Increased risk of bladder cancer recurrence due to bacillus Calmette-Guérin shortage in Brazil

SUMMARY OBJECTIVE: Our study aimed to evaluate the impact of bacillus Calmette-Guérin shortage on recurrence and progression in patients with non-muscle invasive bladder cancer in a Brazilian cohort. METHODS: We retrospectively reviewed the clinicopathological data of 409 patients who had their first transurethral resection of the bladder tumor for intermediate or high-risk non-muscle invasive bladder cancer between June 2014 and May 2021 in a tertiary public hospital in Brazil. Patients included had non-muscle-invasive urothelial carcinoma of the bladder resected completely for the first time, regardless of bacillus Calmette-Guérin use. Low-risk disease patients were excluded from the analysis. Demographic, clinicopathological, and bacillus Calmette-Guérin use data were collected from our database. Recurrence and progression data were obtained from patient records or through telephone interviews. Recurrence-free survival and progression-free survival were calculated from the date of transurethral resection of the bladder tumor until the events of recurrence, progression, last office visit, or phone interview. RESULTS: Within a median follow-up period of 26.7 months, 168 (41.1%) patients experienced a recurrence in a median time of 27 months (95%CI 16.1-38). Bacillus Calmette-Guérin was administered to 57 (13.9%) individuals after transurethral resection of the bladder tumor. Patients with ≥3 lesions (p<0.001), those with lesions >3 cm (p=0.02), and those without bacillus Calmette-Guérin treatment (p<0.001) had shorter recurrence-free survival. According to a Cox multivariate regression model, bacillus Calmette-Guérin use was independently associated with a reduced recurrence rate, with an HR of 0.43 (95%CI 0.25-0.72). Out of the patients studied, 26 (6.4%) experienced progression. T1 stage (p<0.001) and high-grade (p<0.001) were associated with shorter progression-free survival. Bacillus Calmette-Guérin did not influence bladder cancer progression. In the Cox multivariate analysis, high-risk disease was independently associated with progression (p<0.001). CONCLUSION: Our study confirms that non-muscle invasive bladder cancer exhibits a high recurrence rate. The use of adjuvant bacillus Calmette-Guérin in intermediate and high-risk patients significantly reduces this rate. Furthermore, the bacillus Calmette-Guérin shortage could have negatively impacted these patients.

Construction of a competing risk model for disease-free survival of patients with non-muscle invasive bladder cancer / 现代泌尿外科杂志

【Objective】 To construct an easy-to-use individual survival prognostic tool based on competing risk analyses to predict the risk of 1-, 2- and 3- year recurrence for patients with non-muscle invasive bladder cancer (NMIBC). 【Methods】 The follow-up data of 419 NMIBC patients were obtained. The patients were randomly divided into training cohort (n=293) and validation cohort (n=126). The variables included age at diagnosis, sex, history of smoking, tumor number, tumor size, histolo-gic grade, pathological stage, and bladder perfusion drug. The cumulative incidence function (CIF) of recurrence was estimated using all variables in the training cohort and potential prognostic variables were determined with Gray’s test. The Fine-Gray subdistribution proportional hazard approach was used as a multivariate competitive risk analysis to identify independent pro-gnostic variables. A competing risk nomogram was developed to predict the recurrence. The performance of the competing risk model was evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and Brier score. 【Results】 Five independent prognostic factors including age, number of tumors, tumor size, histologic grade and pathological stage were used to construct the competing risk model. In the validation cohort, the AUC of 1-, 2- and 3- year recurrence were 0.895 (95%CI: 0.831-0.959), 0.861(95%CI: 0.774-0.948) and 0.827(95%CI: 0.721-0.934), respectively, indicating that the model had a high predictive performance. 【Conclusion】 We successfully constructed a competing risk model to predict the risk of 1-, 2- and 3-year recurrence for NMIBC patients. It may help clinicians to improve the postoperative management of patients.

