Detection rate of clinically insignificant prostate cancer increases with repeat prostate biopsies

To analyze if clinically insignificant prostate cancer (CIPC) is more frequently detected with repeat prostate biopsies, we retrospectively analyzed the records of 2146 men diagnosed with prostate cancer after one or more prostate biopsies. The patients were divided into five groups according to the number of prostate biopsies obtained, e.g. group 1 had one biopsy, group 2 had two biopsies and group 3 had three biopsies. Of the 2146 patients diagnosed with prostate cancer, 1956 (91.1%), 142 (6.6%), 38 (1.8%), 9 (0.4%) and 1 (0.1%) men were in groups 1, 2, 3, 4 and 5, respectively. Groups 4 and 5 were excluded because of the small sample sizes. The remaining three groups (groups 1, 2 and 3) were statistically analyzed. There were no differences in age or prostate-specific antigen level among the three groups. CIPC was detected in 201 (10.3%), 28 (19.7%) and 9 (23.7%) patients in groups 1, 2 and 3, respectively (P<0.001). A multivariate analysis showed that the number of biopsies was an independent predictor to detect CIPC (OR=2.688 for group 2; OR=4.723 for group 3). In conclusion, patients undergoing multiple prostate biopsies are more likely to be diagnosed with CIPC than those who only undergo one biopsy. However, the risk still exists that the patient could have clinically significant prostate cancer. Therefore, when counseling patients with regard to serial repeat biopsies, the possibility of prostate cancer overdiagnosis and overtreatment must be balanced with the continued risk of clinically significant disease.     

Perioperative complications of radical retropubic prostatectomy in patients with locally advanced prostate cancer: a comparison with clinically localized prostate cancer

Radical prostatectomy (RP) continues to be an effective surgical therapy for prostate carcinoma, particularly for organ-confined prostate cancer (PCa). Recently, RP has also been used in the treatment of locally advanced prostate cancer. However, little research has been performed to elucidate the perioperative complications associated with RP in patients with clinically localized or locally advanced PCa. We sought to analyse the incidence of complications in these two groups after radical retropubic prostatectomy (RRP). From June 2002 to July 2010, we reviewed 379 PCa patients who underwent RRP in our hospital. Among these cases, 196 had clinically localized PCa (T_1a–T_2c: group 1), and 183 had locally advanced PCa (≥T_3a: group 2). The overall complication incidence was 21.9%, which was lower than other studies have reported. Perioperative complications in patients with locally advanced PCa mirror those in patients with clinically localized PCa (26.2% vs. 17.8%, P=0.91). Our results showed that perioperative complications could not be regarded as a factor to consider in regarding RP in patients with cT₃ or greater.     

A-I型前列腺穿刺器活检筛选前列腺癌的临床意义

目的验证A-I型前列腺穿刺器对临床上前列腺特异性抗原(PSA)>4ng/ml和(或)前列腺直肠指诊、B超发现结节者进行前列腺癌筛查的临床意义。方法采用A-I型前列腺穿刺器,对36例PSA>4ng/ml或有前列腺结节者,在食指引导下进行前列腺左右叶的尖、中间、尾部和触及结节处活检。结果有结节者17例中发现前列腺癌(PCA)5例(29.4%);PSA>4.0ng/ml的34例中,PCA检出15例(44.12%)。分析显示:A-I型前列腺穿刺器与B-超引导系统相比较,对血清PSA>4.0ng/ml者的PCA检出率有明显的差异(x2=5.568,　P<0.05)。结论A-I型前列腺穿刺器完全可以满足临床对筛查前列腺癌的要求,是一种操作简便、易用、费用低廉的前列腺疾病的诊断器械,值得临床推广。     

In vitro propagated dendritic cells from prostate cancer patients as a component of prostate cancer immunotherapy

T cell-mediated cancer immunotherapy requires efficient antigen-presenting cells. Dendritic cells (DCs) are arguably the most efficient antigen-presenting cells studied to date. Individuals with prostate cancer often undergo various therapies which may compromise their immune system, including the state of their DC precursors. We report the in vitro propagation of DCs from peripheral blood of patients with prostate cancer, most of whom are in clinical stages D₁ or D₂ and have undergone radiation therapy. After 7 days in culture, the number of DCs recovered were 20-50-fold higher than those isolated directly from peripheral blood. This number is comparable to findings of previous studies with healthy individuals. Cultured patients' DCs were capable of presenting tetanus toxoid to autologous T cells in vitro. Furthermore, T cells from 2 of 4 patients proliferated when cultured with their DCs and the lysate of a human prostate cancer cell line (LNCaP), demonstrating the potential role of autologous DCs in prostate cancer immunotherapy studies. © 1995 Wiley-Liss, Inc.     

Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging

Background

Knowledge about the staging significance of the prostate cancer antigen 3 (PCA3) score to better identify pathologic features after radical prostatectomy (RP) is limited and controversial.

Objective

Our aim was to study the clinical staging significance of PCA3 to identify pathologic favorable and/or unfavorable features in the RP specimen.

Design, setting, and participants

Complete retrospective clinical and pathologic data of consecutive men who had undergone RP from three tertiary referral centers including preoperative PCA3 scores (n = 305) and computer-assisted planimetrically measured tumor volume data (n = 160) were available.

Intervention

All patients were treated with RP.

Measurements

PCA3 scores were assessed using the PROGENSA assay (Gen-Probe, San Diego, CA, USA). Beyond standard risk factors (age, digital rectal examination, prostate-specific antigen, prostate volume, biopsy Gleason score, percentage of positive cores), five different PCA3 codings were used in logistic regression models to identify five distinct pathologic end points: (1) low-volume disease (<0.5 ml), (2) insignificant prostate cancer (PCa) according to the Epstein criteria, (3) extracapsular extension (ECE), (4) seminal vesicle invasion (SVI), and (5) aggressive disease defined as Gleason sum ≥7. Accuracy estimates of each end point were quantified using the area under the curve (AUC) of the receiver operator characteristic analysis in models with and without PCA3.

Results and limitations

PCA3 scores were significantly lower in low-volume disease and insignificant PCa (p ≤ 0.001). AUC of multivariable low-volume disease (+2.4 to +5.5%) and insignificant PCa models (+3 to +3.9%) increased when PCA3 was added to standard clinical risk factors. In contradistinction, regardless of its coding, PCA3 scores were not significantly elevated in pathologically confirmed ECE (p = 0.4) or SVI (p = 0.5), respectively. Higher PCA3 scores were associated with aggressive disease (p < 0.001). Importantly, the addition of PCA3 to multivariable intermediate- and high-grade models did not improve prediction. Despite reporting the largest pathologic PCA3 study, the main limitation resides in its small sample size.

Conclusions

PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant PCa. Further exploration of its role as an additional marker to select patients for active surveillance may be warranted. In contradistinction, assessment of pathologically advanced or aggressive PCa is not improved using PCA3.     

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.     

Cancer stem cells in prostate cancer

Prostate cancer (P-Ca) remains a leading cause of cancer-related death in men. Lately, increasing evidence for a hierarchically organized cancer stem cell (CSC) model emerged for different tumors entities, including P-Ca. CSCs are defined by several characteristics including self-renewal, pluripotency and tumorigenicity and are thought to be responsible for tumor recurrence, metastasis and cancer related death. In this review we discuss the recent research in the field of CSCs, its limitations and therapeutical implications in general and specifically in P-Ca.     

Narrative review: prostate-specific membrane antigen-radioligand therapy in metastatic castration-resistant prostate cancer

Radioactive-labelled ligands targeting the prostate-specific membrane antigen (PSMA), a transmembrane protein overexpressed in prostate cancer (PC), have shown promising activity in treatment of metastatic castration-resistant prostate cancer (mCRPC). PSMA-617 and PSMA-I&T (imaging and therapy), both labeled to the beta-emitter lutetium-177 (Lu177), are most frequently used in clinical routine and have shown a favorable side-effect profile. Common side effects are transient xerostomia. Severe side effects, e.g., treatment-associated myelosuppression, are rare. Currently treatment with Lu177-PSMA outside clinical trials is available for compassionate use for patients who exhausted conventional therapies. Previous retro- and prospective studies reported promising results with ≥50% PSA declines observed in at least one third of patients. Retrospective data suggests worse biochemical response in patients with visceral metastases. Preliminary data from the randomized phase II (TheraP) trial showed an improved biochemical response rate of Lu177-PSMA as compared to cabazitaxel in patients progressing after docetaxel. Following these promising data, the results of the randomized, prospective phase III VISION study are eagerly anticipated. A major challenge remains resistance to radioligand therapy with Lu177-PSMA. As an alternative, a PSMA-ligand labeled to the alpha-emitter Actinium-225 (Ac-225) may be offered to patients, which shows promising activity in patients developing progression under Lu177-PSMA at the cost of higher toxicity. Mostly permanent xerostomia is a relevant side effect resulting in treatment discontinuation in up to a quarter of patients. This review summarizes the literature on activity and toxicity of PSMA-targeted radioligand therapy in mCRPC.     

