Postoperative Instillation Research Articles

Alopecia as an uncommon side effect of single postoperative instillation of gemcitabine in patients with non-muscle-invasive urothelial carcinoma of the bladder.

274 Background: Single-dose administration of intravesical gemcitabine is a common part of clinical practice following transurethral resection (TURBT) of non-muscle invasive bladder cancer (NMIBC). Although the side effect profile for gemcitabine is well characterized in systemic and local therapy, rare side effects continue to be identified with ongoing use. Here we identify several cases of treatment-related alopecia with adjuvant single dose intravesical administration for NMIBC after TURBT. Methods: Using our single-institutional IRB-approved Cysview registry database, we identified patients who underwent TURBT for NMIBC and received a single dose of intravesical gemcitabine post-TURBT between January 2020 and June 2023 at Keck Hospital of USC. Patients with a history of low grade NMIBC or those undergoing their first TURBT received 2g of gemcitabine dissolved in 100 cc of saline 1h after tumor resection. We reviewed patient-reported adverse events and included patients who reported alopecia following gemcitabine instillation. Patients were questioned on the degree and length of hair loss and information was collected from patient charts. Results: Overall, 9 patients (2 male, 7 female) reported hair loss following single dose intravesical gemcitabine after the TURBT. One patient had an autoimmune disease. The hair loss started within a few days of gemcitabine instillation and resolved spontaneously. The table shows the clinicopathologic characteristics of this cohort in detail. Three patients experienced severe hair loss. The resection extent during TURBT was classified as small (<2 cm), medium (2-5 cm), or large (>5 cm). Three patients had a large resection, 2 patients a medium one and 3 patients a small resection. None of the patients had previous intravesical gemcitabine; however, 2 patients had a history of intravesical BCG and 1 had intravesical mitomycin before. Conclusions: This study demonstrates that hair loss is a rare but possible adverse effect of intravesical gemcitabine after TURBT. Prior to surgery, patients should be counseled regarding this potential side-effect. Additional research and multicenter studies are required to describe the occurrence and cause of this adverse event. Demographic, clinical, and pathologic characteristics of patients. Patient ID Age Sex History of other IVT Pathology of TURBT Number of prior TURBT Resection extent Severity of hair loss Prior UBC 1 73 M None LGTa 1 large moderate LGTa 2 88 M MMC LGTa multiple large severe LGTa 3 76 F BCG CIS multiple small moderate HGT1 in upper tract,HGTa & LGTa in bladder 4 56 F BCG HGTa multiple large severe LG+HGTa 5 66 F None HGTa none small moderate None 6 84 F None LGTa none small severe None 7 62 F None LGTa 1 medium moderate LGTa 8 68 F None HGTa multiple medium mild LGTa 9 64 F None LGTa none medium severe None LG= Low Grade, HG = High Grade.

Recurrence after postoperative intravesical instillation therapy in Hunner type interstitial cystitis

We performed a prospective, single-arm study comparing outcomes between transurethral ablation plus postoperative instillation of hyaluronic acid and chondroitin sulfate (HACS group) and transurethral ablation only in patients with Hunner type interstitial cystitis (historical control group). A total of 78 patients were enrolled, and 51 were included in the per-protocol analysis set. The 2-year recurrence rate was 47.1% (95% CI, 32.9–61.5) in the HACS group, which was significantly lower than that in the control group (86.2%; 95% CI, 74.6–93.9, P < 0.001). After instillation therapy, the hazard ratio for recurrence was 0.38 (95% CI, 0.23–0.65, P < 0.001). The HACS group had an increased recurrence-free survival with the median interval not being reached, while it was 11.4 months in the control group (95% CI, 8.8–13.8, P < 0.001). Regardless of the instillation treatment, there were significant improvements in all symptom questionnaire scores and pain compared to the baseline. However, in the instillation group, improvement was stable even after 12 months. In patients with Hunner type interstitial cystitis, intravesical instillation of hyaluronic acid and chondroitin sulfate after transurethral ablation significantly reduced the recurrence rate and maintained symptom improvement for more than 1 year.

The relationship between inflammatory response markers and the prognosis of non-muscle invasive bladder cancer and the development of a nomogram model.

