UROLOGICAL SURVEY
Urological oncology
Should all patients with non-muscle-invasive bladder cancer receive early intravesical chemotherapy after transurethral resection? The results of a prospective randomised multicentre study
Gudjónsson S, Adell L, Merdasa F, Olsson R, Larsson B, Davidsson T, Richthoff J, Hagberg G, Grabe M, Bendahl PO, Månsson W, Liedberg F
Lund University Hospital, Lund, Sweden
Eur Urol. 2009; 55: 773-80
BACKGROUND: To decrease recurrences in non-muscle-invasive bladder cancer (NMIBC), the European Association of Urology (EAU) guidelines recommend immediate, intravesical chemotherapy after transurethral resection (TUR) for all patients with Ta/T1 tumours.
OBJECTIVE: To study the benefits of a single, early, intravesical instillation of epirubicin after TUR in patients with low- to intermediate-risk NMIBC.
DESIGN, SETTING, AND PARTICIPANTS: In this prospective randomised multicentre trial, 305 patients with primary as well as recurrent low- to intermediate-risk (Ta/T1, G1/G2) tumours were enrolled between 1997 and 2004. Patients were randomly allocated to receive 80 mg of epirubicin in 50 ml of saline intravesically within 24 h of TUR or no further treatment after TUR.
MEASUREMENTS: The primary end point was time to first recurrence.
RESULTS AND LIMITATIONS: A total of 219 patients remained for analysis after exclusions. The median follow-up time was 3.9 yr. During the study period, 62% (63 of 102) of the patients in the epirubicin group and 77% (90 of 117) in the control group experienced recurrence (p=0.016). In a multivariate model, the hazard ratio (HR) for recurrence was 0.56 (p=0.002) for early instillation of epirubicin versus no treatment. In a subgroup analysis, the treatment had a profound recurrence-reducing effect on patients with primary, solitary tumours, whereas it provided no benefits in patients with recurrent or multiple tumours. Furthermore, patients with a modified European Organisation for Research and Treatment of Cancer (EORTC) risk score of 0-2 with and without single instillation had recurrence rates of 41% and 69%, respectively (p=0.003), whereas the corresponding rates for those with a risk score of > or = 3 were 81% and 85%, respectively (p=0.35).
CONCLUSIONS: A single, early instillation of epirubicin after TUR for NMIBC reduces the likelihood of tumour recurrence; however, the benefit seems to be minimal in patients at intermediate or high risk of recurrence. Future trials will determine the value of early instillation in addition to serial instillations in NMIBC.
Editorial Comment
Bladder cancer has a high rate of recurrence. Two pathways are considered responsible for this behavior, namely genetically instable urothelium resulting in truly new tumor formation, and re-implantation (seeding) of tumor cells resulting in new occurrences from the previous tumor. The best way to date to interfere with the second pathway, seeding of tumor cells, is immediate post-TUR single shot instillation of cytotoxic drugs. However, is this sufficient therapy for all tumors? The authors answer this important question in their randomized study. First, they show that single-shot instillation (in this study given within 24 hours, but best within 6 hours after TUR) indeed is highly effective, resulting in a significant overall reduction of recurrences. This effect was pronounced in the low risk group with single primary tumors, whereas barely evident in the intermediate risk group or that with multiple tumors. The numbers needed to treat (NNT) was 3.5, which supports similar figures from previous calculations.
The authors state correctly that single-shot treatment has little or no impact on genetically instable urothelium. Therefore, next to singe shot instillation therapy, all intermediate to high-risk group patients with bladder cancer deserve more instillation therapy, be it regular courses of cytostatics or BCG.
Dr. Andreas Bohle
Professor of Urology
HELIOS Agnes Karll Hospital
Bad Schwartau, Germany
E-mail: boehle@urologie-bad-schwartau.de
Publication Dates
-
Publication in this collection
31 May 2010 -
Date of issue
Apr 2010
