Course of localized adenocarcinoma of the prostate treated by radical prostatectomy

Among 562 patients with histologic stage B-1, B-2, or C adenocarcinoma of the prostate treated by radical prostatectomy and pelvic lymphadenectomy, analysis revealed that increasing histologic stage, tumor size, degree of capsular invasion, seminal vesicle involvement, and histologic grade all were highly correlated with both local and systemic progression (log-rank two-sided P less than or equal to 0.0001). No variable correlated with survival--a result that may reflect appropriate adjuvant therapy given at the time of progression. The death rate from prostatic cancer did appear to rise progressively with increase of stage. Overall, the projected 10-year survival was 76%.     

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.     

‘Insignificant’ prostate cancer on prostatectomy and cystoprostatectomy: variation on a theme ‘low‐volume/ low‐grade’ prostate cancer?

Although ‘insignificant’ prostate cancer has been examined separately in radical prostatectomy (RP) and radical cystoprostatectomy (RCP) studies, it is not entirely clear whether cancers designated as ‘insignificant’ on RP and RCP represent the same, similar or different forms of prostate cancer. Insignificant prostate cancer has been traditionally defined based on the pathological findings in the whole prostate gland. In addition to the pathological determinants of ‘insignificant’ prostate cancer, it is also important to account for the biological and the clinical context of the disease, as well as patient age and health status to designate a prostate cancer ‘insignificant’. This review examines and compares prostate cancers described as ‘insignificant’ on RP and RCP. We conclude that in most cases these low‐volume/low‐grade prostate cancers represent an early stage and clinically ‘silent’ disease, which are only detected in different clinical settings.     

Characterization of PacMetUT1, a recently isolated human prostate cancer cell line

BACKGROUND: Existing prostate cancer cell lines have limitations. METHODS: Cells were characterized using Western blotting, immunohistochemistry, invasion into Matrigel, and by studying xenograft tumors. RESULTS: We describe a cell line (PacMetUT1) isolated from a lymph node of a 57-year-old male with prostate cancer. Compared to existing prostate cancer cell lines, the growth rate of PacMetUT1 xenograft tumors is slower with tumors occurring at injection sites and with metastases to lung and liver. Androgen receptor (AR) was detected in vivo by Western blotting and the cells responded to methyltrienolone (R1881). PacMetUT1 cells are more invasive in Matrigel than DU-145, PC-3, and LNCaP cells, and showed greater anchorage-independent growth in soft agar. The cells do not express prostate specific antigen (PSA) in vitro or in xenografts. However, the green fluorescent protein (GFP) gene was introduced and stably expressed in PacMetUT1 cells, allowing tumor imaging in vivo. Xenograft tumors show epithelial features and are positive for keratin, epithelial membrane antigen, EGF receptor, and E cadherin. In contrast, fibroblast markers vimentin, desmin, and Factor VIII, were negative. Karyotyping showed losses of 6p, 7q, 8p, 18q, and 22q, and gains of 8q and 9q; additional genetic material was observed at 2q and 12p. CONCLUSION: The PacMetUT1 cell line allows metastases to be assessed using a single animal model. Because of its slower growth, PacMetUT1 more closely mimics the human disease. Studies of tumor progression or metastasis can be conducted over a longer period of time.     

前列腺癌组织中前列腺癌抗原-1的表达及临床意义

目的：探讨PCa组织中前列腺癌抗原-1（PCA-1）的表达及其临床意义。方法：采用逆转录-聚合酶链反应（RT-PCR）技术,检测45例PCa组织、30例前列腺高分级上皮样内瘤样病变组织（HG-PIN）、43例BPH组织和39例其他肿瘤组织标本中PCA-1 mRNA的表达。免疫组织化学检测不同前列腺组织中PCA-1蛋白的表达。结果：PCa与HG-PIN组织标本中PCA-1 mRNA的阳性表达率分别为80.0%（36/45）和60.0%（18/30）,BPH组织及其他肿瘤组织中均未见PCA-1 mRNA的表达。PCA-1 mRNA表达与PCa的临床病理参数之间无明显相关性,差异均无统计学意义（P〉0.05）。PCa与HG-PIN组织标本中PCA-1蛋白的阳性表达率分别为75.6%（34/45）和50.0%（15/30）,BPH组织及其他肿瘤组织中未见PCA-1蛋白阳性表达。结论：PCA-1仅在PCa组织中表达,且与PCa的临床病理参数无关,有可能作为特异性的肿瘤标志物对PCa进行早期诊断。     

