Electromotive Drug Administration Research Articles

Patient-reported subjective outcome after electromotive drug administration for Peyronie’s disease

Patient-reported subjective outcome after electromotive drug administration for Peyronie’s disease

Alternative Therapy to Intravesical Bacillus Calmette–Guerin in Nonmuscle Invasive Bladder Cancer

Summary Intravesical Bacillus Calmette-Guerin (BCG) is recommended as an adjuvant therapy for intermediate and high-risk bladder cancers following complete resection. However, up to 45% of patients receiving BCG experience treatment failure. High failure rates along with increased toxicity and a global shortage of BCG availability have led to the search for alternative agents which can replace BCG. These agents can be used as second-line therapies after BCG failure before considering patients for radical cystectomy. Intravesical chemotherapeutic agents such as gemcitabine, docetaxel, valrubicin, sequential gemcitabine-docetaxel, and sequential valrubicin-docetaxel have been shown to yield comparable or better outcomes compared to BCG with low toxicity. Newer methods of drug delivery such as chemohyperthermia (CHT), electromotive drug administration (EMDA) and targeted releasing system 200 (TAR-200) have been reported to amplify drug delivery and enhance outcomes. The immune checkpoint inhibitor pembrolizumab has been used for BCG unresponsive disease with satisfactory response rates but with a higher risk of adverse events. A newer immunotherapeutic agent, ALT-803/N-803, which is an interleukin 15 superagonist, has shown promising short-term results. Novel oncolytic viral delivery systems such as nadofaragene-firadenovac, CG0070, CG0070-pembrolizumab have been shown to alter immune response and destroy malignant cells with good short-term outcomes. The number of BCG alternatives has surged in the recent past and newer agents continue to emerge. Expanding the study populations and long-term follow-up will enable affirming these alternatives as BCG equivalents in the future.

Device-Assisted Therapy in Non-Muscle-Invasive Bladder Cancer.

Intravesical therapy is a critical component in the management of non-muscle-invasive bladder cancer (NMIBC), as it reduces rates of disease recurrence and progression. However, the presence of physiologic barriers in the urothelium reduces the penetration and distribution of intravesical chemotherapy, thereby limiting the therapeutic potential. Much progress to overcome this challenge has been made in the realm of intravesical device-assisted therapy. Novel device-assisted treatments include hyperthermia, the radiofrequency-induced thermochemotherapy effect, electromotive drug administration, and implantable drug delivery systems. Notably, chemotherapy enhanced by these device-assisted systems has shown improved oncologic efficacy relative to standard intravesical chemotherapy and comparable outcomes relative to Bacillus Calmette-Guérin (BCG) therapy in patients with intermediate- or high-risk NMIBC. Recent studies also support the utility of device-assisted therapy as a salvage treatment option in patients with BCG-unresponsive disease. Ongoing randomized controlled trials and prospective investigations will further help clarify indications and long-term safety outcomes of these treatment modalities in NMIBC. Herein, we present a comprehensive review of device-assisted therapies and discuss their clinical utilities for the management of NMIBC in the modern era.

Electromotive Drug Administration in the Porcine Renal Pelvis: First Report.

Introduction: Electromotive Drug Administration (EMDA) amplifies drug delivery deep into targeted tissues. We tested, for the first time, the ability of EMDA to deliver methylene blue into the urothelium of the renal pelvis. Materials and Methods: In an anesthetized female pig, both proximal ureters were transected two inches distal to the ureteropelvic junction. An 8F dual lumen catheter and a 5F fenestrated catheter with an indwelling silver wire were inserted into both renal pelvises following which methylene blue (0.1%) was infused at a rate of 5 mL/min for 20 minutes. In one pelvis, a 4 mA positive pulsed electrical current was applied to the silver wire. Results: In contrast to the control pelvis, the EMDA side macroscopically exhibited dense homogeneous staining; microscopy revealed penetration of methylene blue into the urothelium/lamina propria. Conclusion: In the porcine renal pelvis, application of EMDA increased the penetration of a charged molecule into the urothelium/lamina propria.

Device-assisted intravesical chemotherapy versus bacillus Calmette-Guerin for intermediate or high-risk non-muscle invasive bladder cancer: a systematic reviewer and meta-analysis.

