Electrically-stimulated intravesical chemotherapy for superficial bladder cancer (interventional procedures consultation)
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE
Interventional Procedure Consultation Document
Electrically-stimulated intravesical chemotherapy for superficial bladder cancer
| This procedure, also known as electromotive drug administration (EMDA) of intravesical chemotherapy, can be used for patients with bladder cancer, either before or after surgery. A solution including a chemotherapy drug is injected into the bladder using a thin tube inserted through the urethra. At the same time, an electrode is inserted in the bladder and other electrodes are placed on the skin of the lower abdomen. An electric current is then created with the aim of improving absorption of the chemotherapeutic drugs. |
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The National Institute for Health and Clinical Excellence is examining electrically-stimulated intravesical chemotherapy for superficial bladder cancer and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. The Institute's Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about electrically-stimulated intravesical chemotherapy for superficial bladder cancer.
Note that this document is not the Institute's formal guidance on this procedure. The recommendations are provisional and may change after consultation. The process that the Institute will follow after the consultation period ends is as follows.
For further details, see the Interventional Procedures Programme manual, which is available from the Institute's website (www.nice.org.uk/ipprocessmanual). NICE is committed to promoting through its guidance race and disability equality and equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and how it might be improved. Closing date for comments: 28 July 2008 |
| Note that this document is not the Institute's guidance on this procedure. The recommendations are provisional and may change after consultation. |
| 1 | Provisional recommendations |
| 1.1 | Current evidence on the safety of electrically-stimulated intravesical chemotherapy for superficial bladder cancer raises no major safety concerns. However, the evidence is based on methodologically inconsistent studies and the efficacy of the procedure is uncertain. Therefore, this procedure should only be used in the context of research. |
| 1.2 | The Institute may review the procedure upon publication of further evidence. |
| 2 | The procedure | ||
| 2.1 | Indications and current treatments | ||
| 2.1.1 | Transitional cell carcinoma is the most common form of bladder cancer. Superficial disease is defined as cancer that is confined to the bladder lining and has not invaded the muscle layer. | ||
| 2.1.2 | Conventional treatment involves transurethral resection (TUR), in which malignant tissue is removed with an electrocautery device during cytoscopy). Intravesical chemotherapy with bacillus Calmette-Guérin (BCG) vaccine or other chemotherapy agents may also be used, either alone or as adjuvant therapy after TUR, to reduce the risk of cancer recurrence. Intravesical microwave hyperthermia has also been used in combination with intravesical chemotherapy. | ||
| 2.2 | Outline of the procedure | ||
| 2.2.1 | Electrically-stimulated or electromotive drug administration (EMDA) of intravesical chemotherapy can be used as a neoadjuvant or adjuvant treatment following TUR. EMDA creates an electric field across the bladder wall, with the aim of stimulating directional ionic and solute movement, so increasing absorption of the chemotherapeutic solution which has been introduced into the bladder. | ||
| 2.2.2 | The procedure is usually performed under general anaesthesia. As in standard intravesical chemotherapy, a chemotherapeutic drug solution (usually mitomycin C in saline or distilled water) is instilled into the bladder. In the procedure, electrode pads are placed on the skin of the patient?s lower abdominal wall and a catheter (with an intravesical electrode) is inserted into the bladder through the urethra. When the catheter and electrodes are in place the chemotherapy drug solution is directed into the bladder. The cutaneous and intravesical electrodes are then connected to a generator that creates a current of up to 25 mA. Treatment sessions usually last for approximately 30 minutes and are repeated weekly for 4–8 weeks, or longer for adjuvant treatment. After the procedure the catheter is removed and the bladder drained. | ||
