Does local treatment of the prostate in advanced and/or lymph node metastatic disease improve efficacy of androgen-deprivation therapy? A systematic review.
ABSTRACT Androgen-deprivation therapy (ADT) plays a pivotal role in the management of locally advanced and metastatic prostate cancer (PCa). When and for how long to apply ADT have remained controversial issues.
To review randomised studies of ADT (orchiectomy or luteinising hormone-releasing hormone analogues) in PCa-both immediate and deferred/adjuvant studies-to elucidate a possible interaction between local treatment and ADT.
Published randomised studies on ADT in various stages of PCa were included in this review.
Studies of immediate versus deferred ADT without local treatment consistently showed only limited benefit for overall survival (OS; hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.83-0.97) and cancer-specific survival (CSS; HR: 0.79; 95% CI, 0.71-0.89). In contrast, ADT as an adjuvant to radiation therapy in patients with high-risk localised disease or locally advanced disease was associated with substantial OS and CSS benefits. A similar benefit was seen in patients with proven systemic disease (node-positive patients after radical prostatectomy). Overall, the data suggest a clinically important survival benefit (HR for OS: 0.69; 95% CI, 0.61-0.79) when a local treatment has been applied to the primary tumour. Possible mechanisms of this therapeutic effect are discussed.
We conclude that an interaction between local treatment and ADT is suggested by this systematic review. In patients with advanced and aggressive disease who are at a high risk to die from PCa and who are treated for their primary tumour with curative intent, immediate and sustained ADT improves OS and CSS significantly. The local therapy in T3 and/or lymph node-positive disease is an essential part of the optimal treatment. However, this intensive treatment is unnecessary in a substantial number of patients with T3 and/or N1 disease with a slow natural history or high competing death risk.
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ABSTRACT: High-risk localized prostate cancer traditionally includes patients with clinical T3 disease but also includes those with apparently localized disease but with adverse prognostic factors such as a Gleason score of 8 to 10, prostate-specific antigen of more than 20 ng/ml, or extensive disease on biopsy. In the past, these patients were treated primarily with radiation therapy due to concerns that surgery was not likely to be curative and was associated with a high incidence of side-effects. In addition, the lack of randomized trials comparing curative treatments for high-risk prostate cancer makes treatment decisions in this patient population difficult. Several retrospective series have reported the long-term efficacy of radical prostatectomy monotherapy in a high-risk population, showing that the 5-year cancer-specific survival rate was more than 80% and the 5-year biochemical recurrence-free survival rate was about 50%. In addition, comparisons of different treatment options by means of nonrandomized trials have shown improved outcomes with surgery compared with radiation therapy or observation. Thus, there is renewed interest in radical prostatectomy as the primary treatment for patients with high-risk prostate cancer. Here, we reviewed the outcomes of radical prostatectomy, with or without neoadjuvant or adjuvant therapies, in high-risk patients and what is known about the choice and timing of adjuvant therapies.Korean journal of urology 09/2010; 51(9):589-95.