To investigate the effectiveness and safety of device-assisted intravesical chemotherapy compared to Bacillus Calmette-Guerin (BCG) in the treatment of patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). In February 2023, a systematic search was conducted on the PubMed, Cochrane, and Embase databases. Following the PRISMA guidelines, a systematic review and meta-analysis of the primary outcomes of interest were performed. The review was prospectively registered on PROSPERO under the registration number CRD42023398559. A total of 10 studies involving 1160 patients were included. The results of the meta-analysis showed that compared to BCG, device-assisted chemotherapy had a lower recurrence rate (OR: 0.63, 95% CI: 0.48-0.84, p = 0.001), longer recurrence-free survival (OR: 0.64, 95% CI: 0.47-0.88, p = 0.006), and lower incidence of fever (OR: 0.18, 95% CI: 0.08-0.44, p = 0.0002). However, no significant differences were observed between the two groups in terms of progression, overall survival, progression-free survival, disease-free survival, overall adverse events, serious adverse events, hematuria, allergy, and general discomfort. Subgroup analysis revealed that neither chemohyperthermia (CHT) nor electromotive drug administration (EMDA) showed statistically significant differences in oncological outcomes compared to BCG. Regarding adverse events, both CHT and EMDA groups showed lower rates of fever compared to the BCG group (OR: 0.26, 95% CI: 0.10-0.67, p = 0.005, and OR: 0.14, 95% CI: 0.05-0.37, p < 0.0001, respectively). No significant differences were observed in the remaining adverse events between either the CHT or EMDA group and the BCG group. Device-assisted intravesical chemotherapy appears to be a safe and viable alternative to BCG for patients with intermediate and high-risk NMIBC, showing comparable oncological outcomes and adverse events.

Sequential Treatment With Bacillus Calmette-Güerin (BCG) and Mitomycin C Administered With Electromotive Drug Administration (EMDA) in Patients With High-Risk Nonmuscle Invasive Bladder Cancer After BCG Failure.

Nowadays, there is no standard non-surgical treatment for patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Güerin (BCG) therapy has failed. To assess the clinical and oncological outcomes of sequential treatment with Bacillus Calmette-Guerin (BCG) and Mitomycin C (MMC) administered with Electromotive Drug Administration (EMDA) in patients with high-risk NMIBC who fail BCG immunotherapy. We retrospectively studied patients with NMIBC who failed BCG and received alternating BCG and Mitomycin C with EMDA between 2010 and 2020. Treatment schedule consisted in an induction therapy with 6 instillations (BCG, BCG, MMC+EMDA, BCG, BCG, MMC+EMDA) and a 1-year maintenance. Complete response (CR) was defined as the absence of high-grade (HG) recurrences during follow-up, and progression was defined as the occurrence of muscle invasive or metastatic disease. CR rate was estimated at 3, 6, 12, and 24 months. Progression rate and toxicity were also assessed. Twenty-two patients were included with a median age of 73 years. Fifty percent of tumors were single, 90% were smaller than 1.5cm, 40% were GII (HG) and 40% were Ta. CR rate was 95.5%, 81% and 70% at 3 and 6 months, 12 months and 24 months, respectively. With a median follow-up of 28.8 months, 6 patients (27%) presented HG recurrence and only 1 patient (4.5%) progressed and ended in cystectomy. This patient died due to metastatic disease. Treatment was well tolerated and 22% of the patients presented adverse effects, being dysuria the most frequent one. Sequential treatment with BCG and Mitomycin C with EMDA achieved good responses and low toxicity in selected patients who did not respond to BCG. Only 1 patient ended in cystectomy and died due to metastatic disease, therefore, cystectomy was avoided in most cases.

Electromotive Drug Administration in the Ureter in an In-Vivo Animal Model: Initial Report.

Electromotive Drug Administration (EMDA) delivers a drug deeply into targeted tissues, such as the bladder. EMDA has never been applied to the ureter. In four in vivo porcine ureters, a unique EMDA catheter containing a silver conducting wire was advanced for the infusion of methylene blue. In two ureters, a pulsed current was delivered via an EMDA machine, while the other two ureters served as a control. After 20 minutes of infusion, the ureters were harvested. In the EMDA ureter, there was diffuse staining of the urothelium; penetration of methylene blue occurred in the lamina propria and muscularis propria. In the control ureter, there was only patchy staining of the urothelium. In this first report of ureteral EMDA, a charged molecule penetrated beyond the urothelium into the lamina propria and muscularis propria of the porcine ureter.

