Prostate Cancer最新文献

Background. The aim of this study was to determine concordance rates for prostatectomy specimens and transrectal needle biopsy samples in various areas of the prostate in order to assess diagnostic accuracy of the transrectal biopsy approach, especially for presurgical detection of cancer in the prostatic apex. Materials and Methods. From 2006 to 2011, 158 patients whose radical prostatectomy specimens had been evaluated were retrospectively enrolled in this study. Concordance rates for histopathology results of prostatectomy specimens and needle biopsy samples were evaluated in 8 prostatic sections (apex, middle, base, and transitional zones bilaterally) from 73 patients diagnosed at this institution, besides factors for detecting apex cancer in total 118 true positive and false negative apex cancers. Results. Prostate cancer was found most frequently (85%) in the apex of all patients. Of 584 histopathology sections, 153 (49%) from all areas were false negatives, as were 45% of apex biopsy samples. No readily available preoperative factors for detecting apex cancer were identified. Conclusions. In Japanese patients, the most frequent location of prostate cancer is in the apex. There is a high false negative rate for transrectal biopsy samples. To improve the detection rate, transperitoneal biopsy or more accurate imaging technology is needed.

A better understanding of multimolecular interactions involved in tumor dissemination is required to identify new effective therapies for advanced prostate cancer (PCa). Several groups investigated protein-glycan interactions as critical factors for crosstalk between prostate tumors and their microenvironment. This review both discusses whether the "galectin-signature" might serve as a reliable biomarker for the identification of patients with high risk of metastasis and assesses the galectin-glycan lattices as potential novel targets for anticancer therapies. The ultimate goal of this review is to convey how basic findings related to galectins could be in turn translated into clinical settings for patients with advanced PCa.

There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of the differences in radiobiology of prostate cancer and the surrounding normal tissues. The preliminary results from clinical studies indicate that abbreviated fractionation programs can result in successful treatment of localized prostate cancer without escalation of late toxicity.

Androgen deprivation therapy (ADT) with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration refractory metastatic prostate cancer (CRPC) and die of their disease. Over the last decade, it has been recognized that despite the failure of ADT, most prostate cancers maintain some dependence on androgen and/or androgen receptor (AR) signaling for proliferation. Furthermore, androgen independent molecular pathways have been identified as drivers of continued progression of CRPC. Subsequently, drugs have been developed targeting these pathways, many of which have received regulatory approval. Agents such as abiraterone, enzalutamide, orteronel (TAK-700), and ARN-509 target androgen signaling. Sipuleucel-T, ipilimumab, and tasquinimod augment immune-mediated tumor killing. Agents targeting classic tumorogenesis pathways including vascular endothelial growth factor, hepatocyte growth factor, insulin like growth factor-1, tumor suppressor, and those which regulate apoptosis and cell cycles are currently being developed. This paper aims to focus on emerging molecular pathways underlying progression of CRPC, and the drugs targeting these pathways, which have recently been approved or have reached advanced stages of development in either phase II or phase III clinical trials.

Since the introduction of robot-assisted radical prostatectomy (RALP), robotics has become increasingly more commonplace in the armamentarium of the urologic surgeon. Robotic utilization has exploded across surgical disciplines well beyond the fields of urology and prostate surgery. The literature detailing technical steps, comparison of large surgical series, and even robotically focused randomized control trials are available for review. RALP, the first robot-assisted surgical procedure to achieve widespread use, has recently become the primary approach for the surgical management of localized prostate cancer. As a result, surgeons are constantly trying to refine and improve upon current technical aspects of the operation. Recent areas of published modifications include bladder neck anastomosis and reconstruction, bladder drainage, nerve sparing approaches and techniques, and perioperative and postoperative management including penile rehabilitation. In this review, we summarize recent advances in perioperative management and surgical technique for RALP.

MicroRNAs are key regulators of gene expression and play critical roles in both normal physiology and pathology. Recent research has demonstrated that these molecules are present in body fluids, such as serum, plasma, and urine, and can be readily measured using a variety of techniques. More importantly, emerging evidence suggests that circulating or urine miRNAs are useful indicators of disease. Here, we consider the potential utility of such miRNAs as noninvasive biomarkers of prostate cancer, a disease that would benefit substantially from novel diagnostic and prognostic tools. The studies aimed at identifying diagnostic, prognostic, and/or predictive miRNAs for prostate cancer are summarised and reviewed. Finally, practical considerations that will influence the translation of this recent research into clinical implementation are discussed.

