Clinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanese men

OBJECTIVE: To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men. PATIENTS AND METHODS: 136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly. RESULTS: Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan-confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume >0.5 cm(3). Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan-confined cancer in the 23 cancers for which PSA density was <0.2 ng/ml/g. The ability of PSA density to predict cancer volume <0. 5 cm(3) was 0.61 using a cut-off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13. CONCLUSIONS: Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.     

Correlation of serum PSA and Gleason score in Nigerian men with prostate cancer

Objective  Prostate cancer is an important cause of morbidity and mortality worldwide. While the predisposing factors are not fully understood, African descent is an important risk factor, and prostate cancer has become the number-one cancer in Nigerian men. This was a retrospective study of the correlation between serum prostate specific antigen (PSA) and Gleason grade and score in patients of Nigerian descent. Patients and Methods  The University College Hospital (UCH) Ibadan Cancer Registry was used to identify and quantify the incidence of prostate cancers occurring between 1998 and 2000. The histological slides of appropriate cases were reviewed to confirm the Gleason grade and score. The serum PSA values were retrieved from the patients' case notes and laboratory files. The data obtained were subjected to statistical analysis to look for associations and correlations. Results  The study included 67 men with prostate adenocarcinoma and PSA measurements who were diagnosed and treated at the UCH Ibadan between January 1998 and December 2000. There was a positive correlation between serum PSA and Gleason grade, as well as between serum PSA and Gleason score in our cohort of Nigerian African men with prostate cancer. PSA levels were significantly lower in patients with stage B disease than in patients with stage D disease. Conclusion  Serum PSA is significantly higher in metastatic than in localized disease. Further studies are necessary to determine biomarkers that complement serum PSA and the Gleason grading system in the prognostication of prostate cancer in African patients.     

Different PSA assays lead to detection of prostate cancers with identical histological features

OBJECTIVE: Because different PSA assays still show a wide inter-assay variation, we wondered what influence these discrepancies could have on the individual tumour characteristics of the cancers that each of these assays detect in a critical low PSA range. We analysed five different PSA assays in a biopsy simulation with PSA cut-offs of 3.0 and 4.0 ng/ml. MATERIALS AND METHODS: Randomly taken samples of 360 men with prostate cancer and 96 with benign prostatic disease from a screened population with PSA range of 1.0-6.0 ng/ml (Tandem-E) were investigated. In all cases the diagnosis was confirmed by sextant biopsies. One hundred and thirty-seven men (38%) underwent radical prostatectomy. Variability amongst assays was illustrated in terms of missed cancers and unnecessary biopsies, and in terms of pathologic features of detected cancers at both PSA cut-offs. RESULTS: Compared to Tandem-E, all assays, except Access, showed significant differences in PSA measurements. Furthermore, none of the assays discriminated significantly between benign and malignant prostatic disease (p>0.05). Tandem-E and Elecsys lead significantly more frequently to the detection of cancers at the cost of more unnecessary biopsies compared to the other assays. Yet, at both PSA cut-offs the proportion of cancers with a certain pathologic grade or stage that were detected by each assay were approximately the same. CONCLUSIONS: Our study shows that the use of different PSA assays only have consequences for the number, and not for the tumour characteristics of the prostate cancers that are detected. Thus, different PSA assays detect prostate cancers with the same tumour features.     

Relationship between initial PSA density with future PSA kinetics and repeat biopsies in men with prostate cancer on active surveillance

The objective of our study is to examine the correlation between PSA density (PSAd) at the time of diagnosis with PSA velocity (PSAV), PSA doubling time and tumour progression, on repeat biopsy, in men with prostate cancer on active surveillance. Data from 102 patients with clinically localized prostate cancer on active surveillance in the period between 1992 and 2007, who had the necessary parameters available, were collected. PSAd was calculated and correlated with PSAV, PSA doubling time (PSADT), Gleason score at diagnosis and local progression on repeated biopsies. PSAV was 0.64 and 1.31 ng ml(-1) per year (P = 0.02), PSADT of 192 and 113 months (P = 0.4) for PSAd below and above 0.15, respectively. The rate of detecting high Gleason score (≥ 7) at diagnosis was 6 and 23% for PSAd below and above 0.15, respectively. A total of 101 patients underwent at least a second biopsy and the incidence of upgrading was 10 and 31% for PSAd below and above 0.15, respectively (P = 0.001). Although low PSAd is an accepted measure for suggesting insignificant prostate cancer, our study expands its role to indicate that PSAd < 0.15 may be an additional clinical parameter that may suggest indolent disease, as measured by future PSAV and repeat biopsy over time.     

