Prostate Cancer最新文献

Background. Prostate cancer (PCa) racial disparity is multifactorial, involving biological, sociocultural, and lifestyle determinants. We investigated the association between selected potentially functional polymorphisms (SNPs) and prostate cancer (PCa) risk in Black (AAM) and White (EAM) men. We further explored if these associations varied by the body mass index (BMI) and height. Methods. Age-matched DNA samples from 259 AAM and 269 EAM were genotyped for 10 candidate SNPs in 7 genes using the TaqMan allelic differentiation analysis. The dominant, recessive, and additive age-adjusted unconditional logistic regression models were fitted. Results. Three SNPs showed statistically significant associations with PCa risk: in AAM, HNF1B rs7501939 (OR = 2.42, P = 0.0046) and rs4430796 (OR = 0.57, P = 0.0383); in EAM, CTBP2 rs4962416 (OR = 1.52, P = 0.0384). In addition, high BMI in AAM (OR = 1.06, P = 0.022) and height in EAM (OR = 0.92, P = 0.0434) showed significant associations. Interestingly, HNF1B rs7501939 was associated with PCa exclusively in obese AAM (OR = 2.14, P = 0.0103). Conclusion. Our results suggest that variation in the HNF1B may influence PCa risk in obese AAM.

Despite the clinical implication and high incidence of bone and spinal metastases, the molecular mechanisms behind prostate cancer metastasis to bone and spine are not well understood. In this review the molecular mechanisms that may contribute to the highly metastatic phenotype of prostate cancer are discussed. Proangiogenic factors such as vascular endothelial growth factor (VEGF) have been shown to not only aid in the metastatic capabilities of prostate cancer but also encourage the colonization and growth of prostate tumour cells in the skeleton. The importance of VEGF in the complex process of prostate cancer dissemination to the skeleton is discussed, including its role in the development of the bone premetastatic niche, metastatic tumour cell recognition of bone, and bone remodeling. The expression of VEGF has also been shown to be upregulated in prostate cancer and is associated with clinical stage, Gleason score, tumour stage, progression, metastasis, and survival. Due to the multifaceted effect VEGF has on tumour angiogenesis, tumour cell proliferation, and bone destruction, therapies targeting the VEGF pathways have shown promising clinical application and are being investigated in clinical trials.

Androgen deprivation therapy is commonly used in combination with radiotherapy as part of the definitive treatment for men with clinically localized and locally advanced prostate cancer. Androgen deprivation has been associated with a wide range of iatrogenic effects impacting a variety of body systems including metabolic, musculoskeletal, cardiovascular, neurocognitive, and sexual. This review aims to provide the radiation oncology community with the knowledge to monitor and manage androgen deprivation therapy toxicity in an effort to provide the highest level of care for patients and to minimize the iatrogenic effects of androgen deprivation as much as possible.

Purpose. Survival following biochemical failure is highly variable. Using a randomized trial dataset, we sought to define a risk stratification scheme in men with locally advanced prostate cancer (LAPC). Methods. The TROG 96.01 trial randomized 802 men with LAPC to radiation ± neoadjuvant androgen suppression therapy (AST) between 1996 and 2000. Ten-year follow-up data was used to develop three-tier post-biochemical failure risk stratification schemes based on cutpoints of time to biochemical failure (TTBF) and PSA doubling time (PSADT). Schemes were evaluated in univariable, competing risk models for prostate cancer-specific mortality. The performance was assessed by c-indices and internally validated by the simple bootstrap method. Performance rankings were compared in sensitivity analyses using multivariable models and variations in PSADT calculation. Results. 485 men developed biochemical failure. c-indices ranged between 0.630 and 0.730. The most discriminatory scheme had a high risk category defined by PSADT < 4 months or TTBF < 1 year and low risk category by PSADT > 9 months or TTBF > 3 years. Conclusion. TTBF and PSADT can be combined to define risk stratification schemes after biochemical failure in men with LAPC treated with short-term AST and radiotherapy. External validation, particularly in long-term AST and radiotherapy datasets, is necessary.

