that might have influenced subsequent PSA levels. The remaining 43 patients are the subjects of this analysis and were evaluated to determine the “clinical threshold” or minimal serum PSA level after RRP indicative of progressive disease. Patients were followed for 6 to 36 months (median 23 months) from the date of the RRP. Failure was defined as a subsequent increase of PSA to greater than 0.3 ng/mL. Freedom from failure was determined using the Kaplan-Meier product limit method.

Results

Of the patients with at least one postoperative serum PSA level of 0.1 ng/mL, the subsequent freedom from failure was 80% at 23 months as compared with 13% in patients with at least one postoperative PSA level of 0.2 ng/mL (p = 0.003).

Conclusions

Following RRP for pathologic Stage C prostate cancer, a solitary PSA level of 0.1 ng/mL (measured with the IMx assay) was followed by a progressive rise in PSA levels in only a minority of patients within the first 2 years after surgery. In contrast, the majority of patients with a postoperative PSA level of 0.2 ng/mL subsequently had progressively rising PSA levels. This indicates that a serum PSA level of 0.2 ng/ mL is reflective of residual prostate cancer.     

PSA velocity for assessing prostate cancer risk in men with PSA levels between 2.0 and 4.0 ng/ml

Objectives. To evaluate the use of prostate-specific antigen (PSA) velocity (PSAV) in assessing prostate cancer risk among men with PSA levels less than 4.0 ng/mL.Methods. The relative risk of, and cumulative probability of freedom from, prostate cancer by PSAV was evaluated in 89 male participants (21 with cancer and 68 controls) of a longitudinal aging study—the Baltimore Longitudinal Study of Aging (National Institute on Aging)—who had serial PSA levels between 2.0 and 4.0 ng/mL for at least 18 months. The relative risk was estimated from a Cox proportional hazards regression model, and the disease-free probability was determined by Kaplan-Meier survival analysis. The sensitivity and specificity of PSAV were calculated as a measure of test validity.Results. The sensitivity and specificity of a PSAV of 0.1 ng/mL per year was 81% and 50%, respectively. The relative risk of prostate cancer was 6.53 (range 1.90 to 22.51) when the PSAV was 0.1 ng/mL per year or more compared with a PSAV of less than 0.1 ng/mL per year (P = 0.0029). At 10 years, the cumulative probability of freedom from prostate cancer was 97.1% (range 91.4% to 100%) and 35.2% (range 14.0% to 56.4%) when the PSAV was less than and greater than 0.1 ng/mL per year, respectively. Survival curves began to differ at less than 5 years after the baseline PSAV determination.Conclusions. The association between PSAV and the subsequent risk of prostate cancer suggests that the PSAV may be useful in the risk assessment of men with lower PSA levels.     

Perception of abnormal serum prostate-specific antigen (PSA) test results amongst family practitioners

INTRODUCTION

With increased use of serum prostate-specific antigen (PSA) testing, prostate cancers are diagnosed at an earlier stage in younger men, when radical curative treatments are appropriate. Modifications of the PSA test such as PSA velocity and age-adjusted values are available to aid in the selection of patients for biopsy. However, it is not clear whether these data are used in general practice.

PATIENTS AND METHODS

A self-administered questionnaire was mailed to all primary care practices within one region in the UK. A series of visual analogue questions designed to identify referral thresholds for age-adjusted PSA levels and PSA velocity were used to identify patterns in referral behaviour.

RESULTS

Individual family practitioners see only small numbers of patients requesting PSA tests or with newly diagnosed prostate cancer each year. The median (range) thresholds considered for referral at ages 45, 55, 65, 75 and 85 years were 4.5 ng/ml (2.5–15.5 ng/ml), 5.5 ng/ml (3.0–15.5 ng/ml), 6.5 ng/ml (3.5–15.5 ng/ml), 6.5 ng/ml (3.5–25.5 ng/ml), and 7.5 ng/ml (3.5–25.5 ng/ml), respectively. Only 5% of practitioners correctly identified the age-specific PSA threshold for referral of a 45-year-old man.

CONCLUSIONS

It is important to remember that younger men (even those in their forties and fifties) may be at risk of prostate cancer even if asymptomatic. It is important in a climate of increasing demand for PSA testing that those who initiate the process understand the implications and limitations of testing, including appropriate triggers for referral to secondary care. The exact approach required for the successful dissemination of this information to primary care is not clear, but our data suggest that a better understanding is required.