Electromotive Drug Administration Chemotherapy with Mitomycin C Versus Bacillus Calmette-Guerin for the Treatment of Non-Muscle Invasive Bladder Cancer.

Devices that increase the penetrance of intravesical chemotherapeutics are emerging as alternatives to classical Bacillus Calmette Guérin (BCG) treatment. To compare the efficacy of mitomycin C applied with the electromotive drug delivery device (MMC-EMDA) versus BCG in patients with intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) without carcinoma in situ (CIS). Prospective non-randomized study in which 47 patients received MMC-EMDA (40 mg of MMC diluted in 50 mg of distilled water at 20 mA for 30 min. Regimen of 6 weekly and then 6 monthly instillations) and 48 patients received BCG (50 mg of OncoCITE® diluted in 50 ml of normal saline for 60 min. Regimen of 6 weekly instillations and then 3 weekly instillations at months 3, 6 and 12). The primary endpoint was the recurrence-free rate (RFR) at 24 months. Secondary endpoints were time to recurrence and progression-free rate (PFR) at 24 months follow-up. Baseline patient assessment and mean follow-up time were similar in both groups (MMC-EMDA group: 26.4 months; BCG group: 28.4 months (p = 0.44)). The RFR at 24 months was 80.9% for the MMC-EMDA group and 77.1% for the BCG group (p = 0.969). The mean time to recurrence was 12.5 months in the MMC-EMDA group and 14 months in the BCG group (p = 0.681). At 24 months, PFR was 97.9% in the MMC-EMDA group and 93.8% in the BCG group (p = 0.419). No differences were found between MMC-EMDA and BCG treatments in patients with high-risk and intermediate-risk NMIBC without CIS.

A systematic review of the efficacy of intravesical electromotive drug administration therapy for non-muscle invasive bladder cancer.

Non-muscle invasive bladder cancer (NMIBC) is characterized by a high rate of recurrence and progression, despite surgery and adjuvant therapies. To analyze the published results on the effectiveness of mitomycin C (MMC) applied with an electromotive drug administration device (EMDA) in the treatment of patients with non-muscle invasive bladder tumors. A systematic review was conducted using the PubMed and Google Scholar search platforms. We selected the studies that included the recurrence and/or progression rates or complete response rate in patients diagnosed with NMIBC according to their treatment and included MMC applied with EMDA. The last search was performed in November 2021. The search yielded 64 articles; 11 articles met the selection criteria. In two of the 11 selected articles, mitomycin C was applied with an EMDA device (MMC-EMDA) as an ablative treatment, avoiding surgery in 50% of the patients. In 1 of the 11 studies, the application of MMC-EMDA was used as an induction treatment using a single preoperative instillation with promising results. In the remaining 8 studies, adjuvant MMC was applied with the EMDA device; in 3 of these 8 cases, treatment with MMC-EMDA alone was applied initially. In another3 cases the same treatment was applied after nonresponse to bacillus Calmette Guerin (BCG), and in the last 2 studies, MMC-EMDA was applied in combination with the classic therapy (BCG). All the studies selected supported the efficacy and safety of MMC-EMDA in patients with intermediate and high- risk bladder cancer. In 3 studies, adjuvant therapy with MMC-EMDA was performed in nonresponders to BCG, finding that adjuvant therapy with MMC-EMDA applied to BCG nonresponders without CIS avoided or delayed surgery. The application of EMDA-enhanced MMC has been studied at different times of disease and with different administration protocols. It appears to delay bladder tumor recurrence and progression in certain populations. However, the methodological limitations of the published studies prevent definitive conclusions about its efficacy.

