Instillation Of Chemotherapy Research Articles

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.

Quality indicators for the management of high-risk upper tract urothelial carcinoma requiring radical nephroureterectomy.

The purpose of this article was to identify quality indicators for an optimized management of high-risk upper tract urothelial carcinoma (UTUC) requiring radical nephroureterectomy (RNU). RNU with bladder cuff resection is the standard treatment of high-risk UTUC. For the bladder cuff resection, two main approaches are accepted: transvesical and extravesical. Lymph node dissection following a dedicated template should be performed in all high-risk patients undergoing RNU as it improves tumour staging and possibly survival. Postoperative bladder instillation of single-dose chemotherapy should be administered after RNU to decrease the risk of intravesical tumour recurrence. Perioperative systemic chemotherapy should always be considered for advanced cancers. Although level-1 evidence is available for adjuvant platinum-based chemotherapy, neoadjuvant regimens are still being evaluated. Optimal management of high-risk UTUC requires evidence-based reproducible quality indicators in order to allow guidance and frameworks for clinical practices. Adherence to quality indicators allows for the measurement and comparison of outcomes that are likely to improve prognosis. Based on the literature, we found four evidence-based accepted quality indicators that are easily implementable to improve the management of high-risk UTUC patients treated with RNU: adequate management of the distal ureter/ bladder cuff, template-based lymph node dissection, single-shot postoperative intravesical chemotherapy, and perioperative systemic treatment.

Expressions of P-Glycoprotein, Multidrug Resistance Protein 1 and Annexin A2 as Predictive Factors for Intravesical Recurrence of Bladder Cancer after the Initial Transurethral Resection and Immediate Single Intravesical Instillation of Adriamycin.

Objective:Immediate single instillation of chemotherapy following transurethral resection of bladder tumor (TURBT) is suggested for non-muscle invasive bladder cancer (NMIBC) patients. However, no study has evaluated molecular marker that was involved in intravesical recurrence (IVR) after single instillation of chemotherapy. Therefore, this study aimed to evaluate whether P-glycoprotein, multidrug resistance protein 1 (MRP1), Annexin A2 (ANXA2) or nucleophosmin (NPM) expression predicts IVR after initial TURBT and immediate single intravesical adriamycin instillation. Methods:We retrospectively reviewed consecutive 443 patients who underwent TURBT. Of these, 54 patients who underwent initial TURBT and single instillation of adriamycin for NMIBC were included. The expressions of P-glycoprotein, MRP1, ANXA2 and NPM were evaluated immunohistochemically and were divided into 2 groups (low or high) according to the staining intensity and/or proportion of positive cells. IVR was assessed by Kaplan-Meier method. Cox`s multivaritate analyses were performed to identify independent predictors for IVR. Results: Nineteen patients (35.1%) had IVR. High P-glycoprotein expression was significantly correlated with multiplicity, pT stage and high grade. High ANXA2 expression was significantly correlated with high grade. MRP1 and NPM were not correlated with any clinicopathological variables. MRP1 expression and ANXA2 expression were significantly correlated with P-glycoprotein expression. Patients with high P-glycoprotein expression had significantly worse IVR-free survival (IVRFS) than those with low P-glycoprotein expression (P =0.015). The difference in IVRFS rates between patients with high ANXA2 expression and those with low ANXA2 expression was nearly significant (P =0.057). Univariate analyses indicated multiplicity, high grade and high P-glycoprotein expression were significant predictors for IVR. Multivariate analysis indicated high grade was an independent predictor for IVR. Conclusions: High P-glycoprotein expression was associated with IVR. Further study was needed to determine significance of P-glycoprotein expression in IVR after single intravesical adriamycin instillation.

Continuous bladder irrigation after transurethral resection of non-muscle invasive bladder cancer for prevention of tumour recurrence: a systematic review.

