Limited evidence exists about preserving neurovascular bundles during radical prostatectomy (RP) for high-risk prostate cancer (HRPCa) patients. Hence, we validated an existing algorithm predicting contralateral extraprostatic extension (cEPE) risk in unilateral high-risk cases. This algorithm aims to assist in determining the suitability of unilateral nerve-sparing RP. Among 264 patients, 48 (18%) had cEPE. The risk of cECE varied: 8%, 17.2%, and 30.8% for the low, intermediate, and high-risk groups, respectively. Despite a higher risk of cECE among individuals classified as low-risk in the development group compared to the validation group, our algorithm's superiority over always/never nerve-sparing RP was reaffirmed by decision curve analysis. Therefore, we conclude that bilateral excision may not always be justified in men with unilateral HRPCa. Instead, decisions can be based on our suggested nomogram.
- MeSH
- algoritmy * MeSH
- hodnocení rizik metody MeSH
- léčba šetřící orgány * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty * chirurgie patologie MeSH
- nomogramy MeSH
- prostata chirurgie inervace patologie MeSH
- prostatektomie * metody MeSH
- roboticky asistované výkony * metody MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
PURPOSE OF REVIEW: Men face distinctive health-related challenges as a result of biological, behavioral, and sociocultural factors. In addition, the modern healthcare system does not offer men equal opportunities and options to ensure sex-specific access and delivery to health services. Men's health concerns are, indeed, often not addressed or even forgotten. In this review, we wanted to assess the impact of biology and sociocultural effects on sex-specific life-expectancy. RECENT FINDINGS: Globally, men have a shorter life expectancy than women. With a 5.8 years gender gap in the USA and 5.4 in the EU-27 (both in 2022). Cardiovascular disease, cancer, and accidents continue to represent the primary causes of mortality for both genders with all having disproportional preponderance in men. In recent years, there has been a notable decline in age-adjusted mortality rates related to cancer, while there has been an increase in deaths from accidental and intentional self-harm. Moreover, in the United States, men are more likely than women to develop and die from nonsex-specific cancers. As a result, men's poor health affects productivity, absenteeism, and employment. SUMMARY: The status of men in healthcare is complex. It is rooted in history, culture, and institutions. To address disparities, we need a comprehensive approach that includes policy reforms, sociocultural changes, and a fair and equitable public discourse. Grassroots and top-down strategies are needed to ensure a value-based societal healthcare system acknowledging the unique health needs of men.
- MeSH
- disparity zdravotní péče statistika a číselné údaje MeSH
- disparity zdravotního stavu MeSH
- dostupnost zdravotnických služeb statistika a číselné údaje MeSH
- lidé MeSH
- naděje dožití * MeSH
- poskytování zdravotní péče statistika a číselné údaje MeSH
- rovnost ve zdraví MeSH
- sexuální faktory MeSH
- zdraví mužů * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Spojené státy americké epidemiologie MeSH
BACKGROUND AND OBJECTIVE: In patients with prostate cancer treated with antiandrogen monotherapy, gynecomastia and breast pain are relatively common. In the setting of androgen receptor pathway inhibitors (ARPIs), the incidence of these adverse events (AEs) remains unclear. In addition, the effect of prophylactic treatment on gynecomastia remains uncertain. We aimed to evaluate the incidence of gynecomastia and breast pain in prostate cancer patients treated with ARPIs compared with androgen deprivation therapy (ADT) and the effect of prophylactic treatment for these AEs due to antiandrogen therapy. METHODS: In June 2024, we queried four databases-PubMed, Scopus, Web of Science, and Embase-for randomized controlled trials (RCTs) investigating prostate cancer treatments involving antiandrogen therapy. The endpoints of interest