Patients with non-muscle invasive bladder cancer (NMIBC) have a high possibility of recurrence after surgery. We aimed to assess the factors associated with tumor recurrence and to construct a nomogram model that can contribute to personalized treatment plans of each patient. 496 patients with primary bladder cancer (BC) from 2 centers were retrospectively analyzed. Preoperative neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and traditional clinical parameters were collected, then using univariate and multivariate Cox regression analysis to find out the independent risk factors associated with tumor recurrence among them, and then these independent factors were incorporated into the nomogram model. The internal calibration curves and the external calibration curves were used to verify their usefulness. In the training cohort, 150 patients (43.1%) experienced recurrence. After Cox regression analysis, the independent risk factors affecting recurrence-free survival (RFS) were tumor grade, immediate postoperative instillation therapy (IPPIT), NLR, and SII. These factors were used to construct a model to predict RFS 1, 2, 3, and 5 years of NMIBC patients after surgery. And then, we found that the constructed model outperforms the conventional model in terms of accuracy and predictability, the results were verified by statistical tests. Preoperative inflammatory response markers have a predictive value for postoperative recurrence in patients with NMIBC. The constructed nomogram model can be helpful in guiding personalized clinical evaluation and subsequent treatment.

Clinical Efficacy of Neoadjuvant Intravesical Mitomycin-C Therapy Immediately Before Transurethral Resection of Bladder Tumor in Patients With Nonmuscle-invasive Bladder Cancer: Preliminary Results of a Prospective, Randomized Phase II Study. Letter.

You have accessJournal of UrologyLetters to the Editor1 Apr 2023Clinical Efficacy of Neoadjuvant Intravesical Mitomycin-C Therapy Immediately Before Transurethral Resection of Bladder Tumor in Patients With Nonmuscle-invasive Bladder Cancer: Preliminary Results of a Prospective, Randomized Phase II Study. Letter. Ashish Ranjan, Ankit Misra, Sanjoy Kumar Sureka, and Uday Pratap Singh Ashish RanjanAshish Ranjan Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author , Ankit MisraAnkit Misra * E-mail Address: [email protected] Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author , Sanjoy Kumar SurekaSanjoy Kumar Sureka Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author , and Uday Pratap SinghUday Pratap Singh Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003363AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail J Urol. 2023;209(1):131-139. To the Editor: We read with great interest the study investigating the novel role of intravesical mitomycin-C (MMC) in nonmuscle-invasive bladder cancer (NMIBC) in a neoadjuvant setting.1 Single, immediate, post-transurethral resection of bladder tumor (TURBT) instillation of MMC is the standard protocol in NMIBC.2 It primarily reduces the recurrence risk by eliminating viable residual tumors and preventing reseeding of the free-floating cancer cells.3 However, fear of extravasation and its associated serious complications has led to its low practical compliance worldwide.4 This study has demonstrated the use of neoadjuvant intravesical MMC for NMIBC with promising therapeutic efficacy, better tolerability, and low significant adverse effects. Although the dose and schedule of neoadjuvant MCC followed in the study were convenient for the patient, we would like to know the scientific basis for using 2 doses at a specific interval. The writers mention a preliminary study for deciding on 2 doses of neoadjuvant MMC, but no reference has been given. Do the authors feel that the control group should have received a single immediate post-TURBT MMC per the standard? Were any morphological or radiological criteria considered before administering the neoadjuvant therapy? The rationale of giving MMC post-TURBT is only to give it to patients with superficial disease on resection. Would it not be an overtreatment and waste of resources on those that eventually come out as muscle invasive? MMC concentration in tumor and normal tissue was measured to know about uptake, but is there any standard concentration in the postoperative instillation setting to which it was matched? Moreover, it would be interesting to know the method used to detect the concentration of MMC in the tissue. Would continuous saline irrigation used during the TURBT have diluted the effect of MMC on the tissue? Multifocal tumors were more in the control arm (24, 63%) than in the intervention arm (15, 46%). Was this difference statistically significant? This could have a bearing on better recurrence-free survival in the intervention arm and more progression in control. Lastly, we appreciate the authors' focus on an important area in NMIBC treatment. REFERENCES 1. . Clinical efficacy of neoadjuvant intravesical mitomycin-C therapy immediately before transurethral resection of bladder tumor in patients with nonmuscle-invasive bladder cancer: preliminary results of a prospective, randomized phase II study. J Urol. 2023; 209(1):131-139. Link, Google Scholar 2. . Trial-based cost-effectiveness analysis of an immediate postoperative mitomycin C instillation in patients with non–muscle-invasive bladder cancer. Eur Urol Open Sci. 2022; 37:7-13. Crossref, Medline, Google Scholar 3. . Continuous saline bladder irrigation in reducing recurrence and progression when compared to immediate mitomycin-C instillation post-resection of bladder tumor: a short communication. Asian Pac J Cancer Prev. 2022; 23(1):171-175. Crossref, Medline, Google Scholar 4. . Systematic review and individual patient data meta-analysis of randomized trials comparing a single immediate instillation of chemotherapy after transurethral resection with transurethral resection alone in patients with stage pTa-pT1 urothelial carcinoma of the bladder: which patients benefit from the instillation?Eur Urol. 2016; 69(2):231-244. Crossref, Medline, Google Scholar Submitted December 19, 2022; accepted February 2, 2023; published 000. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue 4April 2023Page: 677-678 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ashish Ranjan Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author Ankit Misra Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India * E-mail Address: [email protected] More articles by this author Sanjoy Kumar Sureka Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author Uday Pratap Singh Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author Expand All Submitted December 19, 2022; accepted February 2, 2023; published 000. 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Risk-Based Assessment Of the Impact Of Intravesical Therapy on Recurrence-Free Survival Rate Following Resection of Suspected Low-grade, Non-muscle-invasive Bladder Cancer (NMIBC): A Southwest Oncology Groups (SWOG) S0337 Posthoc Analysis.

