Version of Record online: 10 OCT 2012
© 2012 THE AUTHOR. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL
Special Issue: Landmarks in Prostate Cancer
Volume 110, Issue Supplement s1, pages 1–2, October 2012
How to Cite
Boccon-Gibod, L. (2012), Foreword. BJU International, 110: 1–2. doi: 10.1111/j.1464-410X.2012.11427.x
- Issue online: 10 OCT 2012
- Version of Record online: 10 OCT 2012
This supplement focuses on landmarks in key aspects of prostate cancer diagnosis and treatment, providing information on new and exciting areas of research, the benefits of which can be expected to have a significant impact in the future. The worldwide estimate for new prostate cancer cases in 2008 was 899 000 and for deaths, 258 000. In Europe, prostate cancer is the most common non-skin cancer in men, with an estimated 382 000 cases in 2008; about one man in 36 will die from the disease. Considering the seriousness of the disease, steps have been taken to improve early diagnosis and by consequence treatment efficacy, in the form of screening. A full review of screening based on prostate-specific antigen (PSA) is provided by F. Schröder, leader of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Increasing levels of PSA are indeed linked to an increased likelihood of prostate cancer, but there is no threshold for distinguishing insignificant cancers that are unlikely to be life-threatening from those that are significant. PSA screening therefore remains a highly controversial area despite the many studies conducted worldwide since the 1980s. Some studies, such as the Prostate, Lung, Colorectal, and Ovarian Screening Study, showed no benefits in terms of prostate cancer-specific deaths or overall mortality. Methodological inadequacies have been identified in several of these studies due to cross-over between the screened and unscreened populations. Other studies, such as the Tyrol Screening Study and the ERSPC have shown reductions in prostate cancer mortality (relative risk reduction of 21%) and occurrence of metastatic disease (31%). However, it is important to emphasise that in order to prevent one death from prostate cancer at 11 years of follow-up, it is necessary to screen 1055 men and treat 37. These findings and the opposing results of the various studies explain the wide variation in recommendations made by different bodies about prostate cancer screening.
Although PSA is the leading diagnostic biomarker in current use, the fact remains that PSA is NOT a tumour marker. Men with very low levels can still have prostate cancer and, conversely, an elevated PSA level can occur in the presence of benign prostatic conditions. This situation explains the continuing efforts to identify biomarkers with optimal sensitivity and specificity. W. Artibani provides an overview of the markers being researched, which includes both blood- and urine-based markers. The most promising to date is prostate cancer antigen 3 (PCA3), which can be identified in urine and was developed as a commercial kit in 2006. More recently the idea of analysing circulating tumour cells in blood as a prognostic indicator in metastatic disease has been examined and a commercial system has been approved by the USA Food and Drug Administration (FDA). Another avenue being explored is the use of a combination of markers. Once again it is important to stress the fact that at this point in time the tools at the clinician's disposal to diagnose prostate cancer are grossly unsatisfactory. Anomalies of serum PSA lead to TRUS-guided biopsy, which is basically a blind procedure that more often than not is unable to target the actual tumour.
The range of therapeutic options for the different stages of prostate cancer continues to expand, which will allow the urologist and uro-oncologists to offer a broader choice of treatments in the future. The review by N. Clarke examines the drugs being researched for castration-resistant and metastatic prostate cancer. Advances have been made from the era where it was thought that prostate cancer was resistant to chemotherapy and today the first-line agent, as recommended by several guidelines, is docetaxel with cabazitaxel recommended as second-line for those patients failing previous docetaxel therapy. Exciting areas of research include immunotherapies based on cellular therapy with agents such as sipuleucel-T, recently approved by the FDA for metastatic castration-resistant prostate cancer, PSA-based vaccines and a range of drugs aimed at relieving the consequences of bone metastases. Molecular therapy is advancing with drugs that target pathways relevant for several cancers. These include vascular endothelial growth factor receptor inhibitors, Src kinase inhibitors and clusterin antisense inhibitor. Faced with such a wide range of existing and new drugs it will be the task of the uro-oncological community to define which drugs to use, alone or in combination, and when to use them in the course of the disease.
The final paper in the supplement by P. Hammerer and S. Madersbacher focuses on one of the most established therapies for prostate cancer, androgen-deprivation therapy (ADT). It has been >70 years since the discovery of the beneficial effects of surgical castration on prostate cancer by Huggins and Hodges, and today ADT represent the principal treatment for men with advanced prostate cancer. Luteinising hormone-releasing hormone (LHRH) agonists, e.g. leuprorelin acetate, have been prescribed for >20 years and are the standard of care in advanced or metastatic prostate cancer. Newer approaches to ADT include intermittent therapy with ‘on-’ and ‘off’-treatment phases to reduce side-effects and the use of LHRH antagonists, which through immediate blockage of hypothalamic receptors induce a rapid and durable testosterone suppression. The introduction of ADT immediately at disease progression or delayed until the patient becomes symptomatic remains controversial due to conflicting study data and it is left to the clinician to individualise, based on well-identified prognostic factors, the best treatment. The benefits of combining LHRH agonists and radiotherapy in locally advanced prostate cancer have now been established through several studies and 3 years is now recommended as the duration of the LHRH agonist. Finally, new exciting agents targeting the androgen receptor axis (orteronel, abiraterone acetate, MDV3100) definitely open new exciting avenues for hormonal therapy once the castration-resistant status has been reached. Here again, one challenge for the future will be to define the exact time at which to introduce these new drugs in the course of the disease.