血清tPSA、PSAD及Gleason评分在前列腺癌分期中的应用价值

目的:探讨血清前列腺特异性抗原(PSA)系列及穿刺组织活检Gleason评分在前列腺癌病理分期的预测价值。方法:回顾性分析我院1999～2008年病理证实为前列腺腺癌的124例患者资料,将该124例患者根据术后病理、骨扫描和CT或MRI结果分为A、B两组。骨扫描、CT、MRI或术后证实为有周围浸润或远处转移者归为A组;无周围浸润且无远处转移者归为B组。比较两组之间以上各指标的差异。通过多因素回归分析筛选前列腺癌病理分期的影响因子。运用工作特征曲线(ROC曲线)比较各指标的预测价值。结果:tPSA、穿刺活检Gleason评分值A组明显高于B组(P<0.05);多元Logistic回归分析中,仅tPSA进入模型,被认为是最主要的预测因子。ROC曲线对前列腺病理分期预测效力比较:联合分析tPSA与穿刺活检Gleason评分预测效果明显高于其他指标,工作特征曲线下面积(AUC)从大到小依次为Gleason评分+tPSA>tPSA>PSAD+tPSA+Gleason评分。结论:tPSA依然是临床上对前列腺癌病理分期较好的预测因素;联合穿刺组织活检Gleason评分,可以提高预测准确度,对指导临床治疗和预后有重要意义。     

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.     

前列腺癌患者血清睾酮水平与前列腺穿刺活检阳性的相关性

目的探讨血清总睾酮水平与前列腺穿刺活检阳性之间的相关性,为临床个体化治疗方案的选择提供理论依据。方法 2015年9月至2019年3月期间在汉中市人民医院泌尿外科接受前列腺穿刺活检的患者,收集患者的年龄、血清总前列腺特异性抗原(tPSA)及性激素等相关资料,观察这些指标对前列腺穿刺活检阳性率的影响。结果在113例患者中,前列腺癌(PCa)患者检出率共89例,穿刺阳性率为78.76%。与穿刺阴性组比较,患者血清tPSA[(12.42±4.64)vs.(5.35±1.66)ng/mL,P<0.001]和催乳素水平[(8.55±2.48)vs.(6.91±1.92)ng/L,P=0.003]升高与前列腺穿刺活检阳性有关,而总睾酮激素水平下降与前列腺穿刺活检阳性有关[(12.64±3.28)vs.(16.85±3.37)nmol/L,P<0.001]。多变量分析证实tPSA[P<0.001,OR=3.383(1.924~5.342)]和血清睾酮[P=0.038,OR=1.361(1.124~1.927)]是预测前列腺穿刺活检阳性的独立预测因子。受试者工作曲线(ROC)显示tPSA水平与前列腺穿刺阳性风险呈正相关,曲线下面积(AUC)为0.989,最佳截断值为8.022,敏感度和特异度分别为87.5%和98.88%;总睾酮激素水平与前列腺穿刺阳性风险呈负相关,AUC为0.786,最佳截断值为17.85,敏感度和特异度分别为66.67%和78.65%,差异具有统计学意义(P<0.001)。结论低血清睾酮激素与前列腺穿刺检测PCa的风险有关,这些结果可能揭示了PCa与睾酮两者关系的潜在机制。     

Permanent prostate brachytherapy for Japanese men: Results from initial 100 patients with prostate cancer

OBJECTIVE: To evaluate the initial results of brachytherapy for prostate cancer with permanent iodine-125 implant in Japan. METHODS: The results obtained with brachytherapy in the initial 100 Japanese patients treated at Nagano Municipal Hospital were reviewed. Patients with a prostate-specific antigen (PSA) level of less than 10 ng/mL and a Gleason's scores of 5, 6, 3 + 4 were classified as having a low risk of recurrence. Patients with a PSA level of 10-20 ng/mL and/or a Gleason's score of 4 + 3 were classified as having an intermediate risk for recurrence. Seventy-eight of the low-risk patients and 19 of the intermediate-risk patients were treated by seed implants alone, or seed implants combined with preceding external radiation, respectively. A total of 53 patients received neoadjuvant hormone therapy. The efficacy and morbidity of brachytherapy were investigated using the serum PSA, International Prostate Symptom Score, quality of life score and uroflowmetry data. RESULTS: The average V100 and D90 obtained by post-implant dosimetry was 94.3 and 113.7%, respectively. Serum PSA decreased gradually after treatment, although it had still not reached a nadir after 1 year. There was little difference of the PSA level between the patients with and without neoadjuvant hormone therapy even at 1 year after seed implantation. There were no PSA biochemical failure or clinical recurrence during the follow-up period. Voiding symptoms worsened until 3 months after treatment, and then gradually improved. Acute urinary retention occurred transiently in one patient (1%). Rectal bleeding and severe diarrhea did not occur. CONCLUSION: Brachytherapy is a feasible and effective option for the treatment of prostate cancer in Japanese men. Brachytherapy may have a different effect in Japanese patients with respect to voiding symptoms. Urinary retention was rare, but voiding symptoms were persistent in Japanese patients. Neoadjuvant hormone therapy deserves investigation to determine whether it can achieve better results, especially in patients with an intermediate risk.     

