Risk Non-muscle Invasive Bladder Cancer Research Articles

Extra-peritoneal vs. Trans-peritoneal Radical Cystectomy pros and cons.

One of the most common cancers of the urinary tract is bladder tumors. Bladder cancers are divided into two groups: non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer.(1) Trans-Peritoneal Radical Cystectomy (RC) with pelvic lymphadenectomy is the standard technique in muscle invasive and high risk non-muscle invasive bladder cancer(2). and Urologist around the world are more familiar with trans-peritoneal technique. In some articles extra-peritoneal Radical Cystectomy (RC) implied as an decreased postoperative complications techniques. In this letter we want to compare these two techniques and find out the pros and cons of these techniques.

PIVOT-006: A phase 3, randomized study of cretostimogene grenadenorepvec versus observation for the treatment of intermediate risk non-muscle invasive bladder cancer (IR-NMIBC) following transurethral resection of bladder tumor (TURBT).

TPS715 Background: Guidelines for Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) recommend adjuvant intravesical (IVE) therapy or surveillance. Despite this, 30–60% of patients still recur, and these Guideline recommendations are lacking level-1 evidence. Thus, there is a considerable gap in knowledge and an unmet medical need for improved therapies in the adjuvant setting. Cretostimogene Grenadenorepvec is an oncolytic adenovirus designed to preferentially replicate in and kill cancer cells. The vector is transcriptionally regulated by the E2F promoter that is up-regulated in retinoblastoma (Rb) pathway-defective tumor cells, common in most IR-NMIBC bladder tumors. Additionally, the virus is engineered to selectively express GM-CSF, in order to induce a robust systemic anti-tumor immune response. PIVOT-006 is an open-label, multi-center, randomized Phase 3 study designed to assess the efficacy and safety of intravesical Cretostimogene after TURBT versus TURBT alone. Methods: Eligibility criteria: age ≥18 years, Eastern Cooperative Oncology Group performance status of 0-2, histologically confirmed IR-NMIBC with absence of nodal or metastatic disease at screening. IR-NMIBC, as defined by American Urologic Association-Society of Urologic Oncology Guidelines on NMIBC, is either a Low Grade (LG) stage Ta tumor that recurs within 12 months of prior LG or High Grade (HG) bladder cancer, a solitary LGTa tumor >3cm in size, multifocal LGTa tumors, primary HGTa lesion < 3cm in size, or a LGT1 tumor. Participants will be stratified by receipt of perioperative chemotherapy and tumor grade. Pts (N~450) will be randomized 1:1 to receive intravesical Cretostimogene (Cohort 1) adjuvant to TURBT or TURBT alone (Cohort 2). Single dose perioperative intravesical chemotherapy at the time of TURBT is permitted. If intravesical NMIBC recurrence is noted in Cohort 2, participants will be eligible to receive intravesical Cretostimogene. In Cohort 1, intravesical Cretostimogene will be instilled in combination with n-dodecyl-B-D-maltoside (DDM, an inactive detergent) for 6 weekly doses during the induction phase, followed by 3 weekly maintenance cycles at months 3 and 6, and culminating in single intravesical doses at months 9 and 12. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and centralized review of pathologic samples. The primary outcome measure is recurrence free survival. Secondary outcome measures include safety, tolerability, progression free survival, and time to next intervention. Exploratory outcome measures include patient-reported quality of life, biomarker analyses, coxsackie adenovirus receptor and E2F promoter expression, neutralizing antibodies, and markers of immunogenicity. Clinical trial information: Pending.

BladderGATE: Atezolizumab + intravesical BCG (bacillus Calmette-Guerin) upfront combination in patients with high risk non-muscle invasive bladder cancer (NMIBC)—Phase I-II ONCOSUR study.

595 Background: Intravesical Bacillus Calmette-Guerin (BCG) induction + BCG maintenance after transurethral resection is the current standard of care for patients (pts) with high-risk non-muscle invasive bladder cancer (NMIBC). Recurrence rate at 2 years and 5 years are around 30-40% and 70-80% respectively. Atezolizumab is a IgG1 monoclonal antibody targeting PD-L1 and is associated with long-term durable remissions in pts with metastatic urothelial cancer (MS. van der Heijden . Eur Urol 2021) and for pts with unresponsive NMIBC (PC. Black . Eur Urol 2023) with excellent results. Atezolizumab in combination with standard BCG could provide synergistic benefit for pts with NMIBC. BladderGATE (NCT04134000) is a phase Ib-II study which evaluates the safety and efficacy of upfront atezolizumab + intravesical BCG in pts with high-risk NMIBC. Methods: Pt had confirmed histopathology of high-risk NMIBC, BCG naïve or stopped >2 years ago, WHO PS 0-2 and adequate hematologic and organ function. Dose-escalation design to identify DLT and MTD (9 pts) and to evaluate safety and efficacy in an expansion cohort (30 pts) were programed. Pt received six weekly induction instillations, and maintenance instillations at 3, 6 and 12 months + intravenously atezolizumab 1200 mg every 3 weeks, up to 1 year. Urine/blood and tissue samples were collected for translational and biomarker correlative study. Primary objective is disease free survival. Secondary objectives include safety profile and quality of life. Results: Finally 36 pt were included, median age 70 years, 86% men, 61% of pt were former smokers, 22% smokers and 17% had never smoked, and tumor size was ≥3 cm in 44% of pt. With a 22 months median follow-up, 56% of pt had completed BCG treatment and 89% had received adequate BCG treatment (5 induction plus at least 2 maintenance instillations). Thirteen pts discontinued atezolizumab due to immune-related AEs (7 pts) (g2 dermatitis, g3 hepatitis, encephalitis, pneumonitis, myocarditis, adrenal insufficiency and psoriasis), due to early-relapse disease (3 pts) and progressive-disease (3 pts). All irAEs were solved and no toxic death were reported. Of the 36 pts analyzed, 6 pts showed local recurrence (17%), 5 pts with high-risk NMIBC (14%) and 1 pt with low-risk NMIBC, 1 pt with UTUC, and 3 pts with local muscle invasive bladder cancer progressive-disease (8 %). Preliminary 2-year disease free survival is 72.8% (95% CI: 56.1% - 89.5%). Conclusions: The combination strategy of atezolizumab + intravesical BCG upfront in high-risk NMIBC pts appears feasible and safe. A 14% of 2-years local recurrence-rate and 8% of local progressive-disease are promising results, pending to randomized Ph3 ALBAN study data (GETUG). Supported by Roche-Spain. Clinical trial information: NCT03425201 .