| Sections 2.3 and 2.4 describe efficacy and safety outcomes which were available in the published literature and which the Committee considered as part of the evidence about this procedure. For more details, refer to the Sources of evidence. | |||
| 2.3 | Efficacy | ||
| 2.3.1 | A randomised controlled trial (RCT) of 212 patients with histologically proven pT1 transitional cell carcinoma of the bladder, including patients with carcinoma in situ, reported longer disease-free survival in patients treated by electromotive drug administration of mitomycin C (EMDA–MCC) plus BCG (58%; 62/107) compared with BCG alone (42%; 44/105) at a mean follow‑up of 88 months (p = 0.0012). | ||
| 2.3.2 | An RCT of 108 patients with bladder carcinoma in situ or papillary transitional cell carcinoma reported a significantly higher complete response rate among patients treated by EMDA–MMC (58%; 21/36) compared with those treated by MMC alone (31%; 11/36) (p = 0.012) at 6-month follow-up (complete response defined as negative histology and cytology). The same study reported no significant difference in estimated 5-year survival (all-cause mortality) between the three groups studied (EMDA–MMC 69%, MMC 63%, BCG 59 %; p = 0.782). However, interpreting differences in efficacy between the treatments beyond 6-month follow-up is difficult, because patients for whom the initial treatment was judged to have failed at 6 months could cross over to a different treatment arm. | ||
| 2.3.3 | A non-randomised controlled trial of 80 patients reported complete response to treatment (defined as negative cystoscopy, cytology, and histology) in 40% (6/15) of patients treated by EMDA–MMC, 28% (10/36) of patients treated by MMC and 66% (19/29) of patients treated by intravesical microwave hyperthermia combined with MMC at 7- to 10-day follow-up (significance not stated). | ||
| 2.3.4 | The Specialist Advisers considered key efficacy outcomes to include tumour recurrence, tumour progression and mortality. One Adviser stated that efficacy remains to be established in appropriate trials. | ||
| 2.4 | Safety | ||
| 2.4.1 | The RCT of 212 patients reported suspension of treatment owing to side effects in 3% (3/107) of patients treated by EMDA–MMC plus BCG and in 3% (3/105) of patients treated by BCG alone (nature of side effects not described). In a case series of 22 patients, 14% (3/22) of patients had 3 out of a total of 91 scheduled EMDA–MMC treatment sessions suspended because of bladder ulcer development in one patient and uninhibited bladder contractions causing leakage of the instillate solution in two patients. | ||
| 2.4.2 | The RCT of 108 patients reported urinary frequency in 19% (7/36) of patients following treatment with EMDA–MMC (exact duration of symptoms not described). A case series of 22 patients reported leakage of the instillate solution because of bladder contractions during 15% (14/91) of procedures. | ||
| 2.4.3 | The RCT of 108 patients and the non-randomised controlled trial of 28 patients reported chemical/drug-induced cystitis in 36% (13/36) and 13% (2/15) of patients, respectively; in the RCT, bacterial cystitis was reported in 19% (7/36) of patients. | ||
| 2.4.4 | Across the included studies between 0% (0/15) and 22% (8/36) of patients treated with EMDA–MMC developed haematuria (defined differently across the studies; duration not reported). | ||
| 2.4.5 | The Specialist Advisers stated that theoretical adverse events include urethral stricture, systemic drug toxicity, bladder contracture and transitory incontinence. | ||
| 2.5 | Other comments | ||
| 2.5.1 | The Committee noted that interpretation of the evidence was difficult because of heterogeneity within and between the studies, including inclusion criteria. | ||
| 3 | Further information | ||
| 3.1 | The Institute has published cancer service guidance on improving outcomes in urological cancers (www.nice.org.uk/CSGUC) and interventional procedures guidance on intravesical microwave hyperthermia with intravesical chemotherapy for superficial bladder cancer (www.nice.org.uk/IPG235) and laparoscopic cystectomy of the urinary bladder (www.nice.org.uk/IPG026). | ||
Bruce Campbell
Chairman, Interventional Procedures Advisory Committee
June 2008
| Appendix: | Sources of evidence |
| The evidence considered by the Interventional Procedures Advisory Committee is described in the overview, available at: www.nice.org.uk/ip697overview. | |
