Transition zone PSA density improves the prostate cancer detection rate both in PSA 4.0–10.0 and 10.1–20.0 ng/ml in Chinese men

ObjectivesWe hypothesized the prostate-specific antigen (PSA) “grey zone” in Chinese men was higher than the traditional value (4.0–10.0 ng/ml) since incidence of prostate cancer (CaP) in Chinese men was relative low. We then assessed the efficiencies of transition zone PSA density (TZPSAD) in the diagnosis of CaP in Chinese men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml.Materials and methodsMen had a prostatic biopsy for detecting CaP from November 1999 to August 2009 were retrospectively retrieved from our computer center. Those had a document of transrectal ultrasound transition zone measurement with a PSA of 4.0–20.0 ng/ml were included. Receiver-operating characteristic (ROC) curve was used to analyze the efficiencies of PSA and TZPSAD in the diagnosis of CaP.ResultsA total of 189 men were included in the study. Of these men, 78 and 111 had a PSA of 4.0–10.0 and 10.1–20.0 ng/ml, respectively. The rate of CaP in men with a PSA of 4.0–10.0 ng/ml was not statistically significantly different compared with those with a PSA of 10.1–20.0 ng/ml (20.5% vs. 21.6%, P = 0.854). The areas under the ROC curve (AUCs) in diagnosis of CaP for PSA and TZPSAD were 0.569 and 0.702 in men with a PSA of 4.0–10.0 ng/ml and 0.463 and 0.730 in men with a PSA of 10.1–20.0 ng/ml, respectively. The best cut-off of TZPSAD in predicting CaP in men with a PSA of 4.0–10.0 ng/ml was 0.370 ng/ml/ml, the sensitivity of which equaled 68.8%, specificity 72.6%. The best cut-off of TZPSAD in predicting CaP in men with a PSA of 10.1–20.0 ng/ml was 0.500 ng/ml/ml. Its sensitivity equaled 70.8%, specificity 70.1%.ConclusionsUsing TZPSAD can improve the efficiency of PSA in diagnosis of CaP and decreases the unnecessary prostatic biopsy in men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml in Chinese men.     

Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml?1

Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0–10.0 ng ml⁻¹, however, it remains controversial whether %fPSA is effective in PSA range of 10.1–20.0 ng ml⁻¹ in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml⁻¹ or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0–10.0 ng ml⁻¹ and 10.1–20.0 ng ml⁻¹, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0–10.0 ng ml⁻¹ and 10.1–20.0 ng ml⁻¹.     

A longitudinal study of PSA and its influential factors in a cohort of Chinese men with initial PSA levels less than 4?ng ml?1

To evaluate the longitudinal change in prostate-specific antigen (PSA) and the influence of initial PSA on the PSA change. We retrospectively analysed health examination data collected at Beijing Hospital from March 2007 to November 2011. Men with an initial PSA levels less than 4 ng ml⁻¹ and an annual PSA test for 5 years were enrolled into the study. The men were separated into four groups by the initial PSA level (0–0.99, 1–1.99, 2–2.99 and 3–3.99 ng ml⁻¹), and the difference in PSA change among the four groups was analysed. A total of 1330 men were enrolled into the study. The mean age, initial PSA and PSA velocity (PSAV) were 58.17±14.63 (range 24–91) years, 1.18±0.79 (range 0–4) ng ml⁻¹ and 0.04±0.25 (range −1.34–2.02) ng ml⁻¹ year⁻¹. Pearson''s correlation analysis showed no correlation between initial PSA and PSAV (r=−0.036, P=0.189). The PSAV of the 0–0.99, 1–1.99, 2–2.99 and 3–3.99 ng ml⁻¹ initial PSA groups was 0.03±0.11, 0.07±0.32, 0.03±0.34 and −0.01±0.43 ng ml⁻¹ year⁻¹, respectively (P=0.06). As the initial PSA increased, the percentage of having a PSAV over 0.75 ng ml⁻¹ year⁻¹ and a negative PSAV both significantly increased. Males with a baseline PSA of 0–0.99, 1–1.99, 2–2.99 and 3–3.99 ng ml⁻¹ had a 1.88%, 6.16%, 16.30% and 57.81% chance, respectively, that their PSA would increase above 4.0 ng ml⁻¹ over the following 4 years (P<0.0001). The PSAV has no correlation with the initial PSA level. However, as the initial PSA increases, the chance that males will have an abnormal PSA or PSAV in the future increases.     