Predictors for muscle invasion of upper tract urothelial carcinoma / 中华泌尿外科杂志

Objective:To explore the predictors of upper tract urothelial carcinoma (UTUC) invading muscle.Methods:The preoperative clinical data of 169 patients with UTUC who underwent radical nephroureterectomy (RNU) in the Department of Urology, Second Hospital of Tianjin Medical University from August 2019 to September 2021 were retrospectively collected. The average age of the patients was (67.7±8.3)years. There were 95 male cases (56.2%).15 cases (15.8%) were with diabetes, 46 cases (48.4%) with hypertension, 68 cases (71.6%) with hematuria, 44 cases (46.3%) with renal pelvis tumor, 74 cases (77.9%) with hydronephrosis and 8 cases (8.4%) with multifocality. There were 15 (20.3%), with diabetes, 40(54.1%) with hypertension, 58(78.4%)with hematuria, 32(43.2%) with renal pelvis tumor, 60(81.1%) with hydronephrosis and 2(2.7%) with multifocality among 74 female patients(43.8%), respectively. Patients’ body mass index (BMI) was (24.2±3.2) kg/m 2.The tumor diameter was (3.4±1.8) cm. The average count of neutrophil (NEU) was (4.2±1.7) ×10 9/L, with monocyte (MON) (0.4±0.2) ×10 9/L, platelet (PLT) (237.8±75.3) ×10 9/L and lymphocyte (LYM) (1.7±0.5) ×10 9/L. Neutrophil-to-lymphocyte ratio (NLR) was 2.7±1.4. Mmonocyte-to-lymphocyte ratio (MLR) was 0.3±0.1 and platelet-to-lymphocyte ratio (PLR) was 151.1±59.6. The concentrations of hemoglobin (Hb) and fibrinogen (FIB) were (127.1±18.3) g/L and(3.5±1.0) g/L. Univariate logistic regression analysis was performed on all preoperative data, and a nomogram was established to predict UTUC invading muscle by stepwise regression combined with multivariate logistic analysis. Concordance index (C-index) was used to evaluate the accuracy of the model, and Hosmer-Lemeshow test was used to check the fit. Using 1000 bootstrap resampling to validate the model and draw calibration plot. Receiver operating characteristics (ROC) curves were used to determine the most appropriate cut-off point of the model to predict tumor invasion and evaluate its sensitivity and specificity. Results:In this study, there were 169 cases. Postoperative pathological results showed that 18 cases (10.6%) were of low grade and 151 cases (89.4%) were of high grade. There were 2 patients (1.2%) with pT a stage, 44 patients (26.0%) with pT 1 stage, 37 patients (21.9%) with pT 2 stage, 81 patients (47.9%) with pT 3 stage and 5 patients (3.0%) with pT 4 stage. According to tumor stage, 46 patients were included into non-muscle invasive disease (NMID, pT a/T is/T 1) group and 123 patients were included into muscle invasive disease (MID, pT 2/T 3/T 4) group. Univariate analysis showed that hydronephrosis ( OR=2.919, 95% CI 1.332-6.387, P=0.007) was significantly correlated with MID. Tumor location in ureter ( OR=1.898, 95% CI 0.960-3.800, P=0.067), higher NLR value ( OR=1.313, 95% CI 0.9901.832, P=0.082) and FIB concentration ( OR=1.436, 95% CI 1.008-2.125, P=0.056) might have potential association with MID. Stepwise regression method was used to screen out PLT, FIB and hydronefrosis as the optimal combination for MID prediction. multivariate analysis suggested that PLT decreasing ( OR=0.727, 95% CI 0.548-0.955, P=0.023), FIB increasing ( OR=1.629, 95% CI 1.084-2.552, P=0.025) and hydronephrosis ( OR=2.500, 95% CI 1.111-5.601, P=0.026) were independent predictors of MID.The C-index of the model constructed by the three factors was 0.682, and the P-value of the goodness of fit was 0.778. The ROC curve showed that the optimal cut-off point for the prediction of high-risk MID by the nomogram was 0.627, achieving 39.1% specificity, 88.6% sensitivity and 0.682 area under the curve (AUC). Conclusions:Preoperative decrease of PLT, increase of FIB and hydronephrosis were independent factors for predicting UTUC invading muscle.