Guiding adjuvant instillation in intermediate-risk non-muscle invasive bladder cancer by drug screens in patient-derived organoids.

TPS711 Background: Recurrence rates in intermediate risk non-muscle invasive bladder cancer (NMIBC) are high and therefore, clinical guidelines recommend adjuvant instillations. However, the exact regimen with an exact number of instillations and the chemotherapeutic agent to be used are not clearly defined. During the last years we have established a standardized pipeline to generate patient-derived organoids (PDO) from cold cup biopsies of NMIBC. We showed that the subsequent organoids maintain key features of the parental tumor and share the molecular landscape. Moreover, our pipeline allows to investigate drug response to different agents in a standardized manner. Methods: In this ongoing, open-label, single center phase II trial, we aim to use drug screens in PDO of patients with intermediate risk NMIBC to guide drug selection for intravesical instillation. Patients with diagnosis of intermediate-risk NMIBC are enrolled. PDO are generated from biopsies prior transurethral resection of the bladder tumor. On the generated PDO drug response is determined to four chemotherapeutic agents that have already been used for bladder instillations in the literature (Epirubicin, Mitomycin C, Gemcitabine and Docetaxel). The most effective drug is selected for adjuvant instillation into the bladder once weekly for 6 instillations. The follow-up thereafter is performed according to European guidelines. The primary endpoint of the study is to determine the proportion of patients for which a specific selection of chemotherapeutic agent for intravesical instillation can be determined by using drug screens in PDOs. Secondary endpoints are recurrence- and, progression free survival, quality of life and translational studies. The null hypothesis, that a drug prediction will only be possible in 65% of patients, will be tested against a one-sided alternative. Assuming that the real proportion is 85%, 31 participants should show a statistically significant result at 5% significance and 80% power (exact binomial test). Due to early termination of 10%, a total number of 34 patients will be included. We are successfully conducting a trial to implement drug screens in PDO into daily routine and to guide patient treatment. This is a novel concept to precise treatment selection in patients with intermediate-risk NMIBC. When the primary endpoint is met, a modification of the trial with larger sample size, novel compounds and a focus oncological outcomes is foreseen. Clinical trial information: NCT05024734 .

P234 - Comparing toxicity and short term outcomes of Hyperthermic Intravesical Chemotherapy with Mitomycin-C versus Intravesical Chemotherapy with Mitomycin-C alone in the management of intermediate risk non-muscle invasive bladder cancer

P234 - Comparing toxicity and short term outcomes of Hyperthermic Intravesical Chemotherapy with Mitomycin-C versus Intravesical Chemotherapy with Mitomycin-C alone in the management of intermediate risk non-muscle invasive bladder cancer

Phase Ib neoadjuvant CG0070 and nivolumab (N) for cisplatin (C)-ineligible muscle invasive bladder cancer (MIBC).

e16613 Background: CG0070 is a replication-competent oncolytic adenovirus engineered to target RB deficient tumor cells and to express GM-CSF. CG0070 has previously demonstrated safety and efficacy against BCG-exposed high risk non-muscle invasive bladder cancer through tumor lysis and anti-tumor immune activation. We tested the safety and efficacy of CG0070 in combination with N as neoadjuvant therapy for MIBC in C-ineligible patients in this study (NCT04610671). Methods: C-ineligible pts with MIBC (cT2-4a, N≤1) were enrolled. Pts received 6 weekly intravesical CG0070 (1x1012vp) and 2 doses of N at wks 2 and 6, followed by radical cystectomy (RC). The primary objective is safety of CG0070+N as measured by CTCAEv5.0. Secondary objective is to assess pathologic response (PaR) (pT0N0) and 1yr event free survival (EFS). Exploratory objectives include the assessment of correlation between PaR with baseline 1) E2F expression; 2) immune infiltration; 3) PD-L1 expression; and 4) TLS expression. Results: Between Nov 2020 and Feb 2023, 21 pts were enrolled with median age 75yrs, 81% male, 33% > cT2; 1 pt refused RC but was included in the ITT population. Treatment was stopped after 1 infusion of CG0070 in 1 pt due to treatment unrelated worsening of renal function. The overall rate of >grade 3 AEs was 12/20 (60%), and the vast majority were related to RC (83%). Immune related AEs were seen in 1 pt, who had grade 2 autoimmune thyroiditis. There was no delay in time to RC and no unexpected surgical complications from treatment. Overall, 1 pt was unevaluable for efficacy, 2 pts progressed prior to RC, PaR was observed in 8/15 (53%) evaluable pts, and an additional pt had negative post-treatment biopsy but refused RC. On exploratory analysis, treatment response correlated with increased maturation of tertiary lymphoid structures and immunogenicity to bespoke tumor neoantigens. Conclusions: Neoadjuvant CG0070+N is safe and effective in C-ineligible pts with MIBC. This combination was well tolerated without any delays in RC and induced an overall response rate of 50%. Clinical trial information: NCT04610671 .