were the incidence of these AEs due to ARPIs and the effect of prophylactic treatment for these. KEY FINDINGS AND LIMITATIONS: Eighteen RCTs, comprising 5036 patients, were included in the systematic review and meta-analysis. ARPIs included enzalutamide, darolutamide, and apalutamide. The results indicated that patients who received ARPI monotherapy had a significantly higher incidence of gynecomastia than those who received ADT monotherapy (risk ratio [RR]: 5.19, 95% confidence interval [CI]: 3.58-7.51, p < 0.001). There was no significant difference in the incidence of gynecomastia between ARPI plus ADT therapy and ADT monotherapy (RR: 1.27, 95% CI: 0.84-1.93, p = 0.2). Prophylactic tamoxifen or radiotherapy reduced significantly the incidence of gynecomastia and breast pain caused by bicalutamide monotherapy. CONCLUSIONS AND CLINICAL IMPLICATIONS: We found that ARPI monotherapy increases the incidence of these AEs significantly compared with ADT. In contrast, ARPI plus ADT therapy did not result in a higher incidence of AEs. The use of either tamoxifen or radiotherapy was effective in reducing the incidence of these AEs due to bicalutamide monotherapy. These prophylactic treatments could reduce the incidence of AEs due to ARPI monotherapy. However, further studies are needed to clarify their efficacy. PATIENT SUMMARY: Although androgen deprivation therapy (ADT) improves overall survival in patients with prostate cancer, it is associated with several complications. Androgen receptor pathway inhibitor (ARPI) monotherapy has emerged as a promising strategy for improving oncological outcomes in these patients. However, ARPI monotherapy increases gynecomastia and breast pain in prostate cancer patients compared with ADT, while ARPI plus ADT did not result in a higher incidence of adverse events.
- Klíčová slova
- Androgen deprivation therapy, Androgen receptor pathway inhibitors, Antiandrogen therapy, Breast pain, Gynecomastia,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To assess the oncological outcomes of patients with high-risk (HR) and very high-risk (VHR) non-muscle-invasive bladder cancer (NMIBC) treated with upfront radical cystectomy (RC) vs Bacillus Calmette-Guérin (BCG) instillations from a contemporary European multicentre cohort. PATIENTS AND METHODS: We conducted a retrospective analysis of 1491 patients diagnosed with HR- or VHR-NMIBC from a European multicentre database between 2015 and 2024. Patients were included if they received either upfront RC or at least five doses of BCG. A 1:1 propensity score matching (PSM) according to clinically relevant variables was applied. Progression was defined as muscle-invasive or metastatic disease. Cumulative incidence plots and multivariable competing risk regression models addressing cancer-specific mortality (CSM) were fitted. RESULTS: Among the 1221 patients with HR- (n = 1221 [90%]) or VHR-NMIBC (n = 121 [10%]), 87 (7.1%) underwent upfront RC. The median follow-up was 2.6 years. After PSM (87 vs 87 patients), the 5-year CSM rate was similar in patients treated with BCG (13%) vs their upfront RC counterparts (16%) (hazard ratio: 1.77, 95% confidence interval [CI] 0.66-4.73; P = 0.3). Of the 1134 patients who initially received BCG, 73 (6.6%) eventually required delayed RC, with 34 (47%) progressing to muscle-invasive bladder cancer before delayed RC. The 3-year CSM rate was comparable in upfront RC (13%) vs delayed RC (11%) among non-progressing patients (P = 0.3). However, patients who progressed before delayed RC had worse 3-year CSM relative to those who did not (13% vs 31%, hazard ratio: 0.32, 95% CI 0.13-0.83; P = 0.018). CONCLUSION: Within a European cohort of patients with HR- and VHR-NMIBC, upfront RC was rarely performed. Patients treated with BCG did not exhibit a CSM disadvantage relative to their upfront RC counterparts. After matching, long-term CSM was similar between BCG therapy and upfront RC. Delayed RC, led to worse outcomes if performed after progression, but matched upfront RC when performed before progression, underscoring importance of timely surgery.