Non-muscle invasive bladder cancer (NMIBC) can recur despite transurethral resection of bladder tumour (TURBT) that clears macroscopic disease, partly from re-implantation of exfoliated cells. Immediate instillation of intravesical chemotherapy (IC) can reduce recurrence, is guideline-recommended but is under-utilized. Continuous bladder irrigation (CBI) immediately post-TURBT is postulated to prevent re-implantation, and may provide a simple, cheap and practical alternative. We undertook a systematic review to assess the effect of CBI on NMIBC recurrence. Following PRISMA guidelines, relevant publications were identified by online search of databases, including Ovid Medline and EMBASE (1980-2019). All published prospective randomized controlled trials comparing CBI post-TURBT to a control group were included. The primary end-point was recurrence. Our search yielded 514 studies, of which six met inclusion criteria. Two studies (935 participants), albeit without peer-reviewed publication, comparing CBI to no CBI both showed a reduction in recurrence at 2 years. Four publications from three trials (331 participants) compared CBI to IC, showing similar recurrence rates at 1year (odds ratio 1.29, 95% confidence interval 0.78-2.13) but a lower risk of adverse events (6-34% versus 27-48%). CBI post-TURBT appears to yield 1-year recurrence rates of NMIBC comparable to immediate IC. However, existing studies are small and of heterogenous design, precluding definitive conclusions. Further trials are required to determine if CBI can be implemented routinely to reduce NMIBC recurrence, as well as the optimal irrigant, volume and duration.

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.

Systemic dissemination of tumor cells during transurethral resection in patients with bladder tumor and its clinical relevance: A follow up study

ObjectiveTumor cells are shed during transurethral resection of bladder tumor (TURBT) and form the basis for use of single dose immediate chemotherapy instillation to reduce recurrences. Systemic dissemination of these cells along with the irrigation fluid is also possible but not consistently proven. In this study, we evaluated such dissemination of tumor cells into the circulation during TURBT and its clinical impact. MethodsPatients with primary presentation of bladder tumor who underwent TURBT were included. Peripheral venous blood samples before and after TURBT were analyzed for circulating tumor cells (CTCs) using flow-cytometry. A CD45 negative cell with positive expression of cytokeratin 18, 19, and EpCam was defined as CTC. The CTC counts, pre and post TURBT, were compared and correlated with final histopathology. The patients were also followed up for any local and/or systemic recurrences. ResultsNine (16.98%) out of 53 patients developed a measurable rise in CTCs after TURBT. All of these patients had high grade and muscle invasive disease. Overall, a measurable rise in CTCs was seen in 9 out of 17 (52.94%) patients with muscle invasive disease. There was no difference in the clinico-pathological stage or the status of cystectomy and/or chemotherapy between those who did or did not show a rise in CTCs. On follow up, 7 patients with muscle invasive disease developed local and/or systemic recurrences and the rise in CTCs was not found to be associated with adverse oncological outcomes. ConclusionsThis study confirms the hypothesis of inadvertent dissemination of tumor cells into the circulation during TURBT, especially in patients with high grade and muscle invasive disease. The long-term oncological impact of such dissemination remains to be confirmed.

Cáncer de vejiga

Bladder cancer is the ninth most frequent neoplasm in the world and the most frequent urinary tract cancer. The most important risk factor is tobacco use in addition to environmental exposure to carcinogens. The most habitual symptom is hematuria. Nonmuscle-invasive bladder cancer includes stages pTa and pT1, although they are two entities with different clinical courses. Their treatment involves transurethral resection (TUR) of the bladder and, depending on the risk stratification, adjuvant intravesical instillation of chemotherapy or immunotherapy as well. Nonmetastatic muscle-invasive bladder cancer is treated with a radical cystectomy and administration of perioperative cisplatin-based chemotherapy. In select cases, multimodal treatment for bladder preservation is an alternative. In metastatic disease, treatment is based on cisplatin-based chemotherapy, immunotherapy, and other new tyrosine kinase inhibitor (TKI) agents and conjugated antibodies.

Audit of immediate instillation of intravesical chemotherapy (mitomycin-C) following transurethral resection for bladder tumour

Audit of immediate instillation of intravesical chemotherapy (mitomycin-C) following transurethral resection for bladder tumour

Single Instillation of Hypertonic Saline Immediately Following Transurethral Resection of Bladder Tumor for Recurrence Prevention -A Phase I Study.