Nonmuscle invasive bladder cancer (NMIBC) has an elevated risk of recurrence, and immediate postresection intravesical instillation of chemotherapy (IVC) significantly reduces the risk of recurrence. Questions remain about which subpopulation may maximally benefit from IVC. Our aim was to develop risk groups based on recurrence risk in NMIBC, and then evaluate the impact of a single, postoperative instillation of IVC on the subsequent risk of recurrence for each risk group. Using the SWOG S0337 trial cohort, we performed a posthoc analysis of 345 patients who were diagnosed with suspected low-grade NMIBC, underwent transurethral resection of the bladder tumor (TURBT), and received post-operative IVC (gemcitabine vs. saline). Using regression tree analysis, the regression tree stratified patients based on their risk of recurrence into low-risk - single tumor and aged < 57 years, intermediate-risk - single tumor and aged ≥ 57 years, and high-risk - multiple tumors. We used Cox proportional hazard models to test the impact of recurrence-free rate, and after adjustment to available covariates. Median age of the cohort was 66.5 (IQR: 59.7-75.8 years) with 85% of patients being males. Median overall follow-up time was 3.07 years (IQR: 0.75-4.01 years). When testing the impact of treatment in each risk group separately, we found that patients in the intermediate-risk treated with gemcitabine had a 24-month recurrence free rate of 77% (95% CI: 68%-86%) vs. 59% (95% CI: 49%-70%) in the saline group. This survival difference was confirmed on multivariable analysis (hazard ratio: 0.39, 95% CI: 23%-66%, P < 0.001). This group represented 53% of our cohort. Conversely, we did not observe a significant difference in recurrence-free survival among patients in the low- (P = 0.7) and high-risk (P = 0.4) groups. Our findings indicate that older patients with a single tumor of suspected low-grade NMIBC at TURBT maximally benefit from immediate postresection IVC (gemcitabine).

Analysis of risk factors for dry eye disease and effect of diquafosol sodium ophthalmic solution on the tear film after vitrectomy in patients with type 2 diabetes mellitus: a preliminary study.

The purpose of this study was to investigate the risk factors of DM associated dry eye syndrome (DMDES) and to explore the effect of diquafosol sodium ophthalmic solution (DQS) on patients with DMDES after vitrectomy. Totally 107 patients (107 eyes) received vitrectomy. The data of age, gender, left/right eye, duration of DM, duration of vitrectomy, fasting blood glucose and glycosylated hemoglobin were collected and analyzed for correlation between these factors and DMDES. Postoperatively, DQS was instilled in experimental group and sodium hyaluronate was instilled in control group. The noninvasive breakup time (NIBUT), tear meniscus height (TMH), Schirmer I test (SIT), corneal fluorescence staining score (CFSS) and ocular surface disease index (OSDI) were recorded before vitrectomy and 1, 2 and 3months after vitrectomy. All data were used for statistical comparison. Gender, duration of DM and glycosylated hemoglobin were relevant factors of DMDES (P < 0.05). At 1, 2 and 3months postoperatively, NIBUT and TMH of experimental group were significantly higher than control group (P < 0.05). Postoperatively, CFSS of experimental group was lower than that before vitrectomy, and CFSS at 2 and 3months after vitrectomy was significantly different between the two groups (P < 0.05). At 1, 2 and 3months postoperatively, SIT increased in both groups, but there was no significant difference between the two groups (P > 0.05). OSDI was significantly lower in experimental group at 1, 2 and 3months postoperatively, compared with that of the control group (P < 0.05). These results suggest that gender, duration of DM and glycosylated hemoglobin are risk factors for DMDES. Postoperative instillation of DQS can improve the tear film quality in patients with DMDES after vitrectomy.