- Klíčová slova
- Bacillus Calmette–Guérin, high risk, non‐muscle‐invasive bladder cancer, survival analysis, upfront radical cystectomy, very high risk,
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVE: Management of metastatic renal cell carcinoma (mRCC) remains complex despite clinical guidelines. The aim of this Delphi study was to achieve consensus among RCC experts on the definition, diagnosis, and first-line treatments for mRCC. METHODS: Between May 2023 and April 2024, 14 experts from ten European countries completed two Delphi rounds of a 51-item questionnaire covering four topics: (1) oligometastatic RCC; (2) first-line treatment for metastatic clear-cell RCC; (3) treatment duration for metastatic clear-cell RCC; and (4) treatment of non-clear-cell RCC. Agreement was scored as absent/poor (<50%), fair (50-74%), or consensus (≥75%). KEY FINDINGS AND LIMITATIONS: Consensus was reached for 12 of 51 items (24%) in the first round and 25 of 49 items (51%) by the study end. Notably, 79% of experts defined oligometastatic RCC as five or fewer metastases and agreed that it typically does not require immediate systemic treatment. All experts (100%) emphasized the importance of clinical performance status in guiding treatment for metastatic clear-cell RCC, with 86% agreeing on additional factors such as International Society of Urological Pathology grade and sarcomatoid features. Nivolumab plus cabozantinib was favored for patients with brain or bone metastases (93% and 86% agreement, respectively), while there was fair agreement on pembrolizumab plus lenvatinib for patients with liver metastases. In addition, 71% supported stopping immune checkpoint inhibitors after 2 yr, while 86% agreed on the undefined duration of tyrosine kinase inhibitor therapy. CONCLUSIONS AND CLINICAL IMPLICATIONS: This Delphi study offers insights into mRCC management, and highlights the importance of multidisciplinary discussions for this challenging disease.
- Klíčová slova
- Consensus, Delphi, Immunotherapy, Metastatic disease, Renal cell carcinoma, Targeted therapy,
- Publikační typ
- časopisecké články MeSH
BACKGROUNDS: SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity. METHODS: Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival. RESULTS: SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis. CONCLUSIONS: In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.
- Klíčová slova
- SMARCD1, SMARCD3, SWI/SNF complex, prognostic marker, prostate cancer,
- MeSH
- chromozomální proteiny, nehistonové * genetika metabolismus MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru patologie metabolismus genetika MeSH
- lymfatické metastázy MeSH
- nádorové biomarkery * genetika metabolismus MeSH
- nádory prostaty rezistentní na kastraci patologie genetika metabolismus MeSH
- nádory prostaty * patologie metabolismus genetika MeSH
- prognóza MeSH
- senioři MeSH
- stupeň nádoru MeSH
- transkripční faktory genetika metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chromozomální proteiny, nehistonové * MeSH
- nádorové biomarkery * MeSH
- SMARCD1 protein, human MeSH Prohlížeč
- transkripční faktory MeSH
BACKGROUND AND OBJECTIVE: Bacillus Calmette-Guérin (BCG) reduces disease recurrence and progression in intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). BCG-associated adverse events during instillations are common, leading to treatment cessation. Prophylactic use of quinolones in conjunction with BCG instillations is one approach for reducing BCG-associated adverse events. Our aim was to delineate the clinical impact of quinolone prophylaxis (QP) in patients receiving adjuvant BCG instillations for NMIBC. METHODS: In October 2024, a systematic search of MEDLINE, Embase, and the Cochrane Central Register of controlled trials was performed. Prospective and retrospective studies reporting comparative outcomes for patients with and without QP during BCG instillations were included. Outcomes were reported in a binary fashion. Random-effects meta-analysis using the weighted mean difference was conducted. Primary outcomes for pooled analyses included BCG-associated toxicities, the completion rate for BCG induction, the likelihood of antituberculosis treatment, and disease recurrence and progression at 12 mo. KEY FINDINGS AND LIMITATIONS: The systematic review included five studies. Four randomised controlled trials were included in the meta-analysis, and one nonrandomised study was also included in the narrative review. The studies involved 445 patients, of whom 194 received QP + BCG and 251 received BCG alone. QP use was associated with lower incidence of class ≥2 (40.8% vs 54.7%; relative risk [RR] 0.79, 95% confidence interval [CI] 0.67-0.94; p = 0.006), and class ≥3 BCG-associated toxicities (25.3% vs 36.4%; RR 0.70, 95% CI 0.50-0.98; p = 0.04) and a higher completion rate for BCG induction (83.0% vs 70.6%; RR 1.16, 95% CI 1.01-1.34; p = 0.04). The 12-mo recurrence rates (14.7% vs 19.4%; RR 0.76, 95% CI 0.46-1.27; p = 0.3) and progression rates (4.5% vs 6.4%; RR 0.86, 95% CI 0.09-8.25; p = 0.9) did not significantly differ for QP + BCG versus BCG alone. CONCLUSIONS AND CLINICAL IMPLICATIONS: The use of QP with adjuvant BCG for NMIBC mitigated debilitating BCG-associated toxicities and improved the completion rate for BCG induction therapy.
