Management of patients with an increasing prostate-specific antigen after radical prostatectomy.
ABSTRACT Since the late 1980s, early detection and monitoring of men for prostate cancer by serum prostate-specific antigen (PSA) measurement has resulted in an increase in the number of men presenting with a potentially curable disease. During the same time, in an attempt to provide a definitive cure, radical prostatectomy has been performed increasingly and now is regarded as the management option of choice for many patients with clinically localized prostate cancer. Radical prostatectomy involves the removal of all of the prostate tissue resulting in the serum PSA level to steadily decline to an undetectable level within 4 to 6 weeks after surgery. Despite improvements in surgical technique and a marked downward stage shift brought about by serum PSA testing, approximately 25% of men ultimately will experience a subsequent increase in serum PSA to a detectable level indicating disease recurrence after radical prostatectomy within 15 years. In this brief review, the factors associated with a high risk for disease recurrence after radical prostatectomy are discussed. Factors indicating whether the increasing serum PSA is caused by local recurrence or metastatic disease and the management options available to address serum PSA recurrence also are discussed.
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ABSTRACT: Although most prostate cancer (PCa) patients nowadays are diagnosed at an early stage of disease, unfortunately still a significant number of patients will develop advanced PCa or will be diagnosed at an advanced (or metastatic) stage of disease. The group of patients showing the highest increase in incidence are those with rising prostate specific antigen (PSA) after radical therapy.In the last quarter of 2004, a Medline search has been performed targeting publications on patients diagnosed with advanced PCa, as well as with PSA relapse after previous radical therapy. This review aims at providing guidance to optimise hormone therapy in those selected groups of patients by addressing three pivotal questions; (i) who should receive hormonal treatment, (ii) what type of hormonal therapy should the patient be offered and (iii) what is the best timing of starting hormonal treatment.In patients relapsing after radical therapy, the PSA doubling time (PSA DT) has become a critical instrument to distinguish patients to have innocuous PSA evolution from patients at high risk for disease progression. A PSA DT of 3 months seems to be the cut-off point for identifying patients at risk. Therefore patients with a PSA DT of less than 3 months should be advised to initiate hormonal therapy. Antiandrogen monotherapy may be considered in this setting as it has been shown to delay progression; however, significant survival data are not yet available. Whether luteinising hormone releasing hormone (LHRH) agonists should be given continuously or intermittently (IHT) remains subject of debate.Surgical castration has been the standard of care in patients diagnosed with advanced PCa. Currently, LHRH agonists have become the preferred way of suppressing testosterone.Combination of an antiandrogen and a LHRH agonist (CAB) shows a modest benefit over LHRH agonist monotherapy. As CAB leads to increased side effects and costs, LHRH agonist monotherapy is preferred in the majority of patients.Conflicting data have been published concerning the optimal timing of LHRH agonist therapy. So it is not clear whether LHRH agonist therapy should be started immediately or deferred until appearance of symptoms. When initiating continuous hormone therapy, patients should be carefully monitored for the risk of long term androgen deprivation (anaemia, osteopenia and osteoporosis).European Urology Supplements - EUR UROL SUPPL. 01/2005; 4(8):21-29.
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ABSTRACT: Objectives Luteinising hormone-releasing hormone (LHRH) agonists have become the mainstay for the treatment of advanced and metastatic prostate cancer (pCA) but are increasingly used in earlier stages of the disease for various indications. Eligard® is a depot formulation of leuprolide acetate using the novel delivery system Atrigel®. Eligard 6 is the first and only LHRH agonist commercially available that extends treatment for 6 mo.European Urology Supplements - EUR UROL SUPPL. 01/2006; 5(18):905-910.
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ABSTRACT: Prostate cancer (PCa) is being diagnosed at an earlier age, and at an earlier stage of disease. Increasing numbers of relatively young patients (Traditionally, most patients diagnosed with localised disease receive radical therapy, either radiation therapy or radical prostatectomy. However, many men have indolent PCa and may not require radical therapy. In contrast, patients with aggressive disease benefit from local therapy. As a consequence, the main clinical challenge is the stratification of patients with localised disease into good risk patients and intermediate-to-high risk patients in order to offer the patient a tailored treatment strategy.Patients diagnosed with good risk disease (stage T1c–T2a, Gleason score ≤6, small volume of disease on biopsy and prostate specific antigen (PSA) ≤10ng/mL) can be closely monitored with periodic biopsies and measurement of the PSA doubling time (DT).Patients diagnosed with an aggressive form of disease (intermediate-to-high risk disease) need immediate curative therapy. Both radical prostatectomy and radiotherapy are currently used in combination with neoadjuvant and/or adjuvant hormonal therapy.Neoadjuvant therapy prior to radical prostatectomy has failed to demonstrate an improvement in PSA progression in numerous randomised trials. However, one trial showed a benefit in high risk patients (PSA >20ng/mL) after 3 months of neoadjuvant therapy, based on retrospective stratification analysis. Overall, some practitioners recommend neoadjuvant therapy for patients with high risk localised PCa. Adjuvant hormonal therapy after surgery has not, to date, demonstrated an improvement in overall or disease specific survival, but does delay PSA progression. The significance of this remains uncertain.Neoadjuvant hormonal therapy prior to radiation therapy is recommended for patients with intermediate-to-high risk disease. The optimal duration of neoadjuvant hormone therapy is not yet defined. However, a 3 to 6 month course of neoadjuvant therapy prior to radiation is widely utilised. Adjuvant hormonal therapy after radiotherapy is also widely used in patients with intermediate-to-high risk disease. The optimal duration of adjuvant therapy is between 6 months and 3 years.For patients with biochemical failure, androgen deprivation therapy is appropriate for those whose clinical and pathologic parameters indicate that local recurrence is unlikely. For such patients who are at high risk (Gleason ≥8, or PSA DTEuropean Urology Supplements - EUR UROL SUPPL. 01/2005; 4(8):12-20.