Immediate post-operative intravesical instillation of a single dose chemotherapy is not superior to continuous saline irrigation

Introduction and objectivesTo evaluate whether there is any difference between immediate postoperative instillation of intravesical chemotherapy (IPOIC) and continuous saline bladder irrigation (CSBI) in terms of bladder cancer (BC) recurrence in patients with primary low- or intermediate-risk non-muscle-invasive BC (NMIBC). Materials and methodsMedical records of 1482 patients who underwent transurethral resection of bladder tumor between March 1994 and August 2020 were reviewed retrospectively. Patients were divided into two groups according to IPOIC and/or CSBI administration status [Group-1 = CSBI alone; Group-2 = CSBI following IPOIC]. Low- and intermediate-risk NMIBC patients were also divided into subgroups according to IPOIC and/or CSBI administration status. ResultsA total of 594 patients with primary NMIBC were included. Of the patients, 86 (14.5%) were female and 508 (85.5%) were male with a median age of 69 (60–78) years. The frequency of patients in Group-1 and Group-2 were 361 (60.8%) and 233 (39.2%), respectively. Recurrent disease was observed in 213 (35.9%) patients. There was no difference between the groups when they were compared for recurrent disease frequency, median time to first recurrence and frequency of recurrence within first 12 months (P = .064, P = .671, and P = .145, respectively). Disease recurrence rates in low-risk NMIBC patients was lower when they were treated with “CSBI following IPOIC” when compared to “CSBI alone” (P = .042). However, no difference was observed in low-risk NMIBC subgroups when they were compared for pathological features of recurrent tumors such as number, size, grade, stage, and presence of carcinoma in situ (P > .05, for each). Conclusions“CSBI following IPOIC” combination was not superior to “CSBI alone” for preventing adverse pathological outcomes in recurrent low- and intermediate-risk NMIBC.

La dosis única de instilación intravesical postoperatoria inmediata de quimioterapia no es superior al lavado continuo con suero

Introduction and objectivesTo evaluate whether there is any difference between immediate postoperative instillation of intravesical chemotherapy (IPOIC) and continuous saline bladder irrigation(CSBI) in terms of bladder cancer(BC) recurrence in patients with primary low- or intermediate-risk non-muscle-invasive BC (NMIBC). Materials and methodsMedical records of 1482 patients who underwent transurethral resection of bladder tumor between March 1994 and August 2020 were reviewed retrospectively. Patients were divided into two groups according to IPOIC and/or CSBI administration status (Group 1: CSBI alone; Group 2: CSBI following IPOIC). Low- and intermediate-risk NMIBC patients were also divided into subgroups according to IPOIC and/or CSBI administration status. ResultsA total of 594 patients with primary NMIBC were included. Of the patients, 86 (14.5%) were female and 508 (85.5%) were male with a median age of 69 (60-78) years. The frequency of patients in group 1 and group 2 were 361 (60.8%) and 233 (39.2%), respectively. Recurrent disease was observed in 213 (35.9%) patients. There was no difference between the groups when they were compared for recurrent disease frequency, median time to first recurrence and frequency of recurrence within first 12 months (P=.064, P=.671, and P=.145, respectively). Disease recurrence rates in low-risk NMIBC patients was lower when they were treated with “CSBI following IPOIC” when compared to “CSBI alone” (P=.042). However, no difference was observed in low-risk NMIBC subgroups when they were compared for pathological features of recurrent tumors such as number, size, grade, stage, and presence of carcinoma in situ (P>.05, for each). Conclusions“CSBI following IPOIC” combination was not superior to “CSBI alone” for preventing adverse pathological outcomes in recurrent low- and intermediate-risk NMIBC.

Assessment of Therapeutic Benefit and Option Strategy on Intravesical Instillation for Preventing Bladder Cancer Recurrence after Radical Nephroureterectomy in Patients with Upper Urinary Tract Urothelial Carcinoma.