- Klíčová slova
- Adjuvant intravesical therapy, Antibiotic prophylaxis, Bacillus Calmette-Guérin, Non–muscle-invasive bladder cancer, Quinolone,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Despite currently used intravesical therapies in non-muscle-invasive bladder cancer (NMIBC), the rate of intravesical recurrence remains very high. We aimed to evaluate the effectiveness of adding nonintravesical interventions to standard intravesical therapies to prevent intravesical recurrence. In April 2024, 3 databases were queried for prospective studies evaluating nonintravesical interventions in addition to standard intravesical therapies for NMIBC (CRD42024490988). The primary outcome was intravesical recurrence-free survival (iRFS). Standard pairwise meta-analyses were performed using hazard ratios (HR) and 95% confidence intervals (95% CI) with a random-effects model. We identified 18 eligible studies (14 RCTs and 4 prospective trials) comprising 4,593 NMIBC patients, which investigated pharmacological interventions (eg, selenium, vitamins, Lactobacillus casei, celecoxib, metformin, mistletoe lectin) and lifestyle modifications (diet). The addition of Lactobacillus casei significantly improved iRFS (HR: 0.50; 95% CI: 0.34-0.73; P < .001). A high western diet pattern significantly worsened iRFS (HR:1.48, 95%CI:1.06-2.06, P = .03). The other nonintravesical interventions were not associated with iRFS. Our comprehensive review of the published literature highlights the need for further research into the efficacy of nonvesical interventions for NMIBC. While Lactobacillus was shown to improve iRFS in 2 RCTs, additional high-quality randomized studies are required to evaluate the effectiveness of other interventions.
- Klíčová slova
- Celecoxib, Diet, Lactobacillus casei, Non-muscle-invasive bladder cancer, Vitamins,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: To evaluate the oncological efficacy and safety of sequential intravesical gemcitabine/docetaxel (Gem/Doce) therapy in a European cohort of patients with high-risk and very-high-risk non-muscle-invasive bladder cancer (NMIBC) after previous Bacillus Calmette-Guérin (BCG) treatment. MATERIALS AND METHODS: Data were retrospectively collected from 95 patients with NMIBC, treated with Gem/Doce at 12 European centres between 2021 and 2024. Patients previously treated with BCG who had completed a full induction course and received at least one follow-up evaluation were included. One-year disease-free survival (DFS), high-grade DFS and progression-free survival (PFS) were estimated using Kaplan-Meier curves. Adverse events (AEs) were recorded through medical interviews. RESULTS: Of 75 patients, 63 (84%) were classified as having high-risk and 12 (16%) as having very-high-risk NMIBC. Over a median (interquartile range) follow-up of 9 (5-14) months, 20 patients (27%) relapsed and five (6.7%) underwent radical cystectomy. The 1-year DFS was 73% (95% confidence interval [CI] 62-86%), 1-year high-grade DFS was 79% (95% CI 68-91%) and 1-year PFS was 95% (95% CI 90-100%). AEs occurred in 34 patients (45%), with six (8.7%) experiencing severe AEs. Limitations of the study include the short follow-up and variability in both treatment dwelling times and dosage across centres. CONCLUSION: The intravesical Gem/Doce regimen demonstrated promising short-term oncological outcomes and was well tolerated in this cohort of patients with high- and very-high-risk NMIBC previously treated with BCG. Prospective studies and randomised trials are awaited to define the ideal candidates for Gem/Doce therapy and to standardise treatment protocols.
- Klíčová slova
- Europe, adverse events, docetaxel, gemcitabine, non‐muscle‐invasive bladder cancer, oncological outcomes,
- Publikační typ
- časopisecké články MeSH
