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1.
Ann Surg Oncol ; 31(3): 2144-2153, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38085392

RESUMEN

BACKGROUND: Systemic and local recurrences of urothelial bladder cancer (UBC) significantly impair survival after radical cystectomy (RC), but little is known about the impact of the recurrence of urothelial cancer in the upper urinary tract (UTUC). This report describes survival outcomes and their predictors for patients who underwent RC followed by radical nephroureterectomy (RNU) for UTUC. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients who underwent RC for UBC and subsequent RNU for UTUC. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for the survival analysis. RESULTS: Overall, 102 patients have undergone RNU within a median of 49 months (interquartile range [IQR], 27-76 months) since RC. Muscle-invasive UTUCs were predominant at RNU (n = 58; 56.7%), but organ-confined bladder tumors were most frequent at RC (n = 42, 41.5%). After RNU, the estimated 5-year overall survival (OS) was 25.9%, the cancer-specific survival (CSS) was 35.6%, the median OS was 23 months (IQR, 11-63 months), and the CSS was 34 months (IQR, 13-132 months). In the multivariable CRR, the factors predictive for CSS after RNU included male gender (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.03-5.42; p < 0.05), muscle-invasive UTUC (HR, 2.20; 95% CI, 1.13-4.28; p < 0.05), and the presence of distant metastasis (HR,11.59; 95% CI, 5.33-25.2; p < 0.001). CONCLUSIONS: In conclusion, the patients who underwent RNU for UTUC after RC for UBC experienced poor OS and CSS. The majority of RNUs were performed for locally advanced tumors. The independent risk factors for worse OS and CSS after RNU were UTUC T stage, presence of metastasis, and male gender.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Renales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Sistema Urinario , Humanos , Masculino , Nefroureterectomía , Cistectomía , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/cirugía , Carcinoma de Células Transicionales/cirugía , Neoplasias Ureterales/cirugía , Neoplasias Renales/cirugía
2.
Ann Surg Oncol ; 31(7): 4773-4786, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38570378

RESUMEN

BACKGROUND: This study aimed to characterize the urinary and tumor microbiomes in patients with non-muscle-invasive bladder cancer (NMIBC) before and after transurethral resection of the bladder tumor (TURBT). METHODS: This single-center prospective study included 26 samples from 11 patients with low-grade Ta papillary NMIBC. Urine samples were collected at the index TURBT and at a 1-year follow-up cystoscopy. The metagenomic analysis of bacterial and archaeal populations was performed based on the highly variable V3-V4 region of the 16S rRNA gene. RESULTS: Phylogenetic alpha diversity of the bladder microbiome detected in urine was found to be lower at the 1-year follow-up cystoscopy compared to the time of the index TURBT (p < 0.01). Actinomyces, Candidatus cloacimonas, Sphingobacterium, Sellimonas, Fusobacterium, and Roseobacter were more differentially enriched taxa in urine at the follow-up cystoscopy than at the index TURBT. Beta diversity of urine microbiome significantly changed over time (p < 0.05). Phylogenetic alpha diversity of the microbiome was greater in tumor tissues than in paired urine samples (p<0.01). Sphingomonas, Acinetobacter, Candidatus, and Kocuria were more differentially overrepresented in tumor tissues than in urine. The enrichment of the abundance of Corynebacterium and Anaerococcus species in urine collected at TURBT was observed in patients who experienced recurrence within the follow-up period. CONCLUSIONS: In patients with low-grade NMIBC, the urine microbiome undergoes changes over time after removal of the tumor. The microbiome detected in tumor tissues is more phylogenetically diverse than in paired urine samples collected at TURBT. The interplay between bladder microbiome, tumor microbiome, and their alterations requires further studies to elucidate their predictive value and perhaps therapeutic implications.


Asunto(s)
Microbiota , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/microbiología , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/orina , Estudios Prospectivos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios de Seguimiento , Pronóstico , Cistectomía , Invasividad Neoplásica , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/análisis , Bacterias/aislamiento & purificación , Bacterias/genética , Bacterias/clasificación , Filogenia , Neoplasias Vesicales sin Invasión Muscular
3.
Prostate ; 83(15): 1504-1515, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37545342