Urologic guidelines recommend perioperative instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) to decrease tumor recurrence, yet implementation of this recommendation is partial due to associated morbidity. Hypertonic saline destroys cells by osmotic dehydration and might present a safer alternative. To evaluate the safety of 3% hypertonic saline (Hypersal) intravesical instillation following TURBT in rats and in humans. In 8 rats whose bladders were electrically injured, intravesical blue-dyed Hypersal was administered. We measured serum sodium levels before and after instillation and pathologically evaluated their pelvic cavity for signs of inflammation or blue discoloration. Twenty-four patients were recruited to the human trial (NIH-NCT04147182), 15 comprised the interventional and 10 the control group (one patient crossed over). Hypersal was given postoperatively. Serum sodium was measured before, 1 hour and 12-24 hours after instillation. Adverse effects were documented and compared between the groups. In rats, average sodium levels were 140.0 mEq/L and 140.3 mEq/L before and following instillation, respectively. Necropsy revealed no signs of inflammation or blue discoloration. In humans the average plasma sodium levels were 138.6 mEq∖L, 138.8 mEq∖L and 137.7 mEq∖L before, 1 hour and 12-24 hours after instillation, respectively. During the postoperative follow-up there was one case of fever. A month after the surgery, dysuria was reported by 5 patients while urgency and hematuria were reported by one patient each. The most severe adverse events were grade 2 on the Clavien-Dindo scale. Adverse events were similar in the control group. Hypersal instillation is safe and tolerable immediately after TURBT.

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.

Effectiveness of an educational program on Nurses' Practices toward Nursing Management of Patients with Transurethral Resection of the Bladder Tumor in Hilla Teaching Hospitals

ABSTRACT: Background: the standard first-line treatment for non-muscle invasive bladder cancer is transurethral resection of bladder tumor (TURBT), followed by instillation of intravesical chemotherapy. The goal of TURBT is to make a correct diagnosis and to remove all visible lesions. Several organizations have published reports on the importance of nursing staff understanding disease process and treatments leading to an improvement in quality of care. Improving the practice process is important to nursing as it improves nursing process, which improves patient outcomes. Aims of the study: To assessing nurses' practices regarding management of patients with transurethral resection of the bladder tumor. And determine the effectiveness of the educational program on nurses' practices concerning management of patients with transurethral resection of the bladder tumor. Methodology: A semi-empirical study was applied that adopted the pre and posttest. The research was conducted in Al-Hilla Teaching Hospital and Al-Imam Al-Sadiq Teaching Hospital in Al-Hilla, and this study continued for the period from 29 \ July \ 2018 to 25 \ December \ 2019. A deliberate sample of 56 nurses from the surgical units of the two aforementioned hospitals was selected. After applying the educational program to the male and female nurses participating in the study for a period of (1 month), a questionnaire consisting of several questions was distributed to assess the extent of the impact of this educational program on the practices of male and female nurses who care for patients who are newly subjected to urethritis. The questionnaire and the educational program were presented to experts in the field to find the truth of the questionnaire. The data were analyzed through a descriptive and deductive statistical analysis.

Topical Instillations of Chemotherapy for Renal Pelvic Urothelial Cancer

Topical Instillations of Chemotherapy for Renal Pelvic Urothelial Cancer

Continuous Bladder Irrigation after Transurethral Resection of Non-Muscle Invasive Bladder Cancer for Prevention of Tumour Recurrence – A Systematic Review

