RESUMO
Sunitinib has greatly improved the survival of clear cell renal cell carcinoma (ccRCC) patients in recent years. However, 20-30% of treated patients do not respond. To identify miRNAs and genes associated with a response, comparisons were made between biopsies from responder and non-responder ccRCC patients. Using integrated transcriptomic analyses, we identified 37 miRNAs and 60 respective target genes, which were significantly associated with the NF-kappa B, PI3K-Akt and MAPK pathways. We validated expression of the miRNAs (miR-223, miR-155, miR-200b, miR-130b) and target genes (FLT1, PRDM1 and SAV1) in 35 ccRCC patients. High levels of miR-223 and low levels of FLT1, SAV1 and PRDM1 were associated with worse overall survival (OS), and combined miR-223 + SAV1 levels distinguished responders from non-responders (AUC = 0.92). Using immunohistochemical staining of 170 ccRCC patients, VEGFR1 (FLT1) expression was associated with treatment response, histological grade and RECIST (Response Evaluation Criteria in Solid Tumors) score, whereas SAV1 and BLIMP1 (PRDM1) were associated with metachronous metastatic disease. Using in situ hybridisation (ISH) to detect miR-155 we observed higher tumoural cell expression in non-responders, and non-tumoural cell expression with increased histological grade. In summary, our preliminary analysis using integrated miRNA-target gene analyses identified several novel biomarkers in ccRCC patients that surely warrant further investigation.
Assuntos
Carcinoma de Células Renais , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , MicroRNAs , Sunitinibe , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , MicroRNAs/genética , Sunitinibe/uso terapêutico , Sunitinibe/farmacologia , Neoplasias Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Adulto , Indóis/uso terapêutico , Indóis/farmacologiaRESUMO
Unfortunately, prostate cancer treatment is not free of complications [...].
RESUMO
Objectives: This study aimed to compare the effectiveness and safety of the adjustable trans-obturator male system (ATOMS®) to treat post-prostatectomy incontinence (PPI) in radiated patients compared with non-radiated patients, using propensity score-matching analysis to enhance the validity of the comparison. Patients and methods: Consecutive men with PPI treated with silicone-covered scrotal port ATOMS (A.M.I., Feldkirch, Austria) in nine different institutions between 2016 and 2022 were included. Preoperative assessment evaluated 24-h pad usage, urethroscopy and urodynamics, if indicated. Propensity score-matching analysis was based on age, length of follow-up, previous PPI treatment, previous bladder neck stricture, androgen deprivation and pad usage. The primary endpoint was dry rate, defined as no pads post-operatively with a security pad allowed. The secondary endpoints were complications, device removal and self-perceived satisfaction with the Patient Global Impression of Improvement (PGI-I) scale. Results: Of the 710 included patients, 342 were matched, and the study groups were balanced for the baseline matched variables. The mean baseline 24-h pad was 4.8 in both groups (p = 0.48). The mean follow-up was 27.5 ± 18.6 months, which was also equivalent between groups (p = 0.36). The primary outcome was achieved in 73 (42.7%) radiated patients and in 115 (67.3%) non-radiated patients (p < 0.0001). The mean pad count at the last follow-up was 1.5 and 0.8, respectively (p < 0.0001). There was no significant difference in complications (p = 0.94), but surgical revision and device explant rates were higher (p = 0.03 and p = 0.01, respectively), and the proportion of patients highly satisfied (PGI-I = 1) was lower in the radiated group (p = 0.01). At sensitivity analysis, the study was found to be reasonably robust to hidden bias. Conclusion: ATOMS implantation significantly outperformed in patients without adjuvant radiation over radiated patients.
