scholarly journals Trends and disparities in the use of neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma

2018 ◽  
Vol 13 (2) ◽  
Author(s):  
Jonathan J. Duplisea ◽  
Ross J. Mason ◽  
Chad A. Reichard ◽  
Roger Li ◽  
Yu Shen ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Standard Of Care ◽  
Partial Cystectomy ◽  
Muscle Invasive Bladder Cancer ◽  
Logistic Regression Models ◽  
Factors Associated ◽  
Muscle Invasive ◽  
Contemporary Study ◽  
Over Time

Introduction: Neoadjuvant chemotherapy (NAC) prior to radical or partial cystectomy is considered the standard of care for eligible patients with muscle-invasive urothelial carcinoma. Despite guideline recommendations, adoption of NAC has historically been low, although prior studies have suggested that use is increasing. In this contemporary study, we examine trends in the use of NAC and explore factors associated with its receipt. Methods: We identified patients in the National Cancer Database who underwent radical or partial cystectomy for cT2-cT4N0M0 urothelial carcinoma from 2006–2014. The proportion of patients receiving NAC during each year was examined. Logistic regression models were used to evaluate clinical and socioeconomic factors associated with the receipt of NAC. Results: A total of 18 188 patients were identified who underwent radical or partial cystectomy for muscle-invasive bladder cancer. Overall, 3940 (21.7%) received NAC. We noted a significant increase in the use of NAC over time, from 9.7% in 2006 to 32.2% in 2014. Factors associated with lower use of NAC include older age, higher comorbidity score, lower cT stage, lower hospital radical cystectomy volume, treatment at a non-academic facility, lower patient income, and receipt of partial cystectomy (all p<0.001). Interestingly, neither sex nor race were associated with receipt of NAC. Conclusions: Use of NAC has increased significantly over time to a modest rate of 32%. However, disparities still exist in the receipt of NAC, and future efforts aimed at mitigating these disparities are warranted.

scholarly journals High-risk bladder cancer: improving outcomes with perioperative chemotherapy

2011 ◽  
pp. 4-8
Author(s):  
Daniel Y.C. Heng ◽  
Jorge A. Garcia
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Meta Analysis ◽  
Standard Of Care ◽  
Muscle Invasive Bladder Cancer ◽  
Advantages And Disadvantages ◽  
High Risk Disease ◽  
Muscle Invasive

Despite treatment with radical cystectomy and pelvic lymph node dissection, muscle invasive bladder cancer has a relapse rate of 50%. Patients can develop regionally advanced or metastatic disease that ultimately leads to death. The addition of neoadjuvant or adjuvant chemotherapy to reduce the risk of relapse and death has been extensively studied over the past two decades. Two contemporary trials coupled with a recent meta-analysis evaluating neoadjuvant chemotherapy demonstrated a modest but real improvement in overall survival. This has made neoadjuvant chemotherapy a standard of care. Clinical trials evaluating adjuvant chemotherapy in patients with high-risk disease have been plagued with statistical flaws and have, therefore, been unable to define the survival impact of this approach. It is hoped that ongoing adjuvant trials that are powered to detect small but meaningful clinical differences will clarify the benefit of chemotherapy after cystectomy. Since there are theoretical advantages and disadvantages to each of these approaches, both are widely used in North America. The evidence behind each approach and potential future developments in this field will be described.

Etiology of Treatment Delays in Patients Receiving Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer

2020 ◽  
Vol 6 (4) ◽  
pp. 435-444
Author(s):  
Ahmad M. El-Arabi ◽  
Syed M. Alam ◽  
Garth Sherman ◽  
William P. Parker ◽  
Jeffrey Thompson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Regression Models ◽  
Invasive Bladder Cancer ◽  
Completion Rates ◽  
Muscle Invasive Bladder Cancer ◽  
Treatment Delays ◽  
Logistic Regression Models ◽  
Muscle Invasive ◽  
Dose Dense