Non-muscle invasive bladder cancer (NMIBC) has a high recurrence rate despite transurethral resection of bladder tumour (TURBT) for clearance of macroscopic disease, partly as a result of seeding from exfoliated malignant cells. The immediate instillation of intravesical chemotherapy (IC) can reduce recurrence and is guideline-recommended but has low usage. It is postulated that continuous bladder irrigation (CBI) immediately post TURBT can itself prevent re-implantation and reduce recurrence, which may provide a simple, cheap and practical alternative to IC. We undertook a systematic review of the literature to assess the effect of CBI on NMIBC recurrence. Following PRISMA guidelines, relevant publications were identified from an online search of the literature using databases including Ovid Medline and EMBASE between 1980 to 2018. All published prospective randomized controlled trials (RCTs) which compared CBI post-TURBT to a control group were included. The primary endpoint of the study was recurrence Our search yielded 514 studies of which six met our inclusion criteria. Two studies (935 participants) comparing CBI to no CBI showed a reduction in recurrence at 2 years. Four publications from 3 trials (331 participants) compared CBI to IC, showing comparable recurrence rates at 1 year (OR 1.29, 95% confidence interval 0.78 to 2.13) but a lower risk of adverse events (6-34% vs 27-48%). CBI post TURBT appears to yield one-year recurrence rates of NMIBC comparable to immediate IC. However, existing studies are small and of heterogenous design, precluding definitive conclusions. Further trials are required to determine if CBI can be implemented routinely to reduce NMIBC recurrence, as well as the optimal irrigant, volume and duration.

Lytic Effects of Water on Bladder Cancer Cell Lines – Implications for Clinical Use of Water Irrigation to Reduce Recurrence

Recurrence of bladder cancer (BC) following initial management with transurethral resection of bladder tumour (TURBT) is observed in 15-60% of patients. Intraoperative tumour spillage can be a concern during TURBT, given that it can lead to tumour cell re-implantation and local recurrence. Immediate post-TURBT instillation of chemotherapy is effective at reducing recurrence, but remains underutilised. There is evidence that mechanically washing out free-floating tumour cells with bladder irrigation may be a comparable but less expensive or toxic alternative. Irrigating with sterile water may be more effective compared to iso-osmotic irrigants (such as saline) by virtue of causing additional osmotic cytolysis, but this has not been well characterised. This in vitro study aimed to ascertain the time-course of osmotic effects of water on BC cell lines to guide its meaningful clinical usage. In-vitro studies were conducted on HT1197 and HT1376 BC cell lines, red blood cells, and white blood cells. Each cell line was exposed to either water, 0.9% saline or 1.5% glycine. Cell counts (in triplicate) were performed at 10, 20, and 40 minutes, and then hourly for up to 5 hours using a haemocytometer. Cell viability was determined using Trypan blue. In both BC cell lines, saline and glycine caused respectively ∼50% and 65% reduction in the number of viable cells after a minimum of 1 hour of exposure (p<0.0001 vs time 0). Conversely, the effect of water was rapid, inducing 100% cell lysis in under 20 minutes (p = 0.0001 vs time 0), while saline and glycine had no measurable effect in this timeframe (p = 0.9255 and 0.0662 vs time 0, respectively). For red blood cells and white blood cells, water also precipitated cell lysis within 10 minutes, whilst saline and glycine had minimal effect. These results suggest that water has a rapid osmolytic effect upon BC cells. If confirmed using ex vivo samples from patients, this suggests that a short period of irrigation with water may potentially be effective in reducing BC recurrence.

Adjuvant Intravesical Chemotherapy in the Management of Superficial Transitional Cell Carcinoma of Urinary Bladder Following Transurethral Resection of Bladder Tumor- Result of Single Dose and Multiple doses of Mitomycin C

