Maximal testosterone suppression in prostate cancer--free vs total testosterone.

Testosterone remains a key target in the treatment of advanced prostate cancer. The relationship of free testosterone to prostate cancer treatment and outcomes remains largely unexplored. A consensus of prostate cancer experts was convened in 2013 to review current knowledge surrounding relationship of total and free testosterone to prostate cancer, discuss the free hormone hypothesis, and highlight future avenues for therapeutics. Free testosterone may better reflect prostate cancer tissue androgen levels than serum total testosterone concentration. Free testosterone deserves more research regarding its relation to clinical outcomes.

Evidence-based guidelines for the treatment of lower urinary tract symptoms related to uncomplicated benign prostatic hyperplasia in Italy: updated summary from AURO.it.

BACKGROUND: The first Italian national guidelines were developed by the Italian Association of Urologists and published in 2007. Since then, a number of new drugs or classes of drugs have emerged for the treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH), new data have emerged on medical therapy (monotherapies and combination therapies), new surgical techniques have come into practice, and our understanding of disease pathogenesis has increased. Consequently, a new update of the guidelines has become necessary. METHODS: A structured literature review was conducted to identify relevant papers published between 1 August 2006 and 12 December 2010. Publications before or after this timeframe were considered only if they were recognised as important milestones in the field or if the literature search did not identify publications within this timeframe. The quality of evidence and strength of recommendations were determined according to the Grading of Recommendations Assessment, Development and Evaluation framework. MAIN FINDINGS: Decisions on therapeutic intervention should be based on the impact of symptoms on quality of life (QoL) rather than the severity of symptoms (International Prostate Symptom Score (IPSS) score). A threshold for intervention was therefore based on the IPSS Q8, with intervention recommended for patients with a score of at least 4. Several differences in clinical recommendations have emerged. For example, combination therapy with a 5α-reductase inhibitor plus α blocker is now the recommended option for the treatment of patients at risk of BPH progression. Other differences include the warning of potential worsening of cognitive disturbances with use of anticholinergics in older patients, the distinction between Serenoa repens preparations (according to the method of extraction), and the clearly defined threshold of prostate size for performing open surgery (>80 g). While the recommendations included in these guidelines are evidence based, clinical decisions should also be informed by patients' clinical and physical circumstances, as well as patients' preferences and actions. CONCLUSIONS: These guidelines are intended to assist physicians and patients in the decision-making process regarding the management of LUTS/BPH, and support the process of continuous improvement of the quality of care and services to patients.

Should we follow-up serum testosterone in patients with advanced prostate cancer?

Agonistic analogs of luteinizing hormone-releasing hormones are indicated for the palliative treatment of metastatic prostate cancer. While the prognostic role of prostate-specific antigen in patients submitted to androgen-deprivation therapy has been extensively investigated in these patients, there is no consensus about the utility of serum testosterone measurements during follow-up and about their possible prognostic value. Recent reports have shown that testosterone levels might be directly related to survival and risk of death. These results need to be confirmed by further prospective studies. Given this concept, lowering testosterone as much as possible should be the goal of androgen-deprivation therapy in patients with metastatic prostate cancer, as this may have an impact on patient survival.

Anti-androgen therapy suspension following prolonged clinical and biochemical response: outcomes in a series of elderly patients with advanced prostate cancer.

AIMS AND BACKGROUND: To describe the outcomes following the suspension of androgen-suppression therapy in a series of elderly patients in an advanced stage of prostate cancer and in prolonged clinical and biochemical response. MATERIAL AND METHODS: Of 371 consecutive patients with advanced prostate cancer and treated with androgen-suppression therapy, 44 older patients were defined as in stable response on the basis of the following: absence of noteworthy dysuria, normal prostate findings on digital rectal examination, and prostate-specific antigen values lower than 0.50 ng/ml. After suspending treatment, it was to be re-scheduled in case of onset of dysuria, evidence of a palpable lesion on digital rectal examination, or a rise in prostate-specific antigen above 10 ng/ml. Progression of disease was defined as a prostate-specific antigen level increase at two subsequent measurements, and/or the appearance of new lesions, and/or evidence of progression of disease on digital rectal examination. RESULTS AND CONCLUSIONS: Median age of patients was 78.5 years at the moment of therapy suspension. After a median follow-up of 93.9 months, fourteen patients (31.8%) showed progression of disease, but only 7 (15.9%) of these died. In 7 (15.9%) patients, serum testosterone levels did not exceed 0.5 ng/ml, indicating an absence of gonadal activity. The median time to progression was 138.2 months, and the median cumulative survival from the start and from the suspension of androgen-suppression therapy was 105.5 months and 64.1 months, respectively. The savings in drug costs amounted to 772,267 Euro. Taking into consideration these outcomes of survival and of savings in drug costs, we can conclude that in these selected elderly patients, this treatment option could be of interest.

Testosterone levels in patients with metastatic prostate cancer treated with luteinizing hormone-releasing hormone therapy: prognostic significance?