RESUMO
Renal cell carcinoma (RCC) ranks among the most prevalent malignancies in Western countries, marked by its notable heterogeneity, which contributes to an unpredictable clinical trajectory. The insufficiency of dependable biomarkers adds complexity to assessing this tumor progression. Imbalances of several components of the intrarenal renin-angiotensin system (iRAS) significantly impact patient prognoses and responses to first-line immunotherapies. In this study, we analyzed the immunohistochemical expression of the Mas-related G-protein-coupled receptor D (MrgD), which recognizes the novel RAS peptide alamandine (ALA), in a series of 87 clear cell renal cell (CCRCCs), 19 papillary (PRCC), 7 chromophobe (ChRCC) renal cell carcinomas, and 11 renal oncocytomas (RO). MrgD was expressed in all the renal tumor subtypes, with a higher mean staining intensity in the PRCCs, ChRCCs, and ROs. A high expression of MrgD at the tumor center and at the infiltrative front of CCRCC tissues was significantly associated with a high histological grade, large tumor diameter, local invasion, and locoregional node and distant metastasis. Patients with worse 5-year cancer-specific survival and a poorer response to antiangiogenic tyrosine-kinase inhibitors (TKIs) showed higher MrgD expression at the center of their primary tumors. These findings suggest a possible role of MrgD in renal carcinogenetic processes. Further studies are necessary to unveil its potential as a novel biomarker for CCRCC prognosis and response to frontline therapies.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Receptores Acoplados a Proteínas G , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Proteínas de Transporte , Rim/metabolismo , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Oligopeptídeos/metabolismo , Oligopeptídeos/farmacologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismoRESUMO
PURPOSE: The treatment of urethral stenosis after a combination of prostatectomy and radiation therapy for prostate cancer is understudied. We evaluate the clinical and patient-related outcomes after dorsal onlay buccal mucosal graft urethroplasty (D-BMGU) in men who underwent prostatectomy and radiation therapy. MATERIALS AND METHODS: A multi-institutional, retrospective review of men with vesicourethral anastomotic stenosis or bulbomembranous urethral stricture disease after radical prostatectomy and radiation therapy from 8 institutions between 2013 to 2021 was performed. The primary outcomes were stenosis recurrence and development of de novo stress urinary incontinence. Secondary outcomes were surgical complications, changes in voiding, and patient-reported satisfaction. RESULTS: Forty-five men were treated with D-BMGU for stenosis following prostatectomy and radiation. There was a total of 7 recurrences. Median follow-up in patients without recurrence was 21 months (IQR 12-24). There were no incidents of de novo incontinence, 28 patients were incontinent pre- and postoperatively, and of the 6 patients managed with suprapubic catheter preoperatively, 4 were continent after repair. Following repair, men had significant improvement in postvoid residual, uroflow, International Prostate Symptom Score, and International Prostate Symptom Score quality-of-life domain. Overall satisfaction was +2 or better in 86.6% of men on the Global Response Assessment. CONCLUSIONS: D-BMGU is a safe, feasible, and effective technique in patients with urethral stenosis after a combination of prostatectomy and radiation therapy. Although our findings suggest this technique may result in lower rates of de novo urinary incontinence compared to conventional urethral transection and excision techniques, head-to-head comparisons are needed.
Assuntos
Estreitamento Uretral , Incontinência Urinária , Humanos , Masculino , Constrição Patológica/cirurgia , Mucosa Bucal/transplante , Prostatectomia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Uretra/cirurgia , Estreitamento Uretral/etiologia , Estreitamento Uretral/cirurgia , Estreitamento Uretral/diagnóstico , Incontinência Urinária/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodosRESUMO
We aimed to determine the risk factors for postoperative overactive bladder (OAB) in patients treated with an adjustable trans-obturator male system (ATOMS) for stress incontinence after radical treatment of prostate cancer. A prospective study was performed on 56 patients implanted with an ATOMS for PPI. Clinical and urodynamic information was recorded before and after ATOMS implantation. We built a multivariate model to find out the clinical and urodynamic factors that independently influenced postoperative OAB and the prognostic factors that influenced the efficacy of medical treatment of OAB. We found that the clinical risk factors were the preoperative intensity of urinary incontinence (number of daily pads used and amount of urinary leakage), International Consultation on Incontinence Questionnaire (ICIQ) score, postoperative number of ATOMS adjustments, final cushion volume, and incontinence cure. The urodynamic data associated with OAB were cystometric bladder capacity, voided volume, volume at initial involuntary contraction (IC), maximum flow rate, bladder contractility index (BCI), and urethral resistance (URA). The prognostic factors for the efficacy of oral treatment of OAB were the volume at the first IC (direct relationship) and the maximum abdominal voiding pressure (inverse relationship). The multivariate model showed that the independent clinical risk factors were the daily pad count before the implantation and the ICIQ score at baseline and after treatment. The independent urodynamic data were the volume at the first IC (inverse relationship) and the URA value (direct relationship). Both predictive factors of treatment efficacy were found to be independent. Detrusor overactivity plays an important role in postoperative OAB, although other urodynamic and clinical factors such as the degree of urethral resistance and abdominal strength may influence this condition.
