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.
"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. "
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Prostate cancers show a slow progression from a local lesion (primary tumor) to a metastatic and hormone-resistant phenotype. After an initial step of hyperplasia, in a high percentage of cases a neoplastic transformation event occurs that, less frequently, is followed by epithelial to mesenchymal transition and invasion of healthy tissues (usually bones). MicroRNA-203 (miR-203) is a tumor suppressor microRNA often silenced in different malignancies. Here, we show that miR-203 is downregulated in clinical primary prostatic tumors compared to normal prostate tissue, and in metastatic prostate cancer cell lines compared to normal epithelial prostatic cells. Overexpression of miR-203 in brain or bone metastatic prostate cell lines (DU145 and PC3) is sufficient to induce a mesenchymal to epithelial transition with inhibition of cell proliferation, migration and invasiveness. We have identified CKAP2, LASP1, BIRC5, WASF1, ASAP1 and RUNX2 as new miR-203 direct target mRNAs involved in these events. Therefore, miR-203 could be a potentially new prognostic marker and therapeutic target in metastatic prostate cancer.
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