Design of clinical trials in advanced prostate cancer: avoiding the dead ends

Despite more than 30 years of clinical trials, investigations in prostate cancer have not succeeded in making advances comparable to those in other branches of research, such as breast cancer. Indeed, prostate cancer trials have repeatedly run into a series of "dead ends", as investigators face the problems of inadequate funding for research, treatments that result in only minimal improvements in survival, and lack of treatment options that have sufficient prospects for success. This article briefly reviews the strategies behind clinical investigations into prostate cancer over the last three decades, evaluates the pitfalls that have hindered research, and makes suggestions for the appropriate design of clinical trials that are safe and beneficial to patients while maintaining cost-effectiveness and accountability to patients and society.     

前列腺癌组织中前列腺癌抗原-1的表达及临床意义

目的:探讨PCa组织中前列腺癌抗原-1(PCA-1)的表达及其临床意义。方法:采用逆转录-聚合酶链反应(RT-PCR)技术,检测45例PCa组织、30例前列腺高分级上皮样内瘤样病变组织(HG-PIN)、43例BPH组织和39例其他肿瘤组织标本中PCA-1 mRNA的表达。免疫组织化学检测不同前列腺组织中PCA-1蛋白的表达。结果:PCa与HG-PIN组织标本中PCA-1 mRNA的阳性表达率分别为80.0%(36/45)和60.0%(18/30),BPH组织及其他肿瘤组织中均未见PCA-1 mRNA的表达。PCA-1 mRNA表达与PCa的临床病理参数之间无明显相关性,差异均无统计学意义(P>0.05)。PCa与HG-PIN组织标本中PCA-1蛋白的阳性表达率分别为75.6%(34/45)和50.0%(15/30),BPH组织及其他肿瘤组织中未见PCA-1蛋白阳性表达。结论:PCA-1仅在PCa组织中表达,且与PCa的临床病理参数无关,有可能作为特异性的肿瘤标志物对PCa进行早期诊断。     

血清前列腺特异抗原测定的临床意义

以12例前列腺癌、102例前列腺良性增生(BPH)、16例直肠指检(DRE)异常、5例前列腺炎及30例正常男性为对象,用酶免法测定血清前列腺特异抗原(Prostate specific antigen,PSA)浓度,用放免法测定其中37例。前列腺癌的PSA浓度明显高于BPH(P<0.01),PSA对前列腺癌诊断的敏感性为91.7％。DRE异常者大于BPH(P<0.05),低于前列腺癌(P<0.01)。BPH高于正常对照(P<0.01)。前列腺切除术后一日的PSA高于术前(P<0.01),术后6～8日同术前无显著性差异(P>0.05)。70岁以上高于70岁以下(P<0.05)。PSA>10ng/ml时酶免检测值低于放免法(0.010.05)。单纯PSA升高并不能说明任何特异性病理过程,前列腺癌的诊断,应结合PSA系列测定值及DRE和经直肠B超(TRUS)来综合分析。     

Neuroendocrine differentiation of human prostatic primary epithelial cells in vitro

BACKGROUND: Dispersed prostatic neuroendocrine cells are involved in growth regulation of the prostate and are considered to play a role in the pathogenesis of prostate carcinoma and benign prostatic hyperplasia (BPH). They are meant either to be derived from the neural crest during embryogenesis or by direct differentiation of the cells from locally present precursor cells. METHODS: An in vitro model was developed for human prostatic epithelial and neuroendocrine cell differentiation. Minced explants from radical prostatectomies were seeded on collagen I-coated plates. RESULTS: The majority of outgrowing cells were basal cells, positive for cytokeratin markers K 5/14 and CD 44, as determined by confocal laser scanning microscopy. A small fraction of interdispersed single cells expressing c-kit, which is found on pluripotent precursors, was identified by immunofluorescence. From these basal cells, in vitro differentiation of cells with neuroendocrine morphology could be achieved within 3 days. These were at rest, i.e., non-bromodeoxyuridine incorporating cells and characteristically coexpressed K 5/14, K 18, and the neuroendocrine marker chromogranin A. Luminal cells staining for K 8 or 18 were not observed. CONCLUSION: Neuroendocrine differentiation of adult prostatic cells was achieved in vitro, favoring the hypothesis that neuroendocrine cells are derived from peripheral precursor cells. The acceleration of this differentiation pathway may be the reason for the increased presence of neuroendocrine cells in areas of epithelial hyperplasia in BPH.     