Transurethral resection of bladder tumor-based bladder preservation therapy for refractory high risk non-muscle invasive bladder cancer: Current landscape and future directions.

Bladder cancer is the most common malignant tumor of urinary system worldwide. Approximately 75% of patients with bladder cancer present with non-muscle-invasive bladder cancer (NMIBC), which is effectively managed with transurethral resection of bladder tumor (TURBT). For refractory high risk NMIBC, patients are typically treated by radical cystectomy (RC). TURBT deserves further evaluation. Growing evidence suggests that repeated TURBT-based bladder-sparing approaches may improve oncological outcomes and quality of life in highly selected patients. Novel imaging techniques and biomarkers may aid in patients selection and postoperative surveillance. With growing interest in adding immunotherapy to refractory bladder cancer, TURBT based approaches enable the bladder preservation therapy for high risk NMIBC. Here we summarize the current landscape, biomarkers for surveillance, and future directions for applying TURBT-based bladder preservation therapy.

LBA02-04 OUTCOMES AND GENOMIC CHARACTERISTICS OF NEWLY DIAGNOSED HIGH GRADE TA PAPILLARY UROTHELIAL CARCINOMA TREATED WITH INTRAVESICAL CHEMOTHERAPY VS BACILLUS CALMETTE GUERIN (BCG): A COMPARATIVE STUDY DURING THE BCG SHORTAGE

You have accessJournal of UrologyCME1 Apr 2023LBA02-04 OUTCOMES AND GENOMIC CHARACTERISTICS OF NEWLY DIAGNOSED HIGH GRADE TA PAPILLARY UROTHELIAL CARCINOMA TREATED WITH INTRAVESICAL CHEMOTHERAPY VS BACILLUS CALMETTE GUERIN (BCG): A COMPARATIVE STUDY DURING THE BCG SHORTAGE Song Jiang, Manuel de Jesus E, Peter A. Reisz, Karissa Whiting, Carissa Chu, Wesley Yip, Andrew T. Lenis, Nicole Benfante, Eugene Cha, Timothy F. Donahue, Irina Ostrovnaya, Alvin Goh, Guido Dalbagni, Bernard H. Bochner, and Eugene J. Pietzak Song JiangSong Jiang More articles by this author , Manuel de Jesus EManuel de Jesus E More articles by this author , Peter A. ReiszPeter A. Reisz More articles by this author , Karissa WhitingKarissa Whiting More articles by this author , Carissa ChuCarissa Chu More articles by this author , Wesley YipWesley Yip More articles by this author , Andrew T. LenisAndrew T. Lenis More articles by this author , Nicole BenfanteNicole Benfante More articles by this author , Eugene ChaEugene Cha More articles by this author , Timothy F. DonahueTimothy F. Donahue More articles by this author , Irina OstrovnayaIrina Ostrovnaya More articles by this author , Alvin GohAlvin Goh More articles by this author , Guido DalbagniGuido Dalbagni More articles by this author , Bernard H. BochnerBernard H. Bochner More articles by this author , and Eugene J. PietzakEugene J. Pietzak More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003361.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Appropriate risk stratification of non-muscle invasive bladder cancer remains a central component of deciding treatment. Current criteria used to determine risk of disease recurrence and progression are based largely on historic cohorts before standardization of adjuvant intravesical treatments. The ongoing BCG shortage emphasizes the need for accurate contemporary data to best allocate BCG when supplies are limited. During periods of BCG shortage, our institution restricted BCG utilization to only those with HGT1 or carcinoma in situ (CIS), thus patients with HGTa without CIS were “naturally randomized” to receive either BCG or intravesical chemotherapy based on the time period of their initial diagnosis. METHODS: Retrospective review of an institutional database identified patients with newly diagnosed HGTa without CIS treated at MSKCC from 2017-2021. BCG restrictions were in effect between 01/19 and 04/20. Progression was defined as ≥T1 disease or radical cystectomy. The association of clinicopathologic variables and recurrence was performed with univariable Cox regression. Kaplan-Meier curves were used to visualize time to recurrence and progression. RESULTS: We identified 307 patients with papillary HGTa without CIS, 236 who were treated with BCG, and 71 with intravesical chemotherapy (N=60 mitomycin C, N=11 gemcitabine). Median follow up was 24 months for the BCG treated group, and 18 months from the chemotherapy treated group. There were no significant differences between the two groups regarding age, gender, tumor size, or tumor multiplicity. Targeted exon sequencing of pre-treatment tumors in 59 patients was performed and demonstrated no significant differences between treatment groups. Cumulative risk of high-grade recurrences was similar between the chemotherapy and BCG groups, with 86% vs 90% and 78% vs 82% recurrence-free survival at 6 and 12 months, respectively. Similarly, progression free survival was 89% at 12 months for both groups, but further follow up is needed. CONCLUSIONS: In this “naturally randomized” study, we report comparable clinical efficacy between chemotherapy and BCG immunotherapy, suggesting that intravesical chemotherapy is a reasonable alternative during the BCG shortage for patients with newly diagnosed HGTa without CIS. While our data is encouraging, there remains a critical need for better alternatives to BCG, especially for patients with higher risk non-muscle invasive bladder cancer. Source of Funding: NCI © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1187 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Song Jiang More articles by this author Manuel de Jesus E More articles by this author Peter A. Reisz More articles by this author Karissa Whiting More articles by this author Carissa Chu More articles by this author Wesley Yip More articles by this author Andrew T. Lenis More articles by this author Nicole Benfante More articles by this author Eugene Cha More articles by this author Timothy F. Donahue More articles by this author Irina Ostrovnaya More articles by this author Alvin Goh More articles by this author Guido Dalbagni More articles by this author Bernard H. Bochner More articles by this author Eugene J. Pietzak More articles by this author Expand All Advertisement PDF downloadLoading ...

