Checkpoint inhibitors in BCG-unresponsive nonmuscle invasive bladder cancer: can they help spare the bladder?

Immunotherapy ◽  
2021 ◽  
Author(s):  
Khalil El Gharib ◽  
Eddy Lilly ◽  
Roy Chebel
Keyword(s):  
Bladder Cancer ◽  
Urothelial Cancer ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Invasive Bladder Cancer ◽  
Second Line Therapy ◽  
Bcg Therapy ◽  
Cancer Of The Bladder ◽  
Intravesical Bcg Therapy ◽  
Nonmuscle Invasive Bladder Cancer

Intravesical BCG therapy has been for years, the standard of care in nonmuscle-invasive bladder cancer. But upon recurrence/relapse, radical cystectomy is imposed, due to the paucity of other therapeutic options. Immunotherapy has been revolutionizing cancer treatment, and its indications continue to broaden. It has been approved for the treatment of advanced urothelial cancer of the bladder, mainly as a second-line therapy. Its activity is being studied in nonmuscle-invasive bladder cancer that is not responsive to BCG; we herein report the trials investigating these checkpoint inhibitors (pembrolizumab, nivolumab, atezolizumab, durvalumab and avelumab) in this particular setting.

Neoadjuvant or adjuvant immunotherapy in bladder cancer: biological opportunity or clinical utility?

2021 ◽  
pp. 030089162110616
Author(s):  
Fausto Petrelli ◽  
Gianluca Perego ◽  
Ivano Vavassori ◽  
Andrea Luciani
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Urothelial Cancer ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Cancer Of The Bladder ◽  
Muscle Invasive

In urothelial cancer of the bladder, the introduction of immunotherapy with immune checkpoint inhibitors represents progress in the management of the disease’s early and advanced stages. In particular, recent studies have implemented these drugs in the neoadjuvant and adjuvant phases to treat muscle-invasive bladder cancer. In some studies, patients received neoadjuvant immune checkpoint inhibitors alone (PURE and ABACUS) to treat muscle invasive bladder cancer, whereas other studies provided this therapy to cisplatin-ineligible patients. Furthermore, a large Phase III study (CheckMate 247) compared placebo with adjuvant nivolumab therapy in patients with high-risk urothelial cancer after neoadjuvant chemotherapy and surgery or surgery alone. Despite some uncertain niches (nonbladder, PD-L1-negative tumors, and node-negative resected cancers), certain biological opportunities (exploring new targets, evaluating in vivo pathologic response, focusing on biomarkers for response) and clinical uses (avoiding chemotherapy at all or in frail patients, attaining similar pathologic complete response rates as in cisplatin-based chemotherapy) are valid reasons for incorporating these agents into the therapeutic armamentarium of medical uro-oncologists.

scholarly journals Evolving Treatment of Advanced Urothelial Cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 309-315 ◽  
Author(s):  
Srikala S. Sridhar
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Metastatic Disease ◽  
Urothelial Cancer ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Standard Of Care ◽  
The United States ◽  
Poor Performance Status ◽  
Cancer Of The Bladder

Urothelial cancer of the bladder is a smoking-related cancer and the fifth most common cancer in the United States. At presentation, up to 25% of patients will have muscle-invasive disease and, despite cystectomy or bladder-sparing trimodality approaches, will develop metastatic disease. Cisplatin-based combination chemotherapy regimens remain the standard of care in first-line metastatic disease. Although response rates to these regimens are high, they are rarely durable, and median overall survival is only 12 to 15 months. Treatment options following progression on cisplatin-based regimens or for patients unfit for cisplatin due to poor performance status, impaired renal function, or comorbidities have been quite limited. However, there is now a new class of drugs known as immune checkpoint inhibitors, which target the programmed cell death 1/programmed cell death-ligand 1 axis and promote antitumor immunity, that are showing both efficacy and tolerability. These drugs have now been approved for use in both cisplatin-treated and most recently cisplatin-unfit patients. Clinical trials are currently ongoing to determine how best to use these drugs and whether they should be used alone or in combination with other treatments. This review will discuss the current standard of care in the management of urothelial cancer and highlight recent trials of immunotherapy in this disease.

scholarly journals Radical Cystectomy after BCG Immunotherapy for High-Risk Nonmuscle-Invasive Bladder Cancer in Patients with Previous Prostate Radiotherapy

ISRN Urology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Manoj V. Rao ◽  
Marcus L. Quek ◽  
Gautam Jayram ◽  
Chandy Ellimoottil ◽  
Timothy Sondej ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Invasive Bladder Cancer ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Prostate Radiotherapy ◽  
Bcg Immunotherapy ◽  
Bcg Therapy ◽  
History Of ◽  
Nonmuscle Invasive Bladder Cancer

Purpose. Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is indicated for high-grade nonmuscle-invasive bladder cancer (NMIBC). The efficacy of BCG in patients with a history of previous pelvic radiotherapy (RT) may be diminished. We evaluated the outcomes of radical cystectomy for BCG-treated recurrent bladder cancer in patients with a history of RT for prostate cancer (PC). Methods. A retrospective chart review was performed to identify patients with primary NMIBC. We compared the outcomes of three groups of patients who underwent radical cystectomy for BCG-refractory NMIBC: those with a history of RT for PC, those who previously underwent radical prostatectomy (RP), and a cohort without PC or RT exposure. Results. From 1996 to 2008, 53 patients underwent radical cystectomy for recurrent NMIBC despite BCG. Those with previous pelvic RT were more likely to have a higher pathologic stage and decreased recurrence-free survival compared to the groups without prior RT exposure. Conclusion. Response rates for intravesical BCG therapy may be impaired in those with prior prostate radiotherapy. Patients with a history of RT who undergo radical cystectomy after failed BCG are more likely to be pathologically upstaged and have decreased recurrence-free survival. Earlier consideration of radical cystectomy may be warranted for those with NMIBC who previously received RT for PC.