Case-control study of prostate cancer and socioeconomic factors

A total of 1,162 prostate cancer cases and 3,124 age-matched hospital controls from several U.S. hospitals were studied to identify associations between prostate cancer and life-style variables. Among white males, college education, professional occupation, and non-Jewish ethnicity were weakly associated with the risk of prostate cancer (ORs = 1.5, 1.8, and 1.3, respectively, P less than 0.01). These relationships retained statistical significance after adjustment for age, marital status, body mass, cigarette smoking, alcohol consumption, and physical activity in multiple logistic regression models. Among black males, similar, though nonsignificant, risk elevations were observed for education and occupation. Weak positive effects of borderline statistical significance were observed for high body mass, low physical exercise, and high serum cholesterol (in elderly males only), and a significant reduction in risk was noted for never married black males. Cigarette smoking and alcohol consumption were not related to the risk of prostate cancer.     

Location of residual cancer after transrectal high-intensity focused ultrasound ablation for clinically localized prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject ? and What does the study add? Transrectal High‐Intensity Focused Ultrasound (HIFU) ablation has been used as a minimally invasive treatment for localized prostate cancer for 15 years. Five‐year disease‐free survival rates of 66–78% have been reported, challenging the results of external‐beam radiation therapy. Usually, a 6‐mm safety margin is used in the apex to preserve the urinary sphincter and potency. The influence of this 6‐mm margin on the results of the treatment has never been assessed. This retrospective study of a cohort of 99 patients who underwent systematic biopsy 3–6 months after HIFU ablation for prostate cancer (with a 6‐mm safety margin in the apex) shows that post‐HIFU residual cancer is found more frequently in the apex. Therefore, new strategies improving the prostate destruction at the apex while preserving the urinary continence need to be found.

OBJECTIVE

? To evaluate whether the location (apex/midgland/base) of prostate cancer influences the risk of incomplete transrectal high‐intensity focused ultrasonography (HIFU) ablation.

PATIENTS AND METHODS

? We retrospectively studied 99 patients who underwent prostate cancer HIFU ablation (Ablatherm; EDAP, Vaulx‐en‐Velin, France) with a 6‐mm safety margin at the apex, and had systematic biopsies 3–6 months after treatment. ? Locations of positive pre‐ and post‐HIFU sextants were compared. ? The present study included two analyses. First, sextants negative before and positive after treatment were recoded as positive/positive, hypothesizing that cancer had been missed at pretreatment biopsy. Second, patients with such sextants were excluded.

RESULTS

? Pre‐HIFU biopsies found cancer in all patients and in 215/594 sextants (36.2%); 55 (25.6%) positive sextants were in the apex, 86 (40%) in the midgland and 74 (34.4%) in the base. ? After treatment, residual cancer was found in 36 patients (36.4%) and 50 sextants (8.4%); 30 (60%) positive sextants were in the apex, 12 (24%) in the midgland and eight (16%) in the base. ? Both statistical analyses found that the locations of the positive sextants before and after HIFU ablation were significantly different (P < 0.001), with a higher proportion of positive apical sextants after treatment. ? At the first analysis, the mean (95% confidence interval) probability for a sextant to remain positive after HIFU ablation was 8.8% (3.5–20.3%) in the base, 12.7% (5.8–25.9%) in the midgland and 41.7% (27.2–57.89%) in the apex. ? At the second analysis, these same probabilities were 5.9% (1.9–17%), 9.9% (3.9–23.2%) and 27.3% (13.7–47%), respectively.

CONCLUSION

? When a 6‐mm apical safety margin is used, residual cancer after HIFU ablation is found significantly more frequently in the apex.     

Magnetic resonance spectroscopic imaging: current status in the management of prostate cancer

In the past decade several advances have been made in the field of nuclear magnetic resonance (NMR) imaging. MR spectroscopic imaging (MRSI) is one such advance which holds promise for detecting biochemical change on imaging of the prostate, and that can be used in several ways for improving the management of patients with prostate cancer. We review the literature, technique and basics of MRSI, with its current status in various situations as applied to the management of prostate cancer.