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Editorial: Postoperative intravesical chemotherapy has an important role in reducing subsequent bladder tumours – why is it not routine?




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Transurethral resection of bladder tumour (TURBT) is a frequent operation performed by urologists worldwide. Although on occasion the procedure can be quite challenging, the majority are relatively straightforward with little morbidity. In most cases, where the medical system allows, it is an outpatient procedure. Nonetheless, with the exception of small low‐grade tumours the patient is anaesthetised. It is costly, as the procedure requires medical clearance, an operating room team and equipment.

Most patients with bladder cancer have Ta or less frequently T1 tumours. Despite an initial TURBT, 30–80% of patients develop another tumour. Most are new tumours and some may be recurrences. The reasons for the high ‘recurrence’ rate are the continued impact of the carcinogen, e.g. cigarettes, incomplete resection, missed tumours, and tumour implantation on the altered urothelium. The urologist can help reduce these events by stressing the importance of limiting carcinogen exposure e.g. smoking cessation, striving to perform a complete TURBT, reviewing the entire bladder after the TURBT to avoid missing tumours (using narrow‐band imaging or fluorescent cystoscopy if available), and limiting implantation of tumour cells on the altered urothelial surface with the use of postoperative intravesical chemotherapy (POIVC).

There is a large body of evidence that POIVC reduces the chance of a subsequent tumour [1]. I became convinced that implantation occurs after animal studies demonstrated that bladder cancer cells placed into the bladder preferentially implant and grow only if the urothelial surface had been cauterised or otherwise damaged prior to exposure to the bladder cancer cells [2]. Prospective randomised trials eventually confirmed the benefit of POIVC [3]. The paper published in this issue of the BJUI by Bosschieter et al. [4] indicates that POIVC is equally effective if given the same day or the day after TURBT. Thus, if there are obstacles to instilling the medication on the day of the TURBT the drug can be administered the following day.

The evidence in favour of POIVC for bladder tumours is particularly impressive for Grade 1–2 Ta tumours. In my view, all patients with primary or ‘recurrent’ single or multiple papillary Grade 1–2 Ta tumours are the optimal candidates to receive POIVC [5]. POIVC is recommended by the European Association of Urology (EAU) and AUA/Society of Urologic Oncology (SUO) [6,7] yet, the adoption of this guideline is far from uniform. I queried my colleagues from the International Bladder Cancer group (IBCG), as they are conversant in the scientific basis for POIVC and represent several countries with different medical systems [8]. Their comments are pertinent and consistent with my understanding of the issues. Here are some of the common reasons for not following the guidelines: (i) Some urologists are not convinced that the reduction in the ‘recurrence’ rate is sufficient to use POIVC. (ii) The most common chemotherapeutic agent for POIVC in the USA is mitomycin C and it is expensive. The cost for 40 mg is ~$1000. It is approximately $500 in Europe. (iii) Hospitals have rules regarding the delivery of chemotherapy and the pharmacy and nursing departments may not make it easy to instil the drug in the postoperative setting. Some hospitals require notification a day before the surgery and the drug is wasted if the drug is not used. (iv) Urologists are concerned about extravasation and uncertainty of the tumour grade and stage. There may be other reasons but these help explain why POIVC is not routine.

On the other hand many patients with bladder cancer require frequent TURBTs. I am certain that following an uneventful TURBT or office cauterisation for Grade 1–2 Ta bladder cancer, they would choose to receive POIVC if properly informed. Urologists are proficient at judging whether a tumour fits the criteria for POIVC and if they underestimate the grade or stage the patient may still benefit. If urologists cannot instil the chemotherapy on the day of the TURBT, they can instil the drug the following day without compromising effectiveness. I believe it is our job to do what we can to help our patients and in this instance we should do our best to minimise subsequent tumour events, which includes the use of adjuvant chemotherapy.

Mark S. Soloway

Memorial Hospital Hollywood, Miami, FL, USA

References

  1. Perlis N, Zlotta AR, Beyene J, Finelli A, Fleshner NE, Kulkarni GS. Immediate post‐ transurethral resection of bladder tumor intravesical chemotherapy prevents non‐muscle invasive bladder tumor recurrence: an updated meta‐analysis on 2548 patients and quality –of‐evidence review. Eur Urol 2013; 64: 421–30
  2. Weldon TE, Soloway MS. Susceptibility of urothelium to neoplastic cellular implantation. Urology 1975; 5: 824–7
  3. Tolley DA, Hargreave TB, Smith PH et al. Effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: interim report from the Medical Research Council Subgroup on Superficial Bladder cancer. Br Med J 1988; 296: 1259–61
  4. Bosschchieter J, von Moorselaar JA, Vis AN et al. The effect of timing of an immediate instillation of mitomycin C after transurethral resection in 941 patients with non‐muscle‐invasive bladder cancer. BJU Int 2018; 122: 571–5
  5. Klaassen Z, Soloway MS. European Association of Urology and American Urological Association/Society of Urologic Oncology guidelines on risk categories for non‐muscle‐invasive bladder cancer may lead to overtreatment for low‐grade Ta bladder tumors. Urology 2017; 105: 14–7
  6. Babjuk M, Böhle A, Burger M et al. EAU guidelines in non‐muscle invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 2017; 71: 447–61
  7. Chang SS, Boorjian SA, Chou R et al. Diagnosis and treatment of non‐muscle invasive bladder cancer: AUA/SUO guideline. J Urol 2016; 196: 1021–9
  8. Brausi M, Witjes F, Lamm D et al. A review of current guidelines and best proactive recommendations for the management of nonmuscle invasive bladder cancer by the International Bladder Cancer Group. J Urol 2011; 186: 2158–67

 

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