scholarly journals Role of checkpoint inhibitors immunotherapy in non-muscle invasive bladder cancer: current methods and future perspectives

2021 ◽  
Vol 9 (3) ◽  
pp. 79-84
Author(s):  
Ayman Agag ◽  
Naufal Naushad ◽  
Asad Manzoor ◽  
Sami A Abbas ◽  
Abdalla Ali Deb ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
High Risk ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Oncological Results ◽  
Muscle Invasive

Immuno-therapy involvement in bladder urothelial malignancies is growing very fast. The use of Immuno-therapy with check-point inhibitor has greatly developed since it was first approved as a second-line treatment for cases who had formerly failed platinum-based chemotherapy. There are recognized applications for first-line metastatic illness in platinum-ineligible or cisplatin-ineligible PD-L1 diagnosed cases, as well as a label for BCG-refractory high-risky non-muscle invasive bladder cancer (NMIBC). It is now being studied in neo-adjuvant and adjuvant muscle invasive bladder cancer (MIBC) clinical trials. This review discusses the clinical trials that led to these FDA agreements, as well as prospective and ongoing trials. Current clinical guidelines support Bacillus Calmette-Guérin (BCG) as the primary treating option for intermediate to high-risk NMIBC. Despite the intra-vesical BCG-instillation, intra-vesical relapse occurs in a considerable number of individuals with intermediate to high risk NMIBC. Furthermore, treating BCG-nonresponsive NMIBC is still difficult. For these individuals with BCG-nonresponsive NMIBC, there are no viable therapy alternatives other than radical cystectomy, which has been shown to have excellent oncological results. In this regard, for the care of BCG-nonresponsive NMIBC, safe and reliable noninvasive or lesser-invasive therapeutic alternatives with adequate oncological results are needed. Regarding the latest introduction of immuno-therapeutic medications, the treatment of progressive or metastatic urothelial cancer has substantially advanced. These developments have sparked a surge in interest in immuno-therapeutic medications for NMIBC, particularly BCG-nonresponsive NMIBC. The goal of this literature review is to provide and debate the most up-to-date information on the function of Immuno-therapy in BCG-nonresponsive NMIBC and the presently accessible treatment options. Furthermore, this page highlights the current research in this topic. We wanted to convey the current state of Immuno-therapy in NMIBC and discuss future directions.

Bladder preservation therapy for muscle invasive bladder cancer: the past, present and future

2020 ◽  
Vol 50 (10) ◽  
pp. 1097-1107
Author(s):  
Tomokazu Kimura ◽  
Hitoshi Ishikawa ◽  
Takahiro Kojima ◽  
Shuya Kandori ◽  
Takashi Kawahara ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
The Past ◽  
Muscle Invasive

Abstract Radical cystectomy is the gold standard treatment for muscle invasive bladder cancer, but some patients have medically inoperable disease or refuse cystectomy to preserve their bladder function. Bladder preservation therapy with transurethral resection of the bladder tumor and concurrent chemoradiotherapy, known as trimodal treatment, is regarded to be a curative-intent alternative to radical cystectomy for patients with muscle invasive bladder cancer during the past decade. After the development of immune checkpoint inhibitors, a world-changing breakthrough occurred in the field of metastatic urothelial carcinoma and many clinical trials have been conducted against non-muscle invasive bladder cancer. Interestingly, preclinical and clinical studies against other malignancies have shown that immune checkpoint inhibitors interact with the radiation-induced immune reaction. As half of the patients with muscle invasive bladder cancer are elderly, and some have renal dysfunction, not only as comorbidity but also because of hydronephrosis caused by their tumors, immune checkpoint inhibitors are expected to become part of a new therapeutic approach for combination treatment with radiotherapy. Accordingly, clinical trials testing immune checkpoint inhibitors have been initiated to preserve bladder for muscle invasive bladder cancer patients using radiation and immune checkpoint inhibitors with/without chemotherapy. The objective of this review is to summarize the evidence of trimodal therapy for muscle invasive bladder cancer during the past decade and to discuss the future directions of bladder preservation therapy in immuno-oncology era.

scholarly journals Current Topics in the Management of Non–Muscle-Invasive Bladder Cancer

2020 ◽  
Vol 18 (7.5) ◽  
pp. 973-976
Author(s):  
Philippe E. Spiess
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
High Risk ◽  
Invasive Bladder Cancer ◽  
Evidence Based ◽  
Bacillus Calmette Guerin ◽  
Muscle Invasive Bladder Cancer ◽  
Nccn Guidelines ◽  
Muscle Invasive

The current NCCN Guidelines for Bladder Cancer reflect the most up-to-date, evidence-based data relating to the evaluation and management of non–muscle-invasive bladder cancer (NMIBC). The most notable revision to the guidelines this year is the addition of pembrolizumab for a high-risk subset of patients not responding to bacillus Calmette-Guérin (BCG). It is anticipated that current BCG shortages will offer unique opportunities to promote and enhance clinical trials for patients with bladder cancer. Recent efforts to more precisely define BCG-unresponsive disease (adopted by the FDA) have been critical to standardizing definitions and evaluating the efficacy of clinical trials in bladder cancer.

