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PURPOSE: To assess prognostic significance of residual tumor at repeat transurethral resection (reTUR) in contemporary non-muscle-invasive bladder cancer (NMIBC) patients. METHODS: Patients were identified retrospectively from eight referral centers in France, Italy and Spain. The cohort included consecutive patients with high or very-high risk NMIBC who underwent reTUR and subsequent adjuvant BCG therapy. RESULTS: A total of 440 high-risk NMIBC patients were screened, 29 (6%) were upstaged ≥ T2 at reTUR and 411 were analyzed (T1 stage: n = 275, 67%). Residual tumor was found in 191 cases (46%). In patients with T1 tumor on initial TURBT, persistent T1 tumor was found in 18% of reTUR (n = 49/275). In patients with high-grade Ta tumor on initial TURBT, T1 tumor was found in 6% of reTUR (n = 9/136). In multivariable logistic regression analysis, we found no statistical association between the use of photodynamic diagnosis (PDD, p = 0.4) or type of resection (conventional vs. en bloc, p = 0.6) and the risk of residual tumor. The estimated 5-yr recurrence and progression-free survival were 56% and 94%, respectively. Residual tumor was significantly associated with a higher risk of recurrence (p < 0.001) but not progression (p = 0.11). Only residual T1 tumor was associated with a higher risk of progression (p < 0.001) with an estimated 5-yr progression-free survival rate of 76%. CONCLUSIONS: ReTUR should remain a standard for T1 tumors, irrespective of the use of en bloc resection or PDD and could be safely omitted in high-grade Ta tumors. Persistent T1 tumor at reTUR should not exclude these patients from conservative management, and further studies are needed to explore the benefit of a third resection in this subgroup.
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Cistectomía , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasia Residual , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Masculino , Estudios Retrospectivos , Femenino , Anciano , Pronóstico , Cistectomía/métodos , Persona de Mediana Edad , Uretra , Medición de Riesgo , Neoplasias Vesicales sin Invasión MuscularRESUMEN
BACKGROUND: Historical external beam radiation therapy (EBRT) for rectosigmoid cancer (RCa) predisposed patients to an increased risk of secondary bladder cancer (BCa). However, no contemporary radiotherapy studies are available. We addressed this knowledge gap. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2000-2020), we identified non-metastatic RCa patients who either underwent radiotherapy (EBRT+) or did not (EBRT-). Cumulative incidence plots and multivariable competing risk regression models (CRR) were fitted to address rates of BCa after RCa. In the subgroup of BCa patients, the same methodology addressed BCa-specific mortality (BCSM) according to EBRT exposure status. RESULTS: Of the 188,658 non-metastatic RCa patients, 54,562 (29%) were EBRT+ vs. 134,096 (73%) who were EBRT-. In the cumulative incidence plots, the ten-year BCa rates were 0.7% in EBRT+ vs. 0.7% in EBRT- patients (p = 0.8). In the CRR, EBRT+ status was unrelated to BCa rates (multivariable HR: 1.1, p = 0.8). In the subgroup of 1416 patients with BCa after RCa, 443 (31%) were EBRT+ vs. 973 (69%) who were EBRT-. In the cumulative incidence plots, the ten-year BCSM rates were 10.6% in EBRT+ vs. 12.1% in EBRT- patients (p = 0.7). In the CRR, EBRT+ status was unrelated to subsequent BCSM rates (multivariable HR: 0.9, p = 0.9). CONCLUSION: Although historical EBRT for RCa predisposed patients to higher BCa rates, contemporary EBRT for RCa is not associated with increased subsequent BCa risk. Moreover, in patients with BCa after RCa, exposure to EBRT does not affect BCSM.