Objective Upper urinary tract urothelial carcinoma (UUT-UC) is a very aggressive disease, characterized by 22%–50% of patients suffering from subsequent bladder recurrence after radical nephroureterectomy (RNU). Although the therapy of intravesical instillation is reported to be effective in preventing bladder recurrence, no study had been reported in Northeast China. The findings relating to the clinical effectiveness of intravesical instillation after RNU are somewhat controversial, and the best efficacy and least adverse effects of instillation drugs have not been widely accepted. Here, we aimed at evaluating the efficacy of intravesical instillation for the prevention intravesical recurrence systematically. Methods In this retrospective cohort study, from October 2006 to September 2017, 158 UUT-UC patients underwent RNU were divided into 4 groups: epirubicin (EPB) instillation group, hydroxycamptothecin (HCPT) instillation group, bacillus Calmette–Guerin (BCG) instillation group, and noninstillation group. Cox univariate and multivariate analyses were employed to identify the risk factors for intravesical recurrence-free survival (IVRFS). The nomogram model was also applied to predict patient outcomes. Subsequently, to evaluate the clinical significance of intravesical instillation comprehensively, several databases including PubMed, Ovid, and Embase were searched and data from published studies with our results were combined by direct meta-analysis. Moreover, a network meta-analysis comparing instillation therapies was conducted to evaluate the clinical efficacy of different instillation drugs. Results In our retrospective cohort study, the Kaplan–Meier survival curve demonstrated noninstillation groups were associated with worsened IVRFS. Meanwhile, multivariate analysis indicated that intravesical instillation was independent protective factors for IVRFS (hazard ratio [HR] = 0.731). Moreover, calibration plots, receiver operating characteristic (ROC) curves, area under the curve (AUC) values, and the C-index showed the priority of nomogram's predictive accuracy. Next, direct meta-analysis including 19 studies showed that intravesical instillation could prevent the recurrence of bladder cancer with a pooled risk ratio (RR) estimate of 0.53. Subgroup analysis by study type, year of intravesical recurrence, first instillation time, and instillation times also confirmed the robustness of the results. Moreover, intraoperative instillation was associated with a decrease in the risk of bladder recurrence compared with postoperative instillation. Then, a network meta-analysis including 7 studies indicated that pirarubicin (THP) (surface under the cumulative ranking curve [SUCRA] = 89.2%) is the most effective therapy to reduce the risk of bladder recurrence, followed by BCG (SUCRA = 83.5%), mitomycin C (MMC) (SUCRA = 53.6%), EPB (SUCRA = 52.6%), and HCPT (SUCRA = 5.1%) after the analysis of the value ranking. Conclusions A maintenance schedule of intravesical instillation prevents the recurrence of bladder cancer after RNU in UUT-UC patients effectively. Large, prospective trials are needed to further confirm its value. Compared with other chemotherapy regimens, THP may be a promising drug with favorable efficacy to prevent bladder recurrence. As included studies had moderate risk of bias, the results of network meta-analysis should be applied with caution.

The Role of Adjuvant Single Postoperative Instillation of Gemcitabine for Non-Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.

Bladder cancer is a heterogeneous disease with variable natural history. Non-muscle-invasive bladder cancer has a favorable prognosis following transurethral resection, but the optimal adjuvant chemotherapy plan is still in debate. The aim of this study was to evaluate the effect of the adjuvant intravesical administration of a single dose of gemcitabine in the outcome of this disease. For that purpose, we performed a systematic review and meta-analysis on available randomized control trials on MEDLINE, EMBASE, Cochrane, Scopus, and Google Scholar databases. Ultimately, two studies were included with a total number of 654 patients. The statistical analysis performed showed that a single post-operative intravesical dose of gemcitabine does not affect the recurrence rate of non-muscle-invasive bladder cancer compared to placebo. Therefore, this therapeutic strategy does not offer any significant improvement on the outcomes of the disease. Nonetheless, due to the plethora of available therapeutic agents and treatment strategies, further research is needed to establish the optimal treatment in this category of patients.

Adjuvant therapies for non-muscle-invasive bladder cancer: advances during BCG shortage.

Non-muscle-invasive bladder cancer (NMIBC) represents a significant global therapeutic challenge, particularly in the era of Bacillus Calmette-Guérin (BCG) shortage. High-risk NMIBC can progress to muscle invasive or metastatic disease in 25% of patients. Optimal treatment selection, according to risk stratification, is imperative. International guidelines slightly differ in their categorisation of low, intermediate and high-risk NMIBC. Nonetheless, a single post-operative instillation of chemotherapy with Mitomycin C (MMC) or Gemcitabine improves relapse-free survival (RFS) in low-risk NMIBC. Induction and maintenance intravesical BCG remains the historical gold standard for patients with intermediate or high-risk NMIBC. However, clinicians may be forced to consider alternatives given the current BCG shortage. Both intravesical MMC and Gemcitabine have been associated with similar efficacy to BCG, albeit in smaller studies. MMC may also be manipulated using a variety of methods to potentiate its effects. BCG treatment delivery may also be modified without affecting efficacy through dose reduction and abbreviation or omission of maintenance therapy. Preliminary data also highlight that directly proceeding to radical cystectomy may not adversely affect long-term quality of life measures. Access to new systemic and intravesical therapies must be prioritised for patients with BCG recurrent or unresponsive disease. When used in conjunction with molecularly defined biomarkers, these agents herald the potential for improved survival outcomes and alleviation of the current BCG shortage.

Predicting Recurrence and Progression in Patients with Non-Muscle-Invasive Bladder Cancer: Systematic Review on the Performance of Risk Stratification Models.