The interpretation of urothelial carcinoma at the 2023 ASCO-GU / 中华泌尿外科杂志

The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) reported several advancements in the field of urothelial carcinoma. Multiple new treatment options for non-muscle invasive bladder cancer (NMIBC) were introduced, providing more choices for bladder preservation in BCG-resistant/failed NMIBC cases. In muscle invasive bladder cancer (MIBC) perioperative treatment, the updated 3-year follow-up data from the CheckMate 274 study demonstrated a clear advantage in disease-free survival for the nivolumab monotherapy adjuvant treatment group. For metastatic urothelial carcinoma (mUC), the final overall survival (OS) report from the IMvigor130 study was published, prompting further considerations for future first-line treatment options in mUC. Additionally, the conference highlighted research progress in upper tract urothelial carcinoma (UTUC).

PD-L1 expression in muscle invasive urothelial carcinoma: Comparison of SP142 and SP263 assay

Introduction: High-grade urothelial carcinoma has a different molecular pathway than superficial low grade urothelial carcinoma, and is characterized by genomic instability. The high tumor mutation burden leads to neoantigen formation, evoking an immune response. The immune response has been keenly studied in last two decades and programmed death ligand-1 (PDL-1) has emerged as acceptable immunohistochemical marker for assessment of response to therapy, prognostication and patient selection for immunotherapy. The targeting of PD-1 and PDL-1 by checkpoint inhibitors (CPIs) is an attractive strategy to unblock the inhibitor and induce cytotoxic cell death. However, the presence of complementary and companion diagnostic testing with multiple PDL-1 assays and platforms for various CPIs make a diagnostic quagmire. Thus, it is the need of hour to harmonize these assays. In this undertaken study we evaluated the concordance in PD-L1 expression between the two PD-L1 clones: SP263 and SP142, in treatment naïve muscle invasive bladder cancer (MIBC). Methods: We evaluated Ventana PD-L1 “SP263 and SP142” qualitative immunohistochemical assay using rabbit monoclonal anti-PD-L1 clones in evaluation of PDL-1 immunoexpression on Ventana autostainer platform. The study includes 30 muscle invasive urothelial carcinomas, with 10 of 30 having nodal metastasis. Results: SP263 assay was statistically more sensitive than SP142 for tumor cell (TC) scoring (P = 0.0009), whereas SP142 was more sensitive for immune cell (IC) scoring (P = 0.0067). There was no statistical significant discordance for TC or IC scoring between primary tumor and metastatic lymph node. Conclusion: PD-L1 testing status can be done on both primary tumor and metastatic site, however in metachronous metastatic setting, testing on recent metastatic site should be preferred. The harmonization of immunoexpression between 2 PD-L1 clones could not be achieved.

Neoadjuvant immune combination therapy for muscle-invasive bladder cancer / 中华泌尿外科杂志

Neoadjuvant therapy leads to the eradication of micrometastasis, thereby providing survival benefit to patients with muscle-invasive bladder cancer (MIBC). In the recent years, multiple clinical trials have corroborated the safety and durability of immune checkpoint inhibitors in the treatment of MIBC. Notably, there is a significantly higher response rate (e.g. pathologic complete response) and comparable occurrence of adverse events in patients treated with neoadjuvant dual immunotherapy, immunotherapy combined with chemotherapy or targeted therapy as compared with that treated with neoadjuvant single-agent immunotherapy. With an overview of breakthroughs in the past years, we believe that immune combination therapy is of great promise and expected to revolutionize the landscape of neoadjuvant therapy of MIBC.

