scholarly journals Neoadjuvant Therapy Using Checkpoint Inhibitors before Radical Cystectomy for Muscle Invasive Bladder Cancer: A Systematic Review

2021 ◽  
Vol 11 (11) ◽  
pp. 1195
Author(s):  
Hadi SHSM ◽  
Usama A. Fahmy ◽  
Nabil A. Alhakamy ◽  
Mohd G. Khairul-Asri ◽  
Omar Fahmy
Keyword(s):  
Systematic Review ◽  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Checkpoint Inhibitors ◽  
Neoadjuvant Treatment ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Grade 3 ◽  
Muscle Invasive ◽  
The Impact

Background: Neoadjuvant chemotherapy is the standard of care before radical cystectomy for muscle invasive bladder cancer. Recently, checkpoint inhibitors have been investigated as a neoadjuvant treatment after the reported efficacy of checkpoint inhibitors in metastatic urothelial carcinoma. Objectives: The aim of this systematic review is to investigate the role of checkpoint inhibitors as a neoadjuvant treatment for muscle invasive bladder cancer before radical cystectomy. Methods: Based on the PRISMA statement, a systematic review of the literature was conducted through online databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Suitable publications were subjected to full-text assessment. The primary outcome of this review was to identify the impact of neoadjuvant immunotherapy on the oncological outcomes and survival benefits. Results: From the retrieved 254 results, 8 studies including 404 patients were included. Complete response varied between 30% and 50%. Downstaging varied between 50% and 74%. ≥Grade 3 AEs were recorded in 8.6% of patients who received monotherapy with either Atezolizumab or Pembrolizumab. In patients who received combination treatment, the incidence of ≥Grade 3 AEs was 16.3% for chemoimmunotherapy and 36.5% for combined immunotherapy. A total of 373 patients (92%) underwent radical cystectomy. ≥Grade 3 Clavien-Dindo surgical complications were reported in 21.7% of the patients. One-year overall survival (OS) and relapse-free survival (RFS) varied between 81% and 92%, and 70% and 88%, respectively. Conclusion: The evidence on the use of immune checkpoint inhibitors in the setting of pre-radical cystectomy is quite limited, with noted variability within published trials. Combination with chemotherapy or another checkpoint inhibitor may boost response, although prospective studies with extended follow-up are needed to report on the survival advantages.

scholarly journals Survival Outcomes of Early versus Deferred Cystectomy for High-Grade Non-Muscle-Invasive Bladder Cancer: A Systematic Review

2020 ◽  
Vol 14 (2) ◽  
pp. 66-73
Author(s):  
Jonathan C. M. Wan
Keyword(s):  
Systematic Review ◽  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Treatment Plan ◽  
Invasive Bladder Cancer ◽  
Survival Outcomes ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Term Survival ◽  
Muscle Invasive

Background: Studies report that survival outcomes in patients with non-muscle-invasive bladder cancer (NMIBC) are worse when cystectomy is delayed. However, no systematic evidence is available. Objective: The aim of this study was to systematically review the literature to compare the long-term survival outcomes of patients with high-grade NMIBC (T1G3, including carcinoma in situ) who have early cystectomy compared to deferred radical cystectomy post-diagnosis. Materials and Methods: A systematic review was carried out by searching MEDLINE and related databases (Google Scholar, National Health Service Evidence) for all relevant studies published from 1946 to present. Additional studies were identified through following the references of relevant papers. Studies were included if they met the following criteria: inclusion of at least 30 patients having high-grade NMIBC, 2 groups treated with either early or deferred cystectomy with a clear temporal cut-off between groups and reported data on survival rate of at least 5 years. Results: Literature was systematically reviewed, and 10 studies were included, totaling 1,516 patients who underwent either primary cystectomy or deferred cystectomy. It was found that patients who underwent early cystectomy show improved 5- to 10-year cancer-specific survival (relative risk = 0.81, p = 0.029) suggesting a significant survival benefit when compared to deferred cystectomy. Conclusions: This study provides systematically gathered evidence showing benefit of early cystectomy. Despite this result, radical cystectomy greatly impairs quality of life and represents overtreatment for a significant minority. This result highlights the importance of a decisive treatment plan to minimize treatment delay.

scholarly journals Downstaging of TURBT-Based Muscle-Invasive Bladder Cancer by Radical Cystectomy Predicts Better Survival

ISRN Urology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-6
Author(s):  
P. R. van Dijk ◽  
M. Ploeg ◽  
K. K. H. Aben ◽  
P. C. Weijerman ◽  
H. F. M. Karthaus ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Relative Survival ◽  
Population Based ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Cancer Specific Survival ◽  
Tumor Downstaging ◽  
Muscle Invasive ◽  
The Impact

Differences between clinical (cT) and pathological tumor (pT) stage occur often after radical cystectomy (RC) for muscle-invasive bladder cancer. In order to evaluate the impact of downstaging on recurrence and survival, we selected patients from a large, contemporary, population-based series of 1,409 patients with MIBC. We included all patients who underwent RC (N=643) and excluded patients who received (neo)adjuvant therapy, those with known metastasis at time of diagnosis, and those with nonurothelial cell tumors. Disease outcomes were defined as recurrence-free survival (RFS) and relative survival (RS), as a good approximation of bladder cancer-specific survival. After applying the exclusion criteria, 375 patients were eligible for analysis. Tumor downstaging was found to be common after RC; in 99 patients (26.4%), tumor downstaging to non-muscle-invasive stages at RC occurred. Hydronephrosis at baseline and positive lymph nodes at RC occurred significantly less often in these patients. In 62 patients, no tumor was left in the cystectomy specimen. pT stage was pT1 in 20 patients and pTis in 17 patients. Patients with tumor downstaging have about a 30% higher RFS and RS compared to those without. Consequently, tumor downstaging is a favorable marker for prognosis after RC.