МODERN NON-INVASIVE METHODS FOR TREATING PEYRONIE'S DISEASE

Summary: Peyronie's disease (PD) is a common disease in men that can lead to significant penile deformity and pain, erectile dysfunction, and mental health problems. So far, surgical correction with plaque removal offers the greatest likelihood of success during the stable phase of the disease. However, for men in the acute phase of PD or those with a milder deformity who choose to avoid surgery, conservative treatment methods are also available. New innovative methods are extracorporeal shock wave therapy (ESWT) and ultrasound therapy. Intralesional therapy with IFN-α2b, verapamil, and Clostridium histolyticum (CCH) collagenase can significantly reduce penile deviation (PD), but these results may not be clinically significant in men with more severe disease. Iontophoresis (EMDA, electromotive drug administration) of verapamil and cortisone have shown reductions in PD and penile pain.Penile traction therapy offers clinically significant improvement in penile length and curvature. It requires daily therapy lasting several hours. Oral therapies with substances such as L-arginine, L-citrulline, vitamin E and phosphodiesterase inhibitors are most helpful as part of a combination regimen rather than as monotherapy. Regenerative therapies with stem cells and platelet-rich plasma, as well as intralesional therapy with botulinum toxin (Botox) have not yet been well clinically studied and their possible application is currently taking place within the framework of clinical research. The combination of various oral, topical, intralesional therapies, extracorporeal shock wave therapy, ultrasound and traction therapies together with clinical psychosexual therapy if needed could provide a more effective treatment, which in turn could prevent or reduce the need for definitive reconstructive penile surgery. Materials and methods: For the purposes of the literature review, a systematic search was conducted for articles in German and English on non-invasive treatment methods for Peyronie's disease. The articles were selected according to their relevance to the given topic. The main findings were summarized and presented in tabular form.

Conservative treatment for high-risk NMIBC failing BCG treatment: who benefits from adding electromotive drug administration (EMDA) of mitomycin C (MMC) to a second BCG induction cycle?

PurposeRadical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course.MethodsPatients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested.ResultsOf the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC.ConclusionCombined treatment improved RFS and PFS only in patients with Ta disease.

A systematic review on the available treatment modalities for Bacillus Calmette-Guérin-unresponsive carcinoma in situ and tumors in patients who are ineligible for or decline radical cystectomy.

Globally, urothelial bladder carcinoma is a disease which carries a poor prognosis. There are various treatment modalities for urothelial bladder carcinoma with intravesical Bacillus Calmette-Guérin immunotherapy being the most efficacious intravesical therapy and the treatment of choice for patients with carcinoma in situ. A number of chemotherapeutic drugs are also available for the management of Ta/T1 tumors such as mitomycin C and epirubicin. However, relapse and progression is quite common. The optimal management of patients with Bacillus Calmette-Guérin-unresponsive disease remains to be a challenge. The purpose of this study was to conduct a systematic review on the treatment modalities available for the management of Bacillus Calmette-Guérin-unresponsive carcinoma in situ and urothelial bladder carcinoma in patients who are ineligible or decline radical cystectomy. Two authors independently searched three databases on the treatment modalities available for the management of Bacillus Calmette-Guérin-unresponsive carcinoma in situ and Bacillus Calmette-Guérin-unresponsive urothelial bladder carcinoma. The systematic search resulted in 15 studies. We recommend the use of intravesical CG0070 adenovirus or hyperthermic intravesical chemotherapy mitomycin C in patients with carcinoma in situ only disease. In patients with carcinoma in situ ± Ta/T1 disease, we recommend the use of intravesical radiofrequency-induced chemohyperthermia or electromotive drug administration of mitomycin C. In patients who have Ta/T1 disease, we recommend the use of either hyperthermic intravesical chemotherapy epirubicin or electromotive drug administration mitomycin C followed by chemohyperthermia mitomycin C. If any of these second line therapies fail, an alternative regimen would be a combination of gemcitabine, cabazitaxel, and cisplatin. This recommendation is subject to the available resources and clinical expertise available in different hospitals. More studies using study designs such as randomized controlled trials comparing multiple drugs with larger sample sizes and regular follow-up intervals should be performed to accurately assess the different medications and aid in designing guidelines to guide the management of Bacillus Calmette-Guérin-unresponsive non-muscle invasive intravesical bladder cancer.

