Editorial comment on: The role of continuous saline bladder irrigation after transurethral resection in patients with high-grade non-muscle-invasive bladder cancer

In this randomized study by Onishi et al. [1] the use of a single immediate instillation of Mitomycin-C (SI) is compared to continuous saline bladder irrigation (CSBI) after transurethral resection (TURBT) in primary, high-grade, non-muscle-invasive bladder tumors (NMIBC). No significant difference was found in 12-, 18- or 24-month recurrence rates, time to recurrence or progression rates during median follow-up of 58 months. No re-TURBT or further adjuvant instillations were given to either group and, thus, the outcome registered is solely the result of the surgery and the subsequent perioperative treatment. The incidence of adverse effects was significantly lower in the CSBI group (35.6 vs 7.7%).

Reducing the all too common recurrences of NMIBC after TURBT remains one of the biggest challenges in the field of urology. Since the 1980s there have been multiple randomized studies, meta-analyses and review articles published on the beneficial effect of SI after TURBT. Theoretically, the main effect of SI is to kill tumor cells floating around in the bladder at the end of TURBT, thus preventing them from implanting and later growing into a recurrent tumor. Based on those results, the use of SI has been recommended by the European Association of Urology (EAU) guidelines for over a decade, although with slight changes during recent years where patients with high-grade tumors as well as those with frequently recurring intermediate-risk tumors are no longer considered to benefit from SI [2]. Nevertheless, less than half of practicing urologists in Europe and even fewer in the U.S. have accepted and implemented the use of SI in their clinics [3]. The reason for the non-adherence to the guidelines is undoubtedly multifactorial [4], related both to cost and logistics, uncertainty of the stage and grade of tumor being treated, but also for safety reasons. Although rare, there are a number of published reports on severe and life-threatening adverse reactions resulting from extravesical leak of the cytotoxic agent after SI [5].

The EAU guidelines currently do not suggest any alternative treatment to SI to prevent tumor cell implantation patients that, for whatever cause, are not receiving SI. This is unfortunate, as tumor cell implantation is the most likely reason for early recurrence after a properly performed TURBT.

Clearly the current study is a small, single center study and a larger, properly powered study is warranted in order to prove equivalence of the methods. However, the outcome indicates CSBI could be considered as an alternative treatment to SI in terms of inhibiting tumor cell implantation and subsequent early recurrences for a urologist not using SI and for patients where SI is not considered safe. The results concur with earlier reports on post-TURBT irrigation. In BJU International from 2017, the authors of the current study published a prospective randomized trial which demonstrated CSBI after TURBT to have similar effects to SI, both in terms of recurrence rates and progression rates in patients with low- and intermediate-risk NMIBC [6]. Also, in a retrospective study, overnight CSBI after TURBT was shown by Do et al. [7] to reduce early recurrences. In a highly cited systematic review and individual patient data meta-analysis by Sylvester et al. [8] on randomized clinical trials on the effect of SI in 1592 patients, those receiving post-operative irrigation were found to have a 21% lower relative recurrence risk compared to those not receiving it, adjusted for the randomized treatment given. Finally, a large randomized trial (866 patients) comparing post-operative irrigation after TURBT for Ta/T1 tumors showed a lower 2-year recurrence rate for the irrigation group (absolute difference 6%, p = 0.05), but unfortunately this study was only published in an abstract form [9]. Interestingly, in a randomized study by Böhle et al. [10] where gemcitabine was used as SI and compared to CSBI, no significant difference in recurrence rate was seen. The results contradict those of a recent randomized study by Messing et al. [11], where the same dose of gemcitabine was used as SI, but no irrigation was given in the control group and a clear significant reduction (absolute difference 12%, p < 0.01) in recurrences was seen in the gemcitabine group at 4-year follow-up. The only real difference in design between these two studies was that in the former study the control group received post-operative irrigation.

A practical drawback of the available evidence on usefulness of post-TURBT irrigation is the long duration of the irrigation used. In the two studies by Onishi et al. [1,6] the bladder was manually irrigated 3–5 times at the end of the procedure with a 50 mL syringe. After that, 2000 mL/h saline was administered during the 1st hour, 1000 mL/h for 2 h and after that 500 m/h for 15 h [5]. No study exists on short-term CSBI in outpatients. This long infusion time does not fit the current practice as, today, many urological clinics are doing the majority of TURBTs in an outpatient setting. Further studies are needed to assess if 2–3 h irrigation with 3000–6000 mL during a typical post-operative recovery in an outpatient clinic is as effective as overnight administration.

In summary, the current study and earlier reports on post-TURBT irrigation indicate that CSBI impacts recurrence risk after TURBT It seems intuitive to rinse the bladder thoroughly of tumor debris after resection and, given the low cost and low risk of adverse effects of CSBI, it should be considered as an alternative treatment in patients where SI is contraindicated or not considered safe. Urologists, that for various reasons have not implemented routine use of SI as suggested in the EAU guidelines, should consider this as an alternative immediate adjuvant treatment after TURBT.

Disclosure statement

No potential conflict of interest was reported by the authors.