High-Risk Prostate Cancer: From Definition to Contemporary Management

Department of Urology, Klinikum der Universität München-Campus Großhadern, Ludwig-Maximilians-Universität, Munich, Germany.
European Urology (Impact Factor: 13.94). 02/2012; 61(6):1096-106. DOI: 10.1016/j.eururo.2012.02.031
Source: PubMed


High-risk prostate cancer (PCa) is a potentially lethal disease. It is clinically important to identify patients with high-risk PCa early on because they stand to benefit the most from curative therapy. Because of recent advances in PCa management, a multimodal approach may be advantageous.
Define high-risk PCa, and identify the best diagnostic and treatment patterns for patients with clinically localized and locally advanced disease. A critical analysis of published results following monomodal and/or multimodal therapy for high-risk PCa patients was also performed.
A review of the literature was performed using the Medline, Embase, Scopus, and Web of Science databases as well as the Cochrane Database of Systematic Reviews.
High-risk PCa accounts for ≤ 15% of all new diagnoses. Compared with patients with low- and intermediate-risk PCa, patients with high-risk PCa are at increased risk of treatment failure. Unfortunately, no contemporary randomized controlled trials comparing different treatment modalities exist. Evaluation of the results published to date shows that no single treatment can be universally recommended. Most often, a multimodal approach is warranted to optimize patient outcomes.
A significant minority of patients continue to present with high-risk PCa, which remains lethal in some cases. Outcomes following treatment of men with high-risk tumors have not substantially improved over time. However, not all high-risk patients are at the same risk of PCa progression and death. At present, a multimodal approach seems the best way to achieve acceptable outcomes for high-risk PCa patients.

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Available from: Hendrik Paul Van Poppel, Jun 17, 2014
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    • "For patients with localized PCa, radical prostatectomy (RP) is considered an ideal therapy [1]. However, several studies have shown that RP as the initial treatment may also show acceptable long-term outcomes in patients with locally advanced PCa [2] [3] [4] [5] [6] [7] [8] [9] [10]. This may be partly due to the fact that a significant portion (13–27%) of cT3a tumors are overstaged and are actually T2 at RP [5] [6] [8] [11]. "
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    ABSTRACT: Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. Retropubic RP and pelvic lymphadenectomy. Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment.
    Full-text · Article · Mar 2014 · European Urology
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    • "Over the past decade, however, there has been a surge in the utilization of radical prostatectomy (RP) as primary treatment in selected patients, followed by EBRT in case of adverse pathological features [5,6]. It is currently accepted that a combined modality-regimen should be pursued in clinical trials, although sequence, timing and intensity of the single treatments are still under scrutiny [8]. "
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    ABSTRACT: The optimal management of high-risk prostate cancer remains uncertain. In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer. This was a prospective phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel-based chemotherapy and long-term androgen deprivation therapy. Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method. Acute gastro-intestinal and genito-urinary toxicity was grade 2 in 23% and 20% of patients, and grade 3 in 9% and 3% of patients, respectively. Acute blood/bone marrow toxicity was grade 2 in 20% of patients. No acute grade >=4 toxicity was observed. Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9% of patients each. No late grade >=3 toxicity was observed. Median follow-up was 63 months (interquartile range 31-79). Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55% (95% confidence interval, 35-75%) and 70% (95% confidence interval, 52-88%), respectively. In our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer, toxicity was acceptably low and mid-term oncological outcome was good. This treatment paradigm, thus, may warrant further evaluation in phase III randomized trials.
    Full-text · Article · Jan 2014 · Radiation Oncology
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    • "Not very long ago, many urologists agreed that RP was not a suitable treatment option for high-risk prostate cancer patients because they accepted that the BCR rate and systemic progression rate after RP was significantly higher than that in other risk prostate cancer patients [18]. However, several recent studies of high-risk prostate cancer have presented another view [19–24]. "
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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.
    Full-text · Article · Sep 2013
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