A phase II clinical study of intravesical photo dynamic therapy in patients with BCG-unresponsive NMIBC (interim analysis).

528 Background: Novel therapies are required for BCG-unresponsive, high risk non-muscle invasive bladder cancer. We report the interim results of a Phase II Clinical Study of Intravesical Photo Dynamic Therapy (PDT) in patients with BCG-Unresponsive Carcinoma In-Situ (CIS) with or without papillary disease. Methods: Out of a planned 125 patients, 42 patients have been enrolled and treated with two Study Treatments (Day 0 and Day 180) consisting of an intravesical instillation of the photosensitizer TLD-1433 (0.70 mg/cm2) followed by activation with a 520 nm intravesical laser under general anesthesia (Study Device TLC-3200) to a total of 90 J/cm2 of laser light. The primary outcome assessed was efficacy, evaluated by Complete Response (CR), at any point in time. The secondary outcome was duration of CR at 12 months, post initial CR. A tertiary objective is safety, evaluated by the incidence and severity of Adverse Events, Grade 4 or higher that do not resolve within 450 days post treatment. Patients with a negative cystoscopy and positive cytology have been defined as indeterminate response (IR), as these patients remain under investigation for lower and upper tract urothelial carcinoma. Results: Interim analyses included the first 42 patients, along with 3 patients treated in a preceding Phase Ib NMIBC clinical study assessing the safety of TLD-1433 PDT who weretreated at the same parameters, for a total of 45 patients. Data for the primary and secondary outcomes are listed in the table.The interim clinical data demonstrates a 90 day CR of 50% and a duration of response at 360 and 450 days of 35% and 21%, respectively.There have been eight Serious Adverse Events (SAE) identified (2 Grade II (tachycardia, hematuria), 3 Grade III (acute kidney injury, cellulitis), 2 Grade IV (urosepsis, depression/anxiety) and 1 Grade V). None of the SAEs were deemed to be directly related to the PDT. Conclusions: The interim data support that treatment with Photo Dynamic Therapy provides a viable treatment option for patients with BCG unresponsive CIS (+/- papillary disease) with an acceptable ongoing safety profile. Clinical trial information: NCT03945162 . [Table: see text]

EP027 - The role of 18F-FDG-PET/CT for staging patients with high risk non-muscle invasive bladder cancer before radical cystectomy

EP027 - The role of 18F-FDG-PET/CT for staging patients with high risk non-muscle invasive bladder cancer before radical cystectomy

138MO A randomized study to compare outcomes of intravesical chemohyperthermia with mitomycin C vs intravesical BCG for intermediate and high risk non-muscle invasive bladder cancer (NMIBC)

With the global shortage of bacillus Calmette-Guerin (BCG) coupled with the high recurrence rates of NMIBC, newer adjuvant intravesical treatment options are required. Although intravesical BCG remains the gold standard, the use of chemohyperthermia (CHT) as an alternative treatment is expanding all over the world. This study looks into the use of CHT with MMC as an alternative for BCG in NMIBC.

BCG downregulates PD1 and PD-L1 expression in bladder cancer cells co-cultivated with peripheral blood mononuclear cells

PurposeBCG is the standard of care to treat high risk non-muscle invasive bladder cancer (NMIBC), reducing recurrence. PD-L1 is a ligand of the co-inhibitory receptor PD1 that has been shown to be expressed by tumor cells of distinct origin related to unfavorable prognosis. The development of a new class of target drugs that inhibit PD-L1 and PD1 has opened a new perspective for urothelial cancer treatment. Although there are few studies searching for the role of BCG over PD1 and PD-L1, many clinical trials are in course using the immune checkpoint inhibitors together with BCG as a new regime to treat NMIBC.Material and methodsWe analyzed the expression of PD1 and PD-L1 using qRT-PCR in RT4 bladder cancer (BCa) epithelial cells co-cultivated with peripheral blood mononuclear cells (PBMC) after treatment with BCG.ResultsThere was a significantly reduction in PD1 and PD-L1 expression by BCa epithelial cells after BCG treatment. In PBMC PD1 was significantly overexpressed.ConclusionOur results suggest that one of the mechanisms related to the success of BCG in reducing tumor recurrence in NMIBC may be related to the negative control of PD1 and PD-L1 in tumor cells.

