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Objective: We performed a systematic review of the literature to assess the efficacy and the safety of second-line agents targeting metastatic castration-resistant prostate cancer (mCRPC) that has progressed after docetaxel. Pooled-analysis was also performed, to assess the effectiveness of agents targeting the androgen axis via identical mechanisms of action (abiraterone acetate, orteronel)., Materials and Methods: We included phase III randomized controlled trials that enrolled patients with mCRPC progressing during or after first-line docetaxel treatment. Trials were identified by electronic database searching. The primary outcome of the review was overall survival. Secondary outcomes were radiographic progression-free survival (rPFS) and severe adverse effects (grade 3 or higher)., Results: Ten articles met the inclusion criteria for the review. These articles reported the results of five clinical trials, enrolling in total 5047 patients. The experimental interventions tested in these studies were enzalutamide, ipilimumab, abiraterone acetate, orteronel and cabazitaxel. Compared to control cohorts (active drug-treated or placebo-treated), the significant overall survival advantages achieved were 4.8 months for enzalutamide (hazard ratio for death vs. placebo: 0.63; 95% CI 0.53 to 0.75, P < 0.0001), 4.6 months for abiraterone (hazard ratio for death vs. placebo: 0.66, 95% CI 0.58 to 0.75, P < 0.0001) and 2.4 months for cabazitaxel (hazard ratio for death vs. mitoxantrone-prednisone: 0.70, 95% CI 0.59 to 0.83, p < 0.0001). Pooled analysis of androgen synthesis inhibitors orteronel and abiraterone resulted in significantly increased overall and progression-free survival for anti-androgen agents, compared to placebo (hazard ratio for death: 0.76, 95% CI 0.67 to 0.87, P < 0.0001; hazard ratio for radiographic progression: 0.7, 95% CI 0.63 to 0.77, P < 0.00001). Androgen synthesis inhibitors induced significant increases in risk ratios for adverse effects linked to elevated mineralocorticoid secretion, compared to placebo (risk ratio for hypokalemia: 5.75, 95% CI 2.08 to 15.90; P = 0.0008; risk-ratio for hypertension: 2.29, 95% CI 1.02 to 5.17; P = 0.05)., Conclusions: In docetaxel-pretreated patients enzalutamide, abiraterone-prednisone and cabazitaxel-prednisone can improve overall survival of patients, compared to placebo or to best of care at the time of study (mitoxantrone-prednisone). Agents targeting the androgen axis (enzalutamide, abiraterone, orteronel) significantly prolonged rPFS, compared to placebo. Further investigation is warranted to evaluate the benefit of combination or sequential administration of these agents. Large-scale studies are also necessary to evaluate the impact of relevant toxic effects observed in a limited number of patients (e.g., enzalutamide-induced seizures, orteronel-induced pancreatitis, and others).

Aim: To perform a retrospective study aimed at analyzing the frequency of erectile dysfunction (ED) among 285 men with cat. II and cat. III chronic prostatitis (CP) syndromes, and its relation with the severity of CP., Methods: The clinical records of patients receiving for the first time a diagnosis of CP at a first level specialized urological outpatient clinic were reviewed. A total of 285 cases were identified and analyzed., Results: The frequency of ED was higher among subjects showing higher total scores of the two administered questionnaires, i.e. the NIH-Chronic Prostatitis Symptoms Index (NIH-CPSI), and the International Prostate Symptoms Score (IPSS). No relation emerged between the frequency of ED and the differential classification of prostatitis into cat. II Chronic Bacterial Prostatitis or cat. III CP/Chronic Pelvic Pain Syndrome. The presence of hemospermia and premature ejaculation was associated with an about 4-fold increased risk of ED. However, the presence of benign prostatic hyperplasia did not increase the risk of ED., Conclusions: The direct relation between the severity of CP symptoms and ED frequency and severity observed in this study may support the hypothesis that the relation between ED and CP may be mediated by organic mechanisms.

