OBJECTIVE: To explore if switching intravesical chemotherapeutic agents is beneficial in short-term recurrences of high-risk non-muscle-invasive bladder cancer (NMIBC) following the failure of preceding intravesical therapy.
METHODS: From June 2010 to October 2015, 205 patients with NMIBC who experienced tumor recurrence within a year after receiving first-line intravesical chemotherapy (IVC) were classified into two groups. After a second complete transurethral resection (TUR) process, we immediately altered the intravesical instillation agent for 107 patients (group A). In contrast, the remaining 98 patients (group B) continued using their original intravesical instillation agent. After transurethral resection of the bladder tumor (TURBT), all patients received either an immediate instillation of epirubicin (EPI), gemcitabine (GEM), or hydroxycamptothecin (HCPT), followed by regular induction and maintenance instillations. Recurrence and progression rates were evaluated using the Chi-square test, and recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method.
RESULTS: In this study, there was no significant difference in either the 5-year tumor recurrence or progression rates between the two groups (p > 0.05) The Kaplan-Meier plot showed no difference in progression-free or recurrence-free survival between the two groups.
CONCLUSIONS: Switching IVC agents does not improve RFS and PFS for patients with short-term recurrent high-risk NMIBC.

OBJECTIVE: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC.
METHODS: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC).
RESULTS: The median follow-up was 5.2 years. Compared with instillation for 1-2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3-6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27-12.41;0.26-9.28;0.07-0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC.
CONCLUSIONS: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.

Bladder cancer is one of the most common malignancies in the urinary system, with high risk of recurrence and progression. However, the difficulty in detecting small tumor lesions and the lack of selectivity of intravesical treatment seriously affect the prognosis of patients with bladder cancer. In the present work, a nanoparticle-based delivery system with tumor targeting, high biocompatibility, simple preparation, and the ability to synergize imaging and therapy was fabricated. Specifically, this nanosystem consisted of the core of doxorubicin (DOX)-loaded polydopamine nanoparticles (PDD NPs) and the shell of hyaluronic acid (HA)-conjugated IR780 (HA-IR780). The HA-IR780-covered PDD NPs (HR-PDD NPs) demonstrated tumor targeting and visualization both in vitro and in vivo with properties of promoted cancer cell endocytosis and lysosomal escape, efficiently delivering drugs to the target site and exerting a killing effect on tumor cells. Encouragingly, intravesical instillation of HR-PDD NPs improved drug retention in the bladder and promoted its accumulation in tumor tissue, resulting in better tumor proliferation inhibition and apoptosis in an orthotopic bladder cancer model in rats. This study provides a promising strategy for the diagnosis and therapy of bladder cancer.

Surgical resection remains the prefer option for bladder cancer treatment. However, the effectiveness of surgery is usually limited for the high recurrence rate and poor prognosis. Consequently, intravesical chemotherapy synergize with immunotherapy in situ is an attractive way to improve therapeutic effect. Herein, a combined strategy based on thermo-sensitive PLEL hydrogel drug delivery system was developed. GEM loaded PLEL hydrogel was intravesical instilled to kill tumor cells directly, then PLEL hydrogel incorporated with CpG was injected into both groins subcutaneously to promote immune responses synergize with GEM. The results demonstrated that drug loaded PLEL hydrogel had a sol-gel phase transition behavior in response to physiological temperature and presented sustained drug release, and the PLEL-assisted combination therapy could have better tumor suppression effect and stronger immunostimulating effect in vivo. Hence, this combined treatment with PLEL hydrogel system has great potential and suggests a clinically-relevant and valuable option for bladder cancer.

