Radiotherapy concurrent with weekly gemcitabine after transurethral tumor resection in muscle ınvasive bladder cancer

On the basis of the discussion of the current state of research on relevant topics of non-muscle-invasive bladder cancer (NMIBC) among a group of experts of the Spanish Oncology Genitourinary (SOGUG) Working Group, recommendations were proposed to overcome the challenges posed by the management of NMIBC in clinical practice. A unified definition of the term ‘microhematuria’ and the profile of the patient at risk are needed. Establishing a ‘hematuria clinic’ would contribute to a centralized and more efficient evaluation of patients with this clinical sign. Second or repeated transurethral resection (re-TUR) needs to be defined, including the time window after the first procedure within which re-TUR should be performed. Complete tumor resection is mandatory when feasible, with specification of the presence or absence of muscle. Budding should be used as a classification system, and stratification of T1 tumors especially in extensive and deep tumors, is advisable. The percentage of the high-grade component should always be reported, and, in multiple tumors, grades should be reported separately. Luminal and basal subtypes can be identified because of possibly different clinical outcomes. Molecular subtypes and immunotherapy are incorporated in the management of muscle-invasive bladder cancer but data on NMIBC are still preliminary.

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Efficacy of Bladder Intravesical Chemotherapy with Three Drugs for Preventing Non-Muscle-Invasive Bladder Cancer Recurrence

Journal of Healthcare Engineering ◽

10.1155/2021/2360717 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Jianglei Zhang ◽

Miao Li ◽

Ze Chen ◽

Jun OuYang ◽

Zhixin Ling

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Recurrence Rate ◽

Tumor Recurrence ◽

Adverse Reactions ◽

Tumor Resection ◽

Intravesical Chemotherapy ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

Epirubicin, gemcitabine, and pirarubicin are widely used as first-line drugs for intravesical chemotherapy to prevent tumor recurrence after transurethral bladder tumor resection for non-muscle-invasive bladder cancer (NMIBC). However, which drug is better is less discussed. A total of 335 NMIBC patients administered intravesical chemotherapy underwent transurethral bladder tumor resection (TURBT) in our hospital from October 2015 to October 2019. After TURBT, all the patients received standard intravesical chemotherapy. Through clinical data collection and telephone follow-up, the tumor recurrence and adverse reactions of all patients after bladder perfusion treatment were counted. Recurrence was defined as new tumor appearance in the bladder. Of the 335 patients who underwent intravesical chemotherapy, 109 patients received epirubicin and 114 patients and 112 patients were given gemcitabine and pirarubicin, respectively. According to the general information of the patients, the patients were divided into intermediate-risk and high-risk bladder cancer and compared separately. There was no statistical difference in clinical and pathological features between different groups ( P > 0.05 ). The recurrence rate of intermediate-risk bladder cancer patients shows no difference between three groups ( P > 0.05 ). As for the high-risk bladder cancer patients, it is found that the 1-year recurrence rate between three groups was not statistically significant ( P > 0.05 ), whereas the 2-year recurrence rate of patients given gemcitabine (9.87%) was significantly lower than that of epirubicin (25.37%) and pirarubicin (24.32%), and the difference was statistically significant ( P < 0.017 , Bonferroni adjusted P value). The Kaplan–Meier survival curves showed that the recurrence-free survival rate of patients received gemcitabine was significantly higher than that of the other two groups. Comparing the incidence of adverse reactions during the infusion of the three groups of patients, the differences were not statistically significant ( P > 0.05 ). In patients with high-risk non-muscle-invasive bladder cancer, the application of gemcitabine intravesical chemotherapy is related with a relatively lower recurrence rate but similar incidence of adverse reactions.