Cryotherapy of prostate cancer

Cryosurgical destruction of primary adenocarcinoma of the prostate was performed via perineal route in 215 patients during a 12-year period. The average age of the patients was 66 years. The stage of the disease varied from stage B to D. In 74% of the patients, no clinical evidence of tumor was found in the prostatic fossa following cryosurgery. Few patients needed transurethral surgery and none needed repeated transurethral resections for obstructive symptoms. This experience suggests that local destruction of prostatic carcinoma can be achieved with little morbidity and mortality. Herein we discuss the method of cryosurgery, stage and histology of tumor, survival, local recurrence, and complications.     

Review: prostate cancer epidemiology

Prostate cancer is common among men in the United States. Factors of possible importance in the etiology of prostate cancer include diet, primarily implicated by ecologic studies of national, regional, and ethnic variation in rates; endocrine function, implicated by the importance of endocrine function in normal prostatic growth and in the treatment of prostate cancer; genetic susceptibility, supported by familial aggregation; some aspect of sexual behavior, suggested by case-control differences in sexual behavior; and occupational exposure, particularly cadmium exposure. Despite the public health importance of prostate cancer, it has received only moderate epidemiologic study; thus the etiologic importance of these and other possible determinants of prostate cancer risk is uncertain [55].     

N-cadherin switching occurs in high Gleason grade prostate cancer

BACKGROUND: The inappropriate expression of non-epithelial N-(neural) cadherin by epithelial cells, called cadherin switching, has been suggested to play a role in prostate cancer (PC) progression. We explored the role of N-cadherin as a biomarker in PC by correlating the expression with clinical parameters. METHODS: Two pathologists blinded to patients' history independently reviewed and scored the intensity and extent of staining of N-cadherin expression in 44 randomly selected radical prostatectomy specimens. The expression was correlated with total Gleason grade, individual Gleason patterns, tumor stage, and preoperative serum prostate specific antigen (PSA) levels and P-values < 0.05 were considered statistically significant. RESULTS: Of the 44 PC specimens, 14 (32%), 23 (52%), 7 (16%) consisted of Gleason grade 5-6, 7, and 8-10, respectively and 20/44 (45%) demonstrated N-cadherin expression. N-cadherin was expressed in 1/14 (7%) of Gleason 5-6 compared to 15/23 (65%) of Gleason grade 7, and 4/7 (57%) of Gleason grade 8-10, demonstrating a significant correlation between N-cadherin switching and higher Gleason grade (P = 0.001). While only about a third of primary or secondary Gleason pattern 3 demonstrated N-cadherin expression, a majority of Gleason patterns of > or = 4 expressed N-cadherin (P > 0.05), further suggesting that N-cadherin switching occurs with higher Gleason pattern. However, N-cadherin expression did not significantly correlate with preoperative serum PSA levels or tumor stage in our study cohort. CONCLUSIONS: We have demonstrated for the first time that N-cadherin switching occurs in higher grade PC and correlates significantly with increasing Gleason patterns. N-cadherin may be as a useful biomarker of aggressive PC.     

Novel non-AR therapeutic targets in castrate resistant prostate cancer

Castrate resistant prostate cancer (CRPC) remains a disease with significant morbidity and mortality. The recent approval of abiraterone and enzalutamide highlight the improvements which can be made targeting the androgen receptor (AR) axis. Nonetheless, resistance inevitably develops and there is continued interest in targeting alternate pathways which cause disease resistance and progression. Here, we review non-AR targets in CRPC, with an emphasis on novel agents now in development. This includes therapeutics which target the tumour microenvironment, the bone metastatic environment, microtubules, cellular energetics, angiogenesis, the stress response, survival proteins, intracellular signal transduction, DNA damage repair and dendritic cells. Understanding the hallmarks of prostate cancer resistance in CRPC has led to the identification and development of these new targets. We review the molecular rationale, as well at the clinical experience for each of these different classes of agents which are in clinical development.