Diagnostic significance of [−2]pro-PSA and prostate dimension-adjusted PSA-related indices in men with total PSA in the 2.0–10.0 ng/mL range

Purpose

One of the most important issues to address when developing an optimal screening system for prostate cancer is investigating appropriate biopsy indications following serum prostate-specific antigen (PSA) measurements in order to maintain high sensitivity and avoid unnecessary biopsy.

Methods

Between April 2004 and December 2007, 239 consecutive men with total PSA levels of 2.0–10.0 ng/mL underwent measurements of PSA, free PSA, and [?2]pro-PSA. We assessed the significance of laboratory-based PSA-related indices including free PSA/total PSA (%f-PSA), p2PSA/free PSA (%p2PSA), p2PSA/%f-PSA, Prostate Health Index (phi, an index combining PSA, free PSA, and p2PSA), total prostate volume (TPV)-adjusted PSA-related indices, including PSA density, %p2PSA density, p2PSA/%f-PSA density, and phi density, and transition zone (TZ) prostate volume-adjusted PSA-related indices such as PSA TZ density (PSATZD), %p2PSA TZD, p2PSA/%fPSA TZD, and phi TZD.

Results

The positive biopsy rate was 22.2 %. When sensitivity was fixed at 95 %, unnecessary biopsies could be avoided in 28 % of men when phi was used as a biopsy indication. In cases where total and transition zone prostate volumes were available, the use of %p2PSA density, phi density, p2PSA/%f-PSA TZD, and phi TZD resulted in the avoidance of 48, 47, 54, and 54 % of unnecessary biopsies, respectively, while maintaining a high sensitivity of 90 %.

Conclusions

At 90 and 95 % sensitivity, laboratory-based indices containing p2PSA, particularly phi, showed significantly greater specificity for prostate cancer as compared with %f-PSA. The diagnostic accuracy of prostate volume-adjusted p2PSA-related indices could be excellent, particularly the transition zone volume-adjusted indices at fixed sensitivities of 95 and 90 %.     

Mass screening of prostate cancer in a Chinese population：the relationship between pathological features of prostate cancer and serum prostate specific antigen

Aim: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a Chinese cohort and their association with serum prostate specific antigen (PSA). Methods: A total of 12027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen tPSA test (by Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA value was > 4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). Results: Of the 12027 cases, 158 (including 137 patients whose serum tPSA values were 4.0 ng/mL and 21 patients [serum tPSA < 4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34%, respectively. A significant linear positive correlation between the serum tPSA and the Gleason scores in the 41 cases of prostatic carcinoma (r = 0.312, P < 0.01) was established. A significant linear positive correlation between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor. Conclusion: This study was the first to conduct mass screening for prostate cancer by testing for serum tPSA values and the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the serum tPSA value in prostate cancer is associated with the Gleason score and the size of tumor.     

Free/total PSA ratio can help in the prediction of high gleason score prostate cancer in men with total serum prostate specific antigen (PSA) of 3–10 ng/ml

