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%.     

‘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.     

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.     

血管生成抑制剂在去势抵抗性前列腺癌治疗中的新发现

近年来,去势抵抗性前列腺癌的治疗方法已由传统的抗雄激素及化疗提升到新的雄激素受体信号抑制剂、新一代紫杉醇及免疫疗法阶段。卡巴他赛、恩杂鲁胺、阿比特龙,放射性同位素镭223和sipuleucel-T随机临床试验显示能延长去势抵抗性前列腺癌患者生存期。然而,最终出现肿瘤抵抗也是难免的,去势抵抗性前列腺癌仍是一种主要临床负担,迫切需求新的治疗方法进一步改善CRPC患者生存期及生活质量。新生血管在前列腺癌的形成和进程中发挥至关重要的作用。部分临床试验显示,对失去手术和内分泌治疗时机的去势抵抗性前列腺癌,抗新生血管形成的靶向治疗是一种有效的补充疗法。本文将综述血管生成抑制剂在去势抵抗性前列腺癌治疗中的新发现。     

Prostate cancer in Asian Americans: incidence, management and outcomes in an equal access healthcare system

Study Type – Therapy (outcomes research)
Level of Evidence 2c What’s known on the subject? and What does the study add? While epidemiological studies have shown a significantly lower incidence of adenocarcinoma of the prostate in Asia than the United States, several studies have demonstrated that Asian Americans present with more advanced stages, higher tumour grades, and worse mortality‐incidence ratios than Caucasian Americans. This study, conducted in an equal access military healthcare system, reveals improved pathological and survival outcomes in Asian Americans compared to other races. This may indicate that worsened outcomes previously reported among Asian Americans diagnosed with adenocarcinoma of the prostate may be related to access to care, language barriers, socioeconomic status, or cultural factors.

OBJECTIVE

? To characterize the incidence, management and clinicopathological characteristics of prostate cancer (CaP) in a population of Asian Americans undergoing mandatory annual screening in an equal access healthcare system.

PATIENTS AND METHODS

? Men registered into the military‐based Center for Prostate Disease Research multi‐institutional database from 1989–2007 with biopsy‐proven CaP and categorized as Asian American, Caucasian or African American were included. ? Demographic information, treatment modality, clinicopathological characteristics and outcomes were compared.

RESULTS

? In total, there were 10 964 patients; 583 (5.3%) were Asian Americans. Asian Americans had lower clinical stage (P < 0.001) but worse biopsy grade (P < 0.001) than other groups. They were more likely to choose radical prostatectomy (RP) (P < 0.001) and showed a higher percentage of organ‐confined disease (P < 0.001). ? Asian Americans had improved biochemical recurrence free (P < 0.01) and overall survival (P < 0.001) rates compared to African Americans or Caucasians treated with RP or external radiation therapy.

CONCLUSIONS

? Asian Americans with CaP treated in an equal access healthcare system have improved pathological outcomes and survival characteristics compared to other races. ? Asian ethnicity’s negative impact on survival noted by others appears to be the result of factors other than the tumour’s intrinsic behaviour, such as language barriers, socioeconomic status and cultural norms.     

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.     

Prostate cancer antigen-1 as a potential novel marker for prostate cancer

Aim： To examine the expression of prostate cancer antigen-1 （PCA-1） in prostate cancer （PCa） and to validate it as a potential marker for diagnosis of PCa. Methods： In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia （BPH）, 16 high-grade prostatic intraepithelial neoplasm （HG-PIN）, 74 PCa and 34 other malignant carcinoma specimens. The level of PCA- 1 expression was semiquanfitatively scored by assessing both the percentage and intensity of PCA- 1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. Results： PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score （P 〈 0.05）, and was unrelated to other clinical parameters of PCa （all P 〉 0.05）. Conclusion： The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.     

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。