Original article
The value of immediate postoperative intravesical epirubicin instillation as an adjunct to standard adjuvant treatment in intermediate and high-risk non–muscle-invasive bladder cancer: A preliminary results of randomized controlled trial

https://doi.org/10.1016/j.urolonc.2018.10.019Get rights and content

Highlights

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    Immediate intravesical instillation did not show superior effect in our study.

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    It neither reduced recurrence/progression rate nor reduced number of recurrences.

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    Immediate instillation should only be spared for low risk patients.

Abstract

Purpose

We aimed at this study to test the value of immediate postoperative intravesical epirubicin instillation in intermediate and high-risk non–muscle-invasive bladder cancer patients.

Materials and Methods

After approval of Institutional Review Board, 260 patients were randomly allocated into 2 groups, including transurethral resection of bladder tumor (TURBT) alone in control group and TURBT plus immediate postoperative epirubicin (50 mg) in test group. Patients were monitored for postoperative complications. Adjuvant instillation therapy was administered according to risk categorization. Patients were followed every 3 months by cystourethroscopy and urine cytology. The primary end points were recurrence, progression, and/or death from cancer.

Results

Of the 260 patients, 236 were eligible and followed for a mean of 29 months. The 2 study groups were comparable regarding perioperative baseline demographic criteria. There was no statistically significant difference between the 2 groups regarding recurrence rate (27.1% vs. 26.2%), interval to first recurrence (16.3 ± 6.6 vs. 16.4 ± 6.4 months) or progression rate to muscle invasion (8.5% vs. 5.9%). Site, size, and number of recurrences were also comparable between the 2 groups. Recurrences and progression-free survival were comparable between the 2 groups (Log-rank P = 0.88 and 0.47, respectively). Postoperative complications were all low-grade according to modified Dindo–Clavian system, with no significant difference in their rate between the 2 groups.

Conclusions

Immediate post-TURBT epirubicin instillation is ineffective in intermediate and high-risk non–muscle-invasive bladder cancer. It neither prolongs time to recurrence and/or progression nor reduces number of recurrences. We advocate strict specification of patient and tumor criteria in which immediate instillation is indicated.

Introduction

Immediate postoperative intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) was shown by many investigators [1], [2], [3] to reduce recurrence by eradication of any floating tumor cells. According to the European Association of Urology (EAU) guidelines, 1 postoperative intravesical instillation of chemotherapy after TURBT of presumably non–muscle-invasive bladder cancer (NMIBC) is recommended [4]. Evidence supporting such practice was strengthened in 2004 by European Organization of Research and Treatment of Cancer (EORTC) meta-analysis incorporating all immediate postoperative chemoprophylaxis trials published to that date. They demonstrated a significant improvement in the likelihood of recurrence for NMIBC patients who received immediate postoperative chemoprophylaxis after TURBT [5]. However, the evidence for the efficacy of this treatment originates from studies that have focused on patients with low risk for recurrence. More precisely, only 126 (16.5%) of the patients had multiple tumors, and 82 (11%) were recurrent cases. Accordingly, the evidence indicating a beneficial influence of single instillation therapy is weaker in patients with intermediate and high risk of recurrence as compared to those who are at low risk [6]. In the present study, we investigated the role of immediate post-TURBT instillation of epirubicin in intermediate and high-risk NMIBC regarding recurrence, progression, and complications.

Section snippets

Study population

After approval of the Institutional Review Board, patients with papillary bladder tumors seen through the outpatient clinic in the urology department (Urology and Nephrology Center, Mansoura University, Egypt) were assessed for eligibility to this randomized controlled trial. Patients who met these criteria were asked to participate in this trial and were provided with an informed consent form.

Inclusion criteria

Inclusion criteria included patients with primary or recurrent papillary bladder tumor for whom

Baseline demographics

From July 2014 to November 2015, 260 patients met the study criteria. As shown in the study flowchart Fig. 2. After excluding patients with bladder cancer other than urothelial carcinoma and muscle-invasive bladder cancer or benign disease, 236 patients were included in the final analysis.

Baseline patients and tumor characteristics were comparable between the 2 groups (Table 1). Regarding patients with recurrent NMIBC, both groups were comparable regarding number of recurrences, interval from

Discussion

The impact of single instillation of chemotherapy on behavior of NMIBC after TURBT have been studied in many previous trials with confirmed efficacy on reduction of recurrence [11]. This is based on its antitumor effect in destroying tumors cells floating in the irrigation fluid and urine after TURBT and on its ablative effect on residual tumor cells at the site of the resection and on small overlooked tumors [12].

The EAU guidelines for NMIBC recommended 1 postoperative intravesical

Conclusions

Unlike the evidence-based value of single immediate post-TURBT instillation of epirubicin on reduction of recurrence rate in low risk NMIBC, it is ineffective in intermediate and high-risk patients. It neither prolongs time to recurrence, time to progression nor reduces the number of recurrences. Patients with recurrence rate more than 1 per year, single papillary tumor more than 3 cm, or multiple papillary tumors are most likely to be intermediate or high-risk patients. So, they should be

Conflict of interest

The authors declare that there is no conflict of interest.

Informed consent

An informed consent was obtained from the patient(s) for their information to be published in this article.

References (19)

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Descriptive running head: In the era of overwhelming date about the recommendation of immediate postoperative intravesical instillation of chemotherapy after transurethral resection of bladder tumor, we aimed at this study to test the value of immediate post transurethral resection of bladder tumor intravesical epirubicin in intermediate and high-risk non–muscle-invasive bladder cancer in a randomized control trial.

Trial registration: clinicaltrials.gov ID: NCT02214602.

Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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