Original article
Perioperative chemotherapy for bladder cancer in the general population: Are practice patterns finally changing?

https://doi.org/10.1016/j.urolonc.2017.11.015Get rights and content

Highlights

  • Use of perioperative chemotherapy for bladder cancer has been low for many years.

  • In this contemporary population-based study practice appears to have changed.

  • Rate of neoadjuvant chemotherapy has increased from 4% to 27%.

  • Rates of referral to medical oncology have increased from 11% to 32%.

  • Patients referred to medical oncology are now more likely to be treated.

Abstract

Background

Uptake of perioperative chemotherapy for muscle-invasive bladder cancer (MIBC) has been historically poor. We describe contemporary use of neoadjuvant (NACT) and adjuvant chemotherapy (ACT) as well as medical oncology (MO) referral patterns in routine practice.

Methods

Electronic treatment records were linked to the population-based Ontario Cancer Registry to identify all MIBC patients treated with cystectomy in Ontario 1994 to 2013. Physician billing records were used to identify consultation with MO. Practice patterns in the contemporary era (2009–2013) are compared with data from 1994 to 2008.

Results

A total of 5,582 patients had cystectomy for MIBC. Use of NACT increased from 4% in 1994 to 2008 to 19% in 2009 to 2013 (P<0.001); rates continued to rise in the most recent era from 12% in 2009 to 27% in 2013 (P<0.001). ACT was delivered to 20% of patients in 2009 to 2013 (19% in 1994–2008, P = 0.875). Use of any chemotherapy (NACT or ACT) in 2009 to 2013 was 35% compared to 23% in 1994 to 2008 (P<0.001). Preoperative referral rates during 2009 to 2013 to MO were greater than 1994 to 2008 (32% vs. 11%, P<0.001); referral rates continued to increase in recent years from 21% in 2009 to 44% in 2013 (P<0.001). The proportion of referred patients ultimately treated with NACT increased substantially; from 32% in 1994 to 1998 to 54% in 2009 to 2013 (P<0.001).

Conclusions

After many years of practice lagging behind evidence, use of NACT in the general population has increased substantially. Our results suggest that increased uptake has been driven by greater preoperative referral to MO as well as greater propensity of MOs to treat referred patients.

Introduction

Muscle-invasive bladder cancer (MIBC) may be locally controlled by cystectomy or radiotherapy but more than 50% of patients ultimately die of distant metastases. International guidelines recommend neoadjuvant chemotherapy (NACT) on the basis of level I evidence [1], [2], [3]. Although less robust than NACT, there is growing evidence to suggest that adjuvant chemotherapy (ACT) might offer a comparable benefit to NACT [4]. In this context, practice recent guidelines are now shifting to recommend either NACT or ACT for MIBC [2].

Despite the pivotal randomized controlled trials in 1999 and 2003 [5], [6], multiple studies showed minimal uptake of NACT and a paradoxical greater uptake of ACT [7], [8], [9]. These initial studies reported practice in the 1990s and mid-2000s. We have previously reported practice patterns in the Canadian province of Ontario during 1994 to 2008 and showed that use of NACT was very low (mean utilization rate 4%) with no clear increase over time [10]. 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]. Recent surveys suggest that physician attitude towards chemotherapy for bladder cancer may be changing [13], [14], and 2 population-based studies have described increasing use of chemotherapy [15], [16]. There remains a paucity of data to describe to what extent MO referral rates have changed over time. We undertook the following study to provide insight into delivery of perioperative chemotherapy and referral patterns to MO in the contemporary era.

Section snippets

Study design and population

This is a population-based, retrospective cohort study to describe use of perioperative chemotherapy and referral to MO among patients with MIBC in the Canadian province of Ontario. We have previously reported practice patterns during 1994 to 2008 [10], [12]; in this report we update this analysis to include patients treated in 2009 to 2013. Ontario has a population of approximately 13.5 million people and a single-payer universal health insurance program. All incident cases of bladder cancer

Study population

During 1994 to 2013, 5,582 patients in Ontario underwent cystectomy for bladder cancer of which 4,250 patients had muscle-invasive urothelial carcinoma (Supplemental eFigure). Most patients (59%) were 70+ years of age and 75% were males (Table 1). A total of 9% (372/4,250) of patients received NACT; 19% (827/4,250) of patients were treated with ACT. Furthermore, 70 patients (2%) were treated with NACT and ACT.

Use of perioperative chemotherapy

Use of NACT increased substantially during the study period from 5% (1994–1998) to 3%

Discussion

We have explored use of perioperative chemotherapy and referral to MO among patients with MIBC in the contemporary era. Several important findings have emerged. First, after many years of practice lagging behind evidence, there has been a substantial increase in use of NACT. Second, increased use of NACT appears to be driven by greater preoperative referral to MO as well as greater propensity of MOs to deliver NACT among referred patients. Third, chemotherapy use and referral patterns are

Acknowledgments

Parts of this material are based on data and information provided by Cancer Care Ontario and the Canadian Institute for Health Information. However, the analysis, conclusions, opinions, and statements expressed herein are those of the authors and not necessarily those of Cancer Care Ontario or the Canadian Institute for Health Information.

Dr. Booth had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

References (30)

  • C.M. Booth et al.

    Delivery of perioperative chemotherapy for bladder cancer in routine clinical practice

    Ann Oncol

    (2014)
  • J. Bellmunt et al.

    Invasive bladder cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up

    Ann Oncol

    (2009)
  • M.I. Milowsky et al.

    Guideline on muscle-invasive and metastatic bladder cancer (European Association of Urology Guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement

    J Clin Oncol

    (2016)
  • J.A. Seah et al.

    Neoadjuvant chemotherapy should be administered to fit patients with newly diagnosed, potentially resectable muscle-invasive urothelial cancer of the bladder (MIBC): a 2013 CAGMO Consensus Statement and Call for a Streamlined Referral Process

    Can Urol Assoc J

    (2013)
  • C.M. Booth et al.

    Benefits of adjuvant chemotherapy for bladder cancer

    J Am Med Assoc Oncol

    (2015)
  • Cited by (0)

    Dr. Booth is supported as a Canada Research Chair in Population Cancer Care. This work was also supported by the Canada Foundation for Innovation and the Canadian Cancer Society Research Institute. This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual Grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred.

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