Impact of sarcopenia for patients with localized muscle invasive bladder cancer treated by neoadjuvant cisplatin based chemotherapy and radical cystectomy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18286-e18286
Author(s):  
Emilien Billon ◽  
Pierre Regnier ◽  
Valeria De Luca ◽  
Serge Brunelle ◽  
Jochen Walz ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Skeletal Muscle Index ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive ◽  
The Impact

e18286 Background: Several studies suggested the prognostic importance of sarcopenia in survival or treatment complications in cancer. The concept of cancer prehabilitation before surgery is gaining wide recognition. The aim of our study was to assess the impact of sarcopenia on chemotherapy toxicities and survival in patients with localized muscle invasive bladder cancer (MIBC). Methods: Between January 2012 and December 2017, patients who underwent neoadjuvant platinum-based chemotherapy (NAC) followed by radical cystectomy (RC) for cT2-T4 N0 M0 MIBC were retrospectively selected, from a single institution cohort. Using CT scan: before NAC, after NAC and after cystectomy, sarcopenia was defined according to the Lumbar Skeletal Muscle Index (SMI) in L3 assessed by two observers blinded to patients’ status. Results: 82 patients were selected, 62 men (75.6%) and 20 women (24.4%), with a median age of 64.5 years (31 to 80). 35 were considered severe sarcopenic (SMI < 35cm2/m2 for women and SMI < 50 cm2/m2 for men) before NAC. The characteristics between severe and non-severe sarcopenic patients were not significantly different except for weight (71.7 vs 81.1kg, p = 0.006) and BMI (24.0 vs 28.4kg/m2, p = 8.0x10-6). Sarcopenia pre-chemotherapy was significantly associated with nausea (p = 0.003), hypokalemia (p = 0.023) and with platinum dose-intensity during NAC (p = 0.007) but was not significantly associated with overall survival (OS) or disease-free survival (DFS). Sarcopenia post-cystectomy was correlated with the OS (HR = 0.94, CI95% [0.89-0.99], p = 0.01), but not DFS. In multivariate analysis, factors associated with OS were post cystectomy sarcopenia (p = 0.038), pN status (p = 0.001) and glomerular filtration rate (p = 0.045). Conclusions: For localized MIBC, sarcopenic status before platinum based NAC could predict some chemotherapy toxicities. After radical cystectomy, sarcopenia is an independent prognostic factor for OS. Improve patients care by prehabilitation during NAC and before surgery, using physical, nutritional and psycho-social supports, could decrease chemotherapy toxicities and improve survival particularly for sarcopenic patients.

Impact of sarcopenia on kidney function during neoadjuvant chemotherapy and post cystectomy complications in patients treated for localized muscle-invasive bladder cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 387-387
Author(s):  
Pierre Regnier ◽  
Valeria De Luca ◽  
Serge Brunelle ◽  
Patrick Sfumato ◽  
Jochen Walz ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Renal Impairment ◽  
Radical Cystectomy ◽  
Invasive Bladder Cancer ◽  
Complication Rates ◽  
Muscle Invasive Bladder Cancer ◽  
Skeletal Muscle Index ◽  
Logistic Regression Models ◽  
Muscle Invasive ◽  
The Impact

387 Background: Sarcopenia is suspected to influence the complication rates in patients undergoing radical cystectomy. The aim of our study was to assess variations in sarcopenia in patients scheduled for neoadjuvant cisplatin-based chemotherapy (NAC) and radical cystectomy for muscle invasive bladder cancer (MIBC) and to explore the impact of sarcopenia on complications linked to NAC and surgery. Methods: Between January 2012 and December2017, 82 consecutive patients who underwent NAC and RC for cT2-T4 N0 M0 MIBC were retrospectively selected. Using CT scan before and after NAC, Lumbar Skeletal Muscle Index (SMI) was assessed by two observers blinded to patient’s status. We defined severe sarcopenia as SMI < 50 cm2/m2 for men and SMI < 35 cm2/m2 for women. We evaluated pre- and post-NAC cisplatin-based chemotherapy renal function and post-operative complication rates after cystectomy using the Clavien-Dindo classification. We explored risk factors of complications by logistic regression models. Results: According to the SMI cut offs, 47 patients (57.3%) were classified as sarcopenic and 35 patients (42.7%) non-sarcopenic. Patients’ characteristics between sarcopenic and non-sarcopenic patients were not significantly different except for BMI (p < 0.001). Among patients non-sarcopenic before NAC, 9 (19.1%) became sarcopenic after NAC. In multivariate analysis, sarcopenia was an independent significant predictor of renal impairment after NAC (OR 3.01; 95% CI 1.13–8.05; p = 0.02). There was a trend towards a higher rate of stage 3B kidney failure (GFR < 45 mL/min/1.73m2) after NAC in sarcopenic patients (OR 2.79; 95% CI 0.70–11.1) but the difference was not statistically significant (p = 0.14). Moreover, sarcopenia and ASA score were independent significant predictors of postoperative early complications ≤90 days (p = 0.01 and p = 0.02 respectively). Conclusions: We observed significant changes in sarcopenic status during NAC. Sarcopenia, estimated by the lumbar SMI measurement, was an independent predictor associated with the risk of renal impairment during NAC and early postoperative complications after RC.

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