重视前列腺癌诊断和治疗的研究

当今,前列腺癌已经成为临床上一个很热门的话题,这不仅是因为前列腺癌的发病率很高,它已经是泌尿外科常见的老年男性恶性肿瘤,泌尿外科临床医师很重视,而且也引起很多男性的关注。老年男性,他们担心自己患前列腺癌,患了前列腺癌的又担心疾病进展和预后;中年男性,他们关心自己进入老年行列以后是否会得前列腺癌。此外,在临床上我们也发现前列腺癌的诊断和治疗又有很多值得研究的现象。     

前列腺癌临床诊治中的有关问题

随着国民生活水平的提高、人均寿命的延长以及血清前列腺特异抗原（PSA）临床检测的普遍应用，前列腺癌的检出率和外科治疗比率逐年提高。但是由于认识上的差异，在前列腺癌的临床诊治过程中尚存在许多有争议性的内容。结合前列腺癌临床研究进展以及我们的临床工作体会就下述问题进行阐述。     

Epigenetic targets in the diagnosis and treatment of prostate cancer

Prostate cancer (PC) is one of leading cause of cancer related deaths in men. Various aspects of cancer epigenetics are rapidly evolving and the role of 2 major epigenetic changes including DNA methylation and histone modifications in prostate cancer is being studied widely. The epigenetic changes are early event in the cancer development and are reversible. Novel epigenetic markers are being studied, which have the potential as sensitive diagnostic and prognostic marker. Variety of drugs targeting epigenetic changes are being studied, which can be effective individually or in combination with other conventional drugs in PC treatment. In this review, we discuss epigenetic changes associated with PC and their potential diagnostic and therapeutic applications including future areas of research.     

Wait times in prostate cancer diagnosis and radiation treatment

Introduction:

Wait times for cancer diagnosis and treatment are a significant concern for Canadians. Men with prostate cancer experience longer waiting times for diagnosis and treatment than those observed for other cancers. Longer waits are associated with both patient and family psychosocial distress and may be associated with worse prognosis.

Methods:

Men referred for treatment of prostate cancer at a single Canadian cancer centre were interviewed. The intervals from suspicion to definitive therapy were calculated, factors associated with delays along this pathway were identified, and common causes of delay identified by patients were described.

Results:

A total of 41 consecutive patients participated. The median interval from suspicion to the first fraction of radiotherapy for all patients was 247 days (interquartile range [IQR] 168–367 d). The median diagnostic interval was 53 days (IQR 28–166 d). The median treatment interval was 127 days (IQR 100–180 d). Patients under 70 years old and patients with <T2c disease had shorter intervals from suspicion to treatment. From diagnosis to start of radiotherapy, patients with low-risk disease had longer intervals. Seventy percent of patients perceived a delay in their care, of which 45%, 31% and 24% of patients felt the delays were due to the health care system, patient or physician factors, respectively.

Interpretation

In this study, 12% and 0% of patients met Canadian Strategy for Cancer Control and Canadian Association of Radiation Oncologists wait time recommendations, respectively. A large component of wait time is patient driven. Alternate strategies should be developed and measured to shorten the intervals between the suspicion and treatment of prostate cancer.     

CEUS在前列腺癌诊治中的应用进展

前列腺癌的发病率逐年增加,早期诊断及治疗对于控制疾病的发展至关重要。CEUS作为一项新的检查手段,不仅可提高前列腺癌的诊断水平,而且可用于前列腺癌的治疗。本研究对CEUS在PCa诊治中的应用进展进行综述。     

