Review articleWhy is perioperative chemotherapy for bladder cancer underutilized?
Introduction
A substantial proportion of patients who undergo cystectomy for muscle-invasive bladder cancer (MIBC) ultimately have recurrence and die from their disease [1]. Beginning in the late 1990s, a series of randomized controlled trials and 2 meta-analyses have reported that long-term survival is improved by approximately 5% with a course of neoadjuvant chemotherapy (NACT) [2], [3], [4], [5]. Based on these data, international guidelines recommend the use of NACT for patients with T2-T4 bladder cancer [6], [7], [8]. The evidence in support of adjuvant chemotherapy (ACT) also suggests that it improves patient outcomes [9], [10]. However, the quality of the data is more limited, and therefore ACT is not as strongly endorsed by practice guidelines [7], [11].
Despite level I evidence and practice guideline recommendations, numerous studies have reported low rates of perioperative chemotherapy in routine care. Porter et al. used Surveillance, Epidemiology and End Results Program-Medicare data to describe the use of NACT among 40,660 patients with MIBC in the United States from 1992 to 2003. They found that NACT was delivered to 1%, 7%, and 11% of patients with stages 2, 3, and 4 disease, respectively [12]. David et al. [13] used records from the National Cancer Data Base in the United States to describe treatment of 7,161 patients with stage III bladder cancer diagnosed between 1998 and 2003. They found that 10% of patients received ACT, whereas only 1% received NACT. In our own population-based study of practice patterns in Ontario, NACT was used in only 4% of the 2,738 patients with MIBC diagnosed between 1994 and 2008 [14]. Moreover, treatment rates did not substantially increase over time: 5% from 1994 to 1998, 3% from 1999 to 2003, and 6% from 2004 to 2008. Contrary to the existing Ontario practice guidelines, the use of ACT was more common than NACT and increased over time: 16% from 1994 to 1998, 19% from 1999 to 2003, and 23% from 2004 to 2008.
In general, patients with MIBC are eligible for perioperative chemotherapy if they have T2-T4 disease, no clinical evidence of metastatic disease, an Eastern Cooperative Oncology Group performance status 0 to 1, and adequate renal function. Raj et al. reviewed the use of NACT at a single tertiary referral center during 2003 to 2008 and found that NACT was given to only 32 of 145 (22%) patients [11]. Among these 145 patients, 70% were eligible based on calculated renal function. Among the 113 patients not treated with NACT, a satisfactory reason for not using NACT was not identified in 66 cases (58%). In the remaining patients, contributing reasons included concerns over age/comorbidity (26%), patient preference (8%), concerns of NACT toxicity (8%), symptoms or active bleeding (5%), and clinically localized disease (17%).
Section snippets
What factors might be driving physician and patient decision making?
In Fig., we depict the care pathway for patients with MIBC and potential provider- and patient-level barriers to the use of NACT/ACT. An important and common up-front barrier is the fact that 30% to 50% of patients are not eligible for treatment on the basis of impaired renal function [15], [16]. In the subsequent sections, we summarize what is known from the published literature about provider- and patient-level barriers to NACT/ACT.
Conclusion
In this commentary, we have reviewed why NACT/ACT may be underutilized in routine practice and have proposed a framework for identifying relevant decision-making steps in the care pathway. The existing literature suggests that the upstream decision by urologists to refer patients to a medical oncologist before cystectomy may be an important focus of future work in knowledge translation. Although this commentary focused on surgical management of MIBC, it is worth noting that the data in support
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Cited by (16)
Perioperative chemotherapy for bladder cancer in the general population: Are practice patterns finally changing?
2018, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :Despite multiple studies describing low use of perioperative chemotherapy, potential reasons for underutilization are not well described. Potential reasons include low referral rate from urology to medical oncology (MO), patient ineligibility owing to renal dysfunction, and patient/physician preference against chemotherapy [11]. Our data showed that during 1994 to 2008 only 10% of patients with MIBC were referred to MO before cystectomy [12].
The effect of concomitant carcinoma in situ on neoadjuvant chemotherapy for urothelial cell carcinoma of the bladder: Inferior pathological outcomes but no effect on survival
2015, Journal of UrologyCitation Excerpt :More dramatically the use of NAC still only reached 47% in a multi-institutional quality care initiative project at Memorial Sloan Kettering Cancer Center.15 In a review of reasons for the disparity between patients eligible for NAC and those who receive chemotherapy Patafio et al cited several reasons, of which the most compelling was concern regarding NAC safety and efficacy in all patients with MIBC.16 There is a well documented survival advantage for NAC.
Complications after neoadjuvant chemotherapy and radical cystectomy for patients with bladder cancer: A propensity score matched analysis
2023, Canadian Urological Association Journal
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This work was funded through salary support provided to Dr Booth as a Cancer Care Ontario Chair in Health Services Research.