Bone and prostate cancer cell interactions in metastatic prostate cancer

The interplay in prostate cancer bone metastases between the 'seed' (the prostate cancer cells) and the 'soil' (the bone microenvironment) has been increasingly recognized as integral to the remarkable tropism for bone shown by prostate cancer. Increasing research into this area is elucidating the mechanisms involved in this complex 'cross-talk'. Recent developments, including the use of bisphosphonates in metastatic disease, highlight the important role of bone cells in the development and progression of metastatic prostate cancer. We review the current reports emphasising these possible mechanisms and indicating possible factors for future treatment directions.     

Hormone-refractory prostate cancer

Hormone-refractory prostate cancer is an advanced stage of the metastatic disease; it has a poor prognosis and a short median survival, about 9 to 18 months. The current article is based on a literature review regarding the prognostic factors and medical treatments, with a focus on recent advances in chemotherapy. With the use of docetaxel that increases the median survival of this disease and improves the symptoms, new clinical protocols have been developed, with promising results; these protocols propose a combination with calcitriol or antiangiogenic agents. Supportive care is also an important part of the treatment due to the high level of bone involvement and its consequences. Such recent advances constitute a real progress in the management of prostate cancer, namely the pharmacological combinations with a promising efficacy and little toxicity.     

Advanced prostate cancer

Both the definition and therapy of advanced prostate cancer is challenging. The advanced prostate cancer session at "The 8th International Prostate Cancer Update" had discussions which tried to answer the questions of management of these patients who either present with advanced disease or fail any form of therapy for clinically confined prostate cancer. This article provides an overview of therapeutic options: monotherapy and minimal androgen blockade options versus maximal androgen blockade, adjuvant therapy, intermittent therapy and timing of therapy as well as chemotherapy when all these measures fail. The impact of these therapies on progression as well as quality of life is reviewed.     

Local-regional prostate cancer

Historically, locally advanced prostate cancer was defined clinically with the digital rectal exam (DRE). With the introduction of screening prostate specific antigen (PSA), further pretreatment stratification of locally advanced prostate cancer was possible. Tables and nomograms have been developed to predict pathologic staging prior to therapy. By combining DRE, PSA, Gleason score, and clinical staging, a patient's probability of treatment failure is estimated, thereby stratifying the risk of locally advanced disease. Pretreatment PSA velocity (PSAV) and PSA doubling time (PSADT) will likely continue to play a role in defining locally advanced prostate cancer. Imaging studies, especially high-field strength pelvic MRI, may provide additional information regarding the presence of locally advanced prostate cancer. In the future, molecular or genetic testing may permit further stratification of patients with locally advanced disease, who are at variable risk for recurrence and death after treatment. Future trials will need to assess the utility of multimodality treatments for patients in the diverse classification of locally advanced prostate cancer.     

Metastatic prostate cancer

Summary For decades the palliation of prostate cancer has centered around hormonal manipulation using orchiectomy or estrogen administration. Newer modalities, such as LHRH agonists and nonsteroidal antiandrogens, are now available. Patients receiving combination therapy enjoy superior progression-free and median survival rates.     

Defining prostate cancer risk before prostate biopsy

Prostate cancer is the most commonly diagnosed cancer in men. At present, patients are selected for prostate biopsy on the basis of age, serum prostate specific antigen (PSA), and prostatic digital rectal examination (DRE) findings. However, due to limitations in the use of PSA and DRE, many patients undergo unnecessary prostate biopsy. A further problem arises as many patients are diagnosed and treated for indolent disease. This review of the literature highlights the strengths and weaknesses of existing methods of prebiopsy risk stratification and evaluates promising serum, urine, and radiologic prostate cancer biomarkers, which may improve risk stratification for prostate biopsy in the future.     

Risk-based prostate cancer screening

Context

Widespread mass screening of prostate cancer (PCa) is not recommended because the balance between benefits and harms is still not well established. The achieved mortality reduction comes with considerable harm such as unnecessary biopsies, overdiagnoses, and overtreatment. Therefore, patient stratification with regard to PCa risk and aggressiveness is necessary to identify those men who are at risk and may actually benefit from early detection.

Objective

This review critically examines the current evidence regarding risk-based PCa screening.

Evidence acquisition

A search of the literature was performed using the Medline database. Further studies were selected based on manual searches of reference lists and review articles.

Evidence synthesis

Prostate-specific antigen (PSA) has been shown to be the single most significant predictive factor for identifying men at increased risk of developing PCa. Especially in men with no additional risk factors, PSA alone provides an appropriate marker up to 30 yr into the future. After assessment of an early PSA test, the screening frequency may be determined based on individualized risk. A limited list of additional factors such as age, comorbidity, prostate volume, family history, ethnicity, and previous biopsy status have been identified to modify risk and are important for consideration in routine practice. In men with a known PSA, risk calculators may hold the promise of identifying those who are at increased risk of having PCa and are therefore candidates for biopsy.