RESUMEN

BACKGROUND: Patients with nonmetastatic prostate cancer (nmPCa) and high prostate-specific antigen (PSA) levels due to the high likelihood of metastasis pose a clinical dilemma regarding their optimal treatment and long-term outcomes after initial local therapy. We aimed to evaluate the oncologic outcomes of patients treated with radical prostatectomy (RP) or radiotherapy (RT) for nmPCa with high PSA levels. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with nmPCa who received RP or RT from 2004 through 2015. We included nmPCa patients with high PSA levels categorized as ≥50 and ≥98 ng/mL, the highest level recorded in SEER. We used the Kaplan-Meier method and Cox proportional hazards to analyze cancer-specific (CSS) and overall survival (OS). RESULTS: We included 6177 patients with nmPCa and PSA ≥ 50 ng/mL at diagnosis; 1698 (27%) had PSA ≥ 98 ng/mL. Of these, 1658 (26.8%) underwent RP and 4519 (73.16%) patients received primary RT. Within a median of 113 months (interquartile range 74-150 months), the 5- and 10-year CSS estimates were 92.3% and 81.5% respectively; 10-year OS was 61%. In the PSA ≥ 98 ng/mL subgroup 5- and 10-year CSS estimates were 89.2% and 76%, respectively. In multivariable analyses for CSS, ISUP grade group (p < 0.001), N stage (p < 0.001), treatment with RP (hazard ratio [HR] = 0.60, 95% confidence interval [CI] 0.43-0.83, p < 0.001), and patient's age (p < 0.05) were associated with improved CSS. In the whole cohort of patients with PSA ≥ 50 ng/mL and RP subgroup, PSA failed to retain its independent prognostic value for CSS. CONCLUSIONS: Patients treated with local therapy for nmPCa with very high PSA at diagnosis have relatively good long-term oncological outcomes. Therefore, among well-selected patients with nmPCa, high PSA levels alone should not preclude the use of radical local therapy. Potential selection bias limits inferences about the relative effectiveness of specific local therapies in this setting.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Pronóstico , Terapia Recuperativa , Prostatectomía/métodos , Estudios Retrospectivos
4.
Ann Surg Oncol ; 30(12): 7892-7902, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37578604

RESUMEN

BACKGROUND AND PURPOSE: Non-muscle-invasive bladder cancer (NMIBC) constitutes a heterogeneous group of tumors with different prognoses. This population-based study aimed to report real-world cancer-specific survival (CSS) of NMIBC and create a prognostic nomogram based on the identified risk factors. METHODS: The Surveillance, Epidemiology, and End Results database was searched for patients diagnosed with NMIBC from 2004 to 2015, who underwent transurethral resection of the bladder tumor. The dataset was divided into development and validation cohorts. Factors associated with CSS were identified using Cox proportional hazards and used to develop a prognostic nomogram. RESULTS: In total, 98,238 patients with NMIBC were included. At the median follow-up of 124 months (IQR 81-157 months), cancer-specific mortality (CSM) was highest for T1HG (19.52%), followed by Tis (15.56%), similar for T1LG and TaHG (10.88% and 9.23%, respectively), and lowest for TaLG (3.76%). Multivariable Cox regression for CSS prediction was utilized to develop a nomogram including the following risk factors: tumor T category and grade, age, tumor size and location, histology type, primary character, race, income, and marital status. In the validation cohort, the model was characterized by an AUC of 0.824 and C-index that reached 0.795. CONCLUSIONS: To conclude, NMIBC is associated with a significant risk of long-term CSM especially, but not only, in patients with T1HG. Rarely diagnosed TaHG and T1LG tumors should be regarded as high-risk due to approximately 10% CSM. T category, grading, and age remain the most powerful determinants of CSS in NMIBC, but sociodemographic factors might also influence its prognosis.


Asunto(s)
Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Pronóstico , Nomogramas , Factores de Riesgo
5.
World J Urol ; 41(5): 1275-1284, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37019997