Background: Bladder cancer is the second most common cancer of the genitourinary tract. Mitomycin C has been commonly used in a perioperative fashion delivered intravesically immediately after TURBT Objective: To compare the results of post TURBT immediate single dose and multidose regimen of Mitomycin C therapy in the management of superficial transitional cell carcinoma of the urinary bladder. Method: The present prospective and comparative interventional study was conducted in the Department of Urology, National Institute of Kidney Diseases and Urology, Sher-E-Bangla Nagar, Dhaka from January 2015 to December 2016. Patients of superficial bladder cancer (tumor size ≤3 cm, number ≤3, grade I, II) were randomly included in the 2 groups. The sample size was seventy four (74). Thirty (30) patients were in each group and fourteen (14) were excluded from the study. In MMC single dose group (Group A), single dose of MMC 40mg/ 40ml was started immediately within 24 hours of TURBT. In MMC multi-dose group (Group B) 1st instillation of chemotherapy was started immediately within 24 hours of TURBT and additional instillation (5 instillations) were given as OPD basis and was continued weekly for 5 weeks. Follow-up was done on 3rd, 6th, 12th month of initial TURBT. Results: In this study mean age was 61.8±13.7 years in group A and 62.7±13.6 years in group B. Male was found 25 (83.3%) in group A and 26 (86.7%) in group B. Female was found 5 (16.7%) in group A and 4 (13.3%) in group B. Mean size of the tumor was found 2.13±0.78 cm in group A and 2.05±0.84 cm in group B. Mean number of tumor was found 1.8±0.8 in group A and 1.9±0.7 in group B. Tumor grade I was found 23 (76.7%) in group A and 25 (83.3%) in group B. Tumor status Ta of superficial bladder was found 25 (83.3%) in group A and 26 (86.7%) group B. Tumor status T1 of superficial bladder was found 5(16.7%) in group A and 4 (13.3%) group B. Five (16.7%) patients was found recurred in group A and 4 (13.3%) in group B at 6th month follow up. At 12th month follow up, 6 (20.0%) patients was found recurred in group A and 5 (16.7%) in group B. Side effect was found in 2 (6.7%) patients in group B and not found in group A. Conclusion: MMC single dose was similar to MMC multi-dose regimen with insignificant difference among the two. Bangladesh Journal of Urology, Vol. 23, No. 1, January 2020 p.62-66

The role of Protopine associated with Nuciferine in controlling adverse events during hyperthermic intravesical chemotherapy instillations. A nutraceutical approach to control adverse event during intravesical instillations.

The aim of this study was to analyse the role of two alkaloid, Protopine and Nuciferine, in the prevention and the treatment of the low and mild grade adverse events related to the use of HIVEC® (Hyperthermic IntraVEsical Chemotherapy) instillations. From September 2017 to September 2019, 100 patients were prospectively randomized into two groups: Group A = Protopine and Nuciferine syrup, 10 ml, once a day, for 8 weeks; Group B = placebo (flavoured coloured water), 10 ml, once a day, for 8 weeks. The primary endpoint was the evaluation of the efficacy of the therapy with Protopine and Nuciferine in controlling of the irritative symptoms. The secondary endpoint was the evaluation of the influences of the treatment on the uroflowmetric parameters. The patients of Group A showed a better International Prostatic Symptoms Score (IPSS) score, a better control of urgency symptoms (PPIUS) and tolerate well the pain (VAS score). The treatment doesn't modify Uroflow-Qmax and seems to improve the Uroflow-Voided Volume (ml) without influencing the Uroflow-Post Void Residual volume (PVR). Moreover, the treatment with Protopine and Nuciferine has been proven to be effective in the treatment of overactive bladder (OAB) symptoms. Patients' evaluation of the two different treatments assessed with Patient Global Impression of Improvement questionnaire (PGI-I), demonstrated improvements in the Group A, while the Group B showed a lower satisfaction. Protopine and Nuciferine can be interesting nutraceutical compounds useful to control irritative and pain related symptoms of intravesical chemo/immunotherapy.

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.

The DaBlaCa-13 Study: Short-term, Intensive Chemoresection Versus Standard Adjuvant Intravesical Instillations in Non–muscle-invasive Bladder Cancer—A Randomised Controlled Trial

BackgroundInstillation therapy for non–muscle-invasive bladder cancer (NMIBC) reduces recurrences but is associated with side effects. Preoperative instillation of chemotherapy could potentially be associated with fewer side effects compared with adjuvant instillations and in some patients make tumour resection (transurethral resection of the bladder tumour [TURBT]) superfluous. ObjectiveTo investigate tumour response and adverse events related to short-term, intensive chemoresection with mitomycin C compared with adjuvant instillations in patients with recurrent NMIBC. Design, setting, and participantsA randomised, controlled trial was conducted in two urological departments in Denmark from January 2018 to June 2019. In total, 120 participants with a history of Ta bladder tumours, low grade or high grade, were included upon recurrence. InterventionIntravesical mitomycin C (40 mg/40 ml) three times a week for 2 wk in the intervention group (59 patients) was compared with TURBT and six weekly adjuvant instillations in the control group (61 patients). Outcome measurements and statistical analysisTumour response was evaluated in the intervention group by flexible cystoscopy after 4 wk. Side effects were prospectively registered in both groups using the National Cancer Institute’s Common Terminology Criteria for Adverse Events. Groups were compared using χ2 or Fisher's exact test. Results and limitationsComplete tumour response was seen in 33 participants (57%) in the intervention group. Fewer adverse events were reported in the intervention group than in the control group. Two patients in each group ceased instillation treatment due to adverse events. The main limitation is the current lack of long-term follow-up. ConclusionsShort-term, intensive chemoresection yields a tumour response of 57%. Hence, only half of those treated with chemoresection needed TURBT. The treatment was furthermore associated with fewer clinically significant side effects. Owing to small numbers, further investigations on Ta high-grade tumours are needed. Patient summaryWe compared a nonsurgical treatment with standard treatment in patients with superficial bladder tumours. We found it to be safe and able to avoid surgery in more than half of the patients.

