Article

Contemporary Management of High-risk Localized Prostate Cancer

Division of Urology, Department of Surgery, and the Department of Radiation Medicine, Oregon Health & Science University, Portland Veterans Administration Medical Center, Portland, OR, 97239, USA.
Current Urology Reports (Impact Factor: 1.51). 05/2010; 11(3):159-64. DOI: 10.1007/s11934-010-0101-0
Source: PubMed

ABSTRACT

The management of high-risk, localized prostate cancer remains a formidable challenge despite significant technical advances in surgery and radiation therapy. Treatment outcomes of radiation therapy are improved by the addition of adjuvant androgen deprivation therapy, whereas, with surgery, oncologic results are enhanced with either postoperative radiation therapy or androgen deprivation therapy in select cases. In high-risk prostate cancer, disease recurrence after primary therapy may occur at either distant or local sites. Ongoing studies are in the process of evaluating systemic therapy for the eradication of local and micrometastatic disease. Neoadjuvant therapies offer the opportunity to maximize local control as a path to improved outcomes and critically evaluate agent effectiveness in the target tissue. The treatment for high-risk localized prostate cancer is in evolution. It is likely that the development of effective strategies based on understanding prostate tumor biology will lead to significant advances in the treatment of this disease.

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    • "It is very well established that circulating androgens are essential for the development of both normal and malignant prostate[1]and as such the chemical removal of androgens, known as androgen deprivation therapy (ADT), remains the most effective treatment option for patients with advanced disease. However, despite an initial response to therapy, most PCas will progress to castration resistant prostate cancer (CRPC) within 2 years of treatment initiation2345678. CRPC progression is a complex process by which PCa cells acquire the ability to survive and proliferate in the absence of androgens. "
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    ABSTRACT: Prostate cancer (PCa) is the leading type of cancer diagnosed in men. Studies on tumour-related extracellular vesicles (EVs) suggest that exosomes play a significant role in paracrine signaling pathways thus potentially influencing cancer progression via different mechanisms.During last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. We have previously described the role of exosomes as potential biomarkers for PCa. Differences in proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirmed that exosomes are good candidates for future biomarker studies. Our extensive proteomic analysis completed alongside with the evidence of exosome uptake into a local tumour microenvironment have encouraged us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa.In this study, we hypothesize that exosomes play a pivotal role in cell-cell communication in the local tumour microenvironment, conferring activation of numerous survival mechanisms during PCa progression and development of therapeutic resistance. Our in vitro results demonstrate that PCa derived exosomes significantly reduce apoptosis in LNCaP and RWPE-1 cells increase cancer cell proliferation and induce cell migration. Consistently with our in vitro findings, we have demonstrated that exosomes increase tumor volume and PSA level in vivo when xenograft bearing mice were administered intravenously with DU145 exosomes.This research suggests that exosomes derived from PCa cells, regardless of the androgen receptor phenotype, attribute positively the of mechanisms that contribute to PCa progression.
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    • "In high-risk prostate cancer patients, the best course of treatment is often unclear, and the oncological outcomes appear heterogeneous. Even though several treatment options, including RP, RT, and hormone therapy (HT) alone or in combination, are available for high-risk prostate cancer patients, the recurrence rate is high regardless of the type of treatment [10,11]. Despite the lack of high-level evidence of treatment benefits for these patients, the high-risk of disease progression and death from the disease may result in making active treatment, including RP, a preferred option. "
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    ABSTRACT: Because of the increase in prostate cancer patients, urologists can detect more clinically localized prostate cancer in patients before the disease has progressed to advanced stages. Nevertheless, some patients are still diagnosed with high-risk prostate cancer. Even though several treatment options are available for high-risk prostate cancer patients, including radical prostatectomy, radiotherapy, and hormone therapy, used alone or in combination, the recurrence rate is high regardless of the type of treatment. Nevertheless, in the experience of many urologists, a substantial proportion of high-risk prostate cancer patients are cured by local definite therapy or multimodality treatment. Thus, several treatment combinations have been attempted as treatments in these patients. Among them, radical prostatectomy is regarded as the first step in high-risk prostate cancer patients, on a selective basis. In some high-risk prostate cancer patients, surgery is a one-step modality in treatment and has an excellent oncological prognosis. However, because of the lack of evidence and well-controlled comparative prospective studies, the best course of treatment can be unclear, and oncological outcomes often appear heterogeneous. We therefore review the current literature on clinical outcomes in high-risk prostate cancer.
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