RESUMEN

PURPOSE: The reliability of magnetic resonance imaging (MRI) as a local and nodal staging tool in radio-recurrent prostate cancer (PCa) is still unclear. The present study aims at evaluating the predictive value of MRI in the detection of extracapsular extension (ECE), seminal vesical invasion (SVI) and nodal involvement (LNI) in patients after primary radio (EBRT) and/or brachytherapy (BT) before salvage radical prostatectomy (SRP). METHODS: This systematic review and meta-analysis were performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Pubmed, Scopus, and Web of Science databases were systemically reviewed to extract the data on diagnostic performance of MRI in radio-recurrent PCa. RESULTS: Four studies comprising 94 radio-recurrent PCa patients were included. The pooled prevalence of ECE, SVI, and LNI was 61%, 41%, and 20%, respectively. The pooled sensitivity for ECE, SVI and LNI detection was 53% (CI 95% 19.8-83.6%), 53% (CI 95% 37.2-68%) and 33% (CI 95% 4.7-83.1%) respectively, whereas specificity was 75% (CI 95% 40.6-92.6%), 88% (CI 95% 71.7-95.9%) and 92% (CI 95% 79.6-96.8%). The sensitivity analysis revealed that a single outlying study using only T2-weighted imaging instead of multiparametric MRI reported significantly higher sensitivity with significantly lower specificity. CONCLUSIONS: This is the first meta-analysis reporting reliability of staging MRI in a radio-recurrent setting. MRI provides poor sensitivity while maintaining high specificity for local and nodal staging before SRP. However, current evidence is limited to the low number of heterogenous studies at meaningful risk of bias.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias de la Próstata , Masculino , Humanos , Reproducibilidad de los Resultados , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Imagen por Resonancia Magnética/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía
6.
Int J Mol Sci ; 23(3)2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35163421

RESUMEN

Despite the unquestionable success achieved by rituximab-based regimens in the management of diffuse large B-cell lymphoma (DLBCL), the high incidence of relapsed/refractory disease still remains a challenge. The widespread clinical use of chemo-immunotherapy demonstrated that it invariably leads to the induction of resistance; however, the molecular mechanisms underlying this phenomenon remain unclear. Rituximab-mediated therapeutic effect primarily relies on complement-dependent cytotoxicity and antibody-dependent cell cytotoxicity, and their outcome is often compromised following the development of resistance. Factors involved include inherent genetic characteristics and rituximab-induced changes in effectors cells, the role of ligand/receptor interactions between target and effector cells, and the tumor microenvironment. This review focuses on summarizing the emerging advances in the understanding of the molecular basis responsible for the resistance induced by various forms of immunotherapy used in DLBCL. We outline available models of resistance and delineate solutions that may improve the efficacy of standard therapeutic protocols, which might be essential for the rational design of novel therapeutic regimens.


Asunto(s)
Resistencia a Antineoplásicos , Linfoma de Células B Grandes Difuso/genética , Animales , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/farmacología , Rituximab/uso terapéutico , Microambiente Tumoral
7.
Int J Mol Sci ; 21(24)2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33333768

RESUMEN

CD37 is a tetraspanin expressed prominently on the surface of B cells. It is an attractive molecular target exploited in the immunotherapy of B cell-derived lymphomas and leukemia. Currently, several monoclonal antibodies targeting CD37 as well as chimeric antigen receptor-based immunotherapies are being developed and investigated in clinical trials. Given the unique role of CD37 in the biology of B cells, it seems that CD37 constitutes more than a docking point for monoclonal antibodies, and targeting this molecule may provide additional benefit to relapsed or refractory patients. In this review, we aimed to provide an extensive overview of the function of CD37 in B cell malignancies, providing a comprehensive view of recent therapeutic advances targeting CD37 and delineating future perspectives.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos de Neoplasias/inmunología , Antígenos de Neoplasias/metabolismo , Antineoplásicos Inmunológicos/uso terapéutico , Linfocitos B/metabolismo , Inmunoterapia/métodos , Leucemia Linfocítica Crónica de Células B/inmunología , Linfoma de Células B/inmunología , Tetraspaninas/inmunología , Tetraspaninas/metabolismo , Linfocitos B/inmunología , Linfocitos B/patología , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/metabolismo , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo
10.
Pol Merkur Lekarski ; 47(281): 187-189, 2019 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-31812973