Conductive hyperthermic chemotherapy versus electromotive drug administration of mitomycin C as intravesical adjuvant treatment of patients with intermediate or high-risk non-muscle invasive bladder cancer

BackgroundDevices that increase the penetration of intravesical chemotherapeutic agents have been developed as alternatives to the use of bacillus Calmette–Guérin, in short supply at a time of increasing global incidence of non-muscle invasive bladder cancer (NMIBC).We performed a prospective observational study to compare 2 of these devices in the treatment of patients with high- and intermediate-risk NMIBC. The primary endpoint was the recurrence-free rate. Secondary endpoints were the rate of progression and adverse events. MethodsAfter undergoing transurethral bladder resection, 98 patients were selected to receive 1 of 2 treatments: hyperthermic intravesical chemotherapy (HIVEC) treatment with 40 mg of mitomycin C (MMC) using Combat BRS System V2.0 at 43 ± 0.5°C and 200 ml/min for 60 minutes (56 patients) or electromotive drug administration (EMDA) with 40 mg of MMC at 20 mA for 30 minutes (42 patients). The treatment schemes were similar: 6 weekly instillations as induction and 6-monthly instillations as maintenance. The recurrence rates were evaluated at 6 and 12 months and the progression rates at 12 months. ResultsThe recurrence-free rate at 12 months was 91,1% in the HIVEC group and 88.1% in the EMDA group (P ≥ 0.05). After the 12-month follow-up, only 1 progression occurred in each treatment group. In terms of adverse events, no significant differences were found between the treatments. ConclusionsHIVEC and EMDA techniques are comparable in terms of recurrence, progression and adverse events at 12 months in the treatment of patients with high- and intermediate-risk NMIBC.

P142 - Electromotive drug administration of mitomycin C versus Bacillus de Calmette Guérin as intravesical adjuvant treatment of non-muscle invasive bladder cancer

P142 - Electromotive drug administration of mitomycin C versus Bacillus de Calmette Guérin as intravesical adjuvant treatment of non-muscle invasive bladder cancer

The clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C after transurethral resection of bladder tumour in patients with nonmuscular invasive bladder cancer: A meta-analysis.

This review and meta-analysis aimed to systematically evaluate the clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C (MMC) in patients with nonmuscular invasive bladder cancer (NMIBC) after transurethral resection of bladder tumour (TURBT). The Embase, PubMed, CNKI, CBM, WANGFANG, VIP, Cochrane Library, and Clinicaltrial.com databases were searched for articles published before April 2022. The experimental group was treated with intravesical instillation of MMC assisted by equipment, including radiofrequency-induced thermochemotherapy, conductive thermochemical therapy, electromotive drug administration, or locoregional hyperthermia. The control group was treated with simple MMC perfusion. The outcomes of interest in the meta-analysis were recurrence, progression, side-effects, gross haematuria, and bladder irritation. A total of 15 studies that enrolled 1,190 patients were included in the meta-analysis. Compared to that of the control group, device-assisted intravesical instillation of MMC significantly reduced both tumour recurrence (odds ratio [OR] = 0.32, 95% confidence interval [CI] [0.24, 0.42], P <0.00001) and progression (OR = 0.29, 95% CI [0.12, 0.67], P = 0.004). There were no significant differences between the two groups in terms of safety (OR = 1.21, 95% CI [0.66,2.21], P = 0.54), bladder irritation (OR = 1.06, 95% CI [0.72,1.55], P = 0.78), or gross haematuria (OR = 1.11, 95% CI [0.64,1.94], P = 0.72). Equipment-assisted intravesical instillation of MMC significantly reduced the recurrence and progression of patients with NMIBC who underwent TURBT and improved their quality of life. Given the significant heterogeneity in research quality and sample size among earlier studies, more prospective, multicentre, large sample randomized controlled trials are needed to supplement and verify this in the future.

Electromotive Drug Administration of Magnesium Sulphate on Spastic Gastrocnemius Muscle of Stroke Patients

Objective: This study aimed to investigate the effects of Magnesium sulfate (MgSO4) iontophoresis on electrical activity and functional ability (step length of the affected side) of the gastrocnemius muscle Methods: A total of 50 patients aged 45_65 years of both genders who were diagnosed with chronic cerebrovascular accident (29 females and 21 males) were recruited in this study and randomly assigned into 2 equal groups. Subjects in Group A received MgSO4 iontophoresis in addition to passive stretching of the gastrocnemius for two session per week for 4 weeks, whereas group B underwent calf, quadriceps and hamstring muscle stretching for two sessions per week for 4 weeks. Electromyography was used to measure the electrical activity of the gastrocnemius muscle during rest and activity times (active plantar flexion) whereas the Biodex Gait Trainer 2 was used to measure the step length of the affected side; thus, patients were evaluated twice before and after allocation to each group. Results: Statistical analysis showed a significant change within all study variables when comparing pretreatment with posttreatment values in group A (p &lt; 0.05) but not in group B (p &gt; 0.05). Between-group analysis showed no significant changes in pretreatment values of all variables as (p &gt; 0.05), whereas a significant change in all variables was observed in posttreatment values (p &lt; 0.05). Conclusion: MgSO4 iontophoresis is more effective than traditional therapy (stretching) in managing the spasticity of poststroke patients.

