Restaging of prostate cancer in patients with biochemical recurrence after radical treatment remains a challenging clinical scenario as current imaging modalities are suboptimal. To date, prostate ...specific membrane antigen positron emission tomography/computerized tomography seems to represent a very promising diagnostic tool in this setting. Therefore, we evaluated the detection rate of several positron emission tomography/computerized tomography prostate specific membrane antigen based tracers in the restaging of prostate cancer in patients with biochemical recurrence.
According to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, a systematic search was performed across MEDLINE®, Embase® and Web of Science™. PICOS (Patient, Intervention, Comparator, Outcome, Study Type), criteria consisted of P: patients with biochemical recurrence after radical prostatectomy and/or radiation therapy as primary treatment; I: studies using gallium-68-prostate specific membrane antigen-11, gallium-68-prostate specific membrane antigen inhibitor for imaging and therapy, gallium-68-trishydroxypyridinone-prostate specific membrane antigen, copper-64-prostate specific membrane antigen-617, fluorine-18-DCFPyL or fluorine-18-prostate specific membrane antigen-1007; C: no control group or positron emission tomography/computerized tomography comparative studies; O: patient specific overall detection rate; and S: retrospective/prospective studies. A meta-analysis of proportions and a network meta-analysis were performed. Heterogeneity was assessed using Cochran Q and I
statistics. Quality was assessed by QUADAS-2 (University of Bristol, Bristol, United Kingdom). Funnel plots and Egger test were used for publication biases.
A total of 43 studies including 5,832 patients were identified and included in the analysis. An overall detection rate of 74.1% (95% CI 69.2%-78.5%) was found, with no differences between tracers. The overall detection rates were 33.7%, 50.0%, 62.8%, 73.1% and 91.7% % in prostate specific antigen subgroups of less than 0.2 ng/ml, 0.2 to 0.49 ng/ml, 0.50 to 0.99 ng/ml, 1.0 to 1.99 ng/ml, and 2.0 ng/ml or greater, respectively. No difference between tracers was found according to prostate specific antigen doubling time or prostate specific antigen velocity. No tracer proved superior to the others through network meta-analysis. High heterogeneity and inconsistency were found across all analyses. Included studies showed a low risk of bias.
Prostate specific membrane antigen positron emission tomography/computerized tomography for prostate cancer restaging in patients with biochemical recurrence achieves best detection rates (over 70%) if prostate specific antigen is below 1 ng/ml. At lower prostate specific antigen levels the detection rate of prostate specific membrane antigen positron emission tomography/computerized tomography is lower (33.7% for levels below 0.2 ng/ml and 50% for levels 0.2 to 0.49 ng/ml), despite being better than "older" tracers such as choline based positron emission tomography or computerized tomography/bone scintigraphy. Furthermore, no prostate specific membrane antigen tracer can be currently considered superior to others. Further studies are needed to better define the diagnostic performance and role of these imaging techniques.
Symptom improvement following therapies for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) is associated with a decrease in Bladder Outlet Obstruction Index ...(BOOI). Surgical therapies for LUTS/BPH provide greater BOOI and symptom improvement than medical therapies.
Symptomatic benefit and urodynamic obstruction relief represent relevant outcomes of therapies for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). We summarized evidence from studies concurrently assessing variations in terms of symptoms severity and invasive urodynamic measures of obstruction following medical and surgical therapies for LUTS/BPH.
We performed a systematic review of PubMed, Scopus, and Web of Science in June 2023.
We identified 29 publications: 14 (872 patients) and 15 (851 patients) studies addressing medical and surgical therapies, respectively. The mean percentage total International Prostate Symptom Score (IPSS) improvements ranged from −2.5% to 56.3% and from 35.1% to 82.1% following medical and surgical therapies, respectively. The corresponding mean percentage Bladder Outlet Obstruction Index (BOOI) improvements ranged from 7.8% to 53.5% and from 22.4% to 138.6%, respectively. Holmium laser enucleation of the prostate (HoLEP) provided IPSS improvements in the higher range and the greatest BOOI reduction.
Globally, based on available evidence, more pronounced symptomatic benefits are observed following treatments providing greater deobstructive effect. In detail, patients undergoing surgery exhibit greater IPSS and BOOI improvements than those receiving medical therapy.
Treatments for lower urinary tract symptoms suggestive of benign prostatic hyperplasia providing greater urodynamic improvements also provide greater symptomatic benefit. Surgical procedures provide greater symptomatic and urodynamic outcomes than medical therapies. Maximal obstruction relief, together with symptomatic benefits in the higher ranges, is observed following holmium laser enucleation of the prostate.
Background
It is a common practice to control efficacy of pharmacological treatment with a placebo group. However, placebo itself may affect subjective and even objective results. The purpose of this ...study was to evaluate the placebo effect on symptoms of CP/CPPS to improve future clinical trials.
Methods
A search at three databases (Scopus, MEDLINE, and Web of Science) was conducted to identify double‐blind placebo‐controlled clinical trials on the treatment of CP/CPPS published until April 2021. The primary outcome – National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI) score. Secondary outcomes: Qmax, PVR, IPSS, and prostate volume.
Results
A total of 3502 studies were identified. Placebo arms of 42 articles (5512 patients, median 31 patients) were included in the systematic review. Systematic review identified positive changes in the primary endpoint, meta‐analysis of 10 articles found that NIH‐CPSI total score results were significantly influenced by placebo, mean difference −4.2 (95% confidence interval CI: −6.31, −2.09). Mean difference of NIH‐CPSI pain domain was −2.31 (95% CI: −3.4, −1.21), urinary domain −1.12 (95% CI: −1.62, −0.62), quality of life domain −1.67 (95% CI: −2.38, −0.96); p < 0.001 for all. In case of the objective indicator – Qmax, there were three articles included in the meta‐analysis. Qmax mean change from baseline was 0.68 (95% CI: −0.85, 2.22, p = 0.38). Systematic review showed no significant changes in pain, measured by VAS or other scores, IPSS and PVR.
