Hormonal treatment for progression

Abstract

A rise of the prostate specific antigen (PSA) following radical prostatectomy (RP) or radiotherapy (RT) with curative intent is the earliest sign of tumour progression. The current definition of tumour progression after RP is a PSA of at least 0.4 ng/mL. Many still consider two consecutive levels of 0.2 ng/mL or greater (EAU guidelines) and further rising; after RT it is defined as a rise of 2 ng/mL or greater above the post-treatment nadir. The prognosis of these patients is very heterogeneous, the relevant prognostic parameters being Gleason score, time to PSA progression and PSA doubling time (PSA DT). Imaging studies are of limited value for the decision on salvage radiotherapy (following RP) as the decision must be taken very early in the course (PSA <0.5 ng/mL) to get acceptable results. Before a local salvage therapy (salvage RP, cryo-surgery, high intensity focused ultrasound [HIFU]) is persued after RT, a biopsy is necessary to confirm local tumour progression and distant metastases should be excluded. Androgen deprivation is widely applied if curative treatment fails primarily, or if local salvage treatment fails secondarily. However, side effects (osteoporosis, anaemia, cardio-vascular diseases) of long-term hormonal therapy are now increasingly recognised. This has to be taken into account as well as the fact that there is a long interval (median 8 years) from PSA progression to clinical progression after radical prostatectomy, if patients are left untreated [1]. Only about 30% of patients with rising PSA following RP and no further therapy reach the stage of clinical metastases [2]. This seems to be more common after RT (up to 75%). Patients after radical prostatectomy with good prognostic factors (long PSA DT, late PSA relapse, Gleason score <8) have a low risk of dying from prostate cancer within 15 years [3]. These figures must be taken into account when hormonal therapy is decided upon. When hormonal therapy is considered in this situation, several questions arise: early versus late treatment, continuous versus intermittent treatment, combined androgen blockade versus monotherapy, and luteinising hormone releasing hormone (LHRH) analogues versus anti-androgens