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INTRODUCTION: Administration of chemotherapy before radical cystectomy (RC) in neoadjuvant setting (NAC) or after RC in adjuvant setting (ADJ) are both associated with a survival benefit relative to RC alone. However, no study directly compared the magnitude of such benefit associated with NAC versus ADJ in locally-advanced UCUB patients (T3-T4N0M0). We addressed this knowledge gap. METHODS: Within the Surveillance, Epidemiology, and End Results database (2007-2020), we identified T3-T4N0M0 UCUB patients who underwent NAC+RC or RC+ADJ. Cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. The same methodology was then re-applied in T3 and then T4 patient subgroups. RESULTS: Of 875 assessable patients, 603 harbored T3 stage (69.0%) and 272 harbored T4 stage (31.0%). Of all 875, 563 (64.0%) underwent RC+ADJ versus 312 (36.0%) NAC+RC. NAC+RC rates increased over time (EAPC=+6.1%, P = .001). Cumulative incidence plots derived five-year CSM rates were 40.3% in NAC+RC versus 36.1% in RC+ADJ patients (P = .2). In multivariable CRR models that also adjusted for OCM, no statistically significant difference in CSM was recorded when NAC+RC was compared to RC+ADJ (HR:0.85, P = .1). Virtually the same observations were made in subgroup analyses where CSM associated with NAC+RC was not different from that recorded in RC+ADJ (HR: 0.89 and P = .4 in T3 stage and HR:0.8 and P = .2 in T4 stage). CONCLUSION: In locally-advanced UCUB, NAC rates have sharply increased over time. However, the approach based on neoadjuvant chemotherapy prior to RC have not resulted in a statistically significant CSM benefit relative to RC+ADJ.
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BACKGROUND: Induction followed by 1 year maintenance instillation of intravesical Bacillus Calmette-Guerin (BCG) is the standard treatment for intermediate-risk (IR) nonmuscle invasive bladder cancer (NMIBC) patients. Few data exist on the efficacy of Mitomycin C (MMC) instillation in this setting. METHODS: We retrospectively analyzed 226 IR-NMIBC patients classified by the International Bladder Cancer Group (IBCG) and 250 IR-NMIBC intravescical treatment-naïve patients classified by the European Association of Urology (EAU). All patients received either a full induction course of BCG or 40 mg/40 ml MMC from 2012 to 2022. Optimal treatment was defined as 1-year maintenance for BCG and 11 monthly maintenance instillations for MMC. Kaplan-Meier analysis estimated recurrence-free survival (RFS) before and after inverse probability of treatment-weighting (IPTW) and progression-free survival (PFS). Multivariable Cox regression was used to evaluate difference in recurrence after adjustment for clinically relevant variables before and after IPTW. RESULTS: Optimal BCG and MMC courses were administered to 21% of IR-IBCG and 23% of IR-EAU patients. At 4-years, patients treated with optimal MMC and BCG treatment had similar RFS and PFS in both EAU and IBCG groups. Patients receiving nonoptimal BCG compared to optimal MMC exhibited lower 4-year RFS after IPTW (82% vs. 68% in EAU and 82% vs. 65% in IBCG). At 4-year optimal MMC had greater PFS non optimal BCG. Optimal MMC treatment predicted recurrence in EAU (adjusted and weighted HR 0.33, 95% CI, 0.11-0.98) and IBCG (adjusted and weighted HR 0.29, 95% CI, 0.08-0.97) groups compared to nonoptimal BCG. CONCLUSIONS: Optimal 40 mg/40 ml MMC treatment was as effective as optimal BCG in IR-IBCG and IR-EAU NMIBC patients, reducing both recurrence and progression compared to nonoptimal BCG. MMC could be a valid first line alternative to BCG for both IR-EAU and IR-IBCG intravescical treatment-naïve patients, during BCG shortages.
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OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.
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BACKGROUND: To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFRâ <â 60 mL/minute per 1.73 m2. RESULTS: Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (Pâ =â .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (nâ =â 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCIâ ≥â 60 mL/minute. CONCLUSIONS: Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute.