RESUMO
(1) Background: Treatment of male stress incontinence in patients with prostate cancer treated with radical prostatectomy and adjuvant pelvic radiation is a therapeutic challenge. The efficacy and safety of the adjustable trans-obturator male system (ATOMS) in these patients is not well established, despite the general belief that outcomes are worse than in patients without radiation. (2) Methods: Retrospective multicenter study evaluating patients treated with silicone-covered scrotal port (SSP) ATOMS implant after radical prostatectomy and radiotherapy in nine different institutions between 2016 and 2022. The primary endpoint was dry patient rate, defined as pad-test ≤ 20 mL/day. The secondary endpoints were complication rate (defined using Clavien-Dindo classification), device removal and self-perceived satisfaction using the Patient Global Impression of Improvement (PGI-I) scale. Wilcoxon rank-sum test, Fisher's exact test and logistic regression were performed using stepwise method with a 0.15 entry and 0.1 stay criteria. (3) Results: 223 patients fulfilled the criteria for inclusion and 12 (5.4%) received salvage prostatectomy after radiation and 27 (12.1%) previous devices for stress incontinence. After ATOMS adjustment, 95 patients (42.6%) were dry and 36 (16.1%) had complications of any grade (grade I, n = 20; grade II, n = 11; grade III, n = 5) during the first 3 months postoperatively. At a mean of 36 ± 21 months follow-up, the device was explanted in 26 (11.7%) patients. Regarding self-perceived satisfaction with the implant, 105 of 125 patients (84%) considered themselves satisfied (PGI-I 1 to 3). In the univariate analysis, dryness was associated to younger age (p = 0.06), primary prostatectomy (p = 0.08), no previous incontinence surgery (p = 0.02), absence of overactive bladder symptoms (p = 0.04), absence of bladder neck stricture (p = 0.001), no need of surgical revision (p = 0.008) and lower baseline incontinence severity (p = 0.0003). Multivariate analysis identified absence of surgical revision (p = 0.018), absence of bladder neck stricture (p = 0.05), primary prostatectomy (p = 0.07) and lower baseline incontinence severity (p < 0.0001) were independent predictors of dryness. A logistic regression model was proposed and internally validated. (4) Conclusions: ATOMS is an efficacious and safe alternative to treat male incontinence after radical prostatectomy and adjuvant radiotherapy. Factors predictive of dryness are identified in this complex scenario to allow for better patient selection.
RESUMO
Radiation therapy (RT) in the management of pelvic cancers remains a clinical challenge to urologists given the sequelae of urethral stricture disease secondary to fibrosis and vascular insults. The objective of this review is to understand the physiology of radiation-induced stricture disease and to educate urologists in clinical practice regarding future prospective options clinicians have to deal with this condition. The management of post-radiation urethral stricture consists of conservative, endoscopic, and primary reconstructive options. Endoscopic approaches remain an option, but with limited long-term success. Despite concerns with graft take, reconstructive options such as urethroplasties in this population with buccal grafts have shown long-term success rates ranging from 70 to 100%. Robotic reconstruction is augmenting previous options with faster recovery times. Radiation-induced stricture disease is challenging with multiple interventions available, but with successful outcomes demonstrated in various cohorts including urethroplasties with buccal grafts and robotic reconstruction.