Atezolizumab + intravesical BCG (Bacillus Calmette-Guerin) in high-risk non-muscle invasive bladder cancer (NMIBC) patients: Institutional clinical and translational study (BladderGATE).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS598-TPS598
Author(s):  
Daniel Castellano ◽  
Guillermo de Velasco ◽  
Maria Cruz Martin Soberón ◽  
Alberto Carretero-González ◽  
Marta Dueñas ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Dose Level ◽  
Invasive Bladder Cancer ◽  
Bacillus Calmette Guerin ◽  
Muscle Invasive Bladder Cancer ◽  
Translational Study ◽  
Metastatic Urothelial Cancer ◽  
Muscle Invasive ◽  
Expansion Cohort

TPS598 Background: Intravesical Bacillus Calmette-Guerin (BCG) induction + BCG maintenance after transurethral resection (TURBT) is the current standard of care for patients (pt) with high-risk non-muscle invasive bladder cancer (NMIBC). Recurrence rate at 2 years is around 30%, which is clearly unsatisfactory. Programmed death ligand 1 (PD-L1) is a surface glycoprotein that functions as an inhibitor of T-cells and plays a crucial role in suppression of cellular immune response. Atezolizumab is a humanized IgG1 monoclonal antibody targeting PD-L1 and is associated with long-term durable remissions in pts with metastatic urothelial cancer (Powles T. Lancet. 2018). Atezolizumab in combination with standard BCG could be beneficial in pts with NMIBC. BladderGATE (NCT04134000) is a phase Ib-II study aims to evaluate the clinical impact and safety of the combination of Atezolizumab + intravesical BGC (medac strain), including a translational study (microbioma and urobioma) in pts with NMIBC. Methods: Eligible pt have confirmed histopathology of NMIBC, BCG naïve or stopped >3 years ago, WHO PS 0-1, no prior radiation to bladder and adequate hematologic and end-organ function. We propose a de-escalation design to enroll patients to identify DLT and MTD proposed to safety and efficacy expansion cohort. Pt will receive induction BCG, 1 instillation every week (qw) (dose level 0) or BCG, 1/2 instillation qw (dose level -1) + intravenously atezolizumab 1200 mg every 3 w (q3w), during 6 w. After induction, BCG will be administered as maintenance treatment at weeks 12, 24 and 48 and atezolizumab 1200 mg q3w up to 1 year. Pt will be accrued to each dose level in cohorts of 10 pt until the MTD is achieved (the highest dose at which <4 out of 10 pt experience DLT). DLT will be evaluated during induction treatment. Additional pt will be included in the expansion cohort up to 40 pt. DLT and safety profile will be evaluated according to NCI-CTCAE v 5.0 criteria. Recurrence-free survival will be assessed per RECIST 1.1. Tissue, plasma and urine sample will be collected for translational study. Clinical trial information: NCT04134000.

scholarly journals Intratumoral heterogeneity of surrogate molecular subtypes in urothelial carcinoma in situ of the urinary bladder: implications for prognostic stratification of high-risk non-muscle-invasive bladder cancer

2021 ◽  
Author(s):  
Stefan Garczyk ◽  
Felix Bischoff ◽  
Ursula Schneider ◽  
Reinhard Golz ◽  
Friedrich-Carl von Rundstedt ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Carcinoma In Situ ◽  
Molecular Subtypes ◽  
Smoking Status ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Prognostic Stratification ◽  
Muscle Invasive

AbstractReliable factors predicting the disease course of non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) are unavailable. Molecular subtypes have potential for prognostic stratification of muscle-invasive bladder cancer, while their value for CIS patients is unknown. Here, the prognostic impact of both clinico-pathological parameters, including CIS focality, and immunohistochemistry-based surrogate subtypes was analyzed in a cohort of high-risk NMIBC patients with CIS. In 128 high-risk NMIBC patients with CIS, luminal (KRT20, GATA3, ERBB2) and basal (KRT5/6, KRT14) surrogate markers as well as p53 were analyzed in 213–231 biopsies. To study inter-lesional heterogeneity of CIS, marker expression in independent CIS biopsies from different bladder localizations was analyzed. Clinico-pathological parameters and surrogate subtypes were correlated with recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Forty-six and 30% of CIS patients exhibited a luminal-like (KRT20-positive, KRT5/6-negative) and a null phenotype (KRT20-negative, KRT5/6-negative), respectively. A basal-like subtype (KRT20-negative, KRT5/6-positive) was not observed. A significant degree of inter-lesional CIS heterogeneity was noted, reflected by 23% of patients showing a mixed subtype. Neither CIS surrogate subtype nor CIS focality was associated with patient outcome. Patient age and smoking status were the only potentially independent prognostic factors predicting RFS, PFS, OS, and PFS, respectively. In conclusion, further clarification of heterogeneity of surrogate subtypes in HR NMIBC and their prognostic value is of importance with regard to potential implementation of molecular subtyping into clinical routine. The potential prognostic usefulness of patient age and smoking status for high-risk NMIBC patients with CIS needs further validation.

scholarly journals Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives

2021 ◽  
Vol 22 (13) ◽  
pp. 7201
Author(s):  
In-Ho Kim ◽  
Hyo-Jin Lee
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Current Evidence ◽  
Future Perspectives ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

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