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Non-muscle Invasive Bladder Cancer Molecular Subtypes Predict Differential Response to Intravesical Bacillus Calmette-Guérin

10.1101/2021.11.30.21266988 ◽

2021 ◽

Author(s):

Florus C. de Jong ◽

Teemu D. Laajala ◽

Robert F. Hoedemaeker ◽

Kimberley R. Jordan ◽

Angelique C.J. van der Made ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Molecular Subtypes ◽

Tumor Resection ◽

Progression Free Survival ◽

Invasive Bladder Cancer ◽

Bacillus Calmette Guerin ◽

Clinical Tool ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

SummaryThe recommended treatment for patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. In case of progression to advanced disease, patients must undergo a radical cystectomy with significant morbidity and have a poor clinical outcome. Identifying tumors least likely to respond to BCG can translate into alternative treatments, such as early radical cystectomy or novel targeted or immunotherapies. Here we present molecular profiling of 132 BCG-naive, HR-NMIBC patients, and 44 post-BCG recurrences (34 matched), which uncovered three distinct BCG Response Subtypes (BRS1-3). Patients with BRS3 tumors have reduced recurrence and progression-free survival compared to BRS1-2. BRS3 tumors expressed high EMT-basal markers and had an immunosuppresive profile, which was confirmed with spatial proteomics. Tumors which recurred post-BCG were enriched for BRS3. BRS stratification was validated in a second cohort of 151 BCG-naive HR-NMIBC patients and the molecular subtypes outperformed guideline recommended risk stratification based on clinicopathological variables. For clinical application, we validated that a commercially approved assay was able to accurately predict BRS3 tumors (AUROC 0.86). Our findings provide a potential clinical tool for improved identification of HR-NMIBC patients at the highest risk of progression, which can be used to select patients for early radical cystectomy or novel subtype-directed therapies.One Sentence SummaryMolecular subtypes are predictive of response to intravesical Bacillus Calmette-Guérin immunotherapy in non-muscle invasive bladder cancer.

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Systematic Review and Meta-Analysis on the Impact of Hexaminolevulinate- Versus White-Light Guided Transurethral Bladder Tumor Resection on Progression in Non-Muscle Invasive Bladder Cancer

Bladder Cancer ◽

10.3233/blc-160060 ◽

2016 ◽

Vol 2 (3) ◽

pp. 293-300 ◽

Cited By ~ 27

Author(s):

Georgios Gakis ◽

Omar Fahmy

Keyword(s):

Systematic Review ◽

Bladder Cancer ◽

White Light ◽

Bladder Tumor ◽

Meta Analysis ◽

Tumor Resection ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive ◽

The Impact

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Bipolar en bloc tumor resection versus standard monopolar TURBT in non-muscle invasive bladder cancer – a medium-term, prospective, randomized-controlled comparison

European Urology Supplements ◽

10.1016/s1569-9056(19)30559-7 ◽

2019 ◽

Vol 18 (1) ◽

pp. e761 ◽

Cited By ~ 1

Author(s):

B. Geavlete ◽

R. Multescu ◽

D. Georgescu ◽

C. Moldoveanu ◽

C. Ene ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Resection ◽

Invasive Bladder Cancer ◽

Medium Term ◽

Muscle Invasive Bladder Cancer ◽

En Bloc ◽

Randomized Controlled ◽

Muscle Invasive

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Sequential intravesical gemcitabine and docetaxel in the treatment of BCG-naive patients with non-muscle invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.469 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 469-469 ◽

Cited By ~ 2

Author(s):

Lewis Thomas ◽

Ryan Steinberg ◽

Kenneth Gerard Nepple ◽

Michael A. O'Donnell

Keyword(s):