Clinicopathological characteristics and prognosis of subsequent upper tract urothelial carcinoma in non-muscle invasive bladder cancer patients after renal transplantation / 中华泌尿外科杂志

Objective:We aim to investigate the clinical characteristics and prognosis of upper tract urothelial carcinoma (UTUC) in patients with non-muscle invasive bladder cancer (NMIBC) after renal transplantation.Methods:We retrospectively analyzed the clinical and follow-up information of 13 kidney recipients with NMIBC admitted to our hospital from January 2014 to June 2022 who subsequently underwent complete transperitoneal laparoscopic nephroureterectomy. There were 8 males and 5 females, aged (56.1±11.5), 3 cases with history of smoking and 10 cases without history of smoking, 4 cases with history of Aristolochic acids and 9 cases with no history of Aristolochic acids. Six and seven cases were treated with transurethral resection of bladder tumor for hematuria and bladder tumors detected by ultrasound or imaging respectively. Single and multiple bladder tumors were 9 and 4 cases; bladder tumor size ≤ 3 cm, >3 cm were 9 and 4 cases respectively; low-and high-grade bladder tumors were 3 and 10 cases separately, with; T a and T 1 of 3 and 10 cases respectively; recurrent bladder cancer and non-recurrent bladder cancer were 5 and 8 cases respectively. Follow-up after transurethral resection of bladder tumor showed that 6 cases with imaging evidence of UTUC for 6-52 months after transurethral resection of bladder tumor were treated with ipsilateral laparoscopic nephroureterectomy, including 2 cases of hydronephrosis, 1 case of renal pelvis mass, and 3 cases of ureteral mass, and 7 cases without imaging evidence of UTUC were performed with bilaterally prophylactic laparoscopic nephroureterectomy. The Kaplan-Meier curve and log-rank test were used for survival analysis to evaluate the prognostic effect of UTUC in kidney recipients with NMIBC. Results:Six of 13 patients named UTUC group were diagnosed with UTUC and 7 of 13 patients named no-UTUC group were not detected with UTUC. There was no statistical difference between these two groups in terms of clinical characteristics, including age( P=0.10), sex( P=0.10), smoking( P=0.19), history of Aristolochic acids( P=0.99), number( P=0.56), grade( P=0.19), stage ( P=0.19)and recurrence of bladder tumor number( P=0.10), and radiological findings of UTUC ( P=0.29). However, patients with larger-sized bladder tumors (larger than 3cm) had a higher rate of UTUC compared to patients with equal or smaller than 3 cm ( P=0.29). In addition, two patients with negative radiological findings developed UTUC following the detection of a large bladder tumor size (larger than 3 cm). The median survival of overall survival time and cancer specific survival time after laparoscopic nephroureterectomy were 42(17, 65) months. Two patients died from any cause during follow-up in patients with UTUC, whereas no significant difference between UTUC group and non-UTUC group in overall survival time and cancer specific survival time, as evaluated by the Kaplan-Meier curves and log-rank tests. ( P=0.29). Conclusions:After kidney transplantation, the diameter of the bladder tumor in NMIBC patients with UTUC was significantly larger than that in patients without UTUC, and no significant difference was observed in the remaining clinical features. Considering the non-functioning kidney after kidney transplantation, prophylactic laparoscopic nephroureterectomy can be considered for NMIBC patients with bladder tumor size >3 cm. Survival analysis showed no significant difference between UTUC group and non-UTUC group.

Advances in the comprehensive treatment of muscle-invasive bladder cancer with preservation of the bladder / 中华泌尿外科杂志

Bladder cancer(BC) ranks the first of genitourinary tumor in China and is one of the most common urological malignancies, in which 25%-30% of patients were diagnosed with muscle-invasive bladder cancer. Radical cystectomy combined with pelvic lymph node dissection is the standard procedure for treatment, which can effectively avoid tumor recurrence or distant metastasis as well as improve the prognosis of patients. However, some patients may not tolerate or refuse to undergo radical bladder surgery due to worry about high complication rate, high morbidity and poor postoperative quality of life. With the increasing understanding of bladder cancer heterogeneity and biological behavior, the treatment of bladder cancer has changed from a surgery-based treatment model to an individualized and comprehensive treatment model by multidisciplinary collaboration. The bladder-preserving treatment can achieve the same oncological prognosis as that of radical bladder surgery with a better quality of life of the patients, which has become a hot topic and focus of research in muscle-invasive bladder cancer treatment. This article reviewed the progress of research related to the comprehensive treatment of muscle-invasive bladder cancer with preservation of the bladder.