Purpose We evaluate the use of free/total prostate specific antigen (PSA) ratio in improving the prediction of cancers of higher Gleason scores. Patients and methods A total of 164 patients with total serum PSA of 3.0–10.0 ng/ml underwent extended TRUS-guided core biopsy. In each man serum free PSA was measured and the free/total (F/T) PSA ratio was calculated. Out of the 164 patients who underwent TRUS-biopsy, cancer was detected in 62 (37.8%) patients. The mean age for the 62 patients with histologically proven prostate cancer was 62.3 ± 5.5 years (49–73). The histological findings were compared with the free/total PSA ratio. Pearson Correlation Coefficient test and Chi-Square test (χ²-test) were used for statistical analysis and p < 0.05 was considered statistically significant. ResultsOf the 62 patients, 37 (59.7%) patients had cancers of low Gleason scores (score 2–6) and 25 (40.3%) patients had cancers of high Gleason scores (score 7–10). Free PSA < 0.15% was found in 19 (30.6%) patients, from 15 to 20% in 23 (37.1%) patients and > 20% in 20 (32.3%) patients. There was a significant positive correlation between total PSA and Gleason score (Pearson Correlation Coefficient test, r = 0.328, p < 0.01). Also, there was a significant increase in Gleason score with lower F/T PSA ratio (r = −0.668, p < 0.001). Among the 19 patients with free PSA ratio < 15%, 14 (73.7%) patients had cancers of high Gleason score while 5 (26.3%) patients had cancers of low Gleason score. In patients (n = 23) with free PSA ratio15–20%, 10 (43.5%) had cancers of high Gleason score and 13 (56.5%) had cancers of low Gleason score. In the 20 patients with free PSA ratio > 20%, 1 patient (5%), had prostate cancer of high Gleason score and the remaining 19 (95%) patients had low Gleason scores. There was a significant relation between lower F/T PSA ratios and higher Gleason scores, Chi-Square test, χ² = 19.3, p < 0.01. Conclusions In this study, men with prostate cancer and lower F/T PSA ratio were at a higher risk of having higher Gleason scores (7–10) and those with higher F/T PSA ratio were more likely to have lower Gleason scores.     

Prostate volume as an independent predictor of prostate cancer in men with PSA of 10–50?ng ml?1

Prostate volume (PV) has been shown to be associated with prostate cancer (PCa) detection rates in men with a prostate-specific antigen (PSA) in the ‘grey zone'' (2.0–10.0 ng ml⁻¹). However, the PSA ‘grey zone'' in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10–50 ng ml⁻¹. Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians (<60 and ≥60 ml), were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk (odds ratio, 0.02; P<0.001) compared to other variables. The PCa rates in men with PVs measuring <60 and ≥60 ml in the 10–19.9 ng ml⁻¹ PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20–50 ng ml⁻¹ were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10–50 ng ml⁻¹. In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10–50 ng ml⁻¹ regarding their PCa risks.     

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.     

Comparison of oncologic outcomes after radical prostatectomy in men diagnosed with prostate cancer with PSA levels below and above 4 ng/mL

Purpose

To assess whether the PSA level (threshold 4 ng/mL) is a prognostic factor in biochemical recurrence-free survival in men with prostate cancer (PCa) with an initial PSA level <10 ng/mL who underwent robotic-assisted laparoscopic radical prostatectomy (RARLP).

Methods

We prospectively recruited data for consecutive patients treated by RARLP for PCa with an initial PSA level below 10 ng/mL between 2003 and 2011 at our institution. We divided the population into two groups: patients with a PSA level below 4 ng/mL (G1; n = 53) and patients with a PSA level between 4 and 10 ng/mL (G2; n = 371). Biochemical recurrence was defined as a single increase in PSA greater than 0.2 ng/mL after surgery. Multivariate analysis was used to assess prognostic factors of recurrence-free survival.

Results

Overall, 424 patients were included, and the median age was 62 (58–67) years. The median PSA was 5.8 ng/mL (4.8–7.7 ng/mL). Overall, 6 patients from G1 and 34 patients from G2 experienced a biochemical recurrence. Overall, the 5-year recurrence-free survival rate was 86.6 %. The PSA level at diagnosis (under or over 4 ng/mL) was not significantly linked to recurrence-free survival (HR = 0.59, p = 0.25). However, positive margins and a Gleason score >7 on the specimen were significantly linked to recurrence-free survival with respective hazard ratios of 4.30 (p < 0.0001) and 6.18 (p < 0.0001), respectively.

Conclusion

A PSA level <4 ng/mL alone appears to be obsolete as a cut-off to define a population of men likely to have indolent disease.     

Are PSA density and PSA density of the transition zone more accurate than PSA in predicting the pathological stage of clinically localized prostate cancer?