Oral 8 - Evaluating the effect of follow-up intensity on the outcomes for patients with intermediate risk non-muscle invasive bladder cancer

Oral 8 - Evaluating the effect of follow-up intensity on the outcomes for patients with intermediate risk non-muscle invasive bladder cancer

Preliminary results from phase Ib/II neoadjuvant CG0070 and nivolumab (N) for cisplatin (C)-ineligible muscle invasive bladder cancer (MIBC).

4574 Background: CG0070 is a replication-competent oncolytic adenovirus engineered to target RB deficient tumor cells and to express GM-CSF. CG0070 has previously demonstrated safety and efficacy against BCG-exposed high risk non-muscle invasive bladder cancer through tumor lysis and anti-tumor immune activation. We tested the safety and efficacy of CG0070 in combination with N as neoadjuvant therapy for MIBC in C-ineligible patients in this study (NCT04610671). Methods: C-ineligible pts with MIBC (cT2-4a, N≤1) were enrolled. Pts received 6 weekly intravesical CG0070 (1x1012vp) and 2 doses of N at wks 2 and 6, followed by radical cystectomy (RC). The primary objective is safety of CG0070+N as measured by CTCAEv5.0. Secondary objective is to assess pathologic response (PaR) (pT0N0). Exploratory objectives include the assessment of correlation between PaR with baseline 1) E2F expression; 2) immune infiltration; 3) PD-L1 expression; and 4) TLS expression. Results from a prespecified interim analysis following accrual of 15 patients is reported herein. Results: Between Nov 2020 and Jan 2022, 15 pts were enrolled with median age 75.5yrs, 73% male, 47% > cT2; 1 patient refused RC but was included in the ITT population. No DLTs were encountered. The overall rate of grade 3-4 AEs was 10/15 (75%), and the vast majority were related to RC (90%). Immune related AEs were seen in one pt, who had grade 2 autoimmune thyroiditis. There was no delay in time to RC and no unexpected surgical complications from treatment. PaR was observed in 6/13 (46%) evaluable pts, and an additional pt had negative post-treatment biopsy but refused RC. Conclusions: Neoadjuvant CG0070+N is safe and effective in C-ineligible pts with MIBC. This combination was well tolerated without any delays in RC and induced an overall response rate of 54%. Clinical trial information: NCT04610671. [Table: see text]

MP54-14 SEQUENTIAL INTRAVESICAL GEMCITABINE/DOCETAXEL PROVIDES A DURABLE REMISSION IN RECURRENT HIGH RISK NMIBC FOLLOWING BCG THERAPY

You have accessJournal of UrologyCME1 May 2022MP54-14 SEQUENTIAL INTRAVESICAL GEMCITABINE/DOCETAXEL PROVIDES A DURABLE REMISSION IN RECURRENT HIGH RISK NMIBC FOLLOWING BCG THERAPY Kendrick Yim, Kevin Melnick, Sarah L. Mott, Vani Gupta, Timothy N. Clinton, Filipe L.F. Carvalho, Matthew Mossanen, Graeme S. Steele, Kent Mouw, Michael A. O'Donnell, and Mark A. Preston Kendrick YimKendrick Yim More articles by this author , Kevin MelnickKevin Melnick More articles by this author , Sarah L. MottSarah L. Mott More articles by this author , Vani GuptaVani Gupta More articles by this author , Timothy N. ClintonTimothy N. Clinton More articles by this author , Filipe L.F. CarvalhoFilipe L.F. Carvalho More articles by this author , Matthew MossanenMatthew Mossanen More articles by this author , Graeme S. SteeleGraeme S. Steele More articles by this author , Kent MouwKent Mouw More articles by this author , Michael A. O'DonnellMichael A. O'Donnell More articles by this author , and Mark A. PrestonMark A. Preston More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002633.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bacillus Calmette-Guerin (BCG) is the standard of care for high risk non-muscle invasive bladder cancer (NMIBC), but half of patients eventually fail BCG and radical cystectomy (RC) remains the alternative with best oncologic outcomes. However, RC is morbid surgery; many patients are poor surgical candidates and desire bladder-sparing alternatives. Intravesical regimens for BCG unresponsive NMIBC are limited. We report the safety and durable efficacy of sequential gemcitabine/docetaxel (gem/doce) in high risk NMIBC after BCG failure. METHODS: Single institution retrospective analysis of patients treated with induction intravesical gem/doce (≥5/6 instillations) for high risk NMIBC from May 2018 to May 2021. BCG failures were grouped as BCG unresponsive, intolerant or early relapsing. Maintenance therapy was provided to patients without evidence of high grade (HG) recurrence on surveillance cystoscopy per physician preference. Kaplan-Meier curves were generated to estimate survival probabilities. RESULTS: Seventy-four patients were included in this study (median age 72.0, median follow-up 18 months). Six-, 12, and 24-month HG recurrence free survival rates (RFS) were 81%, 67%, and 49% respectively (Figure 1A). Four patients experienced disease progression on transurethral resection. Fourteen patients underwent radical cystectomy (median 22 months from induction) (Figure 1B), with only 4 patients progressing to muscle invasion. Forty-eight (65%) patients experienced mild to moderate grade adverse effects (AE), but only 7% experienced a delay in treatment schedule. Most common AE were urinary frequency/urgency in 36 (49%) and dysuria in 12 (16%). CONCLUSIONS: In an independent study of high-risk BCG failures, sequential intravesical gem/doce appears to be an effective and well tolerated alternative to early cystectomy, validating prior reports of its utility. A prospective trial is warranted to better characterize efficacy and compare to other intravesical therapies. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e932 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kendrick Yim More articles by this author Kevin Melnick More articles by this author Sarah L. Mott More articles by this author Vani Gupta More articles by this author Timothy N. Clinton More articles by this author Filipe L.F. Carvalho More articles by this author Matthew Mossanen More articles by this author Graeme S. Steele More articles by this author Kent Mouw More articles by this author Michael A. O'Donnell More articles by this author Mark A. Preston More articles by this author Expand All Advertisement PDF DownloadLoading ...