Conclusions
Placebo significantly affected the subjective parameters (NIH‐CPSI) and limitedly affected various other measurements of pain (visual analog scale, McGill pain questionnaire). There was no long‐term effect on IPSS and objective measurements (Qmax, PVR). This study can be used in further clinical trials to develop general rules of CPPS treatment assessment.
Low intensity extracorporal shock wave therapy (Li-ESWT) may induce tissue regeneration, neo-angiogenesis and improve endothelial function. This has shown promise in the treatment of erectile ...dysfunction (ED). The aim of this narrative review was to describe potential therapeutic areas of Li-ESWT in sexual medicine other than ED. An extensive literature search and review of the most recent guidelines revealed that Li-ESWT has been used in the treatment of Peyronie's disease (PD) and is being investigated as a method of improving stem cell therapy. In PD, Li-ESWT has been shown to decrease pain but no clinically relevant benefits regarding plaque size or penile curvature have been shown in randomized clinical trials. For stem cell optimization, only two preclinical studies have been conducted within the realm of sexual medicine. These show that application of Li-ESWT to the tissue after stem cell transplantation may increase the erectile response following cavernous nerve or diabetes damage. More research is needed to bring this concept from bench to bedside. In addition to this, Li-ESWT has shown promise in pelvic pain and it's effects on testicles have been preliminarily investigated in preclinical studies.
Despite early detection and regular surveillance of non-muscle invasive bladder cancer (NMIBC), recurrence and progression rates remain exceedingly high for this highly prevalent malignancy. Limited ...visualization of malignant lesions with standard cystoscopy and associated false-negative biopsy rates have been the driving force for investigating alternative and adjunctive technologies for improved cystoscopy. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Out of 1,087 studies reviewed, 17 prospective non-randomized and randomized controlled trials met inclusion criteria for the study. We demonstrated that tumor resection with either PDD and NBI exhibited lower recurrence rates and greater diagnostic sensitivity compared to WLC alone. NBI demonstrated superior disease sensitivity and specificity as compared to WLC and an overall greater hierarchical summary receiver operative characteristic. Our findings are consistent with emerging guidelines and underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC.
A systematic review and meta‐analysis was carried out to evaluate the efficacy and safety of mirabegron 50 mg and 100 mg in the treatment of storage lower urinary tract symptoms/overactive bladder in ...comparison with a placebo and tolterodine 4 mg. A total of 491 articles were collected and eight randomized studies were identified as eligible for this meta‐analysis. Overall, eight trials were included in the meta‐analysis evaluating 10 248 patients. Mirabegron at both doses of 50 mg and 100 mg, and and tolterodine 4 mg were significantly associated with the reduction of incontinence episodes per 24 h, reduction of mean number of micturitions per 24 h, increase of voided volume and reduction of urgency episodes per 24 h, compared to a placebo. Both mirabegron 50 mg and mirabegron 100 mg were associated with a significant reduction of nocturia episodes when compared with a placebo. Conversely, tolterodine 4 mg did not prove to be more effective than a placebo in the reduction of nocturia episodes. Furthermore, mirabegron 50 mg showed a slightly, but significantly, better efficacy than tolterodine 4 mg in the improvement of nocturia episodes. Mirabegron 50 mg and mirabegron 100 mg shared the same risk of overall treatment‐emergent adverse events rate with the placebo. Otherwise, tolterodine 4 mg was associated with a significantly greater risk than the placebo. However, mirabegron 100 mg showed a slight trend toward an increased risk of hypertension (odds ratio 1.41; P = 0.08) and cardiac arrhythmia (odds ratio 2.18; P = 0.06). Mirabegron is an effective treatment for patients with storage lower urinary tract symptoms/overactive bladder, providing a reduction of incontinence, urgency and frequency; an improvement of voided volume with a slight, but statistically, significant improvement of nocturia; with a good safety profile. These findings should be considered for the treatment planning of patients with storage lower urinary tract symptoms/overactive bladder.
Benign prostate hyperplasia (BPH) is one of the most prevalent diseases in aging men. It may adversely affect quality-of-life due to the presence of low urinary tract symptoms (LUTS) and its effects ...on sexuality.
The impact of α1-blockers, 5α-reductase inhibitors (5-ARI), and phosphodiesterase 5 inhibitors (PDE-5i) on erectile and ejaculatory functions in men with BPH are covered. Endocrinological aspects have also been addressed, including the management of hypogonadism, which affects many patients with BPH, and the impact of the use of 5-ARI use on bone health.
The adverse-event profile of α1-blockers depends on their affinity for the α1-adrenoceptors rather than selectivity. The probability of ejaculatory dysfunction is highest with silodosin than other nonselective drugs (tamsulosin, alfuzosin, doxazosin, and terazosin). Concerning the impact of finasteride and dutasteride on sexual desire, erectile function, and ejaculation, the vast majority of the studies have shown a low prevalence of treatment-related adverse events. Due to the benefits of erection, PDE5i represents the perfect class of drugs for the treatment of LUTS-BPH in patients with erectile dysfunction. Testosterone replacement therapy could be considered in some hypogonadal patients with BPH. Finally, current evidence support the safety of 5-ARI on bone tissue.
Multidisciplinary approach to prostatitis Magri, Vittorio; Boltri, Matteo; Cai, Tommaso ...
Archivio italiano di urologia, andrologia,
2019-Jan-18, Letnik:
90, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for ...localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.
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