Should we administer single-dose chemotherapy to the bladder after removing the kidney and ureter for the treatment of renal pelvis and ureter cancer?

Review question

In people with cancer of the inner lining of their kidney and ureter (the tube that transports urine from the kidney to the bladder) who are having surgery to remove the kidney and ureter, what are the effects of a one-time dose of chemotherapy into their bladder after surgery.

Background

In people with cancer of the inner lining of the bladder, one-time chemotherapy put into the bladder (after the tumour has been removed) is helpful in making the cancer less likely to come back. We don't know whether the same is true for people in whom the same type of cancer is found in the inner lining of the kidney and ureter. Even if it does, it may also make these people have serious unwanted effects. We performed this study to summarise the best available evidence on the effects of one-time dose of chemotherapy in these people after removal of the kidney and ureter for cancer.

Study characteristics

We found two randomised controlled studies (RCTs), with a total of 361 participants that compared a single-dose chemotherapy placed in the bladder to no chemotherapy in people having their kidney and ureter removed for cancer of the inner lining of the kidney or ureter, or both. These findings are based on a literature search up to April 15, 2019.

Key results

We found that a one-time dose of chemotherapy put into the bladder after surgery may reduce the risk of this type of tumor coming back in the bladder over time compared to no chemotherapy. We found no evidence whether this affects the time to death from this type of cancer. Serious unwanted effects appear to be rare and not increased with chemotherapy, but we are uncertain of this finding.

Certainty of the evidence

Our confidence in the evidence for the effect on the risk of recurrence within the bladder is low. This means that the true effect may be very different from what this review shows. The certainty of evidence for the effects of one-time chemotherapy put into the bladder on serious unwanted effects was very low. This means that we are very uncertain about this result.

Authors' conclusions: 

For patients who have undergone nephroureterectomy for upper tract urothelial carcinoma, single-dose intravesical chemotherapy instillation may reduce bladder cancer recurrence after nephroureterectomy. However, we are uncertain as to the risk of serious (and minor) adverse events. We found no evidence for the outcome of time to death from upper tract urothelial carcinoma. We were unable to conduct any of the preplanned subgroup analyses, particularly those based on operative approach, pathologic stage, and method of bladder cuff excision.

Read the full abstract...
Background: 

Single-dose, postoperative intravesical chemotherapy reduces the risk of bladder cancer recurrence after transurethral resection of bladder tumours. However, there is limited evidence whether single-dose intravesical chemotherapy is similarly effective at preventing bladder cancer recurrence after nephroureterectomy.

Objectives: 

To assess the effects of single-dose intravesical chemotherapy instillation after nephroureterectomy for upper tract urothelial carcinoma.

Search strategy: 

We performed a comprehensive literature search using multiple databases (MEDLINE, Cochrane Library, Embase, Scopus, Web of Science, and LILACS), trials registries, other sources of grey literature, and conference proceedings published up to April 15 2019, with no restrictions on language or status of publication.

Selection criteria: 

We included randomised controlled trials in which participants either received or did not receive single-dose intravesical chemotherapy instillation after nephroureterectomy.

Data collection and analysis: 

Two review authors screened and independently assessed studies and extracted data from included studies. We performed statistical analyses using a random-effects model. We rated the certainty of evidence according to the GRADE approach.

Main results: 

The search identified two studies (a multicenter study from Japan and the United Kingdom) with 361 participants.

Primary outcomes

Our results indicate that single-dose intravesical chemotherapy instillation may reduce the risk of bladder cancer recurrence over time compared to no instillation (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.32 to 0.82, low-certainty evidence). After 12 months follow-up, this would result in 127 fewer bladder cancer recurrences (95% CI: 182 to 44 fewer bladder cancer recurrences) per 1000 participants. We downgraded the certainty of evidence by two levels due to study limitations and imprecision.

We found no trials that reported on the outcomes of time to death from upper tract urothelial carcinoma. The effect of single-dose intravesical chemotherapy instillation on serious adverse events is uncertain (risk ratio [RR]: not estimable, 95% CI: not estimable, there were no events, very low-certainty evidence). We downgraded the certainty of evidence by one level due to study limitations and by two levels due to imprecision.

Secondary outcomes

We found no trials that reported on the outcomes of time to death from any cause and participants’ disease-specific quality of life. The effect of single-dose intravesical chemotherapy instillation on minor adverse events is uncertain (risk ratio [RR]: not estimable, 95% CI: not estimable, there were no events, very low-certainty evidence). We downgraded the certainty of evidence by one level due to study limitations and by two levels due to imprecision.

Share/Save