Bladder-sparing treatment following noninvasive down-staging after transurethral resection of bladder tumor plus systemic chemotherapy for muscle-invasive bladder cancer / 中华泌尿外科杂志

Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.

Multimodality bladder-sparing treatment options for muscle-invasive bladder cancer / 中华泌尿外科杂志

With the development of new drugs, advances in medical technology and progressions in tumor molecular biology, organ preservation surgery has become the new trend for tumor treatment. Here, we discussed how to select right muscle-invasive bladder cancer patient with strict criteria for multimodality bladder-sparing treatment, and we reviewed the new treatment options, outcomes and trend of development for bladder-sparing treatments.

Preliminary efficacy observation of carbon ion radiotherapy in the treatment of muscle-invasive bladder cancer in phase Ⅰ/Ⅱ clinical trials / 中华放射医学与防护杂志

Objective:To evaluate the feasibility and safety of carbon ion radiotherapy (CIRT) in the treatment of muscle-invasive bladder cancer in phase Ⅰ/Ⅱ clinical trials.Methods:Clinical stage T 2-3 patients with muscle-invasive bladder cancer (without distant metastasis) were studied. A three-fraction treatment was applied, including the local irradiation with the dose from 12 Gy to 24 Gy and 11 fractions of whole-bladder irradiation with a dose of 44 Gy. The carbon ion irradiation dose is determined with relative biological effectiveness (RBE) of 3.0. The total dose for bladder tumor was 56-68 Gy in 14 fractions. The primary endpoints included tumor treatment-related side effects, dose-limiting toxicity (DLT) responses, and local control (LC) rate, and the secondary endpoints included progression-free survival (PFS). Results:Nine patients received CIRT of various doses in the clinical trials, with the dose gradually increasing to 68 Gy. The patients did not suffer from DLT response, acute adverse effects of radiation therapy of grade ≥3, and late radiation adverse reactions during follow-up. When the dose to the tumor reached 68 Gy, there were 2 cases of grade 2 acute urogenital tract reaction and 1 case of acute lower gastrointestinal tract symptom. For the group with a dose above 62 Gy, three cases of grade 1 late radiation bladder reaction were observed and their symptoms included urinary frequency and microscopic hematuria. At the end of treatment, hematuria disappeared, dysuria was relieved, and urine red blood cell value significantly decreased for all the patients. Three months and six months after treatment, the LC rates were 100% and 88.9%, respectively, and the objective response rates were both 88.9%. One patient developed local recurrence and was treated with salvage surgery six months after treatment.Conclusions:The preliminary efficacy observation of CIRT in the treatment of muscle-invasive bladder cancer showed significant short-term efficacy, obvious symptom relief, and good tolerability for patients, without DLT. Therefore, CIRT is safe and feasible.

Bladder-sparing comprehensive therapy for muscle invasive bladder cancer / 国际外科学杂志

Bladder cancer is one of the most common tumors of the urinary system. More than a quarter of the new bladder cancer cases in China are muscle invasive bladder cancer. The standard treatment of muscle invasive bladder cancer is radical cystectomy plus pelvic lymph node dissection. This operation has limitations such as large trauma, high postoperative complication rate and serious impact on the quality of life of patients. To control the condition of bladder cancer and improve the quality of life of patients, a comprehensive treatment and follow-up system after bladder sparing are being explored. In addition to the classic trimodal treatment which is consisted of "maximum transurethral resection of the tumor, chemotherapy and external radiotherapy" , the treating modes of single drug, multi-drug or combined chemotherapy/radiotherapy based on immune checkpoint inhibitors are in their heyday. Meanwhile, antibody-drug conjugates have been in the ascendant. The purpose of this article is to review the current situation of bladder sparing therapy for muscle invasive bladder cancer and look forward to the development direction of bladder sparing therapy in the current era of oncoimmunology.

