Impact of Time to Re-staging Transurethral Resection on Recurrence and Progression Rates
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms; Recurrence
Study type: Interventional

Summary: 
      Purpose To investigate the significance of time to re-staging transurethral resection
      (re-TUR) on recurrence and progression rates in patient with high-risk non-muscle-invasive
      bladder cancer.

      Methods Patients diagnosed with primary high risk non-muscle-invasive bladder cancer were
      included to the study. The patients were randomly seperated into 3 groups acoording to Re-TUR
      timing. In group 1,2, and 3, the time interval between initial and re-TUR were 14-28 days,
      29-42 days, and 43-56 days respectively. Kaplan -meier plots were used to estimate
      differences in recurrence free survival (RFS) and progression free survival (PFS) rates. Cox
      regression analysis was used to assess the effect of time from initial TUR to re-TUR on
      oncological outcomes.

      Results A total of 109 patients with high risk non-muscle-invasive bladder cancer were
      randomly divided into 3 groups. Twenty patients in group 1 (14-28 days), 22 patients in group
      2 (29-42 days), and 29 patients in group 3 (43-56 days) completed the study. The mean
      follow-up was 20 ± 8.9 months. Kaplan-Meier plots showed no differences in RFS and PFS rates
      between the three groups. Cox regression analysis demonstrated that only tumor number was
      found to be a prognostic factor on RFS rates.

      Conclusion Our prospective study demonstrated that time laps from initial TUR to re-TUR did
      not significantly affect on RFS and PFS rates.
    

Detailed description: 
      This study was performed between August 2016 and December 2020 after obtaining the approval
      of local ethics committee (0651-5479). Patients diagnosed with primary high risk
      non-muscle-invasive bladder cancer at our clinic as well as the patients who were referred to
      our clinic with the same diagnosis were included to the study. All patients gave their
      written informed consent. The patients were randomly separated into 3 groups according to
      Re-TUR timing with the random number table envelope method. The names of the groups were
      written on small papers with the same size, they were folded, put in an envelope, and drawn
      by the doctors. In group 1,2, and 3, the time interval between initial and re-TUR were 14-28
      days, 29-42 days, and 43-56 days respectively. Separate analysis was also performed for
      patients who had re-TUR at ≤ 42 and >42 days. All patients received six weekly instillations
      of BCG therapy, and at least 1 year of maintenance BCG therapy (3 weekly instillations
      administered at 3, 6, 12 months).

      Patients with a tumor pathology other than transitional cell carcinoma, incomplete resection
      at initial TUR, who cannot complete 1 year of maintenance BCG treatment, did not attend their
      regular cystoscopic control or wanted to leave from the study voluntarily and lastly, with a
      diagnosis of muscle-invasive cancer on re-TUR were excluded. Inclusion criteria were having a
      high grade Ta or T1 transitional cell carcinoma with or without carcinoma in situ (CIS) after
      a complete initial TUR of bladder carcinoma, and receiving six weekly induction BCG therapy
      with at least 1 year maintenance.

      Re-TUR contained resection of all visible tumor, deep resection of previously resected areas
      and adequate sampling of muscle layers. Cystoscopic control was performed according to EAU
      guideline recommendations for high-risk non-muscle-invasive bladder cancer [5,6]. Progresson
      was defined as an increase in the pathological stage (Ta to T1 or T1 to T2).

      Demographic data of the patients like age, gender, and parameters related to bladder cancer
      such as tumor grade, T stage, concomitant CIS, number of tumors, main tumor size, application
      of early single dose chemotherapy, recurrence and progression were noted. Primary end points
      of the current study were recurrence free survival (RFS) and progression free survival (PFS)
      rates. Pathologic investigations were made by single expert uropathologist at our hospital.

      The data analyses were performed with PASW 18 (SPSS, IBM, Chicago, IL) software.
      Kolmogorov-Smirnov and P-P plot tests were used to verify the normality of the distribution
      of continuous variables. The results were reported as means standard deviations, or in
      situations in which the distributions were skewed, as the median (minimum-maximum).
      Categorical variables were given as percentages. For parameters that did not show normal
      distribution, the nonparametric Kruskal Wallis One Way analysis of variance was used to
      compare them. Multivariable semi-parametric Cox regression analysis was used to evaluate
      predictors of RFS and PFS rates. Kaplan-Meier curves were constructed for RFS and PFS and
      groups were compared with the long-rank test. The study power and sample size were calculated
      with G power 3.1.9.7 version (A priori). When effect size is set to 0.33 (medium size) with
      80% power, the total number of patients required to be included in the study was 73. A p
      value <0.05 was considered as statistically significant.
    

Intervention name(s): Second transurehral resection of bladder tumour
Intervention type(s): Procedure
Intervention description(s): Remove of the bladder tumour as endoscopically
Allocation: Randomized
Intervention model: Single Group Assignment
Intervention model description: This is a clinical study. Patients with high grade non-muscle invasive bladder canser divided three groups according to time lapse.
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Bladder cancer; Restaging transurethral resection