RESUMEN

The prevalence of heart failure (HF) in developed countries exceeds 10% in adults over 70 year old. At the following report we aim to present a case of HF worsening complicated by gout attack. CASE REPORT: 80-year old patient was admitted to the hospital, with the suspicion of pneumonia, because of 3-day history of dyspnoe, cough and fever. Patient reported redness, swelling and pain in the area of left elbow. Prior to admission patient was diagnosed with bursitis and treated with antibiotic without symptoms resolution. There was past medical history of atrial fibrillation, hypertension, intermittent claudication, COPD. One month before, patient was hospitalized due to HF worsening. Diuretics' dosage was increased at that time and symptoms resolved. On admission: blood pressure 145/88 mm Hg, HR 96/min irregular, saturation O2 88% without oxygen therapy. On physical examination, bilateral pulmonary crackles, redness, tenderness of left elbow were found. Laboratory tests demonstrated elevated parameters of inflammation - leukocytosis 13.4G/L, neutrophilia 11G/L, CRP 142.5 mg/L, but normal procalcitonin 0.27 ng/ml. Moreover, high NTproBNP 8573 pg/ml and hyperuricemia 13.1 mg/dl were detected. Chest X-ray indicated pulmonary venous congestion. ECG revealed atrial fibrillation with QRS rate of 100/min, left axis deviation. Therefore, gout attack was diagnosed and after colchicine administration symptoms resolved quickly. CONCLUSIONS: Clinical signs including fever, elevated parameters of inflammation and dyspnoe justify pneumonia consideration in differential diagnosis. Importantly, non-infectious causes of inflammatory conditions, like gout must be also considered. Patients with HF often develop hyperuricemia due to diuretic treatment, aggravated catabolism and often co-prevalent chronic kidney disease.


Asunto(s)
Insuficiencia Cardíaca , Anciano de 80 o más Años , Enfermedad Crónica , Tos , Fiebre , Gota , Humanos
11.
14.
Cancers (Basel) ; 16(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38730636

RESUMEN

The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events with specific implications. We aimed to evaluate the accuracy of available risk models and identify additional risk factors for HG RFS and PFS among NMIBC patients treated with Bacillus Calmette-Guérin (BCG). We retrospectively included 171 patients who underwent transurethral resection of the bladder tumor (TURBT), of whom 73 patients (42.7%) experienced recurrence and 29 (17%) developed progression. Initially, there were 21 low-grade and 52 high-grade recurrences. EORTC2006, EORTC2016 and CUETO recurrence scoring systems lacked accuracy in the prediction of HG RFS (C-index 0.63/0.55/0.59, respectively). EAU2021 risk stratification, EORTC2006, EORTC2016, and CUETO progression scoring systems demonstrated low to moderate accuracy (C-index 0.59/0.68/0.65/0.65) in the prediction of PFS. In the multivariable analysis, T1HG at repeat TURBT (HR = 3.17 p < 0.01), tumor multiplicity (HR = 2.07 p < 0.05), previous history of HG NMIBC (HR = 2.37 p = 0.06) and EORTC2006 progression risk score (HR = 1.1 p < 0.01) were independent predictors for HG RFS. To conclude, available risk models lack accuracy in predicting HG RFS and PFS in -NMIBC patients treated with BCG.

15.
Urol Oncol ; 42(1): 22.e1-22.e11, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37981503

RESUMEN

PURPOSE: Although kidney-sparing surgery (KSS) is a nonminor option for low-risk upper urinary tract urothelial cancer (UTUC), its oncological benefits in high-risk UTUC remain unclear when compared to radical nephroureterectomy (RNU). This study aimed to compare the oncological outcomes of RNU and KSS in patients with UTUC. METHODS: We searched the SEER database for patients treated for primary non-metastatic UTUC with either RNU or a kidney-sparing approach (segmental ureterectomy (SU) or local tumor excision (LTE)) between 2004 and 2018. RESULTS: The study included 6,659 patients with primary non-metastatic UTUC treated with surgery; 2,888 (43.4%) and 3,771 (56.6%) patients presented with ureteral and renal pelvicalyceal tumors, respectively. Finally, 5,479 (82.3%) patients underwent RNU, 799 (12.0%) were treated with SU, and 381 (5.7%) patients received LTE. For confounder control, propensity score matching (PSM) of patients treated with SU and RNU was performed to adjust for T stage, grade, age, gender, tumor size, and lymphadenectomy performance. PSM analysis included 694 patients treated with RNU and 694 individuals who underwent SU. In multivariable Cox regression and Kaplan-Meier analyses, we found no difference in either CSS or OS between RNU and SU, even in the subgroup of high-grade and/or muscle-invasive UTUC including pT3-T4 tumors (all p > 0.05). CONCLUSION: In this population-based study, SU provides equivalent CSS and OS compared to RNU, even in high-risk and locally advanced ureteral cancer. Due to the unavoidable risk of selection bias, further prospective studies are expected to overcome the limitations of this study and support the wider implementation of KSS.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Renales , Uréter , Neoplasias Ureterales , Humanos , Nefroureterectomía/efectos adversos , Neoplasias Ureterales/patología , Estudios Prospectivos , Riñón/patología , Uréter/cirugía , Uréter/patología , Neoplasias Renales/patología , Carcinoma de Células Transicionales/patología , Estudios Retrospectivos
16.
Int Urol Nephrol ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38819576