Efficacy of intravesical gemcitabine and docetaxel for non-muscle invasive urothelial bladder cancer: A review of current literature

OBJECTIVE@#To determine the efficacy of sequential intravesical Gemcitabine and Docetaxel (siGD) in patients with non-muscle invasive bladder cancer (NMIBC) in preventing disease recurrence after transurethral resection, as an alternative to BCG-naïve patients or to failed intravesical BCG therapy.@*METHODS@#An extensive literature search on the use of siGD for BCG-naïve or BCG-refractory NMIBC was done using the following terms: non-muscle invasive bladder cancer, intravesical Gemcitabine and Docetaxel. Search results were filtered to include all retrospective studies and randomized controlled trials reporting the oncological outcomes of siGD published over the last 5 years from the conception of this study. Information on the safety profile and adverse events related to therapy were also reported, if available.@*RESULTS@#The authors’ search yielded 8 retrospective articles describing the efficacy of siGD for NMIBC, 5 of which had complete and accessible English manuscripts. A total of 476 low to high-risk NMIBC patients were included in the 5 eligible studies, 31 (6.5%) of which were BCG-naïve, while the rest failed BCG therapy. The reported one and two-year success rates were 54-69% and 34-55%, respectively. The recurrence-free survival rates at 1 and 2 years were 49-60% and 29-46%, respectively. Bladder cancer-specific mortality at 1 and 2-years were 1-3% and 4-11%, respectively. Treatment-related adverse reactions were mostly mild, the most common of which were urinary frequency, urgency, hematuria, and dysuria.@*CONCLUSION@#Sequential intravesical Gemcitabine and Docetaxel is a feasible alternative for BCG-naïve and BCG-refractory NMIBC patients. Oncological outcomes are comparable to BCG therapy with less adverse effects.

Status and progress of partial cystectomy in the treatment of myometric invasive bladder cancer / 中国综合临床

Bladder cancer is one of the most common malignant tumors in the urinary system, and the current standard treatment for muscle-invasive bladder cancer(MIBC) is radical cystectomy combined with pelvic lymphadenectomy.However, radical cystectomy is a surgical method with serious damege and high incidence of perioperative complications, leading to a low postoperative quality of life for patients.In recent years, with the improvement of chemotherapy regimens and the development of radiotherapy techniques, bladder preservation comprehensive therapy based on partial cystectomy(PC) has attracted the attention of domestic and foreign scholars again.This article reviews the current application and treatment progress of PC.

Research progress on prevention and intervention of incision-related complications after orthotopic neobladder surgery for bladder cancer / 中国肿瘤临床

The incidence of bladder cancer is increasing in China. Each year, nearly one third of newly diagnosed cases are muscle invasive bladder cancer (MIBC). The standard treatment for patients with MIBC is radical cystectomy (RC) with pelvic lymphadenectomy. Orthotopic neobladder (ONB) surgery is the primary method of urinary diversion after RC. However, ONB surgery is associated with many post-operative complications related to the urinary tract, intestine, and incision site. Here, we review the mechanism, prevention, and treatment measures of incision complications after ONB surgery.

A prospective observational study to evaluate the role of restaging transurethral resection of bladder tumour in patients with non-muscle invasive bladder cancer

Background: Transurethral resection of bladder tumour (TURBT) is the primary treatment modality for Non-muscle invasive bladder cancer (NMIBC). Restaging transurethral resection of bladder tumour (RETURBT) is indicated to reduce risk of residual disease and correct staging errors after primary TURBT. The aim of the study is to evaluate the risk of residual tumour and upstaging in NMIBC after TURBT and to investigate the risk factors for the same.Methods: A prospective observational study was carried out over 4 years and 87 patients were included in the study. Patients with NMIBC underwent RETURBT after 2-6 weeks of primary TURBT. The incidence of residual tumour and upstaging in RETUBRT was correlated with various histopathological and morphological parameters in primary TURBT.Results: Out of 87 patients, who underwent RETURBT, residual disease was present in 51 patients (58.6%) and upstaging occurred in 22 patients (25.2%).On univariate analysis, T1 stage (p=0.01), high grade (p=0.01), Carcinoma in situ(CIS) (p=0.01) and multifocality (p=0.05) were predictive for residual disease in RETURBT. High grade (p=0.01), CIS (p=0.01) and absence of detrusor muscle in specimen (p=0.03) were risk factors for upstaging in RETURBT.Conclusions: NMIBC have high incidence of residual disease and upstaging after primary TURBT. T1 stage, high tumour grade, CIS, and multifocality are risk factors for residual disease after primary TURBT. High tumour grade, CIS and absence of detrusor muscle are strongly associated with upstaging during RETURBT.