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INTRODUCTION: Consensus for Enhanced Recovery After Surgery (ERAS) in pediatrics has been achieved in neonatal intestinal surgery, yet it is not widely utilized in pediatric urology. We investigated the application of ERAS guidelines in pediatric urology, and determined its effects given the available level of evidence supporting the ERAS protocol in children. EVIDENCE ACQUISITION: A systematic literature review including series providing adoption of fast-track recovery protocols for pediatric urology procedures was carried out. Main outcome measures were study characteristics, adherence to the 19 ERAS items, complication rates and length of hospital stay. Sub-group analysis by surgery type (hypospadias versus major surgery) was performed. EVIDENCE SYNTHESIS: Nine series with data from 1272 surgical pediatric cases were included. An enhanced recovery pathway was applied in 67.3% of the reports. Two series included patients undergoing hypospadias repair and ERAS items were insufficiently reported. Studies including children undergoing major procedures mentioned a median of 15 ERAS items, yet applied a median of 11 items. Median compliance rate was 88.9% (range 50-100). More ERAS guideline items were reported (applied or mentioned) in the most recently published studies. CONCLUSIONS: There is limited reporting and use of the ERAS guidelines in urologic surgery particularly in hypospadias repair; whilst in major surgery in children, adherence and compliance rates vary widely. In more recent series there was an increase in ERAS items that have been mentioned and applied. Future research is needed to identify barriers and to overcome them in order to fully adopt and benefit from the ERAS pathway.
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Recuperación Mejorada Después de la Cirugía , Adhesión a Directriz , Guías de Práctica Clínica como Asunto , Procedimientos Quirúrgicos Urológicos , Humanos , Procedimientos Quirúrgicos Urológicos/efectos adversos , Procedimientos Quirúrgicos Urológicos/normas , Niño , Adhesión a Directriz/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricosRESUMEN
BACKGROUND: The relationship between venous thromboembolism (VTE) and solid malignancy has been established over the decades. With rising projected rates of bladder cancer (BCa) worldwide as well as increasing number of patients experiencing BCa and VTE, our aim is to assess the impact of a preoperative VTE diagnosis on perioperative outcomes and health-care costs in BCa cases undergoing radical cystectomy (RC). METHODS: Patients ≥18 years of age with BCa diagnosis and undergoing open or minimally invasive (MIS) RC were identified in the Merative™ Marketscan® Research Databases between 2007 and 2021. The association of previous VTE history with 90-day complication rates, postoperative VTE events, rehospitalization, and total hospital costs (2021 USA dollars) was determined by multivariable logistic regression modeling adjusted for patient and perioperative confounders. Sensitivity analysis on VTE degree of severity (i.e., pulmonary embolism [PE] and/or peripheral deep venous thrombosis [DVT]) was also examined. RESULTS: Out of 8759 RC procedures, 743 (8.48%) had a previous positive history for any VTE including 245 (32.97%) PE, 339 (45.63%) DVT and 159 (21.40%) superficial VTE. Overall, history of VTE before RC was strongly associated with almost any worse postoperative outcomes including higher risk for any and apparatus-specific 90-days postoperative complications (odds ratio [OR]: 1.21, 95% CI, 1.02-1.44). Subsequent incidence of new VTE events (OR: 7.02, 95% CI: 5.93-8.31), rehospitalization (OR: 1.25, 95% CI: 1.06-1.48), other than home/self-care discharge status (OR: 1.53, 95% CI: 1.28-1.82), and higher health-care costs related to the RC procedure (OR: 1.43, 95% CI: 1.22-1.68) were significantly associated with a history of VTE. CONCLUSIONS: Preoperative VTE in patients undergoing RC significantly increases morbidity, post-procedure VTE events, hospital length of stay, rehospitalizations, and increased hospital costs. These findings may help during the BCa counseling on risks of surgery and hopefully improve our ability to mitigate such risks.
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Cistectomía , Complicaciones Posoperatorias , Neoplasias de la Vejiga Urinaria , Tromboembolia Venosa , Humanos , Cistectomía/efectos adversos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/economía , Tromboembolia Venosa/etiología , Masculino , Femenino , Estados Unidos/epidemiología , Anciano , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/etiología , Neoplasias de la Vejiga Urinaria/cirugía , Costos de la Atención en Salud/estadística & datos numéricos , Procedimientos Quirúrgicos Mínimamente Invasivos/economía , Readmisión del Paciente/estadística & datos numéricos , Readmisión del Paciente/economía , Estudios Retrospectivos , Periodo PreoperatorioRESUMEN
BACKGROUND: Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. METHODS: The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). RESULTS: The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. CONCLUSIONS: Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified.
