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Article of the Month: Effect of the Interval Between First and Second TUR on Outcomes in NMIBC

Every Month the Editor-in-Chief selects the Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Ilker Gökce, discussing his paper. 

If you only have time to read one article this week, it should be this one.

Significance of time interval between first and second transurethral resection on recurrence and progression rates in patients with high risk non muscle invasive bladder cancer treated with maintenance intravesical Bacillus Calmette-Guerin

 

Sumer Baltacı, Murat Bozlu*, Asıf Yıldırım, Mehmet Ilker Gokce, İlker TinayGuven Aslan§, Cavit Can, Levent Turkeri,Ugur Kuyumcuoglu** and Aydın Mungan††

 

Department of Urology, Ankara University School of Medicine, Ankara , *Department of Urology, University of Mersin School of Medicine, Mersin,Department of Urology, Istanbul Medeniyet University School of Medicine, ‡Department of Urology, Marmara University School of Medicine, Istanbul§Department of Urology, Dokuz Eylul University School of Medicine Inciralti, IzmirDepartment of Urology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir**Department of Urology, Trakya University School of Medicine, Edirneand ††Department of Urology, Bulent Ecevit University School of Medicine, Zonguldak, Turkey

 

OBJECTIVES

To evaluate the effect of the interval between the initial and second transurethral resection (TUR) on the outcome of patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with maintenance intravesical Bacillus Calmette-Guérin (BCG) therapy.

PATIENTS AND METHODS

We reviewed the data of patients from 10 centres treated for high-risk NMIBC between 2005 and 2012. Patients without a diagnosis of muscle-invasive cancer on second TUR performed ≤90 days after a complete first TUR, and received at least 1 year of maintenance BCG were included in this study. The interval between first and second TUR in addition to other parameters were recorded. Multivariate logistic regression analysis was used to identify predictors of recurrence and progression.

RESULTS

In all, 242 patients were included. The mean (sd, range) follow-up was 29.4 (22.2, 12–96) months. The 3-year recurrence- and progression-free survival rates of patients who underwent second TUR between 14 and 42 days and 43–90 days were 73.6% vs 46.2% (P < 0.001) and 89.1% vs 79.1% (P = 0.006), respectively. On multivariate analysis, the interval to second TUR was found to be a predictor of both recurrence [odds ratio (OR) 3.598, 95% confidence interval (CI) 1.885–8.137; P = 0.001] and progression (OR 2.144, 95% CI 1.447–5.137; P = 0.003).

CONCLUSIONS

The interval between first and second TUR should be ≤42 days in order to attain lower recurrence and progression rates. To our knowledge, this is the first study demonstrating the effect of the interval between first and second TUR on patient outcomes.

Editorial: Is 42 days the ‘magic number’ for repeat TURBT?

Gökçe et al. [1] have evaluated a group of 242 patients from 10 centres with high-risk non-muscle-invasive bladder cancer (NMIBC) who underwent repeat resection and subsequent follow-up treatment, including induction and maintenance BCG for at least 1 year. They included patients who had repeat transurethral resection (TUR) within 90 days and excluded anyone who was upstaged to T2 or who did not complete 1 year of maintenance BCG. They divided patients into two groups according to time to second TUR, Group A (14–42 days) and Group B (43–90 days). The groups were similar in terms of patient age and gender, tumour multifocality, presence of carcinoma in situ (CIS), and stage and grade. The only factors on multivariable analysis that were statistically significant predictors of recurrence were grade, associated CIS, and time to second TUR. Only grade and time to second TUR were significant predictors of progression.

Figures 1 and 2 in the paper show an enormous difference in both recurrence-free survival and progression-free survival according to time to second TUR. For both outcomes, 42 days seemed to be the ‘magic number’, since re-TUR after 42 days was associated with much worse outcome. Patients who had repeat TUR at >42 days had nearly double the rate of both recurrence and progression than those who had repeat TUR within 6 weeks.