Role of serum CA 19-9 as a tumor marker in TCC bladder

Background: There is a dearth of reliable blood and urine markers for transitional cell carcinoma of urinary bladder. CA 19-9 is a well-known marker for gastrointestinal malignancies and is being investigated for other malignancies including carcinoma bladder. In this prospective study, we evaluated the role of serum CA 19-9 as a tumor marker and correlated its level with tumor grade and stage.Methods: One hundred and fifteen patients with transitional cell carcinoma of urinary bladder and 69 healthy volunteers, as controls were included in the study. Preoperative blood sample was analysed for level of CA 19-9 using ELISA kit (normal - 0 U/ml to 37U/ml) and were correlated with grade and TNM stage of tumor.Results: The range of the control group is 2-38U/ml (mean: 17.67±9.68U/ml); TCC group is 1-94U/ml (mean: 37.12±31.52U/ml) (p=0.304). When CA 19-9 level >37IU/ml was taken as cut-off for a positive test, sensitivity of detecting T3 disease, T4 disease, MIBC, presence of node and high grade tumour were 80%, 75%, 70.3%, 78% and 57.8% respectively. However, there was a statistically significant increase in levels of CA19-9 in relation to higher grade (<0.001), presence of muscle invasion (<0.001), T stage (<0.001) and N stage (<0.001).Conclusions: Serum CA19-9 is almost invariably raised in patients with high grade and invasive disease. Thus, it has a place as a prognostic marker rather than as a diagnostic tool due to its low sensitivity for TCC bladder.

Prognostic value of serum paraoxonase-1 in patients with non-muscle-invasive bladder cancer / 中国医师进修杂志

Objective@#To explore the prognostic value of serum paraoxonase-1(PON-1) in patients with non-muscle-invasive bladder cancer.@*Methods@#Serum levels of paraoxonase-1 (PON-1) in one hundred and twenty non-muscle-invasive bladder cancer patients (bladder cancer group) and fifty healthy controls (healthy control group) in Hankou Hospital of Wuhan were detected using spectrophotometric rate assay with p-nitrophenol as the substrate. The overall survival and disease-free survival curve was drawn by Kaplan-Meier method in different serum PON-1 levels, and independent prognostic factors were analyzed by Cox proportional hazards model.@*Results@#The serum levels of PON-1 in bladder cancer group was (116.52 ± 21.91) U/L, in healthy control group was (237.96 ± 46.97) U/L, and there was significant difference (t=23.004, P < 0.01). The patients in bladder cancer group were divided into high PON-1 group (≥ 116.52 U/L, 64 patients) and low PON-1 group (< 116.52 U/L, 56 patients) by the median of PON-1(116.52 U/L). Serum PON-1 levels were closely correlated with age of bladder cancer patients (P < 0.05), but not correlated with gender, Karnofsky score, anesthesia risk grading(ASA grade), tumor multiplicity, T stage, pathological grade and tumor size (P > 0.05). The median over-all survival time of the high PON-1 group was 62 months, and 52 months in the low PON-1 group, and there was significant difference (Log-rank=7.004, P=0.008). The median disease-free survival time of the high PON-1 group was 57 months, and 49 months in the low PON-1 group, and there was significant difference (Log-rank=4.068, P=0.044). Cox multivariate regression analysis showed that T stage, serum PON-1 levels was independently associated with overall survival and disease-free survival of patients with non-muscle invasive bladder cancer (P < 0.05).@*Conclusions@#Serum PON-1 levels is increased in non-muscle invasive bladder cancer patients, and PON-1 is an independent prognostic indicator of overall survival and disease-free survival in patients with bladder cancer.