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Sistema de Registros , Neoplasias Ureterales , Humanos , Factores de Riesgo , Femenino , Masculino , Incidencia , Persona de Mediana Edad , Anciano , Neoplasias Ureterales/epidemiología , Adulto , Salud Global , Adulto Joven , Adolescente , Anciano de 80 o más Años , Carga Global de Enfermedades/tendenciasRESUMEN
BACKGROUND AND OBJECTIVE: Pathological features in non-muscle-invasive bladder cancer specimens are pivotal in determining correct patients' therapeutic management. Sparse data exist regarding the importance of second opinion performed by an expert uropathologist. This study aimed to assess the importance of a second opinion by an expert uropathologist in the management of bladder cancer. METHODS: The study relied on 272 bladder cancer specimens from 231 patients seeking a pathology second opinion after transurethral resection of the bladder for a clinical suspicion of bladder cancer, relapse, or second-look procedure. Pathology second opinion was offered by an experienced fellowship-trained uropathologist. Discrepancies were recorded considering primary tumor staging, the presence of muscularis propria, and the presence of histological variants. Cases were categorized as no significant discordance, major discordance without management change, and major discordance with management change according to the European Urology Association (EAU) guidelines. KEY FINDINGS AND LIMITATIONS: Among 272 second opinion cases, 39% (108/272) had major discordance and 28% (75/272) had major discordance with change in management according to the EAU guidelines. Upstaging and downstaging were reported in 66 (24%) patients. Improper identification of the presence of muscularis propria was found in 46 (17%) cases, of which 11 (4%) were deemed clinically relevant. Differences regarding the presence of histological variants were diagnosed in 40 cases (15%), resulting in eight (3%) changes in clinical management. In ten specimens (4%), multiple clinically relevant discrepancies were found. CONCLUSIONS AND CLINICAL IMPLICATIONS: The second opinion evaluation changed the clinical management in 25% of the cases. These results support the importance of specimen review by an expert uropathologist as a major driver in the correct bladder cancer management. PATIENT SUMMARY: We investigated the importance of a second opinion performed by an expert uropathologist in the management of bladder cancer. We found that 25% had their treatment plan changed due to the revised pathological report.
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Background: Photodynamic diagnosis (PDD) during transurethral resection of bladder tumor (TURBT) is guideline recommended, as it improves bladder cancer detection rates. However, the extent to which PDD is implemented in everyday clinical practice has not been thoroughly assessed. We aimed to evaluate the current trends and major perioperative outcomes of TURBT with PDD. Methods: The present study evaluated the GeRmAn Nationwide inpatient Data (GRAND) from 2010 (the year when PDD started to be coded separately in Germany) to 2021, which were made available from the Research Data Center of the German Bureau of Statistics. We undertook numerous patient-level and multivariable logistic regression analyses. Results: Overall, 972,208 TURBTs [228,207 (23%) with PDD and 744,001 (77%) with white light] were performed. Patients offered PDD during TURBT were younger (p < 0.001), presented fewer comorbidities (p < 0.001) and were discharged earlier from hospital (p < 0.001). PDD was associated with additional costs of about EUR 500 compared to white-light TURBT (p < 0.001). The yearly TURBT cases remained relatively stable from 2010 to 2021, whereas utilization of PDD underwent a 2-fold increase. After adjusting for major risk factors in the multivariate regression analysis, PDD was related to lower rates of transfusion (1.4% vs. 5.6%, OR: 0.29, 95% CI: 0.28 to 0.31, p < 0.001), intensive care unit admission (0.7% vs. 1.4%, OR: 0.56, 95% CI: 0.53 to 0.59, p < 0.001) and 30-day in-hospital mortality (0.1% vs. 0.7%, OR: 0.24, 95% CI: 0.22 to 0.27, p < 0.001) compared to white-light TURBT. On the contrary, PDD was related to clinically insignificant higher rates of bladder perforation (0.6% versus 0.5%, OR: 1.3, 95% CI: 1.2 to 1.4, p < 0.001), and reoperation (2.6% versus 2.3%, OR: 1.2, 95% CI: 1.1 to 1.2, p < 0.001). Conclusions: The utilization of PDD with TURBT is steadily increasing. Nevertheless, the road toward the establishment of PDD as the standard of care for TURBT is still long, despite of the advantages of PDD.