PD26-04 A RANDOMIZED STUDY TO COMPARE OUTCOMES OF INTRAVESICAL CHEMOHYPERTHERMIA WITH MITOMYCIN C VS INTRAVESICAL BCG FOR INTERMEDIATE AND HIGH RISK NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC)

You have accessJournal of UrologyCME1 May 2022PD26-04 A RANDOMIZED STUDY TO COMPARE OUTCOMES OF INTRAVESICAL CHEMOHYPERTHERMIA WITH MITOMYCIN C VS INTRAVESICAL BCG FOR INTERMEDIATE AND HIGH RISK NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) Karandeep Guleria, Rajeev Sood, Hemant Goel, Umesh Sharma, and Anurag Singla Karandeep GuleriaKarandeep Guleria More articles by this author , Rajeev SoodRajeev Sood More articles by this author , Hemant GoelHemant Goel More articles by this author , Umesh SharmaUmesh Sharma More articles by this author , and Anurag SinglaAnurag Singla More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002574.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: With the global shortage of bacillus Calmette-Guerin (BCG) coupled with the high recurrence rates of NMIBC, newer adjuvant intravesical treatment options are required. Although intravesical BCG remains the gold standard, the use of chemohyperthermia (CHT) as an alternative treatment is expanding all over the world. This study looks to compare the efficacy, safety, and tolerability of intravesical CHT with MMC vs BCG for intermediate and high risk NMIBC. METHODS: Between 2019 and 2021, 140 consenting NMIBC patients were randomised in a single centre study for 1-yr CHT (six weekly treatments and monthly maintenance treatments till 1 year) and 1-yr BCG immunotherapy (six weekly treatments and three weekly maintenance treatments at months 3, 6, and 12). Patients and physicians giving the interventions were aware of assignment and set protocols. Follow up was done by 3 monthly cystoscopy and urine cytology. Adverse effects were graded by using the Modified Clavien Dindo Classification. RESULTS: The 12 month Recurrence Free Survival (RFS) was 97.10% in the CHT group compared with 94.30% in the BCG group (p = 0.53). No progression in the NMIBC was seen in the CHT group whereas progression rate was 1.7% in the BCG group. Regarding the side-effects, during the induction phase initially the side effects were more in the BCG group, but with the progression of the induction cycles the side effects of the CHT group increased, with the most common side effects being LUTS, UTI, Fever and Bladder spasms. Side effects during the maintenance phase were comparable between the CHT and BCG groups. All the side effects were classified as either grade 1 or grade 2 based on the Modified Clavien Dindo Classification. A concern of the study is that the follow up period was short and thus the study is underpowered. Furthermore, blinding of treatment for patients and physicians was impossible; this may have resulted in unavoidable bias. CONCLUSIONS: CHT is a safe and effective treatment option in patients with intermediate- and high-risk NMIBC. A higher 12 month RFS in the CHT group was seen along with a comparable side effect profile. Based on the results above, CHT is an alternative option to intravesical BCG therapy as adjuvant treatment for intermediate and high-risk NMIBC. Source of Funding: No Source of funding © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e488 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Karandeep Guleria More articles by this author Rajeev Sood More articles by this author Hemant Goel More articles by this author Umesh Sharma More articles by this author Anurag Singla More articles by this author Expand All Advertisement PDF DownloadLoading ...