To clarify the necessity and effect of a single intraoperative instillation of chemotherapy during radical cystectomy.
Patients who underwent radical cystectomy for bladder cancer between January 2013 and April 2019 were retrospectively evaluated and divided into a non-instillation group and an instillation group according to the intraoperative instillation of chemotherapy. Univariate and multivariate Cox regression was used to determine the clinical predictors of overall survival and disease-free survival. Kaplan-Meier analysis and log-rank tests were performed to analyze overall survival and disease-free survival.
Of the 320 patients who were enrolled in the study, 113 underwent radical cystectomy with intraoperative instillation of chemotherapy. Univariate Cox analysis showed that intraoperative instillation was not a risk factor for overall survival or disease-free survival (HR: 1.04, 95% CI: 0.66-1.63, p = 0.864; HR: 1.11, 95% CI: 0.76-1.62, p = 0.602, respectively). As shown in the Kaplan-Meier analysis, no significant differences were noted in overall survival (p = 0.857) and disease-free survival (p = 0.600) between the two groups. A subgroup analysis demonstrated that intraoperative instillation was not associated with a statistically better overall survival and disease-free survival in the nonmuscle invasive (p = 0.852 and 0.836) and muscle-invasive (p = 0.929 and 0.805) patients.
A single intraoperative instillation of chemotherapy during radical cystectomy was not related to better disease-free survival or overall survival. It is unnecessary to consider single instillation of chemotherapy as a regular procedure during radical cystectomy.

UNASSIGNED: The inflammatory response plays a potential role in postoperative recurrence in patients with non-muscular invasive bladder cancer (NMIBC). We aimed to investigate whether platelet-to-lymphocyte ratio (PLR), mean platelet volume to lymphocyte ratio (MPVLR), and the systemic immune-inflammatory index (SII) have prognostic values in NMIBC treated with conventional intravesical chemotherapy or intravesical Chemohyperthermia (CHT) and the differences between them.
UNASSIGNED: A retrospective cohort study was conducted on 222 patients with NMIBC treated with Intravesical Chemotherapy or Intravesical CHT between January 2016 and December 2020. Within a week before surgery, PLR, MPVLR, and SII were determined based on routine blood settling. The optimal cutoff value of each index was determined using the receiver operating characteristic curve, and various groups were categorized accordingly. The factors influencing the prognosis of NMIBC patients receiving various treatments were investigated using the Kaplan- Meier survival curve and the Cox regression model.
UNASSIGNED: 69 cases (46.3%) in the gemcitabine (GEM) group had tumor recurrence and 19 (12.8%) of them progressed to muscle-invasive bladder cancer (MIBC) or got metastasis, while 19 cases (26.0%) in the CHT group recurred and 2 (2.7%) progressed. Elevated PLR, MPVLR, and SII were associated with higher recurrence rates in the GEM group. Meanwhile, PLR and MPVLR were the independent risk factors. While in the CHT group, high PLR and SII were related to postoperative recurrence and none of them were independent risk factors.
UNASSIGNED: The preoperative clinical inflammatory indexes PLR, SII, and MPVLR have certain predictive value for the postoperative recurrence-free survival (RFS) in NMIBC patients treated with intravesical chemotherapy while PLR and SII can predict the prognosis of NMIBC patients treated with intravesical CHT, which indicates that intravesical CHT may stop tumor recurrence by influencing the effect of mean platelet volume on tumor growth through some unknown mechanisms.

To evaluate the safety and efficacy of a novel hyperthermic intravesical chemotherapy (HIVEC) device in combination with gemcitabine.
A pilot clinical trial was performed on patients with high-risk non-muscle invasive bladder cancer (NMIBC), who received HIVEC via the novel device (BR-PRG). Treatment regimen included eight weekly instillations of intravesical GEM (3 g in 150 mL normal saline [NS]) at a temperature of 45 °C for 60 min. Assessment of adverse events (AEs) was the primary objective of the trial. Disease recurrence and the thermal stability of GEM were also analyzed.
A total of 116 HIVEC treatments were delivered. Fifteen and eighteen patients were included in the effectiveness and safety analysis, respectively. Median follow-up was 12 months; five patients experienced a disease recurrence. One-year cumulative incidence of recurrence was 23.8% in EORTC intermediate risk group and 37.5% in high-risk group. Ten patients experienced at least one AE, with the most common being acute urinary tract infection, followed by urinary tract pain, and hematuria. Two patients experienced acute cystitis (grade 3 AE) and instillations were postponed until full recovery. Other AEs were minor, and no systemic toxicity was observed. The contents of GEM in solution of 0.9% NS or NS mixed with artificial urine were stable at 25 °C, 37 °C, 43 °C, 45 °C, 47 °C and 50 °C for 2 h.
GEM can be an ideal drug for use in HIVEC due to its good thermal stability. BR-PRG, combined with GEM was safe and effective in administering HIVEC.

