Global update on defining and treating high-risk localized prostate cancer with leuprorelin: a Japanese perspective--the effect of primary androgen deprivation therapy on stage C prostate cancer.
ABSTRACT Stage C prostate cancer, where the tumour has extended beyond the capsule of the prostate, is typically a high-risk disease. According to the National Cancer Institute Physician Data Query the treatments of choice for stage C disease comprise external beam radiation therapy (with or without the addition of adjuvant hormone therapy), androgen deprivation by either surgery or hormone therapy, radical prostatectomy, or careful observation. From 2001, the Japanese Urological Association initiated computer-based registration of all patients with prostate cancer in Japan. Data show that overall, 57% of all patients and 46% of those with T1c to T3 disease had primary androgen deprivation therapy (PADT). Similarly, the Japanese Prostate Cancer Group undertook a large-scale epidemiological surveillance study in Japan and found that the most commonly used hormone therapy is PADT, regardless of disease stage. To date, two randomized, controlled trials of the effect of PADT on stage C prostate cancer in elderly (> or =75 years old) patients have been undertaken in Japan. The results showed that patients with locally advanced prostate cancer treated with PADT are likely to have a life-expectancy similar to that of the normal population. In one study, combined androgen blockade (CAB) with leuprorelin plus chlormadinone appeared to prolong time to disease progression when compared with leuprorelin monotherapy, but there was no difference in survival between these treatment groups. In a second study CAB with an luteinizing hormone-releasing hormone (LHRH) agonist plus bicalutamide was found to prolong time to progression when compared with LHRH agonist monotherapy, but survival results for these regimens are still awaited.
- SourceAvailable from: Atsushi Mizokami
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ABSTRACT: One of the mechanisms through which advanced prostate cancer (PCa) usually relapses after androgen deprivation therapy (ADT) is the adaptation to residual androgens in PCa tissue. It has been observed that androgen biosynthesis in PCa tissue plays an important role in this adaptation. In the present study, we investigated how stromal cells affect adrenal androgen dehydroepiandrosterone (DHEA) metabolism in androgen-sensitive PCa LNCaP cells. DHEA alone had little effect on prostate-specific antigen (PSA) promoter activity and the proliferation of LNCaP cells. However, the addition of prostate stromal cells or PCa-derived stromal cells (PCaSC) increased DHEA-induced PSA promoter activity via androgen receptor activation in the LNCaP cells. Moreover, PCaSC stimulated the proliferation of LNCaP cells under physiological concentrations of DHEA. Biosynthesis of testosterone or dihydrotestosterone from DHEA in stromal cells and LNCaP cells was involved in this stimulation of LNCaP cell proliferation. Androgen biosynthesis from DHEA depended upon the activity of various steroidogenic enzymes present in stromal cells. Finally, the dual 5alpha-reductase inhibitor dutasteride appears to function not only as a 5alpha-reductase inhibitor but also as a 3beta-hydroxysteroid dehydrogenase inhibitor in LNCaP cells. Taken together, this coculture assay system provides new insights of coordinate androgen biosynthesis under the microenvironment of PCa cells before and after ADT, and offers a model system for the identification of important steroidogenic enzymes involved in PCa progression and for the development of the corresponding inhibitors of androgen biosynthesis.Endocrine Related Cancer 08/2009; 16(4):1139-55. DOI:10.1677/ERC-09-0070 · 5.26 Impact Factor
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ABSTRACT: Among the heterogeneous population of patients with prostate cancer, a high-risk group with locally advanced prostate cancer (LAPC) present a diagnostic and therapeutic dilemma. Although the incidence of LAPC has decreased with screening since the introduction of prostate-specific antigen (PSA) testing, significantly many patients are still diagnosed with LAPC. These patients are by definition at higher risk of metastatic disease and worse outcomes. The role of radical prostatectomy (RP) in this population has been debated, as the combination of radiotherapy and hormonal therapy is becoming used more frequently for LAPC. Unfortunately, the clinical staging and evaluation of LAPC is a challenge that results in possibly understaging or overstaging these patients. This further complicates therapeutic decision-making, and as a result no established standard treatment has been proposed. Like other patients with prostate cancer, individualized therapeutic choices are essential and depend on a multitude of factors. Herein we examine the role of RP for managing LAPC and attempt to emphasize how the risk of distant disease and difficulty with clinical staging might favour incorporating a surgical approach as part of the therapy for patients with LAPC.BJU International 09/2009; 104(4):449-54. DOI:10.1111/j.1464-410X.2009.08741.x · 3.13 Impact Factor