PD42-08 REAL-WORLD PERFORMANCE OF MRI AFTER TURBT IN PREDICTING FINAL PATHOLOGIC OUTCOMES IN BLADDER CANCER

You have accessJournal of UrologyCME1 May 2022PD42-08 REAL-WORLD PERFORMANCE OF MRI AFTER TURBT IN PREDICTING FINAL PATHOLOGIC OUTCOMES IN BLADDER CANCER Michael Chandra, Thomas Gerald, Suzanne Cole, Liwei Jia, Jeffrey Howard, Aditya Bagrodia, Xiaosong Meng, Vitaly Margulis, Yair Lotan, Alberto Diaz de Leon, and Solomon Woldu Michael ChandraMichael Chandra More articles by this author , Thomas GeraldThomas Gerald More articles by this author , Suzanne ColeSuzanne Cole More articles by this author , Liwei JiaLiwei Jia More articles by this author , Jeffrey HowardJeffrey Howard More articles by this author , Aditya BagrodiaAditya Bagrodia More articles by this author , Xiaosong MengXiaosong Meng More articles by this author , Vitaly MargulisVitaly Margulis More articles by this author , Yair LotanYair Lotan More articles by this author , Alberto Diaz de LeonAlberto Diaz de Leon More articles by this author , and Solomon WolduSolomon Woldu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002603.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder cancer staging by transurethral resection of a bladder tumor (TURBT) is often inaccurate due to limited sampling. For higher risk non-muscle invasive bladder cancer, the current standard is to repeat TURBT, an invasive procedure with associated risk and cost. Additionally, interest in bladder preservation following systemic therapy is limited by concerns regarding the accuracy of cystoscopic assessment of response. Bladder MRI has emerged as a potential non-invasive and accurate means of bladder cancer staging. We sought to examine the ability of MRI after TURBT to predict residual tumor and muscle-invasive bladder cancer (MIBC) in a real-world cohort of patients subsequently undergoing re-TURBT or cystectomy. METHODS: This prospectively maintained cohort evaluated 70 patients with bladder cancer who received a multiparametric pelvic MRI from 2019-2021 after TURBT. The MRI was protocoled for bladder cancer evaluation and included T2-, diffusion, and T1-weighed images with and without IV contrast. MRIs were evaluated for restricted diffusion, enhancement and signal intensity features indicative of residual tumor and MIBC. These results were then compared to final pathology at subsequent re-TURBT (n=42) or cystectomy (n=28). RESULTS: Among re-TURBT cases, 24 (57.1%) and 3 (7.1%) had residual tumor and MIBC, respectively. Among cystectomy cases, 22 (78.6%) and 18 (64.3%) demonstrated residual tumor and MIBC, respectively. In detecting residual tumor among patients undergoing cystectomy, MRI showed a sensitivity, specificity, AUC, and positive post-test probability (PTP) of 90.9%, 66.7%, 0.788 (p=0.033), and 91%, respectively. In detecting MIBC among patients undergoing re-TURBT, MRI had a sensitivity, specificity, AUC, and negative PTP of 100%, 82.1%, 0.910 (p=0.019), and 0%, respectively. CONCLUSIONS: In this real-world setting, MRI showed high performance in ruling out MIBC in patients undergoing re-TURBT and in predicting the presence of residual disease prior to cystectomy. Performance characteristics in other settings were less accurate. These findings support the continued refinement of MRI in bladder cancer and as a potentially important adjunct in specific scenarios. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e698 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Chandra More articles by this author Thomas Gerald More articles by this author Suzanne Cole More articles by this author Liwei Jia More articles by this author Jeffrey Howard More articles by this author Aditya Bagrodia More articles by this author Xiaosong Meng More articles by this author Vitaly Margulis More articles by this author Yair Lotan More articles by this author Alberto Diaz de Leon More articles by this author Solomon Woldu More articles by this author Expand All Advertisement PDF DownloadLoading ...

This Month in Adult Urology

You have accessJournal of UrologyThis Month in Adult Urology1 Jun 2022This Month in Adult Urology D. Robert Siemens D. Robert SiemensD. Robert Siemens More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002499AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Lower Urinary Tract Symptoms and Increased Mortality in Men Lower urinary tract symptoms (LUTS) are common and frequently associated with significant bother and decreased quality of life in the aging male. However, there is some mounting evidence that severe LUTS could potentially serve as a prognostic factor for premature death with several theoretical relationships. Åkerla et al (page 1285) from Finland further explore this concept among middle-aged and elderly men utilizing population-based surveys spanning 1994–2018.1 Their analysis included 1,167 men and demonstrates an association of daytime frequency and nocturia with increased mortality. Although no cause-effect correlation can be inferred from these observations, the authors interestingly show this link between LUTS and mortality is independent of associated bother, which might be the more usual complaint to drive subsequent investigation and management. Frailty and Adverse Outcomes after Sling Surgery As our population ages, preoperative assessment and prehabilitation will become increasingly important to optimize outcomes for even mildly complex interventions. Increasing evidence has pointed to some evaluation of frailty, rather than simply age and co-morbid illness, as being more useful to assess postoperative sequelae in the elderly. Van Kuiken et al (page 1276) from San Francisco, California examine the impact of frailty on outcomes of sling surgery for stress urinary incontinence in all Medicare beneficiaries over 65 years of age.2 They observed that frailty is associated with an increased risk of 30-day complications, need for repeat procedures as well as 1-year mortality. The authors suggest that frailty should be strongly considered for an elderly woman considering the pros and cons of even such a relatively minor surgical procedure. A practical assessment of frailty such as TUG (Timed Up & Go) could be easily implemented in our clinics. Risk of an Elevated Hematocrit on Testosterone Therapy Despite direction from guidelines, it has been observed that routine assessment of bloodwork after initiation of testosterone therapy (TT) is less than ideal. One important potential adverse outcome that may then be missed is secondary erythrocytosis. Although this can be a common dose-limiting effect, there are few data that examine the association of a rising hematocrit and cardiovascular outcomes for those on TT. Ory et al (page 1295) from Miami, Florida and Halifax, Canada using a multi-institutional database explored these associations and demonstrate that the incidence of major adverse cardiovascular events or venous thromboembolic events was associated with developing erythrocytosis in the first year of TT.3 These results underscore the importance of assuring guideline-concordant followup for men on TT. The Impact of Hematuria after Post-Prostatectomy Radiotherapy Considerations of prostate cancer survivorship issues are paramount when counseling patients, perhaps specifically so when discussing the potential need for post-prostatectomy radiation. Although experientially a frequent occurrence, hematuria following post-prostatectomy radiation is not fully characterized. Turchan et al (page 1236) from Chicago, Illinois add to our understanding with a contemporary, single-institution study that describes in detail the long-term risks of hematuria and patient-reported urinary quality of life in men after salvage radiation.4 They show a relatively high incidence of hematuria, with only 55% of patients remaining free of a significant episode of hematuria, and 15% required some intervention. Unsurprisingly, they show a strong association between hematuria and radiation dose to the bladder as well as anticoagulation/antiplatelet therapy; however, the hematuria was generally self-limited and importantly the patient-reported urinary quality of life was not significantly impacted. Smoking Cessation and Bladder Cancer Recurrence Cigarette smoking is the single greatest preventable cause of disease in many jurisdictions, and after a cancer diagnosis, those who continue to smoke have a significant increase in adverse outcomes. Smoking cessation after a cancer diagnosis in some studies has been associated with improved outcomes such as reduced recurrence, perhaps reversing impaired DNA repair pathways and allowing some recovery of carcinogenesis defense mechanisms. Furberg at al (page 1200) from New York, New York add more detail to this discussion with a prospective study of 354 patients with bladder cancer and assessing biochemically verified post-diagnosis smoking exposure.5 In this cohort, most with higher risk nonmuscle-invasive bladder cancer, smoking exposure was detected in 22% of patients. After a median followup of 3.6 years, the authors were unable to detect any association between post-diagnosis smoking exposure and recurrence risk. Although the authors conclude that late smoking cessation, after the diagnosis of bladder cancer, may not substantially affect early disease recurrence, they stress that smoking cessation remains a critical component of bladder cancer care given the benefits beyond short-term recurrence rates.