OBJECTIVE: To determine if the testosterone level achieved with androgen-deprivation therapy (ADT) is directly related to survival and risk of death in men with metastatic prostate cancer, as agonistic analogues of luteinizing hormone-releasing hormones (LHRH) are indicated for palliative treatment of these patients, but there is no consensus about the utility of serum testosterone measurements during the follow-up, and their possible prognostic value. PATIENTS AND METHODS: We retrospectively reviewed 129 consecutive patients with a histological diagnosis of metastatic bony-only prostate cancer and previously untreated with ADT. They were treated with 3 months of goserelin. Testosterone and prostate-specific antigen (PSA) levels were measured in all patients every 3 months for the duration of the follow-up. The following variables were recorded: age, stage, Gleason score, basal PSA level, basal testosterone level, PSA nadir, time to PSA nadir, testosterone after 6 months, testosterone nadir and time to testosterone nadir. Data were analysed using Cox's proportional hazards models, with the primary endpoint being cancer-specific survival. RESULTS: The mean (SD) basal PSA level was 185.8 (344.1) ng/mL, and the mean nadir PSA level 2.7 (8.6) ng/mL. The mean testosterone levels at baseline, 6 months and the nadir were 440 (200), 40 (40) and 21 (15) ng/dL. With a mean follow-up of 47.5 (29.7) months, 71 patients were dead (55%) and 78 were alive (45%) at the time of analysis. Statistical analysis using Cox's model showed that in these patients the risk of death was directly correlated not only to Gleason score (P < 0.01) and to the 6-month PSA level (P < 0.01), but also to the 6-month serum testosterone level (hazard ratio 1.32, P < 0.05). CONCLUSION: These results suggest a direct correlation between the risk of death and testosterone levels achieved during ADT. Based on the present results, lowering the testosterone level as much as possible should be the goal of ADT in patients with metastatic prostate cancer, as this might affect patient survival.

Quality of life evaluation by the EORTC QLQ-C30 questionnaire in patients treated with hormonal treatment in Italy. A QuABIOS group study.

OBJECTIVES: An observational study was planned by the QuABIOS group, to survey the hormonal treatment administered to prostate cancer patients in Italy within a time window of 12 months. We report here a prospective quality of life (QOL) evaluation over time and by hormonal treatment modalities. METHODS: Patients with diagnosis of prostate cancer and treated with hormonal therapy were eligible for this study. The EORTC QLQ-C30 v.3 questionnaire was administered at enrolment, after 6 months and after 12 months from enrolment. RESULTS: 587 patients were enrolled by 33 urological centers. When 1518 visits were considered together independently of time, antiandrogen monotherapy was associated with a significantly better QOL than LHRH-analogue containing treatment modalities in almost all functional scales; cyproterone acetate demonstrated a better physical function and general health status than bicalutamide. When QOL was analyzed in a prospective 12-month window, a worsening of physical function and general health status was observed, notwithstanding, antiandrogens remained significantly associated to a better QOL than LHRH-analogue therapies also over time: a favourable physical function and general health status appeared again to be related to cyproterone acetate than bicalutamide. CONCLUSIONS: Androgen deprivation therapy is associated with decline in QOL, particularly in the domains of physical function, energy, and general health status. This survey demonstrated that antiandrogens had a better QOL profile than LHRH-analogue containing therapies;furthermore, a more favourable tolerability for cyproterone acetate as compared to bicalutamide is suggested.

Evidence-based guidelines for the management of lower urinary tract symptoms related to uncomplicated benign prostatic hyperplasia in Italy: updated summary.

BACKGROUND AND SCOPE: Despite the high prevalence and huge socio-economic impact of benign prostatic hyperplasia (BPH) in Italy, no national guidelines have been produced so far. This is a summary of the first Italian guidelines on the diagnosis and treatment of lower urinary tract symptoms (LUTS) related to uncomplicated BPH, prepared by a multidisciplinary panel under the auspices of the Italian Association of Urologists and introduced in Italy in 2003. An update compiled by the authors is also included. METHODS: Relevant papers published from 1998 to 2003 (updated to 2006) were identified through a structured literature review and the quality of evidence presented therein was graded according to the Centre for the Evaluation of Effectiveness in Health Administration (CeVEAS) system. Recommendations were based on evidence from the literature, but also on feedback from practitioners and specialists. MAIN FINDINGS/RECOMMENDATIONS: Given the prevalence of BPH, all men aged > or = 50 years of age should be asked about LUTS and informed about disease characteristics and therapeutic options, while sexual function should always be assessed in patients with severe and long-standing LUTS. Initial assessment should include medical history (including drug and co-morbidity history), digital rectal examination, urinalysis, International Prostate Symptom Score-Quality of Life (IPSS-QoL) and a voiding diary, while prostate-specific antigen (PSA) and measurement of prostate volume by suprapubic ultrasonography are indicated in fully informed patients with a life expectancy of > or = 10 years in whom BPH progression could influence treatment choices. QoL considerations should dictate whether to start active treatment. When QoL is not affected by LUTS, watchful waiting is indicated if symptoms are mild, acceptable if they are moderate. When QoL is affected, medical therapy with alpha1-blockers or 5alpha-reductase inhibitors (the latter indicated in patients with increased prostate volume) is appropriate. Combined therapy with alpha1-blockers + 5alpha-reductase inhibitors should only be considered in patients at high risk for progression (prostate volume > 40 mL or PSA > 4 ng/mL), since the incremental cost of combination therapy vs. monotherapy with alpha1-blockers or finasteride is prohibitive. Selection of the type of surgery should be based on the surgeon's experience, the presence of co-morbid conditions and the size of the prostate. Open prostatectomy and transurethral resection of the prostate (TURP) are recommended in patients with acute or chronic retention of urine, and acceptable in obstructed patients with moderate/severe symptoms and worsened QoL. Transurethral incision of the prostate (TUIP) is acceptable when prostate volume is < or = 30 mL. Holmium laser enucleation of the prostate (HoLEP) may be proposed to motivated patients where expert surgeons are available. Transurethral microwave thermotherapy (TUMT) or transurethral needle ablation (TUNA) may be proposed to motivated patients who prefer to avoid surgery and/or do not respond to medical treatment. The possible effects of medical or surgical treatments on sexual function should always be discussed. CONCLUSIONS: These guidelines are intended to provide a framework for health professionals involved in BPH management in order to facilitate decision-making in all areas and at all levels of healthcare.