This is quite a dramatic result, and it is hard to imagine biologically how such an effect could be explained. Second TUR has two primary objectives, to identify occult muscle-invasive disease, and to remove tumour that was inadvertently left behind at the first resection. Both of these goals have been shown to be important and to result in better outcomes compared with no repeat TUR [2]. However, in this study [1], patients who had repeat TUR at >6 weeks after the initial resection had a progression rate similar to those in prior studies who had no second TUR at all [2]. What could be occurring that would cause a delay of just a few weeks in second TUR to double the risk of subsequent progression of disease?

This is a retrospective study without centralised pathology review, and no information is available about the reasons that patients had repeat TUR at an earlier or later interval, nor about the pathological findings at the repeat TUR. One must be wary that there is significant selection bias involved. There is a hint of this in the fact that the rate of residual tumour at repeat TUR in the two groups is very different (35% vs 53%). Perhaps the later group also had a higher rate of residual invasive components on the repeat resection? Herr et al. [3] have shown that residual T1 disease on repeat TUR is highly predictive of subsequent progression. Or alternatively, perhaps it is the delay in administration of BCG that really results in the worse outcome? Patients with a longer delay to repeat TUR by definition also have at least an equivalent delay in starting BCG.

Although high-risk NMIBC can certainly be aggressive, it seems highly unlikely that a week or two-one way or another in terms of treatment would make such a huge difference in the outcome. However, this is a provocative study that remains to be validated. It will be useful to see if other groups with similar patient populations can duplicate these findings. For the time being, as a routine practice it makes sense to repeat the TUR sooner rather than later whenever possible.

Eila C. Skinner

 

Thomas A. Stamey Research Professor of Urology, Chair, Department of Urology, Stanford University, Stanford, CA, USA

 

References

Video: Significance of time interval between first and second TUR on recurrence and progression rates in BCG-treated NMIBC

Significance of time interval between first and second transurethral resection on recurrence and progression rates in patients with high risk non muscle invasive bladder cancer treated with maintenance intravesical Bacillus Calmette-Guerin

 

Sumer Baltacı, Murat Bozlu*, Asıf Yıldırım, Mehmet Ilker Gokce, İlker TinayGuven Aslan§, Cavit Can, Levent Turkeri,Ugur Kuyumcuoglu** and Aydın Mungan††

 

Department of Urology, Ankara University School of Medicine, Ankara , *Department of Urology, University of Mersin School of Medicine, Mersin,Department of Urology, Istanbul Medeniyet University School of Medicine, ‡Department of Urology, Marmara University School of Medicine, Istanbul§Department of Urology, Dokuz Eylul University School of Medicine Inciralti, IzmirDepartment of Urology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir**Department of Urology, Trakya University School of Medicine, Edirneand ††Department of Urology, Bulent Ecevit University School of Medicine, Zonguldak, Turkey

 

OBJECTIVES

To evaluate the effect of the interval between the initial and second transurethral resection (TUR) on the outcome of patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with maintenance intravesical Bacillus Calmette-Guérin (BCG) therapy.

PATIENTS AND METHODS

We reviewed the data of patients from 10 centres treated for high-risk NMIBC between 2005 and 2012. Patients without a diagnosis of muscle-invasive cancer on second TUR performed ≤90 days after a complete first TUR, and received at least 1 year of maintenance BCG were included in this study. The interval between first and second TUR in addition to other parameters were recorded. Multivariate logistic regression analysis was used to identify predictors of recurrence and progression.

RESULTS

In all, 242 patients were included. The mean (sd, range) follow-up was 29.4 (22.2, 12–96) months. The 3-year recurrence- and progression-free survival rates of patients who underwent second TUR between 14 and 42 days and 43–90 days were 73.6% vs 46.2% (P < 0.001) and 89.1% vs 79.1% (P = 0.006), respectively. On multivariate analysis, the interval to second TUR was found to be a predictor of both recurrence [odds ratio (OR) 3.598, 95% confidence interval (CI) 1.885–8.137; P = 0.001] and progression (OR 2.144, 95% CI 1.447–5.137; P = 0.003).

CONCLUSIONS

The interval between first and second TUR should be ≤42 days in order to attain lower recurrence and progression rates. To our knowledge, this is the first study demonstrating the effect of the interval between first and second TUR on patient outcomes.

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