Prediction of non-muscle-invasive bladder cancer recurrence during intravesical BCG immunotherapy by use of peripheral blood eosinophil count and percentage: a preliminary report.

To determine whether there is an association between blood eosinophil count and percentage with the recurrence of nonmuscle invasive bladder cancer (NMIBC) during Bacillus Calmette-Guérin (BCG) maintenance therapy with our preliminary results. A total of 53 patients with NMIBC underwent BCG immunotherapy between January 2015 and September 2018, and met our inclusion criteria were included in the study. The parameters age, gender, smoking status, comorbidity, blood neutrophil, lymphocyte and eosinophil counts, blood eosinophil percentage, previous single postoperative intravesical chemotherapy instillation, tumor characteristic, and total and maintenance dose numbers of BCG were extracted from our medical records and compared between patients with response and with recurrence. Blood eosinophil count and percentage were significantly higher in patients with recurrence compared to patients with response (0.263 ± 0.37 vs. 0.0134 ± 0.021, p = 0.01 and 0.31 ± 0.29 vs. 0.17 ± 0.27, p = 0.01). Other parameters were similar in patients with recurrence and response. Receiver-operating characteristic analysis showed a considerable diagnostic value of blood eosinophil count and percentage in the prediction of bladder cancer recurrence during BCG immunotherapy. Blood eosinophil count and percentage in patients with NMIBC can predict the disease recurrence during the BCG immunotherapy. Our research raised new questions and assumptions about the role of eosinophils during BCG immunotherapy.

Intraoperative prophylactic intravesical chemotherapy to reduce bladder recurrence following radical nephroureterectomy

PurposeSingle, postoperative instillation of prophylactic intravesical chemotherapy (pIVC) is effective in reducing bladder cancer recurrences following radical nephroureterectomy (RNU). Despite high level evidence, pIVC is underutilized. Intraoperative pIVC (I-pIVC) may be easier and safer to implement than postoperative pIVC (P-pIVC). We aimed to evaluate the efficacy of I-pIVC during RNU. Materials and methodsRetrospective analysis of patients undergoing RNU and I-pIVC or postoperative pIVC (P-pVC) with 20 to 40 mg mitomycin-C or 1 to 2 g gemcitabine. Recurrence rates were evaluated using the Kaplan-Meier curves and log rank test. Cox regression was used for univariable and multivariable analysis. ResultsOne hundred and thirty-seven patients were included in the final analysis. 81% (111/137) had I-pIVC and 19% (26/137) had P-pIVC. In the I-pIVC group higher rates of HG, muscle invasive disease and gemcitabine use were observed. Overall, 74% (101/137) and 26% (36/137) had mitomycin-C and gemcitabine instillations, respectively. Within 12 months 14% (19/137) of the patients experienced bladder recurrence. Median time to bladder recurrence was 7 months (range 3–27). Twelve months bladder recurrence-free survival rates were 82% for the I-pIVC group, and 72% for the P-pIVC group ((log rank P = 0.365). ConclusionsI-pIVC during RNU may reduce bladder recurrence rates. Bladder recurrence rates are comparable to those reported using postoperative instillations. Intraoperative instillations may be easier to implement and may increase usage rates.