Indication of repeat prostate biopsy for the diagnosis of prostate cancer

There is no standard criterion for repeat prostate biopsy in cases with a negative initial biopsy. We retrospectively analyzed our experience of repeat prostate biopsy to establish its indication for the diagnosis of prostate cancer. From April 1997 to March 2005, 35 consecutive patients underwent repeat prostate biopsy at the department of Urology, Asahikawa Medical College Hospital because of clinically suspicious prostate cancer despite a negative initial biopsy. We compared patients' age, number of cores obtained during repeat biopsy, digital rectal examination findings, total prostate volume, the time from the first to the last biopsy, total prostate specific antigen (PSA) value, free PSA/total PSA ratio, PSA density and PSA velocity between cancer-positive and cancer-negative groups. Prostate cancer was detected in 17 of 35 patients (49%). Fifteen patients with prostate cancer were diagnosed by the first repeat biopsy and other 2 patients were diagnosed by the second repeat biopsy. A statistically significant difference was only noted in age and PSA density. Persistently elevated total PSA and a higher PSA density in cases with a negative initial biopsy might be a good indication of repeat prostate biopsy for the diagnosis of prostate cancer.     

Future perspectives of prostate cancer therapy

We summarize several recent laboratory advances to tackle the problem of tumor-stroma-immune cell microenvironment interaction with the hope of developing and advancing new concepts and therapeutic strategies for prostate cancer therapy by improving bone and soft tissue metastases in prostate cancer patients. Given the emerging enthusiasm for immunotherapy in prostate cancer due to (I) improved understanding of the role of immune cells in the tumor microenvironment, (II) approval by the FDA of an immunotherapeutic drug to treat prostate cancer, and (III) recognition of immunotherapy as a novel approach to treat solid tumors by the Nobel Prize Committee (for discovery of dendritic cells that are used in immunotherapy), the field of tumor immunology is poised for growth in the next decade with the hope of developing new immunomodulatory drugs which will compliment and perhaps eventually replace traditional chemotherapeutic drugs. In this article, we provide a timely review of recent advances in the field of immunotherapy for prostate cancer, lessons learned from successes and failures, the contributory factors in the tumor microenvironment that could be rendered hostile to cancer cells, an exciting area of future research.     

Perspectives on prostate cancer diagnosis and treatment: a roundtable

This roundtable was held September 30, 2000. It addressed, first of all, the accuracy and proper interpretation of the available prostate-specific antigen assays. Dr. Brawer presented data to demonstrate the specificity of the complexed prostate-specific antigen assay. Dr. Stamey counterpoised evidence that pretreatment prostate-specific antigen levels less than 9 ng/mL are attributable to benign prostatic hyperplasia and therefore are of little value as an indicator of when to initiate treatment for prostate cancer. The other roundtable participants offered reviews and new data regarding hormonal therapy as primary or adjunctive treatment of prostate cancer. Dr. Fowler presented a large retrospective series of men with locally advanced prostate cancer for whom androgen ablation was the primary therapy. Dr. Droller discussed his center's experience in integrating hormonal therapy with brachytherapy. Finally, Dr. Messing reviewed and critiqued the evidence that the combination of hormonal and radiation therapy improves survival.     

Modeling prostate cancer in mice: limitations and opportunities

The complex dynamics of the tumor microenvironment and prostate cancer heterogeneity have confounded efforts to establish suitable preclinical mouse models to represent human cancer progression from early proliferative phenotypes to aggressive, androgen-independent, and invasive metastatic tumors. Current models have been successful in capitulating individual characteristics of the aggressive tumors. However, none of these models comprehensively mimics human cancer progression, establishing the challenge in their exploitation to study human disease. The ability to tailor phenotypic outcomes in mice by compounding mutations to target specific molecular pathways provides a powerful tool toward disruption of signaling pathways contributing to the initiation and progression of castration-resistant prostate cancer. Each model is characterized by unique features contributing to the understanding of prostate tumorigenesis, as well as limitations challenging our knowledge of the mechanisms of cancer development and progression. Emerging strategies utilize genomic manipulation technology to circumvent these limitations toward the formulation of attractive, physiologically relevant models of prostate cancer progression to advanced disease. This review discusses the current value of the widely used and well-characterized mouse models of prostate cancer progression to metastasis, as well as the opportunities begging exploitation for the development of new models for testing the antitumor efficacy of therapeutic strategies and identifying new biomarkers of disease progression.     