BACKGROUND: Perioperative intravesical chemotherapy (IVC) at or around the time of radical nephroureterectomy (RNU) reduces the risk of intravesical recurrence. Guidelines since 2013 have recommended its use. The objective of this study is to examine IVC utilization and determine predictors of its administration within a large international consortium.
METHODS: Data was collected from 17 academic centers on patients who underwent robotic/laparoscopic RNU between 2006 and 2020. Patients who underwent concomitant radical cystectomy and cases in which IVC administration details were unknown were excluded. Univariate and multivariate analyses were utilized to determine predictors of IVC administration. A Joinpoint regression was performed to evaluate utilization by year.
RESULTS: Six hundred and fifty-nine patients were included. A total of 512 (78%) did not receive IVC while 147 (22%) did. Non-IVC patients were older (P < 0.001), had higher ECOG scores (P = 0.003), and had more multifocal disease (23% vs. 12%, P = 0.005). Those in the IVC group were more likely to have higher clinical T stage disease (P = 0.008), undergone laparoscopic RNU (83% vs. 68%, P < 0.001), undergone endoscopic management of the bladder cuff (20% vs. 4%, P = 0.008). Multivariable regression showed that decreased age (OR 0.940, P < 0.001), laparoscopic approach (OR 2.403, P = 0.008), and endoscopic management of the bladder cuff (OR 7.619, P < 0.001) were significant predictors favoring IVC administration. Treatment at a European center was associated with lower IVC use (OR 0.278, P = 0.018). Overall utilization of IVC after the 2013 European Association of Urology (EAU) guideline was 24% vs. 0% prior to 2013 (P < 0.001). Limitations include limited data regarding IVC timing/agent and inclusion of minimally invasive RNU patients only.
CONCLUSIONS: While IVC use has increased since being added to the EAU UTUC guidelines, its use remains low at academic centers, particularly within Europe.

Bladder cancer is one of the most common malignant tumors in urinary system. Intravesical chemotherapy is a common adjuvant therapy after transurethral resection of bladder tumors. However, it has several disadvantages such as low drug penetration rate, short residence time, unsustainable action and inability to release slowly, thus new drug delivery and new modalities in delivery carriers need to be continuously explored. Nano-drug delivery system is a novel way in treatment for bladder cancer that can increase the absorption rate and prolong the duration of drug, as well as sustain the action by controlling drug release. Currently, nano-drug delivery carriers mainly included liposomes, polymers, and inorganic materials. In this paper, we reveal current researches in nano-drug delivery system in bladder cancer intravesical chemotherapy by describing the applications and defects of liposomes, polymers and inorganic material nanocarriers, and provide a basis for the improvement of intravesical chemotherapy drugs in bladder cancer.

UNASSIGNED: Kidney-sparing surgery (KSS) for upper tract urothelial carcinomas (UTUCs) has been gradually performed in selected patients beyond the recommendation of guidelines. However, there is still a lack of tools to evaluate postoperative local recurrence. Herein, a new nomogram was established to predict the local recurrence risk after KSS.
UNASSIGNED: Patients were randomly divided into two cohorts (training: testing cohorts = 7:3). Cancer samples after KSS were used for immunohistochemical tests to detect molecules missing in previous pathology reports. Then, the total number of molecules were screened by the least absolute shrinkage and selection operator (LASSO) method to construct an IHCscore, which was further tested in the validation cohort. Finally, the IHCscore and other clinicopathologic parameters were combined to develop a more accurate model using univariate and multivariate Cox regression methods.
UNASSIGNED: In total, 200 patients were included. The Kaplan-Meier test showed that high Ki-67 and loss of Uroplakin III and E-cadherin were correlated with poor recurrence-free survival. The individual IHCscore was calculated based on the expression levels of Ki-67, Her2 and E-cadherin. Based on the IHC score, patients were further classified as low- or high-risk, and a significant difference in the recurrence-free survival was observed between the two groups. Then, the nomogram was developed based on Gender, surgical margin and IHCscore; this nomogram had a higher AUC (0.847) in predicting 3-year recurrence-free survival than the IHCscore alone (0.788).
UNASSIGNED: This easy-to-use nomogram shows better prediction accuracy in recurrence-free survival after KSS and may guide individualized intravesical chemotherapy. However, a larger sample is required for external validation.