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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.
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BACKGROUND AND OBJECTIVE: Intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) encompasses a broad spectrum of disease, with heterogeneous outcomes in terms of disease recurrence and progression. The International Bladder Cancer Group (IBCG) recently proposed an updated scoring model for IR substratification that is based on five key risk factors. Our aim was to provide a clinical validation of the IBCG scoring system and substratification model for IR NMIBC. METHODS: This was an international multicenter retrospective study. Patients diagnosed with IR NMIBC between 2012 and 2022 and treated with transurethral resection of the bladder and adjuvant intravesical chemotherapy were included. According to the presence or absence of risk factors, patients with IR NMIBC were further categorized in IR-low (no risk factors), IR-intermediate (1-2 risk factors), and IR-high (≥3 risk factors) groups. The 1-yr and 3-yr rates for recurrence-free survival (RFS) and progression-free survival (PFS) were evaluated for each subgroup. Cox regression analyses were used to compare oncological outcomes between the groups. KEY FINDINGS AND LIMITATIONS: Of the 677 patients with IR NMIBC included in the study, 231 (34%), 364 (54%), and 82 (12%) were categorized in the IR-low, IR-intermediate, and IR-high groups, respectively. There were significant differences in RFS and PFS rates between these groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: We provide the first clinical validation of the IBCG scoring system and model for substratification of IR NMIBC. PATIENT SUMMARY: Our study demonstrates that patients with intermediate-risk non-muscle-invasive bladder cancer can be correctly classified into three distinct subgroups according to their risk of both disease recurrence and progression. Our results support use of this scoring system in clinical practice.
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Background: Non-muscle invasive bladder cancer (NMIBC) patients are affected by a high risk of recurrence. The topography of collagen fibers represents a hallmark of the neoplastic extracellular microenvironment. Objective: Assess the topographic change associated with different stages of bladder cancer (from neoplastic lesions to bona fide tumor) and whether those changes favour the development of NMIBC. Design Setting and Participants: Seventy-one clinical samples of urothelial carcinoma at different stages were used. Topographic changes preceding tumor onset and progression were evaluated in the rat bladder cancer model induced by nitrosamine (BBN), a bladder-specific carcinogen. The preclinical model of actinic cystitis was also used in combination with BBN. Validated hematoxylin-eosin sections were used to assess the topography of collagen fibrils associated with pre-tumoral steps, NMIBC, and MIBC. Findings: Linearization of collagen fibers was higher in Cis and Ta vs. dysplastic urothelium, further increased in T1 and greatest in T2 tumors. In the BBN preclinical model, an increase in the linearization of collagen fibers was established since the beginning of inflammation, such as the onset of atypia of a non-univocal nature and dysplasia, and further increased in the presence of the tumor. Linearization of collagen fibers in the model of actinic cystitis was associated with earlier onset of BBN-induced tumor. Conclusions: The topographic modification of the extracellular microenvironment occurs during the inflammatory processes preceding and favoring the onset of bladder cancer. The topographic reconfiguration of the stroma could represent a marker for identifying and treating the non-neoplastic tissue susceptible to tumor recurrence.
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INTRODUCTION: Trimodal therapy (TMT) is guideline-recommended for the management of organ confined urothelial carcinoma of urinary bladder (UCUB). However, temporal trends in TMT use and cancer-specific mortality free-survival (CSM-FS) between historical TMT versus contemporary TMT have not been assessed. We addressed this knowledge gap. MATERIAL AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified nonmetastatic UCUB patients with cT2-T4aN0-N2 treated with TMT, defined as the combination of transurethral resection of bladder tumor, chemotherapy and radiotherapy. Temporal trends described TMT use over time. Subsequently, patients were divided between historical (2004-2012) versus contemporary (2013-2020) cohorts. Survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM-FS. Separate analyses addressed patients with organ confined (OC: cT2N0M0) versus nonorgan confined (NOC: cT3-4a and/or cN1-2) clinical stages. RESULTS: Of 4,097 assessable UCUB TMT patients, 1744 (43%) were treated in the historical period (2004-2012) versus 2353 (58%) in the contemporary period (2013-2020). TMT use increased over time in OC patients (EAPC:+3.4%, P < .001), as well as in NOC (EAPC:+2.7%, P < .001). In OC stage, median CSM-FS was 55.3% in historical versus 49.0% in contemporary patients (HR:0.75, P < .001). Similarly, in NOC stage, 5-year median CSM-FS was 43.0% in historical versus 32.8% in contemporary patients (HR:0.78, P = .01). CONCLUSION: TMT rates have increased over time in both OC and NOC patients. Contemporary TMT patients benefit of better cancer-specific survival. Interestingly, this benefit applies equally to OC and NOC TMT-treated patients.