Future prospects in prostate cancer.

BACKGROUND: Prostate cancer has displayed an increase in incidence unparalleled by any other tumor in the last two decades, with a steady, more gradual increase in mortality rate. Current curative strategies are focused on the detection and treatment of early-stage (T1-2 N0 M0), clinically significant tumors. METHODS: To this aim, refinement of surgical approaches, with appropriate adjuvant therapies, will ensure more complete cancer control, while minimizing associated morbidity. New delivery systems for radiotherapy, as well as other energy sources, are evolving, while a number of promising pharmacological agents, including angiogenesis inhibitors and drugs which alter signal transduction pathways, are currently under investigation. Early detection is also being facilitated by a more widespread implementation of screening programs. Advances in tumor markers, and imaging and biopsy techniques, will allow more accurate preoperative staging. These, coupled with improvements in prognostic markers, aid the physician and patient alike in deciding on the suitability of treatment options with better estimation of outcome. Perhaps the most exciting developments in prostate cancer will come from knowledge of the molecular mechanisms underlying carcinogenesis. The potential for the development of diagnostic and therapeutic tools is immense. The efficacy of treatment can be studied at a molecular level, and strategies for preventing or slowing the development of malignancy can be formulated. RESULTS AND CONCLUSIONS Application of this knowledge in the form of gene and cellular therapy and in the development of novel systemic agents is beginning to enter the realm of clinical practice, and it may be in this field that means for cure and prevention of prostate cancer will eventually be found.     

Deferred treatment for prostate cancer

The clinical outcome of 278 prostate cancer patients managed by a deferred treatment policy was analysed retrospectively. Following TURP or biopsy, all patients were asymptomatic and deemed suitable for management by a deferred treatment policy, i.e. hormone therapy or other forms of treatment were only initiated if and when symptomatic progression occurred. The overall 5-year survival rate was 30%; 18% of patients died from other causes without needing treatment for their prostate cancer; 11% were alive and untreated after 5 years' follow-up; 17% died from prostate cancer without further treatment. Poor tumour grade, anaemia, metastatic disease, a short history, presentation with retention, and a raised serum creatinine at presentation were associated with a poor prognosis.     

Under diagnosis and over diagnosis of prostate cancer

PURPOSE: We quantified the rates of over and under diagnosis of prostate cancer in 2 large patient cohorts during the last 15 years. MATERIALS AND METHODS: A total of 2,126 men with clinical stage T1c prostate cancer were treated with radical prostatectomy during 1 of the 3 periods 1989 to 1995, 1995 to 2001 and 2001 to 2005. The respective proportions of men with a tumor that met our criteria for over diagnosis (0.5 cm3 or less, confined to the prostate with clear surgical margins and no Gleason pattern 4 or 5) and under diagnosis (nonorgan confined, pathological stage T3 or greater, or positive surgical margins) were examined. RESULTS: The proportion of men with an over diagnosed tumor was 1.3% to 7.1%. The proportion with prostate cancer that was under diagnosed was 25% to 30%. An ancillary finding was that decreasing the prostate specific antigen threshold for biopsy from 4.0 to 2.5 ng/ml in the screened population resulted in a lower rate of under diagnosis from 30% to 26%, a higher rate of over diagnosis from 1.3% to 7.1% and an increase in the 5-year progression-free survival rate from 85% to 92%. Men who were 55 years or younger were significantly more likely to meet our criteria for over diagnosed cancer. CONCLUSIONS: Under diagnosis of prostate cancer continues to occur more frequently than over diagnosis. Lowering the prostate specific antigen threshold for recommending biopsy to 2.5 ng/ml resulted in a lower rate of under diagnosis and a higher progression-free survival rate.