Bladder Cancer ◽

Treatment Success ◽

Single Agent ◽

Tumor Resection ◽

Cancer Recurrence ◽

Standard Of Care ◽

Intravesical Chemotherapy ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

469 Background: Bacillus Calmette-Guerin (BCG) is the standard of care for patients with new non-muscle invasive bladder cancer (NMIBC) after transurethral tumor resection. While BCG has been compared to single agent intravesical chemotherapy as first-line therapy, few studies exist comparing BCG to sequential intravesical chemotherapy regimens. The objective of this work was to determine the efficacy of sequential intravesical gemcitabine and docetaxel (Gem/Doce) in BCG naïve patients with NMIBC. Methods: Patients without prior BCG exposure who underwent Gem/Doce intravesical treatments were retrospectively identified. These patients had been treated with 6 weekly instillations of gemcitabine (1 gram of gemcitabine in 50 ml of sterile water) followed immediately by docetaxel (37.5 mg of docetaxel in 50 mL of saline). Patients without recurrence then underwent maintenance therapy with monthly instillations for two years. Treatment success was defined as no bladder cancer recurrence and no cystectomy. Survival analysis was performed using the Kaplan Meier method. Results: 30 patients were treated with a median follow-up of 18 months. Eighty percent (n=24) of patients had high risk disease. Median age was 78 years old. The most common indications for Gem/Doce therapy were “advanced age/frailty” (n=15), “immunosuppression” (n=4), and “BCG Shortage” (n=4). Treatment success was 96% at 3 months, 89% at 1 year, and 89% at 2 years. No patients progressed or required cystectomy. Treatments were generally well tolerated, with only one patient unable to finish induction and two patients declining maintenance. Side-effects included urinary urgency/frequency (30%), dysuria (26%), and hematuria (23%). A need for dose reduction or delay was uncommon (16%). The all-cause mortality rate was 3.5% at 1 year, and 16.5% at 2 years. Neither bladder cancer nor the treatments were the cause of any of the deaths. Conclusions: Sequential intravesical gemcitabine and docetaxel is an effective treatment for BCG naïve NIMBC. Treatments are generally well tolerated even in a frail and comorbid patient population. Further evaluation of this combination therapy for BCG naïve disease is warranted.

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Oncologic outcomes of complete transurethral resection prior to neoadjuvant chemotherapy for muscle-invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17029 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17029-e17029 ◽

Cited By ~ 1

Author(s):

Jamie Sungmin Pak ◽

Christopher R Haas ◽

Helena Vila Reyes ◽

Christopher B. Anderson ◽

Guarionex Joel DeCastro ◽

...

Keyword(s):

Bladder Cancer ◽

Neoadjuvant Chemotherapy ◽

Tumor Resection ◽

Selection Criterion ◽

Oncologic Outcomes ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Subset Analysis ◽

Variant Histology ◽

Muscle Invasive

e17029 Background: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC). Prior studies have shown that pT0 response at RC can be attributed to NAC and high-quality transurethral resections (TURBT) prior to NAC. Therefore, we sought to assess the association of completeness of pre-NAC TURBT with response and survival outcomes. Methods: This was a single-institution, retrospective review of patients who received NAC for clinically localized MIBC (≥cT2, N0) from 2000 to 2017. Exclusion criteria were receipt of non-cisplatin-based NAC or radiation (n = 15), and insufficient documentation of TURBT (n = 26). Complete TURBT (cTURBT) was defined as tumor resection in entirety and/or resection to normal appearing muscle in operative reports, or repeat pre-NAC TURBT revealing clinical T0 (cT0). After NAC, patients either underwent repeat TURBT or immediate RC, as per the treating physician. Patients refusing RC were placed on an active surveillance/delayed intervention (ASDI) protocol of cytology, cystoscopy, and imaging at 3-4 month intervals. Primary endpoint was durable complete response (dCR): pT0 at RC or remaining cT0 on ASDI for ≥1 year. Secondary endpoints included OS and durable down-staging (dDS): ≤pT1 at RC or remaining ≤cT1 on ASDI for ≥1 year. Results: Of a total 93 patients, 62 (67%) underwent pre-NAC cTURBT. Those with cTURBT had lower rates of variant histology (13% vs 32%, p = 0.03), hydronephrosis (15% vs 39%, p < 0.01), and more often pursued ASDI (60% vs 26%, p = 0.01). Patients with cTURBT were more likely to attain dCR (37% vs 13%, p = 0.01) and dDS (60% vs. 26%, p < 0.01). On multivariate (MV) analysis, cTURBT was a significant predictor of dCR and dDS; this remained true on subset analysis excluding 11 patients with ≥cT3 on restaging TURBT. On Kaplan-Meier analysis, patients with cTURBT had improved 5-year OS (78% vs. 46%, p < 0.01). On MV analysis controlling for variant histology, lymphovascular invasion, and hydronephrosis, cTURBT was the only significant predictor of OS, also on subset analysis excluding the 11 patients with ≥cT3 on restaging TURBT. Conclusions: A pre-NAC cTURBT is associated with improved oncologic outcomes and OS in this MIBC cohort. The extent to which cTURBT represents a selection criterion for having lower clinical stage or a therapeutic advantage in response to NAC is difficult to isolate from a retrospective study. However, this study suggests cTURBT should be pursued when feasible to potentially optimize outcomes after NAC.

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