Several classifications have been reported to stratify non-muscle-invasive bladder cancer (NMIBC) in risk groups according to the probability of recurrence and progression. To systematically review the current evidence regarding risk stratification of NMIBC. The systematic review was performed in accordance with the PRISMA statement. Studies providing data on development and/or external validation cohorts of models and risk stratification tables for recurrence and/or progression for patients with NMIBC, reporting at least one discrimination measure (AUC or C-Index) were included. Twenty-five studies involving 22,737 patients were included. Six classifications were identified, three of them were predictive models (EORTC, CUETO, EAU 2021) and three were based on expert opinion (EAU 2020, AUA, NCCN). A high risk of bias was present in the majority of the studies. Certain heterogenicity was found among the studies regarding adjuvant therapy, postoperative instillation or second resection. The definition of oncological outcomes was not standardized in the included studies. CUETO and EORTC scoring systems are the most validated. In general, validations showed a poor discrimination capability to predict recurrence, slightly better for progression. The EAU 2021 model overestimates the risk of progression in patients treated with BCG. Carcinoma in situ is underrepresented in all the studies analyzed. The existing classifications show poor discrimination capability for recurrence and possibly helpful discrimination capability for progression in NMIBC patients. These results highlight the unmet need to develop novel accurate risk models for patients with NMIBC, which could be improved with the combination of clinicopathological and molecular information.

A Nomogram Model to Predict Recurrence of Non-Muscle Invasive Bladder Urothelial Carcinoma After Resection Based on Clinical Parameters and Immunohistochemical Markers

Objective This study aims to establish a nomogram model by combining traditional clinical parameters with immunohistochemical markers to predict the recurrence of non-muscle invasive bladder urothelial carcinoma (NMIBUC) after resection. Methods In total, 504 patients were included in this study. Of these patients, 353 underwent transurethral resection of bladder tumor (TURBT) in the Yongchuan Hospital of Chongqing Medical University and were identified as a training cohort. Univariate and multivariate Cox regression analyses were used to determine the risk factors associated with recurrence in the training cohort and to establish a nomogram model. A total of 151 patients who were hospitalized in the Second Affiliated Hospital of Chongqing Medical University (validation cohort) were used for further validation. The calibration curve was generated for internal and external model validation. The clinical practicability of this model was further verified by comparing the consistency index (C-index) among various models. Results The mean follow-up time of the training cohort was 45.6 months (range 4–90). In total, 146 patients relapsed in training cohort. After univariate analysis, multivariate analysis further confirmed tumor grade (p=.034), immediate postoperative instillation therapy (p=.025), Ki67 (p=.047), P53 (p=.038) and CK20 (p=.049) as independent risk factors for recurrence, and these factors were included in the nomogram model. The model more accurately predicted recurrence compared with other models based on the highest C-index of 0.82 (95% CI, 0.78–0.86) in the training cohort and 0.80 (95% CI, 0.77–0.83) in the validation cohort. Conclusions This proposed nomogram model based on traditional clinical parameters and immunohistochemical markers can more accurately predict postoperative recurrence in patients with NMIBUC.

Pre-operative pyuria predicts tumor recurrence in patients undergoing transurethral resection of bladder tumor with post-operative instillation of BCG

BACKGROUND &amp; OBJECTIVE: In Pakistan, urinary bladder cancer is one of the top ten malignancies. The most important concern after its treatment is tumor recurrence. Recent literature claimed that pre-operative pyuria in patients undergoing transurethral resection of bladder tumor was associated with significantly higher frequency of recurrence. However, there was controversy in existing literature and no such local published material was available which necessitated the present study. To determine the frequency of pre-operative pyuria in patients undergoing transurethral resection of bladder tumor for non-muscle invasive bladder cancer (NMIBC) with post-operative instillation of Bacillus Calmette Guerin (BCG) and to compare the frequency of tumor recurrence in patients with and without pre-operative pyuria.&#x0D; METHODOLOGY: It was a comparative study. This study involved 280 patients of both genders aged between 20-80 years. Pre-operative pyuria was diagnosed if early morning midstream urine specimen showed ≥10 white blood cells/HPF. Outcome variable was frequency of recurrence after 12 weeks of treatment on check cystoscopy.&#x0D; RESULTS: The mean age of the patients was 57.1±8.5 years. There were 236 (84.3%) male and 44 (15.7%) female patients in the study. 155 (55.4%) patients were tobacco smoker. Pre-operative pyuria was diagnosed in 127 (45.4%) patients while tumor recurrence was observed in 183 (65.4%) patients. The frequency of tumor recurrence was significantly higher in patients with pre-operative pyuria (85.8% vs. 48.4%; p&lt;0.001).&#x0D; CONCLUSION: Pre-operative pyuria was a frequent finding in patients with non-muscle invasive bladder tumor and was associated with higher frequency of tumor recurrence which warrants routine screening of such patients for pyuria and increased frequency of tumor recurrence.