PURPOSE: To assess whether PSA density (PSAD) and PSA density of the transition zone (PSADTZ) are more accurate than PSA alone in predicting the pathological stage of prostate cancer. MATERIALS AND METHODS: One hundred and nine consecutive patients with clinically localized prostate cancer and preoperative PSA values over the whole range, treated with radical retropubic prostatectomy and limited pelvic lymph node dissection were included in this prospective study. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. PSA, PSAD, and PSADTZ were compared to percentage of positive biopsy cores (% PC), biopsy and surgical Gleason score, and pathological stage, using univariate and multivariate analysis. RESULTS: Pathological stage was pT2a, pT2b, pT3a, and pT3b in 25.6%, 37.7%, 25.6%, and 11.1% of patients, respectively. Lymph node metastases were found in 4.6% of patients. PSA, PSAD, and PSADTZ were significantly related to % PC, biopsy, and surgical Gleason score and pathological stage (P < 0.001), and were equally able to predict higher pathological stage, i.e., seminal vesicle invasion and lymph node metastases. Only by adding % PC in multivariate analysis was it possible to discriminate intra- from extracapsular tumors. CONCLUSIONS: The results of the present study demonstrate that PSAD and PSADTZ failed to outperform PSA in preoperative stage prediction of prostate cancer, possibly because the formula used to calculate them does not eliminate the contribution to total PSA of the nonmalignant portion of the gland.     

The relation of prostate biopsy results and ratio of free to total PSA in patients with a total PSA between 4–20 ng/mL

Objective: In this study our aim was to investigate the efficacy of free tototal PSA ratio in discrimination of benign prostate hyperplasia andprostate cancer.Materials and methods: A total of 194 patients, 52 to 82 years old (mean66.06 ± 0.47 years) with PSA levels between 4 to 20 ng/mL wereincluded into this study. Each patient underwent sextant prostate biopsyunder transrectal ultrasound guidance. The patients were divided into twogroups as PSA 4–10 and 10–20 ng/mL. Patients with benign and malignresults were compared with respect to age, total PSA level, free PSA leveland free/total (f/t) PSA ratio.Results: Biopsies revealed prostate cancer in 16 of 130 patients (12.3%)with serum PSA 4–10 ng/mL and in 10 of 64 patients (15.6%) with serumPSA 10–20 ng/ml. In both PSA groups free PSA and f/t PSA levels werestatistically significant, where total PSA levels were not. In patients with4–20 ng/mL total PSA levels and a cut off level of < 0.18 for f/t PSA, thesensitivity, specificity and positive predictive value for prostate cancerwere 88.5%, 53.6% and 20.4% respectively.Conclusion: Higher levels of PSA suggest prostate cancer, but stilladditional parameters are needed for patients with PSA 4–20 ng/mL, suchas free PSA and f/t PSA. Although a cut off level of < 0.18 for f/t PSA seemsto be the most accurate one to discriminate benign and malign diseasesfurther studies on larger groups of patients are needed.     

When is a bone scan study appropriate in asymptomatic men diagnosed with prostate cancer？

Aims： To determine when a bone scan investigation is appropriate in asymptomatic men diagnosed with prostate cancer. Methods： Between November 2005 and July 2006, 317 men with prostate cancer underwent a bone scan study; 176 men fulfilled the inclusion criteria. Prostate-specific antigen （PSA） cut-offs as well as univariate and multivariate logistic regression analyses using digital rectal examination finding, biopsy Gleason scores and age were performed to determine when a bone scan study is likely to be of value. Results： Only 1/61 men （1.6%） with a serum PSA 〈 20 ng/mL had a positive bone scan. However, 2/38 men （4.7%） with a serum PSA 20.1-40.0 ng/mL, 3/20 men （15%） with a serum PSA 40.1-60.0 ng/mL, 7/19 men （36.8%） with a serum PSA 60.1-100.0 ng/mL and 19/38 men （50%） with a serum PSA 〉 100.0 ng/mL had positive bone scans. Univariate and multivariate logistic regression analyses were uninformative in these groups. Conclusion： Based on our findings, a bone scan is of limited value in asymptomatic prostate cancer patients presenting PSA 〈 20 ng/mL. Therefore, this investigation can be eliminated unless a curative treatment is contemplated. Furthermore, digital rectal examination finding, biopsy Gleason score and age are unhelpful in predicting those who might harbor bone metastasis.