RESUMO
(1) Background: The adjustable trans-obturator male system (ATOMS) is a surgical device developed to treat post-prostatectomy incontinence (PPI) after prostate cancer treatment. We review the current literature on this anti-incontinence device with the intention of assessing the effectiveness, safety and duration of the silicone-covered scrotal port (SSP) ATOMS, the only generation of the device that is currently available. (2) Material and Methods: Non-systematic literature review is performed. Forty-eight full-text articles are assessed for eligibility. Case reports, expert opinions or commentaries without specific data reported (n = 6), studies with patients who underwent intervention before 2014 (IP or SP ATOMS; n = 10), and studies with incontinence after transurethral resection of the prostate (TUR-P; n = 2) are excluded for analysis. Thirty studies with SSP ATOMS are included in a qualitative synthesis that incorporates systematic reviews (n = 3), articles partially overlapping with other previously published studies (e.g., follow-up or series updates; n = 9), and studies focusing on specific populations (n = 8). Only articles revealing outcomes of SSP ATOMS were included in the quantitative synthesis of results (n = 10). (3) Results: the pooled data of 1515 patients from the 10 studies with SSP ATOMS confirmed very satisfactory results with this device after adjustment: dry rate: 63-82%, improved rate: 85-100%, complication rate: 7-33%, device infection rate: 2.7-6.2% and explant rate: 0-19%. The durability of the device is reassuring, with 89% of devices in place 5 years after implantation. (4) Conclusion: Despite the absence of randomized controlled studies, the literature findings confirm results of SSP ATOMS appear equivalent to those of artificial urinary sphincters (AUSs) in terms of continence, satisfaction and complications, but with a lower rate of revision in the long-term. A prospective study identified that patients with daily pad test results <900 mL and a Male Stress Incontinence Grading Scale (MSIGS) of not 4 (i.e., early and persistent stream or urine loss) are the best candidates. Future studies centered on the elder population at higher risk of impaired cognitive ability and in patients including radiation as prostate cancer treatment are needed.
Assuntos
Neoplasias da Próstata , Slings Suburetrais , Ressecção Transuretral da Próstata , Humanos , Masculino , Idoso , Estudos Prospectivos , Resultado do Tratamento , Desenho de Prótese , Neoplasias da Próstata/cirurgiaRESUMO
This Special Issue includes 12 articles and 3 reviews dealing with several basic and clinical aspects of prostate, renal, and urinary tract cancer published during 2022 in Cancers, and intends to serve as a multidisciplinary chance to share the last advances in urological neoplasms [...].
RESUMO
The coronavirus disease 2019 (COVID-19) pandemic has caused a significant disruption to cancer diagnosis, treatment and prevention worldwide that could have serious consequences in the near future. We intend to evaluate the weight of this backlog on a community-wide scale in Madrid during the period 2020-2021, and whether a stage shift towards the advanced stage has occurred. Cancer diagnoses in the Madrid tumor registry (RTMAD) from 2019-2021 were evaluated. Absolute and percentage differences in annual volume and observed-to-expected (O/E) volume ratios were calculated. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated using the O/E ratio. The SIR for 2020-2021 compared to 2019 was 94.5% (95% CI 93.8-95.3), with unequal gender-specific cancer diagnosis recovery (88.5% for males and 102.1% for females). Most cancer types were underdiagnosed in 2020. The tendency worsened in 2021 for colorectal and prostate cancers (87.8%), but lung cancer recovered (102.1%) and breast cancer was over-diagnosed (114.4%) compared with reference pre-COVID-19 data. These changes have modified the ranking of the most frequent malignancies diagnosed in Madrid. Breast cancer has overtaken colorectal and prostate cancers, displaced to second and third position, respectively. Not only was colorectal cancer diagnosis affected more as a consequence of the COVID-19 pandemic but diagnosis of this malignancy at the advance stage also increased by 3.6% in 2020 and 4.2% in 2021 compared to the reference period of 2019. In summary, there is a large volume of undetected cancer in Madrid caused by the reduced access to care secondary to the COVID-19 pandemic, especially regarding colorectal and prostate cancer. Strategies are needed to recover the backlog of diagnoses and effectively treat these cases in the future and solve the negative impact that will be caused by the diagnostic delay. Analyzing the impact of new diagnoses suffered by each different malignancy and their recovery will help to understand how the future allocation of resources should look.