Conclusions

PSA testing may serve as the foundation for a more risk-based assessment. However, the decision to undergo early PSA testing should be a shared one between the patient and his physician based on information balancing its advantages and disadvantages.     

Androgens and prostate cancer

Over 60 years ago Huggins and Hodges demonstrated the importance of androgens and prostate cancer. Since then, significant research has revealed that this relationship is multi-faceted and is interwoven with different signaling cascades and protein coactivators. The complex interrelationship between hormone and cancer is best exemplified by the recurrence and progression of prostate cancer after hormonal therapy to a lethally resistant phenotype despite initially encouraging therapeutic responses. If we are to significantly improve survival with novel therapies, further understanding of the emergence of this resistant phenotype is essential. The purpose of this article is to review the mechanisms of androgen action and its relation to hormonal therapy and mechanisms of hormonal resistance.     

Echograms of prostate cancer: inside echo patterns of localized prostate cancer

Transrectal ultrasonography has been considered useful for the diagnosis of prostate cancer. There have been few reports on localized cancer in the prostate diagnosed by echogram. In this paper, we discuss echograms of the prostate in cases of localized cancer, advanced cancer and well-controlled cancer. Hypoechoic lesions seem to suggest prostate cancer.     

微小核糖核酸与前列腺癌

微小核糖核酸(microRNAs,miRNAs)是一类长度约为22个核苷酸,参与基因转录后水平调控的非编码小分子RNA。参与生命的多个过程且与癌症发生发展有着密切的关系。最近研究发现,一些miRNA在前列腺癌(PCa)组织中异常表达,表明miRNA在PCa发病的分子机制中起着重要作用。随着人血清/血浆miRNA的不断深入研究,血清miRNA有望作为诊断PCa的潜在分子标志物。     

miRNA在前列腺癌中的研究进展

前列腺癌(PCa)是男性泌尿系最常见的恶性肿瘤之一,微小RNA(miRNA)是一类内源性的非编码小RNA,研究发现miRNA与PCa的发生和发展密切相关,多种miRNA在PCa中表达异常。本文通过描述miRNA在PCa中表达差异及其与预后的相关性,进一步分析miRNA与放化疗、雄激素受体,以及PCa转移的相关性,来阐明miRNA在PCa发生发展中的的作用。     

Screening for prostate cancer

Carcinoma of the prostate gland is the secondmost common cancer among men with anage-adjusted incidence of 635 cases per 100,000men aged 65 and older. While there are severalproven methods for detecting prostate cancer,debate continues as to the best way to detectit early as well as who should receiveparticular screening. There are differingopinions as to proven benefit even when canceris detected. Fortunately, newer methodscontinue to be developed that will hopefullyreduce false positive detection rates whileinsuring an adequate level of screeningprotection.     

PET and prostate cancer

The diagnosis of prostate cancer leaves some questions without answers. The different diagnostic techniques are limited in three situations: (1) staging of the tumour: identification of node involvement, (2) quantification of the tumour volume and its location inside the gland, (3) premature identification of relapse after radical treatment. These are the three problems that we need to consider in the diagnosis of prostate carcinoma. Imaging techniques can tell us the morphological alterations in the structures and organs. Positron emission tomography (PET) introduces a new way of identifying damage by counting metabolic activity. The tracers are substances that are marked with a radioactive molecule that is picked up more readily by the tumours. The presence of these substances in a set anatomic zone means higher consumption and therefore more metabolic activity. The radiotracer most frequently used in PET is glucose marked with fluoride 18. The first studies with marked glucose and prostate tumours started at the end of the 1990s. There are many contradictions in the results of these studies due to renal elimination, which produces an accumulation in the urinary tract and does not correctly show the prostate zone and iliobturator nodes area, and its capitation by zones with inflammatory process or prostatic hyperplasia. Choline is a substance that is present in cellular membranes. When it is marked with carbon 11, it changes to a new tracer. This radiotracer has affinity with prostate damage and allows the better differentiation of malignant from benign processes. It also has the advantage of the absence of renal elimination. Trials that used choline marked with carbon 11 (11C choline) are beginning to obtain very promising results. This union of a method that identifies metabolic activity with an imaging technique increases the sensitivity in the diagnostic test and can help find the exact location of the 11C choline deposits. The PET-CT combines the PET with computerised tomography. The 11C choline PET-CT is presented as a promising technique for answering the three problems mentioned above.