Impact of Effective Intravesical Therapies on Quality of Life in Patients with Non-Muscle Invasive Bladder Cancer: A Systematic Review.

Background: Conventional and newly emerged intravesical modalities have demonstrated prophylactic effectiveness that may improve quality of life (QoL) in non-muscle invasive bladder cancer. The purpose of this study is to analyze existing QoL evidence in patients receiving any form of intravesical therapy. Methods: A PubMed search without time restriction was conducted to identify all relevant studies in accordance with the PICOT question. Additionally, a search was also performed in the Cochrane library database, Internet, and citation. The CONSORT 2010 checklist and STROBE statement checklist were used to evaluate the risk of bias of the included studies. Results: A total of 24 eligible articles were included, which consisted of 11 interventional and 13 observational studies. Intravesical therapy with Bacillus Calmette–Guérin (BCG) or certain chemotherapeutic agents worsens symptom burdens and functional performance during the initial induction phase while continuous improved is observed throughout the maintenance treatment and beyond. Hyperthermia has shown a positive trend in enhancing QoL of patients receiving intravesical chemotherapy, which requires more investigations. However, QoL data were unavailable for other forms of immunotherapy, immune checkpoint inhibitors, electromotive drug administration, and photodynamic therapy. Conclusions: Limited studies suggested the long-term positive impact of intravesical BCG immunotherapy and chemotherapy. However, existing evidence was lacking to clarify the impact of many emerging intravesical therapies that have suggested to be effective and safe, which demands treatment-specific QoL studies.

Electromotive Drug Administration of Mitomycin C (EMDA/MMC) versus Intravesical Immunotherapy with Bacillus Calmette-Guérin (BCG) in Intermediate and High Risk Non Muscle Invasive Bladder Cancer

Background: Although TURB of tumor (TURBT) by itself can eradicate a non-muscle-invasive bladder cancer (NMIBC) completely, these tumors commonly recur and can progress to MIBC. It is, therefore, necessary to consider adjuvant therapy in most patients. The primary objective of the present study was to report our experience with EMDA/MMC and BCG, considering efficacy, progression, and recurrence, as adjuvant therapy in NMIBC patients; the secondary objective was to assess the efficacy of EMDA/MMC versus BCG as a comparative treatment. Methods: Between April 2016 and February 2020, a series of 216 patients, with a diagnosis of intermediate- and high-risk NMIBC after TURBT, underwent adjuvant intravesical therapy. In 26 cases with a failure of the treatment, in patients unfit and unwilling for radical cystectomy, a repeated intravesical therapy was performed (2 had a twice repetition). Out of 244 adjuvant therapies, 140 EMDA/MMC and 104 BCG treatments were done. The following data were collected for each patient: baseline demographics and clinical data and perioperative and postoperative data. Overall patients’ adjuvant intravesical therapies were included in a prospectively maintained institutional database, and a retrospective chart review was performed. We collected data on 2 main outcomes, recurrence-free survival (defined as a negative cystoscopy, cytology, and/or histology at the evaluation time point) and progression-free survival (defined as a negative cystoscopy or a nonprogressive tumor recurrence). Results: The NMIBC progression rate was higher in BCG than EMDA/MMC but not statistically significant (respectively, 4.2% vs. 2.5%; p = 0.703). In the overall population, the risk of NMIBC recurrence was higher after BCG than EMDA/MMC (p = 0.025). In the subgroups of 59 paired patients with similar characteristics, no difference was observed between groups in NMIBC progression and recurrence. Conclusions: Our findings suggest that EMDA/MMC and BCG are safe and reproducible approaches as adjuvant treatment in NMIBC. EMDA/MMC permits to achieve a fine oncological management as adjuvant treatment in NMIBC, which is not less than that obtained with BCG.