RESUMO
This randomized clinical trial evaluates the success rate of neuro-adaptive therapy (NAT), applied with a specific neuro-adaptive regulator device, the Self-Controlled Electro Neuro-Adaptive Regulation (SCENAR), versus a sham for urge incontinence due to an overactive bladder (OAB). From February 2019 to May 2021, 66 patients were recruited. All subjects were randomized 1:1 at the first intervention visit to the NAT or sham procedure. Inclusion criteria were females between 18 and 80 years old with leakages due to an overactive bladder with unresponsiveness to medical therapy. Subjects were scheduled to receive up to eight weekly 20 min intervention sessions to obtain a complete (CR) or partial response (PR). Patients with no response after three sessions were considered as a failure. The primary end point of this trial was to assess the efficacy of NAT compared to an inactive sham intervention, evaluated 1 month after the last session. Analysis showed 23 (70%) patients responded (20 complete and 3 partial response) in the NAT group compared to 16 (48%) patients (all complete response) in the placebo arm (p = 0.014). Significant differences were maintained after the intervention, with persistent response at 3 months in 19 (58%) patients after active treatment and 14 (42%) after the placebo (p < 0.001), and at 6 months in 18 (55%) vs. 11 (33%) (p = 0.022), respectively. The number of sessions to achieve CR was similar in both arms, with 4.3 ± 1.9 in NAT and 3.9 ± 1.8 in the sham group (NS). Significant differences were observed between both groups for patients' satisfaction (p = 0.01). The binary model selected age as a predictor of response at the last follow-up. The odds ratio indicates that each year of increase in age, the probability of a positive response to treatment at 6 months decreases 0.95 (95% CI 0.9-0.99) times (p = 0.03). In conclusion, this pilot randomized trial gives evidence that neuro-adaptive electrostimulation is effective to treat refractory urge urinary incontinence due to OAB. The security and long-term efficacy of this treatment merits further evaluation. Moreover, its favorable profile and the economic advantages of the device make the evaluation of this promising technique mandatory in a primary therapeutic scenario.
RESUMO
Castration-resistant prostate cancer (CRPC) development is the foremost concern after treatment of patients with high risk with locally advanced or metastatic prostate cancer. Androgen receptor (AR) is the main driver of CRPC development, through its interaction with epigenetic modifier genes, placing epigenetics modifications in the forefront of CRPC development. Comparing the DNA methylation and expression profile of androgen-sensitive and -refractory prostate cancer cells, we describe the epigenetic silencing of claudin-3 (CLDN3) in AR positive cells resistant to androgen deprivation (LNCaP-abl). CLDN3 silencing was associated with DNA methylation, loss of histone acetylation and H3K27 methylation, and was re-expressed by the combined treatment with the epigenetic modulators Aza and SAHA. From a functional point of view, CLDN3 loss was associated with increased cellular invasion. Immunohistochemical analysis showed decreased CLDN3 expression in samples from CRPC patients. Interestingly, CLDN3 expression was significantly decreased in samples from patients with high total Gleason score (≥8) and locally advanced tumors. Finally, CLDN3 loss of expression was associated with worse disease-free survival and time to clinical progression. In conclusion, our findings strongly indicate that epigenetic silencing of CLDN3 is a common event in CRPC that could be useful as a molecular marker for the prognosis of prostate cancer patients and to discriminate aggressive from indolent prostate tumors.
Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Claudina-3/genética , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Prognóstico , Receptores Androgênicos/metabolismo , Linhagem Celular TumoralRESUMO
BACKGROUND: Optimising therapeutic strategies of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC) is needed. OBJECTIVE: To compare recurrence-free survival (RFS) with adjuvant intravesical mitomycin C (MMC) at normothermia or hyperthermia using the COMBAT bladder recirculation system at 43⯰C for 30 and 60 min. DESIGN, SETTING, AND PARTICIPANTS: A prospective open-label, phase 3 randomised controlled trial (HIVEC-1) accrued across 13 centres between 2014 and 2020 in Spain. After complete transurethral resection of the bladder and immediate postoperative MMC instillation, patients with IR-NMIBC were randomised (1:1:1) to four weekly followed by three monthly 40-mg MMC instillations at normothermia (control; nâ¯=â¯106), 43⯰C for 30 min (nâ¯=â¯107), or 43⯰C for 60 min (nâ¯=â¯106) were investigated. Therapeutic compliance was defined as four or more instillations. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was RFS at 24 mo in the intention-to-treat (ITT) and per-protocol (PP) populations. The secondary outcomes included progression-free survival at 24 mo, safety outcome measures, and changes in health-related quality of life. Log-rank, Fisher, χ2, and analysis of variance tests were used. RESULTS AND LIMITATIONS: The ITT 24-mo RFS was 77% for control, 82% for 43⯰C-30 min, and 80% for 43⯰C-60 min (pâ¯=â¯0.6). The PP 24-mo RFS was 77% for control, 83% for 43⯰C-30 min, and 80% for 43⯰C-60 min (pâ¯=â¯0.59). Six patients progressed to muscle-invasive disease in the ITT population (four in the control, 43⯰C-30 min, and 43⯰C-60 min groups each) and four in the PP population (all controls). Serious adverse events occurred in 26 patients (8.1%), and we were unable to demonstrate a difference between groups (pâ¯=â¯0.5). Adverse events, mainly dysuria and spasms, occurred in 124 patients (33% in control, 35% in 43⯰C-30 min, and 48% in 43⯰C-60 min; pâ¯=â¯0.05). The total International Prostate Symptom Score worsened by 1.2⯱â¯7.3 points, similarly across groups (pâ¯=â¯0.29). The Functional Assessment of Cancer Therapy-Bladder domains and indexes showed no significant change. CONCLUSIONS: Four-month adjuvant hyperthermic MMC using the COMBAT system for 30 and 60 min in IR-NMIBC is well tolerated, but we did not find it to be superior to normothermic MMC at 24 mo. PATIENT SUMMARY: We were unable to demonstrate the effectiveness of hyperthermia using the COMBAT system in intermediate-risk non-muscle-invasive bladder cancer. Further evaluation of long-term recurrence and progression, and maintenance regimens appears mandatory.