The purpose of this work is to determine appropriate radiation therapy beam margins to account for intrafraction prostate translations for use with real-time electromagnetic position monitoring and correction strategies. Motion was measured continuously in 35 patients over 1157 fractions at 5 institutions. This data was studied using van Herk's formula of (αΣ + γσ') for situations ranging from no electromagnetic guidance to automated real-time corrections. Without electromagnetic guidance, margins of over 10 mm are necessary to ensure 95% dosimetric coverage while automated electromagnetic guidance allows the margins necessary for intrafraction translations to be reduced to submillimeter levels. Factors such as prostate deformation and rotation, which are not included in this analysis, will become the dominant concerns as margins are reduced. Continuous electromagnetic monitoring and automated correction have the potential to reduce prostate margins to 2-3 mm, while ensuring that a higher percentage of patients (99% versus 90%) receive a greater percentage (99% versus 95%) of the prescription dose.

Tissue markers may be helpful in enhancing prediction of radiation therapy (RT) failure of prostate cancer (PCa). Among the various biomarkers tested in Phase III randomized trials conducted by the Radiation Therapy Oncology Group, p16, Ki-67, MDM2, COX-2, and PKA yielded the most robust data in predicting RT failure. Other pathways involved in RT failure are also implicated in the development of castration-resistant PCa, including the hypersensitive androgen receptor, EGFR, VEGF-R, and PI3K/Akt. Most of them are detectable in PCa tissue even at the time of initial diagnosis. Emerging evidence suggests that RT failure of PCa results from a multifactorial and heterogeneous disease process. A number of tissue markers are available to identify patients at high risk to fail RT. Some of these markers have the promise to be targeted by drugs currently available to enhance the efficacy of RT and delay disease progression.

Prostate cancer is one of the most prevalent cancers among men in the United States, second only to nonmelanomatous skin cancer. Since prostate-specific antigen (PSA) testing came into widespread use in the late 1980s, there has been a sharp increase in annual prostate cancer incidence. Cancer-specific mortality, though, is relatively low. The majority of these cancers will not progress to mortal disease, yet most men who are diagnosed opt for treatment as opposed to observation or active surveillance (AS). These men are thus burdened with the morbidities associated with aggressive treatments, commonly incontinence and erectile dysfunction, without receiving a mortality benefit. It is therefore necessary to both continue investigating outcomes associated with AS and to develop less invasive techniques for those who desire treatment but without the significant potential for quality-of-life side effects seen with aggressive modalities. The goals of this paper are to discuss the problems of overdiagnosis and overtreatment since the advent of PSA screening as well as the potential for targeted focal therapy (TFT) to bridge the gap between AS and definitive therapies. Furthermore, patient selection criteria for TFT, costs, side effects, and brachytherapy template-guided three-dimensional mapping biopsies (3DMB) for tumor localization will also be explored.

Field cancerization denotes the occurrence of genetic, epigenetic, and biochemical aberrations in structurally intact cells in histologically normal tissues adjacent to cancerous lesions. This paper tabulates markers of prostate field cancerization known to date and discusses their potential clinical value in the analysis of prostate biopsies, including diagnosis, monitoring progression during active surveillance, and assessing efficacy of presurgical neoadjuvant and focal therapeutic interventions.

Purpose. To examine the associations among intake of refined grains, whole grains and dietary fiber and aggressiveness of prostate cancer in African Americans (AA, n = 930) and European Americans (EA, n = 993) in a population-based, case-only study (The North Carolina-Louisiana Prostate Cancer Project, PCaP). Methods. Prostate cancer aggressiveness was categorized as high, intermediate or low based on Gleason grade, PSA level and clinical stage. Dietary intake was assessed utilizing the NCI Diet History Questionnaire. Logistic regression (comparing high to intermediate/low aggressive cancers) and polytomous regression with adjustment for potential confounders were used to determine odds of high prostate cancer aggressiveness with intake of refined grains, whole grains and dietary fiber from all sources. Results. An inverse association with aggressive prostate cancer was observed in the 2nd and 3rd tertiles of total fiber intake (OR = 0.70; 95% CI, 0.50-0.97 and OR = 0.61; 95% CI, 0.40-0.93, resp.) as compared to the lowest tertile of intake. In the race-stratified analyses, inverse associations were observed in the 3rd tertile of total fiber intake for EA (OR = 0.44; 95% CI, 0.23-0.87) and the 2nd tertile of intake for AA (OR = 0.57; 95% CI, 0.35-0.95). Conclusions. Dietary fiber intake was inversely associated with aggressive prostate cancer among both AA and EA men.