BACKGROUND: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) improves overall survival in muscle-invasive bladder cancer (MIBC), but successful completion rates of NAC are low. A retrospective analysis was undertaken to determine the etiology of deviations of NAC administration for MIBC. METHODS: We performed a retrospective review of MIBC patients in an institutional database who received NAC followed by RC from 2008 to 2016. Patients were characterized as having completed NAC without deviation (“No Deviation”) or with deviation (“Deviation”). Factors associated with “Deviation” were assessed with logistic regression models. RESULTS: 172 MIBC patients received NAC followed by RC; 49 were excluded due to incomplete NAC data. Of the remaining 123 patients, 80 (65%) received Gemcitabine and Cisplatin (GC) and 25 (20%) received dose-dense MVAC (ddMVAC). In all, 85 (69%) patients had “Deviation” in planned NAC administration, while the remaining 38 (31%) patients had “No Deviation.” Twenty-six (33%) of GC patients experienced delays (mean = 21.5±17.0 days) and 6 (24%) ddMVAC patients experienced delays (mean = 10.5±9.5 days). Receipt of GC was associated with higher likelihood of “Deviation” in comparison to ddMVAC (OR = 15.4; 95% CI 4.43–53.72, p < 0.01), and administration of NAC at our institution was associated with lower likelihood of “Deviation” in comparison to receipt in the community (OR = 0.25; 95% CI 0.25–0.72, p = 0.01). CONCLUSIONS: Deviations in administration of NAC were common in our cohort (69%) and were associated with receipt of GC and administration of NAC at an outside institution.

scholarly journals Predictors of referral for neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer and changes in practice over time

2015 ◽  
Vol 9 (7-8) ◽  
pp. 236 ◽  
Author(s):  
Geoffrey T. Gotto ◽  
Melissa Shea-Budgell ◽  
M. Sarah Rose ◽  
J. Dean Ruether
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Local Treatment ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Curative Therapy ◽  
Kaplan Meier ◽  
Muscle Invasive ◽  
Over Time

Introduction: In patients with non-metastatic muscle-invasive bladder cancer (MIBC) fit for curative therapy, a multidisciplinary approach consisting is recommended. This approach includes local treatment (usually radical cystectomy), ideally combined with neoadjuvant chemotherapy (NACT). Despite a survival benefit with NACT, uptake remains low. We assessed NACT consultation in Alberta and examined associative factors, as well as the relationship to survival.Methods: Patients with MIBC were identified through the Alberta Cancer Registry. Demographic and clinicopathologic information was collected from electronic medical records between 2007 and 2011. In addition to descriptive statistics, logistic regression was used to determine factors associated with receiving NACT consultation. Overall survival was described using a Kaplan-Meier estimate.Results: Of the 315 radical cystectomy patients, 140 (45.1%, 95% confidence interval [CI] 39.5, 50.8) received NACT consultation. Patients ≥80 years (odds ratio [OR] 0.21, 95% CI 0.08, 0.57, p = 0.002) and those treated in Calgary (OR 0.11, 95% CI 0.05, 0.25, p < 0.001) were less likely to receive NACT consultation. The rate of NACT consultation increased steadily from 2007 to 2011 (OR 1.23, 95% CI 1.04, 1.45 per year of diagnosis, p = 0.018). After a median follow-up of 28.1 months (range: 14.6–50.3), median survival was 54.7 months for patients who received NACT consultation versus 31.2 months for those who did not (p = 0.030).Conclusions: NACT consultation in patients with MIBC undergoing radical cystectomy has improved over time; however, regional differences underscore the need for a standardized approach to NACT consultation, including common referral mechanisms.

scholarly journals Cisplatin-Based Neoadjuvant Chemotherapy for Elderly Patients with Muscle-Invasive Bladder Cancer: Is It Feasible?

2021 ◽  
Vol 5 (4) ◽  
pp. 1-1
Author(s):  
Clément Dumont ◽  
◽  
Madeleine Lefèvre ◽  
Quiterie Aussedat ◽  
Pierre-Louis Reignier ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Elderly Patients ◽  
Standard Of Care ◽  
Invasive Bladder Cancer ◽  
Hematological Toxicity ◽  
Routine Practice ◽  
Muscle Invasive Bladder Cancer ◽  
Increased Risk ◽  
Muscle Invasive