Nadir PSA level and time to PSA nadir following primary androgen deprivation therapy are the early survival predictors for prostate cancer patients with bone metastasis

The purpose of this study was to identify the early predictor of survival for prostate cancer patients with bone metastasis. We reviewed 87 prostate cancer patients with bone metastasis who had received primary androgen deprivation therapy (PADT) at our institution. The medical records of the patients were examined with respect to laboratory data, pathological results, PSA response to PADT and clinical outcome. The overall survival (OS) rates were analyzed with reference to the nadir PSA level and time to PSA nadir (TTN) following PADT by Kaplan-Meier method. In all, 59 patients (67%) had progression to castration-resistant prostate cancer. Nadir PSA <0.2?ng?ml(-1) (lower PSA nadir) during PADT were observed in 47 patients (54%). Multivariate analysis revealed that the extent of disease on bone scan (P=0.04), lower PSA nadir following PADT (P=0.003), albumin (P=0.04) and lactate dehydrogenase (P=0.01) were independent prognostic factors for survival. OS rates in the patients with lower PSA nadir were significantly higher. Longer TTN (>9 months) identified patients with prolonged OS in both lower and higher PSA nadir groups. PSA nadir <0.2?ng?ml(-1) and prolonged TTN (>9 months) following PADT might be the most important early predictors for longer survival in prostate cancer patients with bone metastasis.     

The impact of obesity on the predictive accuracy of PSA in men undergoing prostate biopsy

Purpose

Obese men have been reported to have lower serum PSA values relative to normal-weight men in population-based studies, screening cohorts, and in men with prostate cancer (CaP) treated with surgery. There are concerns that PSA may be less accurate in detecting prostate cancer in men with increased body mass index (BMI). We determine whether the diagnostic potential of PSA is negatively influenced by obesity by comparing its operating characteristics across BMI categories among men undergoing prostate biopsy.

Methods

Demographic, clinical, and histopathological data on 917 men who underwent trans-rectal ultrasound-guided prostate needle biopsy from 2002 to 2010 at a University hospital in Italy were used in the study. Men were categorized for BMI as follows: <25 kg/m² (normal weight), 25–29.9 kg/m² (overweight), and ≥30 kg/m² (obese). Receiver operator characteristics (ROC) curves were used to assess PSA accuracy for predicting prostate cancer overall and then stratified according to digital rectal examination (DRE) findings using the area under the ROC curve (AUC).

Results

The obesity rate of the study cohort was 21 %. There was no statistically significant difference in the overall AUCs of PSA for predicting CaP among normal-weight (AUC = 0.56), overweight (AUC = 0.60), and obese men (AUC = 0.60; p = 0.68) in either DRE-positive or negative men.

Conclusions

In a cohort of Italian men undergoing prostate biopsy, the performance accuracy of PSA as a predictor of CaP is not significantly altered by BMI. Obesity does not negatively impact the overall ability of PSA to discriminate between CaP and benign conditions.     

Differences in biopsy features between prostate cancers located in the transition and peripheral zone

OBJECTIVE: To identify the zonal location of prostate cancers before surgery, by analysing the mapping of ultrasonography-guided systematic sextant biopsies for differences between cancers located in the transition zone (TZ) and peripheral zone (PZ); and to compare the correlation between Gleason scores of needle biopsies and those of radical prostatectomy (RP) specimens. PATIENTS AND METHODS: In all, 186 patients with TZ (46) and PZ cancers (140) underwent ultrasonography-guided systematic sextant biopsy and RP at the same institution. The clinical and pathological characteristics, and the anatomical location of positive biopsies, were determined and compared using t-tests and chi-square tests. Differences between Gleason scores of needle biopsies and those of RP specimens were evaluated and compared by Cohen kappa testing. RESULTS: TZ cancers had a significantly lower rate of positive biopsies in the middle (63% vs 80%) and base (50% vs 80%) of the prostate than had PZ cancers. Positive biopsies were exclusively obtained from the apex in 19.6% of TZ and 5% of PZ cancers (P = 0.002). There was exact agreement between Gleason scores of needle biopsies and those of RP specimens in 15.2% of TZ (kappa = 0.02) and 55% of PZ cancers (kappa = 0.25), respectively. CONCLUSION: Compared with PZ cancers, TZ cancers had a different anatomical pattern of positive biopsies, with lower rates in the middle and base of the prostate. The finding of positive biopsies exclusively in the apex favoured prostate cancer located in the TZ. Furthermore, the correlation between needle biopsy Gleason scores and those of the RP specimens was clearly lower in TZ cancers.     