PD-L1 expression and BCG response in nonmuscle invasive bladder cancer.

545 Background: Intravesical bacillus Calmette Guerin (BCG) is the standard of care adjuvant therapy for high risk non-muscle invasive bladder cancer (NMIBC), yet many patients experience recurrence or disease progression. The mechanism of action of BCG is believed to be related to stimulation of immune surveillance. Relatedly, systemic immune checkpoint inhibition is currently being utilized in advanced bladder cancer and approved for BCG unresponsive NMIBC. We sought to determine the association between PD-L1 expression and BCG treatment. Methods: We identified 102 BCG-naïve patients with high grade (HG) NMIBC treated with BCG. All patients underwent initial transurethral resection (TUR) for pathologic diagnosis. Dako 22c3 assay was used to determine PD-L1 expression. Patients were defined as PD-L1 positive if the combined positive score (CPS) > 0. BCG unresponsiveness was defined by presence of high grade disease at 6 months following adequate BCG (one induction and maintenance cycle or two induction cycles) for pT1 or 12 months for CIS or presence of pT1 at 3 months following induction. HG relapse was defined as presence of any HG disease after being followed for 6 months after BCG. Results: The median follow-up time was 57 months. Median number of BCG maintenance cycles was 1, and 17 (16.7%) patients underwent immediate reinduction BCG. PD-L1 expression was observed 5.9% of pTa, 30.0% of pT1, and 3.6% of CIS. BCG unresponsiveness and HG relapse were observed in 32 (35.6%) and 29 (34.5%) patients, respectively. On univariate analysis, PD-L1 expression was inversely associated with BCG unresponsiveness (OR = 0.112; 95% CI 0.014-0.898) but not high grade relapse (OR = 0.296; 95% CI 0.061-1.440). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression for BCG responsiveness were 22%, 97%, 93%, and 41%, respectively. The post-test probability of BCG responsiveness was 93% in patients positive for PD-L1 based on a positive likelihood ratio of 7.33 for PD-L1 expression. On multivariate regression, pT1 (OR = 0.159; 95% CI 0.045-0.600), CIS (OR = 0.247; 95% CI 0.071-0.857), and PD-L1 expression (OR = 15.625; 95% CI 1.779-142.857) were independently associated with BCG responsiveness. Conclusions: PD-L1 expression in HG NMIBC was low, and patients with PD-L1 expression at initial TUR were more likely to harbor invasive disease. Patients showing PD-L1 expression were more likely to demonstrate BCG responsiveness. These findings suggest a role of PD-L1 in the immune surveillance mechanism of BCG at initial pathologic diagnosis and may assist in predicting responses to BCG among patients with HG NMIBC. Further investigation is required to determine if additional immune checkpoint markers have strong correlation with BCG response, particularly among patients without PD-L1 expression.

A0237 - A randomized study to compare outcomes of intravesical chemohyperthermia with mitomycin c vs. intravesical BCG for intermediate and high risk Non-Muscle Invasive Bladder Cancer (NMIBC)

A0237 - A randomized study to compare outcomes of intravesical chemohyperthermia with mitomycin c vs. intravesical BCG for intermediate and high risk Non-Muscle Invasive Bladder Cancer (NMIBC)