RESUMEN

PURPOSE: Our study aimed to develop a noninvasive model using a combination of the set of clinical data and uroflowmetry (UFL) to differentiate between detrusor underactivity (DU) and bladder outlet obstruction (BOO) in non-neurogenic male patients with lower urinary tract symptoms (LUTS). METHODS: Data from 229 men with LUTS, diagnosed with DU or BOO on a pressure-flow study (PFS), were retrospectively analyzed, including medical history, Core Lower Urinary Tract Symptoms score (CLSS) questionnaire, UFL and PFS. Uni- and multivariate logistic regression were utilized for the prediction analyses. RESULTS: Of the cohort, 128 (55.9%) patients were diagnosed with DU. A multivariate logistic regression analysis identified less prevalent nocturia (OR 0.27, p < 0.002), more prevalent intermittency (OR 2.33, p = 0.03), less prevalent weak stream (OR 0.14, p = 0.0004), lower straining points in CLSS (OR 0.67, p = 0.02), higher slow stream points in CLSS (OR 1.81, p = 0.002), higher incomplete emptying points in CLSS (OR 1.31, p < 0.02), lower PVR ratio (OR 0.20, p = 0.03), and present features of fluctuating (OR 2.00, p = 0.05), fluctuating-intermittent (OR 3.09, p < 0.006), and intermittent (OR 8.11, p = 0.076) UFL curve shapes as independent predictors of DU. The above prediction model demonstrated satisfactory accuracy (c-index of 0.783). CONCLUSION: Our 10-factor model provides a noninvasive approach to differentiate DU from BOO in male patients with non-neurogenic LUTS, offering a valuable alternative to invasive PFS.

17.
Oncoimmunology ; 13(1): 2362454, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846084

RESUMEN

Rituximab (RTX) plus chemotherapy (R-CHOP) applied as a first-line therapy for lymphoma leads to a relapse in approximately 40% of the patients. Therefore, novel approaches to treat aggressive lymphomas are being intensively investigated. Several RTX-resistant (RR) cell lines have been established as surrogate models to study resistance to R-CHOP. Our study reveals that RR cells are characterized by a major downregulation of CD37, a molecule currently explored as a target for immunotherapy. Using CD20 knockout (KO) cell lines, we demonstrate that CD20 and CD37 form a complex, and hypothesize that the presence of CD20 stabilizes CD37 in the cell membrane. Consequently, we observe a diminished cytotoxicity of anti-CD37 monoclonal antibody (mAb) in complement-dependent cytotoxicity in both RR and CD20 KO cells that can be partially restored upon lysosome inhibition. On the other hand, the internalization rate of anti-CD37 mAb in CD20 KO cells is increased when compared to controls, suggesting unhampered efficacy of antibody drug conjugates (ADCs). Importantly, even a major downregulation in CD37 levels does not hamper the efficacy of CD37-directed chimeric antigen receptor (CAR) T cells. In summary, we present here a novel mechanism of CD37 regulation with further implications for the use of anti-CD37 immunotherapies.


Asunto(s)
Antígenos CD20 , Inmunoterapia , Linfoma de Células B , Rituximab , Tetraspaninas , Humanos , Antígenos CD20/inmunología , Antígenos CD20/metabolismo , Antígenos CD20/genética , Rituximab/farmacología , Rituximab/uso terapéutico , Tetraspaninas/genética , Tetraspaninas/metabolismo , Línea Celular Tumoral , Linfoma de Células B/inmunología , Linfoma de Células B/terapia , Linfoma de Células B/genética , Linfoma de Células B/tratamiento farmacológico , Inmunoterapia/métodos , Antígenos de Neoplasias/inmunología , Antígenos de Neoplasias/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Ciclofosfamida/farmacología , Ciclofosfamida/uso terapéutico , Vincristina/farmacología , Vincristina/uso terapéutico , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/metabolismo , Regulación Neoplásica de la Expresión Génica
18.
Eur Urol Oncol ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38902138

RESUMEN

BACKGROUND AND OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence. METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible. KEY FINDINGS AND LIMITATIONS: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84% (95% confidence interval [CI] 79-89%), 75% (95% CI 68-82%), and 51% (95% CI 40-63%) for patients treated with MMC induction plus maintenance, and 88% (95% CI 83-94%), 78% (95% CI 67-89%), and 66% (95% CI 57-75%) for patients treated with bacillus Calmette-Guérin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76% (95% CI 69-84%) for 40 mg MMC (2 studies) and 66% (95% CI 60-72%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78% vs 76%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr). CONCLUSIONS AND CLINICAL IMPLICATIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens. PATIENT SUMMARY: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Guérin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.