Assuntos
Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Masculino , Humanos , Mitomicina/uso terapêutico , Qualidade de Vida , Estudos Prospectivos , Administração Intravesical , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Adjuvantes Imunológicos/uso terapêuticoRESUMO
AIMS: To estimate the prevalence of lower urinary tract symptoms (LUTS) in patients with prostate cancer scheduled to receive LHRH analogs, and to assess the effectiveness of LHRH analogs on LUTS in patients presenting moderate/severe symptoms. METHODS: Prospective, noninterventional, multicenter study conducted at 28 centers in Spain and Portugal. LUTS were evaluated using the International Prostate Symptom Score (IPSS) at baseline, 24 and 48 weeks after initiation of treatment. Subanalyses were performed according to age and concomitant treatment (radiotherapy, alpha-blockers, and antiandrogens). RESULTS: A total of 354 patients were treated with LHRH analogs for 48 weeks. The percentage of patients with moderate/severe LUTS (IPSS > 7) decreased from 60.2% (n = 213/354) at baseline to 52.8% (n = 187/354) at Week 48. Among patients with moderate/severe LUTS at baseline: 73.7% (n = 157/213) still had moderate/severe LUTS at Week 48; percentage reductions of patients with LUTS at Week 48 were statistically significant (p < 0.05) overall and by age or concomitant treatment, except for alpha-blockers (84.2% patients receiving them still had moderate/severe LUTS at Week 48). All IPSS items, including quality of life for urinary symptoms, improved throughout the study. The only predictor of response to treatment with LHRH analogs that improved IPSS by 3 points after 48 weeks was baseline testosterone levels. Lower baseline testosterone levels were associated with greater improvement in IPSS after treatment with LHRH analogs (odds ratio 0.998, 95% confidence interval 0.996-1.000, p = 0.0277). CONCLUSION: LHRH analogs have a positive effect in patients with locally advanced or metastatic prostate cancer presenting moderate/severe LUTS regardless of age or concomitant treatment received (radiotherapy, antiandrogens, or alpha-blockers).
Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Hormônio Liberador de Gonadotropina/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/diagnóstico , Estudos Prospectivos , Hiperplasia Prostática/complicações , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico , Qualidade de Vida , Testosterona/uso terapêuticoRESUMO
(1) Background: Male stress incontinence in patients with previously treated urethral or bladder neck stricture is a therapeutic challenge. The efficacy and safety of the adjustable trans-obturator male system (ATOMS) in these patients is unknown. (2) Methods: All patients with primary ATOMS implants in our institution between 2014 and 2021 were included. The outcomes of patients with previously treated urethral or bladder neck stricture (≥6 months before ATOMS implant) and stable 16Ch urethral caliber were compared to those without a history of stricture. The primary endpoint was the dry patient rate, defined as the pad test ≤ 20 mL/day, and complication rate, including device removal. The secondary variable was self-perceived satisfaction using the Patient Global Impression of Improvement (PGI-I) scale. Wilcoxon rank sum test, Fisher's exact test and logistic regression were performed. (3) Results: One hundred and forty-nine consecutive patients were included, twenty-one (14%) previously treated for urethral or bladder neck stricture (seven urethroplasty, nine internal urethrotomy and five bladder neck incision). After ATOMS adjustment, 38% of the patients with treated stricture were continent compared to 83% of those without (p < 0.0001). After weighted matched observations using propensity score pairing, the proportion of continent patients without a previous stricture was 56% (p = 0.236). Complications occurred in 29% of the patients with stricture and in 20% of those without (p = 0.34). The severity of the complications was distributed evenly among the groups (p = 0.42). Regarding self-perceived satisfaction with the implant, 90% of the patients with stricture perceived the results satisfactorily (PGI-I 1−3) compared to 97% of the rest (p = 0.167). Stricture was associated with radiotherapy (p < 0.0001) and time from prostatectomy to implantation (p = 0.012). There was a moderate correlation between previous stricture and the severity of incontinence, both evaluated according to the 24-h pad test (Rho = 0.378; p < 0.0001) and the ICIQ-SF questionnaire (Rho = 0.351; p < 0.0001). Multivariate analysis for the factors predictive of failure after ATOMS adjustment revealed previous stricture (OR 4.66; 95% CI 1.2−18.87), baseline 24-h pad test (per 100 mL, OR 1.28; 95% CI 1.09−1.52) and final cushion volume (per mL, OR 1.34; 95% CI 1.19−1.55). This model predicted dryness with an AUC of 92%. After the PSMATCH procedure using a propensity score, the model remained unchanged, with the previous stricture (OR 8.05; 95% CI 1.08−110.83), baseline 24-h pad test (per 100 mL, OR 1.53; 95% CI 1.15−2.26) and final cushion volume (per mL, OR 1.45; 95% CI 1.17−2) being independent predictors and an AUC of 93%. (4) Conclusions: ATOMS can be used to treat male stress incontinence in patients with a history of stricture, although the effectiveness of the device is reduced. On the other hand, the security and perceived satisfaction were equivalent for both groups.
RESUMO
The objective of this subset analysis was to evaluate and compare the efficacy and tolerability of two combination treatments for men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Data were from a real-world, open-label, prospective, and multicenter study performed in outpatient urology clinics. Men with moderate-to-severe LUTS/BPH received 6-month treatment with tamsulosin (TAM) in combination with either the hexanic extract of S. repens (HESr) or a 5-alpha-reductase inhibitor (5ARI). Changes in urinary symptoms and quality of life were measured using the IPSS and BII questionnaires, respectively. Treatment tolerability was assessed by recording adverse effects (AEs). Patients in the two study groups were matched using iterative and propensity score matching approaches. After iterative matching, data were available from 136 patients (n = 68 treated with TAM + 5ARI, n = 68 with TAM + HESr). After 6 months of treatment, mean (SD) IPSS total score improved by 7.7 (6.3) and 6.7 (5.0) points in the TAM + 5ARI and TAM + HESr groups, respectively (p = 0.272); mean BII total scores improved by 3.1 (2.9) and 2.9 (2.4) points (p = 0.751), respectively. AEs were reported by 26.5% and 10.3% of patients in the same groups, mostly affecting sexual function (p < 0.027). When used in a real-world setting to treat patients with moderate-severe LUTS/BPH, 6-month treatment with TAM + HESr was as effective as TAM + 5ARI, but with better tolerability.
RESUMO
PURPOSE OF REVIEW: Intratumor heterogeneity (ITH) is an inherent characteristic of most tumors and its detection remains a key task for pathologists. However, the clinical significance of the degree of development of this feature is still poorly understood. RECENT FINDINGS: A series of 28 clear cell renal cell carcinomas (CCRCC) have been exhaustively analyzed with two different sampling protocols [multisite tumor sampling (MSTS) and total sampling] to evaluate to what point the level (low vs. high) of histological ITH detected in routine practice influences tumor behavior and patients' survival. All CCRCC (n = 14) pursuing an aggressive clinical course presented low levels of ITH. A significant worse survival was detected in CCRCC with low ITH (p < 0.001). The simple quantification of the level of ITH using extensive sampling protocol may be of help in predicting tumor evolution, since all CCRCC with aggressive behavior demonstrated low levels of histological ITH.