P0736 - Very low risk of severe complications after a single, post-operative instillation of intravesical chemotherapy in patients with low- or intermediate risk urothelial carcinoma of the bladder

P0736 - Very low risk of severe complications after a single, post-operative instillation of intravesical chemotherapy in patients with low- or intermediate risk urothelial carcinoma of the bladder

Low Risk of Severe Complications After a Single, Post-Operative Instillation of Intravesical Chemotherapy in Patients with TaG1G2 Urothelial Bladder Carcinoma.

EAU guidelines recommend a single instillation (SI) of intravesical chemotherapy (e.g. Mitomycin C) within 24 hours after transurethral resection of a bladder tumour (TURBT) in patients with low- to intermediate risk non-muscle invasive bladder cancer without (suspected) bladder perforation or bleeding requiring bladder irrigation. However, remarkable variation exists in the use of SI. The risk of severe complications is likely to contribute to this variation, but evidence is limited. To investigate the absolute severe complication and mortality risk after SI in low- and intermediate risk bladder cancer. In this observational, historic cohort study, data on 25,567 patients diagnosed with TaG1G2 urothelial bladder carcinoma (UBC) between 2009 and 2018 who underwent TURBT were collected from the Netherlands Cancer Registry. Data were supplemented with information on cause of death and severe complications after cancer treatment by re-examining the electronic health records and the 14-day complication risk and the 30-day mortality risk were evaluated. On average, 55% of patients had a SI after TURBT, varying from 0->80% between hospitals. The 30-day mortality risk was 0.02% and the 14-day risk of severe complications was 1.6%. As the absolute risk of mortality and severe complications is very low, SI after TURBT can be considered a safe treatment in patients with low- to intermediate UBC without contraindications for SI. These results imply that a part of eligible patients is denied effective treatment.

What influences adherence to guidance for postoperative instillation of intravesical chemotherapy to patients with bladder cancer?

To understand the barriers and facilitators to single instillation of intravesical chemotherapy (SI-IVC) use after resection of non-muscle-invasive bladder cancer (NMIBC) in Scotland and England using a behavioural theory-informed approach. In a cross-sectional descriptive study of practices at seven hospitals, we investigated care pathways, policies, and interviewed 30 urology staff responsible for SI-IVC. We used the Theoretical Domains Framework (TDF) to organise our investigation and conducted deductive thematic analyses, while inductively coding emergent beliefs. Barriers to SI-IVC were present at different organisational levels and professional roles. In four hospitals, there was a policy to not instil SI-IVC in theatre. Six hospitals' staff reported delays in mitomycin C (MMC) ordering and/or local storage. Lack of training, skills and perceived workload affected motivation. Facilitators included access to modern instilling devices (four hospitals) and incorporating reminders in operation proforma (four hospitals). Performance targets (with audit and feedback) within a national governance framework were present in Scotland but not England. Differences in coordinated leadership, sharing best practices, and disliking being perceived as underperforming, were evident in Scotland. High-certainty evidence shows that SI-IVC, such as MMC, after NMIBC resection reduces recurrences. This evidence underpins international guidance. The number of eligible patients receiving SI-IVC is variable indicating suboptimal practice. Improving SI-IVC adherence requires modifications to theatre instilling policies, delivery and storage of MMC, staff training, and documentation. Centralising care, with bladder cancer expert leadership and best practices sharing with performance targets, likely led to improvements in Scotland. National quality improvement, incorporating audit and feedback, with additional implementation strategies targeted to professional role could improve adherence and patient outcomes elsewhere. This process should be controlled to clarify implementation intervention effectiveness.

Holmium Laser En-bloc Resection Versus Conventional Transurethral Resection of Bladder Tumors for Treatment of Non–muscle-invasive Bladder Cancer: A Randomized Clinical Trial