An increasing number of preclinical data, epidemiological evidences and clinical trials point to a potential role of natural compounds like herbal extracts, carotenoids and specific metals in the prevention and/or treatment of different prostate conditions, like hyperplasia, inflammation, cancer. The present article reviews some of the major and most recent findings on the therapeutic properties of three of the most widely used compounds, i.e. Serenoa repens, lycopene and selenium. Although the mechanism of action of these compounds ought to be further characterized by focused investigation, it appears that a common feature of these agents may be a dual activity on proliferative disorders as well as on inflammatory conditions at the level of the prostate gland.

We identified from our clinical database a total of 471 patients affected by cat. II chronic bacterial prostatitis (CBP), cat. III (IIIa and IIIb) chronic pelvic pain syndrome (CP/CPPS), or cat. IV asymptomatic inflammatory prostatitis (AIP), according to NIH criteria. 132 intent-to-treat patients, showing levels of PSA > or =4 ng/mL, were subjected to a 6-week course of combination pharmacological therapy with 500 mg/day ciprofloxacin, 500 mg/day azithromycin (3 days/week), 10 mg/day alfuzosin and 320 mg b.i.d. Serenoa repens extract. At the end of treatment, 111 per-protocol patients belonging to all categories of prostatitis showed a total 32.5% reduction of PSA levels. In the same group, 66 patients (59.4%) showed "normalization" of PSA values under the 4 ng/mL limit. Patients affected by cat. IIIb CP/CPPS showed the highest PSA reduction and normalization rates (40% and 68.4%, respectively). Follow-up data show that, after a marked, significant reduction at completion of therapy, PSA levels, urine peak flow rates and NIH-CPSI symptom scores remained constant or decreased throughout a period of 18 months in patients showing normalization of PSA values. Prostatic biopsy was proposed to 45 patients showing persistently high PSA values (> or = 4 ng/mL) at the end of treatment. Fourteen patients rejected biopsy; of the remaining 31, 10 were diagnosed with prostate cancer. Four months after a first biopsy, a second biopsy was proposed to the 21 patients with a negative first diagnosis and persistently elevated PSA levels. Three patients rejected the procedure; of the remaining 18, four were diagnosed with prostatic carcinoma. In summary, combination pharmacological therapy decreased the number of patients undergoing prostatic biopsy from 111 to 45. Normalization of PSA values in 59.4% of patients--not subjected to biopsy--increased the prostate cancer detection rate from 12.6% (14/111) to 31.1% (14/45). The reduction of PSA after a 6-week course of therapy was calculated in patients affected by cat. II, IIIa, IIIb and IV prostatitis after stratification with respect to the concomitant presence or absence of benign prostatic hyperplasia (BPH). PSA was reduced by 41% in cat. II CBP patients without BPH, compared to a 12.7% reduction in patients affected by BPH. Cat. IIIa CP/CPPS patients without BPH showed a 58.3% reduction of PSA levels, compared to a 20.7% reduction observed in CPPS/BPH patients. These data show that the presence of BPH may prevent the reduction of PSA induced by combination pharmacological therapy, and suggest that care has to be taken in the adoption of PSA as a marker of therapeutic efficacy in the presence of confounding factors like BPH. PSA should in our opinion be used as a significant component of a strategy integrating multiple diagnostic approaches.

We performed a comparative analysis of microbiological and clinical responses to combination therapy in 104 symptomatic patients showing evidence of infection by traditional uropathogens (TU) or by unusual pathogens (UP) at the prostatic level. Eighty-two pathogens out of a total of 104 isolated microorganisms were eradicated at the end of a 6-week course of combination therapy with ciprofloxacin, azithromycin, alfuzosin and a S. repens extract. The TU and UP groups showed eradication rates of 75.5% and 82.3%, and clinical success rates of 78.8% and 85.7%, respectively. Thus, a similar response to therapy was observed in patients infected by TU or by UP. Intergroup differences were not significantly different, with the exception of higher scores relative to the impact of the disease on quality of life in TU-patients. Long-term improvement of signs and symptoms of prostatitis indicates that combination therapy is beneficial for symptomatic patients showing evidence of infection by unusual pathogens at the prostatic level. Our data support the hypothesis that organisms other than the traditionally recognized uropathogens may play a role in the onset of prostatitis.