Second-Line Conservative Device-Assisted Intravesical Treatment in Selected Patients With Recurrent High-Risk Non-Muscle-Invasive Bladder Cancer.

In cases of recurrent high-risk non-muscle-invasive bladder cancer, radical cystectomy (RC) is recommended. We compared oncologic and treatment-related outcomes of second-line conservative device-assisted therapy to RC. In a retrospective cohort study, we analyzed 209 consecutive patients with recurrent bacillus Calmette-Guérin-unresponsive high-risk non-muscle-invasive bladder cancer; 107 subjects refused RC and were offered electromotive drug administration (n= 44) or chemohyperthermia (n= 63) (group A), and 102 patients underwent RC (group B). In group A, patients who did not benefit from device-assisted treatment underwent RC. The endpoints were high-grade disease-free survival, progression-free survival, cancer-specific survival, overall survival, and treatment-related complications. Follow-up was based on international guideline recommendations. Analyses were performed with log-rank and Fisher exact tests. The median follow-up was 59 months (SD ± 5.3). When comparing group A to B, overall survival rates were 91.6% and 90.2%, respectively (P > .05); cancer-specific survival was 94.4% and 96.1%, respectively (P > .05); high-grade disease-free survival was 43% and 74.5%, respectively (P< .05); and progression-free survival was 59.8% and 75.5%, respectively (P< .05). Patients with carcinoma-in-situ had worse oncologic outcomes compared to patients with papillary disease. In the multivariate analysis, multifocality, disease recurrence, and progression risk group were independently associated with device treatment failure. The 90-day RC-related overall complications rates were 63.9% in group A and 66.6% in group B (P= .63); grade 3 to 5 complications were 9.8% in group A and 9.8% in group B(P= .99). Complications within group A were comparable (P > .05). Device-assisted treatment may a represent a valid second-line conservative tool in selected patients with recurrent high-risk non-muscle-invasive bladder cancer.

Sequential administration of Bacillus Calmette-Guerin (BCG) and Electromotive Drug Administration (EMDA) of mitomycin C (MMC) for the treatment of high-grade nonmuscle invasive bladder cancer after BCG failure

BackgroundThere is a need for effective nonsurgical treatment options in patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Guerin (BCG) therapy has failed. ObjectiveWe aimed to determine the efficacy of Electromotive Drug Administration (EMDA) of mitomycin C (MMC) with NMIBC after BCG failure. Design, Setting, and ParticipantsA retrospective review of 26 NMIBC patients in whom BCG therapy failed who received BCG/EMDA-MMC between 2013 and 2017 was performed. All but 4 patients fulfilled the FDA criteria for BCG unresponsive disease. Progression and recurrence-free survival (RFS)were calculated using Kaplan-Meier curves. Progression was defined as development of muscle invasive disease, presence of metastasis on imaging or treatment. We used FDA-defined criteria as complete response (CR) for single-arm trials of BCG-unresponsive patients. Results and LimitationsTwenty-six patients were included. Initial pathology was carcinoma in situ (CIS) in 53.8% (14/26), pT1 in 34.6% (9/26), and pTa HG disease in 11.6% (3/26). Twelve of 26 patients progressed (46.2%). Following BCG/EMDA-MMC treatment, progression-free survival rates were 58.3% (95% confidence interval [CI] 41.1–82.1) at 1 year and 48.9% (95% CI 48.9) at 2 years from the date of induction of BCG/EMDA-MMC, respectively. RFS was 41.9% (95% CI 25.9–67.8) at 1 year and 27.2% (95% CI 13.6–54.4) at 2 years. CR at 6, 12, and 18 months was observed in 16 (61.5%), 11 (44.0%), and 7 patients (30.4%), respectively. Side effects included dysuria (19.2%), hematuria (19.2%), and frequency (11.5%). Three patients were admitted for side effects but managed conservatively. Four patients (15.4%) died of bladder cancer over the course of the study. ConclusionsEMDA-MMC BCG represents a viable option in patients with BCG unresponsive NMIBC with close to 50% progression-free survival at 2 years. However, these patients have a high risk of death from bladder cancer (15% in our cohort at 2 years) thus warranting extremely close surveillance.