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Carcinoma de Células Transicionales , Programa de VERF , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/patología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/terapia , Carcinoma de Células Transicionales/patología , Estadificación de Neoplasias , Terapia Combinada , Cistectomía , Anciano de 80 o más Años , Estudios Retrospectivos , Invasividad Neoplásica , Estimación de Kaplan-MeierRESUMEN
Background: Follow-up after radical cystectomy (RC) for bladder cancer can be divided into oncological and functional surveillance. It remains unclear how follow-up after RC should ideally be scheduled. The aim of this report was to gain insight into the organization of follow-up after RC in Europe, for which we conducted a roundtable inventory within the EAU Young Academic Urologists Urothelial Cancer working group. Methods: An inventory semi-structured survey was performed among urologists of the EAU Young Academic Urologists Urothelial Cancer working group to describe the organization of follow-up. The surveys were analyzed using a deductive approach. Similarities and differences in follow-up after RC for bladder cancer were described. Results: The survey included 11 urologists from six different European countries. An institutional follow-up scheme was used by six (55%); three (27%) used a national or international guideline, and two (18%) indicated that there was no defined follow-up scheme. Major divergent aspects included the time points of follow-up, the frequency, and the end of follow-up. Six centers (55%) adopted a risk-adapted follow-up approach tailored to (varying) patient and tumor characteristics. Laboratory tests and CT scans were used in all cases; however, the intensity and frequency varied. Functional follow-up overlapped with oncological follow-up in terms of frequency and duration. Patient-reported outcome measures were only used by two (18%) urologists. Conclusions: Substantial variability exists across European centers regarding the follow-up after RC for bladder cancer. This highlights the need for an international analysis focusing on its organization and content as well as on opportunities to improve patients' needs during follow-up after RC.
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BACKGROUND: The application of precision medicine in clinical practice implies a thorough evaluation of actionable genomic alterations to streamline therapeutic decision making. Comprehensive genomic profiling of tumor via next-generation sequencing (NGS) represents a great opportunity but also several challenges. During the 2023 San Raffaele Retreat, we aimed to provide expert recommendations for the optimal use of NGS in urothelial carcinoma (UC). MATERIALS AND METHODS: A modified Delphi method was utilized, involving a panel of 12 experts in UC from European and United States centers, including oncologists, urologists, pathologists, and translational scientists. An initial survey, conducted before the meeting, delivered 15 statements to the panel. A consensus was defined when ≥70% agreement was reached for each statement. Statements not meeting the consensus threshold were discussed during the meeting. RESULTS: Nine of the 15 statements covering patient selection, cancer characteristics, and type of NGS assay, achieved a consensus during the survey. The remaining six statements addressing the optimal timing of NGS use, the ideal source of tumor biospecimen for NGS testing, and the subsequent need to evaluate the germline nature of certain genomic findings were discussed during the meeting, leading to unanimous agreement at the end of the conference. CONCLUSION: This consensus-building effort addressed multiple unanswered questions regarding the use of NGS in UC. The opinion of experts was in favor of broader use of NGS. In a setting where recommendations/guidelines may be limited, these insights may aid clinicians to provide informed counselling and raise the bar of precision and personalized therapy.
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Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/normas , Técnica Delphi , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/terapia , Medicina de Precisión/métodos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias Urológicas/genética , Neoplasias Urológicas/terapia , ConsensoRESUMEN
OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.