BackgroundEn-bloc resection of bladder tumors achieves complete tumor removal, improves the quality of resection, decreases perioperative complication, and potentially improves recurrence rates. ObjectiveTo assess the efficacy and safety of holmium laser en-bloc resection (HolERBT) versus conventional transurethral resection of bladder tumor (cTURBT). Design, setting, and participantsBetween September 2015 and September 2018, 100 patients with non–muscle-invasive bladder cancer were randomly allocated to cTURBT or HolERBT. Outcome measurements and statistical analysisThe primary endpoint was detection of residual tumor in reTURBT specimens at 4 wk after the primary resection. Operative parameters, specimen quality, perioperative complications, and recurrence-free survival (RFS) were compared. Independent sample t tests, χ2 tests, and Kaplan-Meier curves were used, as appropriate. Results and limitationsThe patient and tumor baseline characteristics were comparable between the groups. Residual tumors were detected in 7% and 27.7% of cases after HolERBT and cTURBT, respectively (p=0.01). Detrusor muscle was sampled in 98% of HolERBT and 62% of cTURBT cases (p<0.001). Lamina propria invasion substaging was feasible in only 68.2% of HolERBT and 18.4% of cTURBT cases (p<0.001). Following HolERBT, catheterization time (p<0.001) and hospital stay (p=0.001) were shorter when compared to cTURBT. Immediate postoperative instillation of chemotherapy in indicated cases was feasible for 100% of the HolERBT group and 91.5% of the cTURBT group (p=0.04). After follow-up of 20 ± 9.9 mo (13–36), RFS was 31.76 mo (95% confidence interval [CI] 28.67–34.86) in the HolERBT group and 28.25 mo (95% CI 24.87–31.64) in the cTURBT group (hazard ratio 0.43, 95% CI 0.17–1.1; p=0.07). However, this study was not powered to detect a difference in RFS. ConclusionsCompared to cTURBT, HolERBT is a safer procedure for bladder tumor resection. It fulfills the oncological criteria of optimized resection with less residual tumor and better specimen quality. Patient summaryEn-bloc resection of bladder cancer tumors using a holmium laser is safer than the conventional technique. It has the advantages of less residual tumor and better specimen quality, with a similar tumor recurrence rate.This study is registered at ClinicalTrials.gov as NCT02555163.

Clinical application of drug sensitive gene detection in postoperative instillation for non-muscle invasive bladder cancer

BackgroundBladder cancer is the most common malignant tumor of the urinary system. One of the biological characteristics of NMIBC is the high recurrence rate after surgery. The implementation of this project aimed to investigate the role of pharmacogenomic testing-guided intravesical perfusion of chemotherapeutic agents in the postoperative perfusion therapy for non-muscle invasive bladder cancer.MethodFrom January 2015 to December 2016, 298 patients with non-muscle-invasive bladder cancer were enrolled in this prospective study. These patients received chemotherapy drugs after electrotherapy. According to the presence or absence of tumor susceptibility gene detection after surgery, they were divided into two groups, including the drug sensitive group(N = 44) and the control group(N = 254). The drug sensitive group received bladder infusion therapy with sensitive chemotherapy drugs based on drug sensitivity gene detection results. The control group received intravesical instillation of pirarubicin. The preoperative general data and tumor grade of patients were recorded. Cystoscopy was performed before and every 3 months after surgery. The chest CT, upper abdomen CT, renal function, and urinary routine tests were performed. Tumor recurrence, metastasis and tumor-related death were recorded and evaluated during follow-up.ResultsThe drug sensitive group, which selected high-sensitivity drugs for intravesical instillation therapy based on gene expression, has a significantly lower relapse rate (11.36% vs 37.40%, P < 0.05) and a significantly longer time to relapse (17.80 ± 7.20 month vs11.20 ± 6.10 month, P < 0.05) compared with the control group. There were no significant differences in the time of mortality and death time between two groups.ConclusionThe pharmacogenomic testing-directed bladder instillation of chemotherapeutic drugs may be more effective than empiric drug administration in reducing the recurrence rate of non-muscle-invasive bladder cancer.

Recurrence- and progression-free survival in intermediate-risk non-muscle-invasive bladder cancer: the impact of conditional evaluation and subclassification.

To assess the change in rates of recurrence-free survival (RFS) and progression-free survival (PFS) based on the duration of survival without recurrence or progression among patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC), and to examine the predictive factors for recurrence at different time points by assessing conditional RFS and PFS. A cohort of 602 patients treated with transurethral resection of bladder tumour and histopathologically diagnosed with IR NMIBC was included in this retrospective study. The conditional RFS rate at 1, 2, 3, 4 and 5years improved with increased duration of RFS; however, the conditional PFS rate did not improve over time. Multivariable analyses showed that recurrent tumour, multiple tumours, tumour size (>3cm), immediate postoperative instillation of chemotherapy, and administration of BCG were independent predictive factors for recurrence at baseline. The predictive ability of these factors disappeared with increasing recurrence-free survivorship. Subclassification of these patients with IR NMIBC into three groups using clinicopathological factors (recurrent tumour, multiple tumours, tumour size) demonstrated that the high IR group (two factors) had significantly worse RFS than the intermediate (one factor, P < 0.001) and low IR groups (no factor, P = 0.005) at baseline. This subclassification stratified conditional risk of RFS also at 1, 3 and 5 years, which provides the basis for distinct surveillance protocols among patients with IR NMIBC. Conditional survival analyses of patients with IR NMIBC demonstrate that RFS changes over time, while PFS does not change. These data support distinct surveillance protocols based on the subclassification of IR NMIBC.