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: 12.48). 02/2012; 61(6):1096-106. DOI: 10.1016/j.eururo.2012.02.031
Source: PubMed

ABSTRACT 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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    • "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.
    European Urology 03/2014; 67(2). DOI:10.1016/j.eururo.2014.03.013 · 12.48 Impact Factor
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    • "However, a better knowledge of the natural history of the disease and developments in treatment options have resulted in more sophisticated risk stratification systems (Marciscano et al. 2012). It is clinically important to identify patients with high-risk PCa early on because they will benefit the most from curative therapy (Bastian et al. 2012). Currently, systemic therapy has a limited role in the treatment of localized prostate cancer, although adjuvant androgen deprivation therapy (ADT) has yielded significant improvement in disease-free survival for men with high-risk features treated with definitive radiation and a significant overall survival advantage for men with Gleason scores of 8 or higher (Dorff et al. 2011). "
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    ABSTRACT: High-risk prostate cancer is a potentially lethal disease that is increasing in the diagnosis of prostate cancer patients. Compared to other prostate cancer patients (medium or low risk), management, diagnosis and treatment are not as successful among high-risk patients. Because the genetic characterization of prostate cancer patients is increasing, we aimed to determine whether genetic information in one of the primary associated genes, such as RNASEL (2', 5'-oligoadenylate-dependent RNase L), could be used as a biomarker to improve the quality of life and treatment among high-risk patients. The main objective is to identify genetic variants of RNASEL that could be associated with high-risk prostate cancer to improve the clinical managing of these patients. A total of 231 prostate cancer patients were genotyped for 7 variants of RNASEL gene. Clinical information was obtained from medical examinations and genetic analysis (amplification and sequencing 7 variants of RNASEL gene) were performed by the researchers. Data were processed by statistical analysis (Chi square and logistic regression) using SPSS v.15.0. Comparisons between genotypes and clinical characteristics of patients revealed that individuals with GG in D541E, AA in R462Q and AG in I97L in RNASEL gene were high-risk patients according to the European Urology Guidelines. Genotyping the RNASEL gene with routine diagnostic techniques could confer a more precise diagnosis of high-risk prostate cancer patients and increase the diagnostic accuracy above the current rate of 70% due to the relation between the genetic variants of RNASEL gene and the risk of this cancer.
    SpringerPlus 09/2013; 2:444. DOI:10.1186/2193-1801-2-444
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    • "Patients with high-risk disease were not even treated with surgery due to the presumed high probability of being affected by systemic disease. All the recent series reporting excellent outcomes after RP in men with high-risk disease have clearly demonstrated the inadequacy of such approach [1]. For those few patients receiving surgery for more aggressive disease, PLND was often not extended beyond the obturator fossa. "
    European Urology 08/2012; 63(3). DOI:10.1016/j.eururo.2012.08.029 · 12.48 Impact Factor
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