Cisplatin-based neoadjuvant chemotherapy (C-NAC) has been the standard of care in localized muscle-invasive bladder cancer (MIBC). However, the feasibility and benefit of C-NAC in elderly patients remain uncertain since this population has always been underrepresented in pivotal trials and is often barred from chemotherapy in routine practice because of their perceived frailty. Therefore, in order to evaluate the effectiveness of C-NAC in elderly patients with MIBS, we retrospectively reviewed the medical files of patients (cT2-4, N0-3, and M0) treated at our institution and aged 75 or older at the time of the first chemotherapy cycle. From May 2012 to March 2020, 51 patients aged 75 to 90 received C-NAC. Among them, 38 patients received methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and 13 patients received gemcitabine and cisplatin (GC). In this study, the primary endpoint was the feasibility of C-NAC, evaluated as the percentage of patients who underwent at least four chemotherapy cycles. Overall feasibility of a complete four-cycle chemotherapy course was 75% (dose-dense MVAC [dd-MVAC]: 76%; GC: 69%). Incidence of grade 3-4 adverse events was 57%, mostly driven by hematological toxicity from dd-MVAC, and the incidence of febrile neutropenia was 6%. These results indicate the feasibility of C-NAC in elderly patients without any contraindication to cisplatin. A coordinated multidisciplinary approach, including a geriatric oncologist, may help to identify patients at increased risk for chemotherapy-induced toxicity, especially in patients aged 85 or older.

Impact of histology and toxicities on outcomes of patients with muscle invasive bladder cancer receiving neoadjuvant chemotherapy.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 540-540
Author(s):  
Catherine Curran ◽  
Gregory Russell Pond ◽  
Andres Acosta ◽  
Amin Nassar ◽  
Sarah Abou Alaiwi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Invasive Bladder Cancer ◽  
Prognostic Impact ◽  
Muscle Invasive Bladder Cancer ◽  
Histologic Subtype ◽  
Muscle Invasive

540 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) extends survival in muscle invasive bladder cancer (MIBC) patients (pts). Pathologic complete response (pCR) is associated with survival. We conducted a retrospective study to examine the prognostic impact of other variables including histologic subtype, location, multifocality, margins, size of tumor and toxicities. Methods: Pts who underwent RC at Dana-Farber for MIBC stage T2-T4N0-1 were studied. Data were collected for demographics, clinical and pathologic variables. Descriptive stats were reported, and Cox proportional hazards regression analyses were conducted to examine the association with recurrence-free survival (RFS) and overall survival (OS). Results: From 2002 to 2018, 150 patients were available. The median age was 66 (range 36-89) and 102 (68%) were male. MVAC/dose dense MVAC, GC and other non-standard regimens were given in 42 (28%), 85 (56.7%) and 23 (15.3%) pts, respectively. The 2-yr RFS was 63.6%, the 5-yr OS was 68.7% and pCR occurred in 38 pts (25.3%). Multivariable analysis identified pure urothelial carcinoma in the residual tumor and absence of pathologic response to be associated with poor RFS and OS. Positive margins were associated with poor RFS, while grade ≥3 toxicities were associated with poor OS. Conclusions: Pure urothelial carcinoma histology was associated with worse RFS and OS following RC after NAC for MIBC, suggesting molecular studies may be useful in these cases. The association of severe toxicities with poor OS suggests that optimal pt selection for NAC and early recognition of toxicities is important.[Table: see text]

scholarly journals ENERGIZE: a Phase III study of neoadjuvant chemotherapy alone or with nivolumab with/without linrodostat mesylate for muscle-invasive bladder cancer

2020 ◽  
Vol 16 (2) ◽  
pp. 4359-4368 ◽  
Author(s):  
Guru Sonpavde ◽  
Andrea Necchi ◽  
Shilpa Gupta ◽  
Gary D Steinberg ◽  
Juergen E Gschwend ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Clinical Activity ◽  
Muscle Invasive Bladder Cancer ◽  
Metastatic Urothelial Carcinoma ◽  
Muscle Invasive

Immune checkpoint inhibitors have revolutionized the treatment of patients with metastatic urothelial carcinoma. In cisplatin-eligible muscle-invasive bladder cancer (MIBC), cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy improves overall survival. Tumor PD-L1 expression increases in MIBC after NAC, suggesting potential synergy in combining PD1/PD-L1 inhibitors with NAC. IDO1 is overexpressed in bladder cancer and is associated with poor outcomes. Linrodostat mesylate (BMS-986205) – a selective, potent, oral IDO1 inhibitor – combined with nivolumab has demonstrated safety and preliminary evidence of clinical activity in metastatic urothelial carcinoma. Here, we discuss the rationale and trial design of the ENERGIZE, a Phase III trial investigating the efficacy of NAC in combination with nivolumab with or without linrodostat followed by postsurgery nivolumab or nivolumab with linrodostat in cisplatin-eligible patients with MIBC. Clinical trial registration number: NCT03661320

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