Prognostic value of serum paraoxonase-1 in patients with non-muscle-invasive bladder cancer / 中国医师进修杂志

Objective To explore the prognostic value of serum paraoxonase-1(PON-1) in patients with non-muscle-invasive bladder cancer. Methods Serum levels of paraoxonase-1 (PON-1) in one hundred and twenty non-muscle-invasive bladder cancer patients (bladder cancer group) and fifty healthy controls (healthy control group) in Hankou Hospital of Wuhan were detected using spectrophotometric rate assay with p-nitrophenol as the substrate. The overall survival and disease-free survival curve was drawn by Kaplan-Meier method in different serum PON-1 levels, and independent prognostic factors were analyzed by Cox proportional hazards model. Results The serum levels of PON-1 in bladder cancer group was (116.52 ± 21.91) U/L, in healthy control group was (237.96 ± 46.97) U/L, and there was significant difference (ti23.004, P < 0.01). The patients in bladder cancer group were divided into high PON-1 group ( ≥116.52 U/L, 64 patients) and low PON-1 group (< 116.52 U/L, 56 patients) by the median of PON-1(116.52 U/L). Serum PON-1 levels were closely correlated with age of bladder cancer patients (P < 0.05), but not correlated with gender, Karnofsky score, anesthesia risk grading( ASA grade), tumor multiplicity, T stage, pathological grade and tumor size (P > 0.05). The median over-all survival time of the high PON-1 group was 62 months, and 52 months in the low PON-1 group, and there was significant difference (Log-ranki7.004, Pi0.008). The median disease-free survival time of the high PON-1 group was 57 months, and 49 months in the low PON-1 group, and there was significant difference (Log-ranki4.068, Pi0.044). Cox multivariate regression analysis showed that T stage, serum PON-1 levels was independently associated with overall survival and disease-free survival of patients with non-muscle invasive bladder cancer (P < 0.05). Conclusions Serum PON-1 levels is increased in non-muscle invasive bladder cancer patients, and PON-1 is an independent prognostic indicator of overall survival and disease-free survival in patients with bladder cancer.

Preoperative Lymphocyte-to-monocyte Ratio Predicts Prognosis in Patients with Stage T1 Non-muscle Invasive Bladder Cancer / 中国医学科学院学报

Objective To investigate the clinical value of preoperative lymphocyte-to-monocyte ratio(LMR)in evaluating the prognosis of patients with stage T1 non-muscle invasive bladder cancer(NMIBC).Methods A total of 215 patients with stage T1 NMIBC who underwent transurethral resection of bladder tumor were enrolled.Clinical data were collected.Patients were followed up and their disease-free survival(DFS)and overall survival(OS)were recorded.The receiver operating characteristic(ROC)curve of preoperative LMR in detecting patient prognosis was used to determine the optimal cut-off value for LMR.Patients were divided into low LMR group(LMR <3.86,=77)and high LMR group(LMR ≥ 3.86,=138).Kaplan-Meier survival curves were explored to compare cumulative DFS and OS rates in patients with different LMR levels,and COX proportional hazards regression model was used to analyze factors associated with DFS and OS.Results All these 215 patients with T1 stage NMIBC were followed up for 2-92 months,and the DFS rate was 59.07% and OS rate was 65.12%.Kaplan-Meier curves showed that the cumulative DFS rate(=4.784,=0.029)and cumulative OS rate(=7.146, =0.008)in the low LMR group were significantly lower than those in the high LMR group.Tumor size ≥ 3 cm(=1.398,95% :1.042-1.875,=0.025),pathological grade G3(=1.266,95% :1.026-1.563,=0.028),and LMR ≥ 3.86(=2.347,95% :1.080-5.101,=0.031)were independent factors associated with DFS in patients with stage T NMIBC.In addition,tumor size ≥ 3 cm(=1.228,95% :1.015-1.484,=0.034),pathological grade G3(=1.366,95% :1.017-1.834,=0.038),and LMR<3.86(=2.008,95% :1.052-3.832,=0.035)were independent factors associated with OS in patients with T1 stage NMIBC. Conclusion Preoperative LMR is an independent factor associated with patients' prognosis in T1 stage NIMBC.Patients with low LMR tend to have higher risk of NMIBC progression and death.