Correlation between serum prostate specific antigen and prostate volume in Taiwanese men with biopsy proven benign prostatic hyperplasia

PURPOSE: We studied the correlation between serum prostate specific antigen and the volume of different zones of the prostate in Taiwanese men with biopsy proven benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 233 patients with a mean age of 71.4 years (range 42 to 89), serum prostate specific antigen less than 10 ng/ml and pathologically confirmed benign prostatic hyperplasia were enrolled in this study. Total prostate and transitional zone volumes were measured with transrectal ultrasonography. Peripheral zone volume was determined by subtracting transitional zone volume from total prostate volume. Correlations between patient age, total serum prostate specific antigen and the volume of each prostate zone were analyzed with the Pearson correlation coefficient. A linear regression model was used to determine the relationship between prostate specific antigen and prostate volume. The prostate specific antigen-prostate volume relationship in our patients was compared with published data on white and Japanese men. RESULTS: Age did not significantly correlate with serum prostate specific antigen and prostate volume. Serum prostate specific antigen significantly correlated with the volume of each prostate zone. After log transformation the Pearson correlation coefficient between total prostate specific antigen and the volume of the whole prostate gland, the transitional zone and the peripheral zone were 0.369, 0.377 and 0.272, respectively (p <0.001). Taiwanese men had lower prostate volume per unit prostate specific antigen comparing with white men, while the prostate specific antigen-total prostate volume relationship between Taiwanese and Japanese men was similar. CONCLUSIONS: In Taiwanese men with biopsy proven benign prostatic hyperplasia the volume of each prostate zone has significantly correlates with serum prostate specific antigen. The prostate specific antigen-total prostate volume relationship in Taiwanese men is different from that in white men. However, the prostate specific antigen-total prostate volume relationship between Taiwanese and Japanese men is similar.     

Characteristics and clinical significance of prostate cancers missed by initial transrectal 12-core biopsy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 3a What's known on the subject? and What does the study add? Initial transrectal 12‐core biopsy has a small but definite risk of missing anterior significant prostate cancers irrespective of age, PSA, prostate volume and DRE findings. Our study yields valuable information for diagnosis and treatment decision of prostate cancer based on transrectal 12‐core biopsy.

OBJECTIVE

• ? To characterize prostate cancers missed by initial transrectal 12‐core biopsy.

PATIENTS AND METHODS

• ? Between 2002 and 2008, 715 men with prostate‐specific antigen levels in the range 2.5–20 ng/mL or abnormal digital rectal examination underwent three‐dimensional 26‐core prostate biopsy (i.e. a combination of transrectal 12‐core biopsy and transperineal 14‐core biopsy) on initial examination.
• ? Of the 257 patients diagnosed with cancer, 120 patients subsequently underwent radical prostatectomy.
• ? Cancers were grouped into TR12‐negative cancers (i.e. not detected through transrectal 12‐core biopsy but detected through transperineal 14‐core biopsy) and TR12‐positive (i.e. detected through transrectal 12‐core biopsy) cancers.
• ? Clinicopathological characteristics of the TR12‐negative and TR12‐positive cancers were evaluated.

RESULTS

• ? TR12‐negative cancers comprised 21% of the three‐dimensional 26‐core biopsy‐detected cancers.
• ? The frequency of cancers with a biopsy Gleason score ≤6 and that of cancers with a biopsy primary Gleason grade ≤3 was higher in TR12‐negative cancers, at 58% and 83%, respectively, than in TR12‐positive cancers, at 25% (P < 0.001) and 53% (P < 0.001), respectively.
• ? The median number of positive cores in TR12‐negative cancers was two out of 26.
• ? TR12‐negative cancers were more frequently located anteriorly than posteriorly.
• ? The incidence of the TR12‐negative cancers was not associated significantly with any clinical variable.

CONCLUSION

• ? Many of the cancers missed by initial transrectal 12‐core biopsy are probably low‐grade and low‐volume diseases, although initial transrectal 12‐core biopsy has a small but definite risk of missing anterior significant cancers.