19.
J Cancer Res Clin Oncol ; 149(6): 2673-2691, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36404390

RESUMEN

OBJECTIVES: Although smoking is a well-recognized causative factor of urothelial bladder cancer and accounts for 50% of cases, less is known about the prognostic significance of smoking on non-muscle invasive bladder cancer (NMIBC) prognosis. This systematic review and meta-analysis aimed to evaluate the effect of smoking on the risk of NMIBC recurrence and progression. MATERIALS AND METHODS: We systematically searched Medline, Web of Science and Scopus databases for original articles published before October 2021 regarding the effect of smoking on NMIBC recurrence and progression. Information about smoking status and the number of events or odds ratio or hazard ratio for event-free survival must have been reported to include the study in the analysis. Quality In Prognosis Studies tool was utilized for the risk of bias assessment. RESULTS: We selected 64 eligible studies, including 28 617 patients with NMIBC with available data on smoking status. In a meta-analysis of 28 studies with 7885 patients, we found that smokers (current/former) were at higher risk for recurrence (OR = 1.68; 95% CI 1.34-2.09; P < 0.0001) compared to never smokers. Subgroup analysis of 2967 patients revealed that current smokers were at a 1.24 higher risk of recurrence (OR = 1.24; 95% CI 1.02-1.50; P = 0.03) compared to former smokers. A meta-analysis of the hazard ratio revealed that smokers are at higher risk of recurrence (HR = 1.31; 95%CI 1.15-1.48; P < 0.0001) and progression (HR = 1.18; 95%CI 1.08-1.29; P < 0.001) compared to never smokers. Detrimental prognostic effect of smoking on progression, but not for recurrence risk was also noted in the subgroup analysis of high-risk patients (HR = 1.30; 95%CI 1.09-1.55; P = 0.004) and BCG-treated ones (HR = 1.15; 95%CI 1.06-1.25; P < 0.001). CONCLUSION: In conclusion, patients with non-muscle invasive bladder cancer and a history of smoking have a worse prognosis regarding recurrence-free and progression-free survival compared to non-smokers.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias Vesicales sin Invasión Muscular , Supervivencia sin Progresión , Fumar , Fumar/efectos adversos , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Neoplasias Vesicales sin Invasión Muscular/mortalidad , Neoplasias Vesicales sin Invasión Muscular/patología , Humanos
20.
Int Urol Nephrol ; 55(9): 2205-2213, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37280316

RESUMEN

PURPOSE: To identify the risk factors for 5-year cancer-specific (CSS) and overall survival (OS) and to compare the accuracy of logistic regression (LR) and artificial neural network (ANN) in the prediction of survival outcomes in T1 non-muscle-invasive bladder cancer. METHODS: This is a population-based analysis using the Surveillance, Epidemiology, and End Results database. Patients with T1 bladder cancer (BC) who underwent transurethral resection of the tumour (TURBT) between 2004 and 2015 were included in the analysis. The predictive abilities of LR and ANN were compared. RESULTS: Overall 32,060 patients with T1 BC were randomly assigned to training and validation cohorts in the proportion of 70:30. There were 5691 (17.75%) cancer-specific deaths and 18,485 (57.7%) all-cause deaths within a median of 116 months of follow-up (IQR 80-153). Multivariable analysis with LR revealed that age, race, tumour grade, histology variant, the primary character, location and size of the tumour, marital status, and annual income constitute independent risk factors for CSS. In the validation cohort, LR and ANN yielded 79.5% and 79.4% accuracy in 5-year CSS prediction respectively. The area under the ROC curve for CSS predictions reached 73.4% and 72.5% for LR and ANN respectively. CONCLUSIONS: Available risk factors might be useful to estimate the risk of CSS and OS and thus facilitate optimal treatment choice. The accuracy of survival prediction is still moderate. T1 BC with adverse features requires more aggressive treatment after initial TURBT.


Asunto(s)
Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Modelos Logísticos , Neoplasias de la Vejiga Urinaria/patología , Cistectomía/métodos , Redes Neurales de la Computación
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