G(1)/S cell cycle proteins as markers of aggressive prostate carcinoma.

P clinical assessment is critical to identify patients who will benefit from treatment for localized prostate cancer. Although initial efforts to stratify patients into good and poor risk categories have focused on stage, grade, and prostate-specific antigen (PSA) levels, studies are currently underway to improve on these clinical parameters by incorporating molecular markers of aggressive disease into the clinical assessment. Recent advances in our understanding of the genetic etiology of prostate cancer have not only identified alterations in cell cycle control as an important step in initiation and progression, but have also implicated these alterations as possible biomarkers. In the following review, we outline data supporting the use of G1/S cell cycle proteins as markers of aggressive disease. To date, nomograms using the clinical parameters of stage, grade, and PSA have proved to be the best tools to predict advanced disease at the time of diagnosis1 or risk of disease recurrence.2 Partin et al.1 used preoperative stage, Gleason score, and PSA to construct tables to predict the likelihood of extracapsular disease, seminal vesicle involvement, and lymph node involvement at radical prostatectomy. Although this information is very useful in discussing the potential benefit of radical prostatectomy with patients, the preoperative criteria do not correctly predict the pathologic stage in many patients. For example, patients with good risk criteria (ie, PSA less than 10 ng/mL, Stage T1c, and Gleason score less than 6) do have an appreciable incidence of adverse pathologic findings at surgery, and conversely, patients with adverse preoperative criteria do have organ-confined disease.1 In addition, pathologic stage is a surrogate end point; patients with adverse pathologic findings do have long-term cures with radical prostatectomy, and patients with low-grade, organ-confined disease do develop metastatic disease. The nomogram by Kattan et al.2 predicts the likelihood of PSA recurrence at 5 years using the preoperative data of stage, Gleason score, and PSA. Although this nomogram predicts outcome as opposed to pathologic stage, it still suffers from an inability to predict outcome in individual patients with 100% accuracy. For example, the Kattan nomogram predicts that 75% of patients with Stage T1c, Gleason score 7, and PSA 9 ng/mL will have an undetectable PSA at 5 years after radical prostatectomy. This also means that 25% of patients will have recurrence.2 It is therefore not surprising that efforts are being made to improve the identification of patients at risk of recurrence or death. Patients with a negligible risk of developing metastases, even without therapy, could be spared the potential morbidity and mortality of aggressive treatment. Conversely, high-risk patients could be targeted for innovative adjuvant or neoadjuvant therapy.