Is there a role for urine cytology following BCG therapy for non-muscle-invasive bladder cancer (NMIBC)?

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 404-404
Author(s):  
Sarah Prattley ◽  
Ruth Jarvis ◽  
Jon Featherstone ◽  
Krishna Narahari ◽  
Murali Varma ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urine Cytology ◽  
Invasive Bladder Cancer ◽  
Positive Cytology ◽  
Muscle Invasive Bladder Cancer ◽  
Flexible Cystoscopy ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Muscle Invasive ◽  
Intravesical Bcg Therapy

404 Background: Voided urine cytology has been used as an adjunct in the diagnosis of non-muscle invasive bladder cancer (NMIBC), with a sensitivity and specificity ranging between 13-75% and 76-100% respectively. There is limited data on the accuracy and utility of cytology following BCG therapy. We reviewed the results of cytology in patients undergoing induction and maintenance BCG immunotherapy in our institution. Methods: Newly diagnosed patients who had received induction and maintenance intravesical BCG therapy from 2004 - 2019 were identified from a prospective database and their outcomes reviewed retrospectively. Histopathology results of biopsies / resected specimens and voided urine cytology results were examined for 273 patients. Results: A total of 2567 cytology results and 638 biopsy results were recorded. The average age was 73.2 years and median number of BCG treatments was four (induction followed by three maintenance courses). Median follow up was 38 months. 94 patients (34.4%) had recurrence following BCG therapy. Of those 33 patients (12.1%) had progression to muscle invasive disease. The number of cytology samples per patient after BCG therapy ranged from 1-23 (median 7), with several patients having repeated, potentially unnecessary negative urine cytology. Overall accuracy of cytology (n = 526) was sensitivity 44.2%, specificity 84.7%, PPV 38.9%, NPV 87.3%. Patients that had an erythematous bladder or red patch at flexible cystoscopy underwent subgroup analysis; this gave a very high NPV of 95.9%, with additional sensitivity being 65.5%, specificity 85.9% and PPV 33.3%. Number of positive cytology results (Chi2 = 44.30, P = 0.002), any positive cytology (Chi2 = 27.94, P < 0.001) and positive cytology after induction BCG therapy (Chi2 = 30.381, P < 0.001) were all strongly associated with recurrence. Conclusions: Positive urine cytology in patients undergoing intravesical BCG therapy predicts increased risk of recurrence and has good specificity. We would recommend using voided urine cytology in patients who have an erythematous bladder or red patch at flexible cystoscopy. If the cytology is positive then proceed to biopsy, however, if it is negative continue with surveillance. [Table: see text]

scholarly journals A retrospective analysis of patients treated with intravesical BCG for high-risk nonmuscle invasive bladder cancer

2019 ◽  
Vol 11 ◽  
pp. 175628721983305 ◽  
Author(s):  
Julie Mariam Joshua ◽  
Meenu Vijayan ◽  
Ginil Kumar Pooleri
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Progression Rate ◽  
Therapeutic Effects ◽  
Free Survival ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Nonmuscle Invasive Bladder Cancer

Background: Adjuvant intravesical immunotherapy with Bacillus Calmette–Guerin (BCG) is considered as the first-line agent in patients with high-risk nonmuscle invasive bladder cancer (NMIBC) after surgery. There are no data in India where there is a high prevalence of tubercle bacillus and inherent immunity against Bacillus sp. The present study aims to evaluate the outcomes of intravesical BCG in the Indian population. Methods: A retrospective study of 101 patients who underwent intravesical BCG for high-risk NMIBC between January 2006 and December 2015 was carried out in a single centre. We compared the recurrence-free rate and progression rate of patients who received induction alone and induction with maintenance BCG therapy. The safety profile of intravesical BCG therapy was also assessed in the study. Results: After a median follow up of 2 years, the disease-free survival (DFS) rates of the induction group and maintenance group were 82% and 88% respectively ( p = 0.233). There was no difference in progression-free survival (PFS) rates at 2 years in those who receive maintenance BCG (95%) and those with induction BCG (94.7%; p = 0.721). A total of 69.36% of our patients had local adverse events. Conclusion: Our results suggest that maintenance therapy does not enhance the therapeutic effects of BCG in patients who respond favourably to 6 weeks of induction. Additional prospective studies are warranted in those countries where tuberculosis exposure is prevalent.

scholarly journals Renal Granulomatosis Post Intravesical Bacillus Calmette–Guerin Therapy for Non-muscle-invasive Bladder Cancer

2018 ◽  
Vol 8 ◽  
pp. 18
Author(s):  
Karen Tran-Harding ◽  
Rashmi T Nair ◽  
Halemane Ganesh
Keyword(s):  
Bladder Cancer ◽  
Invasive Bladder Cancer ◽  
Bacillus Calmette Guerin ◽  
Muscle Invasive Bladder Cancer ◽  
Contrast Enhanced ◽  
Bcg Therapy ◽  
Muscle Invasive ◽  
Intravesical Bcg Therapy ◽  
Enhanced Computed Tomography ◽  
Contrast Enhanced Computed Tomography

Intravesical Bacillus Calmette–Guerin (BCG) immunotherapy is a proven, effective treatment for intermediate- and high-risk non-muscle-invasive bladder cancer. Minor side effects are common and expected but systemic effects can occur in <5% of treated patients. We present a rare case of a 49-year-old male that presented with fever and chills after 3 weeks of intravesical BCG therapy post transurethral resection of bladder tumor. New renal lesions were present on contrast-enhanced computed tomography scan which was histologically proven to be necrotizing renal granulomatosis.

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