Previous researches involving dietary methods have shown conflicting findings. Authors sought to assess the association of prostate cancer risk with blood levels of omega-3 polyunsaturated fatty acids (n-3 PUFA) through a meta-analysis of human epidemiological studies in available online databases (July, 2012). After critical appraisal by two independent reviewers, Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used to grade the studies. Six case control and six nested case control studies were included. Results showed nonsignificant association of overall effect estimates with total or advanced prostate cancer or high-grade tumor. High blood level of alpha-linolenic acid (ALA) had nonsignificant positive association with total prostate cancer risk. High blood level of docosapentaenoic acid (DPA) had significant negative association with total prostate cancer risk. Specific n-3 PUFA in fish oil, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) had positive association with high-grade prostate tumor risk only after adjustment of interstudy variability. There is evidence that high blood level of DPA that is linked with reduced total prostate cancer risk and elevated blood levels of fish oils, EPA, and DHA is associated with high-grade prostate tumor, but careful interpretation is needed due to intricate details involved in prostate carcinogenesis and N-3 PUFA metabolism.

Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibiting RANK-L mediated bone resorption. While several radiopharmaceuticals were approved for pain palliation in mCRPC including strontium and samarium, alpharadin is the first radiopharmaceutical to show significant overall survival benefit. Contemporary therapeutic options including enzalutamide and abiraterone have effects on pain palliation and SREs as well. Other novel bone-targeted agents are currently in development, including the receptor tyrosine kinase inhibitors cabozantinib and dasatinib. Emerging therapeutics in mCRPC has resulted in great strides in preventing one of the most significant sources of complications of bone metastases.

Background: Ki-67 is a robust predictive/prognostic marker in prostate cancer; however, tumor heterogeneity in prostate biopsy samples is not well studied.

Methods: Using an MRI/US fusion device, biopsy cores were obtained systematically and by targeting when indicated by MRI. Prostate cores containing cancer from 77 consecutive men were analyzed. The highest Ki-67 was used to determine interprostatic variation. Ki-67 range (highest minus lowest) was used to determine intraprostatic and intralesion variation. Apparent diffusion coefficient (ADC) values were evaluated in relation to Ki-67.

Results: Interprostatic Ki-67 mean ± standard deviation (SD) values for NCCN low (L), intermediate (I), and high (H) risk patients were 5.1 ± 3.8%, 7.4 ± 6.8%, and 12.0 ± 12.4% (ANOVA P = 0.013). Intraprostatic mean ± SD Ki-67 ranges in L, I, and H risk patients were 2.6 ± 3.6%, 5.3 ± 6.8%, and 10.9 ± 12.3% (ANOVA P = 0.027). Intralesion mean ± SD Ki-67 ranges in L, I, and H risk patients were 1.1 ± 0.9%, 5.2 ± 7.9%, and 8.1 ± 10.8% (ANOVA P = 0.22). ADC values at Ki-67 > and <7.1% were 860 ± 203 and 1036 ± 217, respectively (P = 0.0029).

Conclusions: High risk patients have significantly higher inter- and intraprostatic Ki-67 heterogeneity. This needs to be considered when utilizing Ki-67 clinically.

Prostate cancer (CaP) is the leading cancer among men of African descent in the USA, Caribbean, and Sub-Saharan Africa (SSA). The estimated number of CaP deaths in SSA during 2008 was more than five times that among African Americans and is expected to double in Africa by 2030. We summarize publicly available CaP data and collected data from the men of African descent and Carcinoma of the Prostate (MADCaP) Consortium and the African Caribbean Cancer Consortium (AC3) to evaluate CaP incidence and mortality in men of African descent worldwide. CaP incidence and mortality are highest in men of African descent in the USA and the Caribbean. Tumor stage and grade were highest in SSA. We report a higher proportion of T1 stage prostate tumors in countries with greater percent gross domestic product spent on health care and physicians per 100,000 persons. We also observed that regions with a higher proportion of advanced tumors reported lower mortality rates. This finding suggests that CaP is underdiagnosed and/or underreported in SSA men. Nonetheless, CaP incidence and mortality represent a significant public health problem in men of African descent around the world.