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DaBlaCa-13 Study: Oncological outcome of short-term, intensive chemoresection with mitomycin in nonmuscle invasive bladder cancer: Primary outcome of a randomized controlled trial

  • Maria S. Lindgren,
  • Erik Hansen,
  • Nessn Azawi,
  • Anna M. Nielsen,
  • Lars Dyrskjøt,
  • Jørgen B. Jensen

Publication: Journal of Clinical Oncology, October 2022


This study aimed to assess long-term follow-up after chemoresection with mitomycin (MMC), a nonsurgical treatment modality for recurrent nonmuscle invasive bladder cancer (NMIBC). At the time of recurrence, chemoresection has previously been shown to reduce the number of patients requiring a procedure (transurethral resection of bladder tumors [TURBT] or office biopsy) by more than 50%. This study investigated the number of patients requiring a procedure during initial treatment and 2-year follow-up in patients treated with short-term, intensive chemoresection with MMC compared with patients undergoing standard surgical treatment of recurrent NMIBC.


A randomized, controlled trial was conducted in two urological departments in Denmark from January 2018 to August 2021. In total, 120 patients with a history of Ta low- or high-grade NMIBC were included upon recurrence. The intervention group received intravesical MMC (40 mg/40 mL) three times a week for 2 weeks and TURBT or office biopsy only if the response was incomplete. The control group received TURBT or office biopsy and 6 weekly adjuvant instillations. The primary outcome was the number of patients undergoing a procedure within 2 years from inclusion, which was compared between groups using the chi-squared test. Recurrence-free survival was analyzed using the Kaplan-Meier method.


Significantly fewer patients were in need of a procedure in the intervention group than in the control group: 71% (95% CI, 57 to 81) and 100% (95% CI, 94 to 100), P < .001. The 12-month recurrence-free survival was 36% (95% CI, 24 to 50) and 43% (95% CI, 30 to 56) in the intervention and control groups, respectively (P = .5).


Short-term intensive chemoresection is an effective treatment strategy for recurrent NMIBC that leads to a reduced number of required procedures without compromising long-term oncological safety.

Dr. Francesco Del Giudice

There is a growing body of evidence exploring the role of chemoresection with Mitomycin-C (MMC) in the management and the surgical algorithm for non-muscle invasive bladder cancer (NMIBC) and upper tract urothelial carcinoma (UTUC). Nevertheless, a shift towards its routine clinical implementation can only be widely accepted when an adequate level of evidence is delivered. The DaBlaCa-13 is a randomised controlled trial that currently offers the highest level of evidence, potentially enabling a more routinary adoption of  chemoresection in case of recurrent low- or high-grade (LG, HG) Ta NMIBCs.

The study is a dual-centred, open-label, RCT conducted at two tertiary Denmark institutions. Patient and tumour inclusion criteria: if there was a previous history of stage Ta LG or HG NMIBC, and the documented existence of bladder recurrence with more than one papillary tumour smaller than 2 cm. Exclusion criteria was: prior treatment with MMC and treatment with Bacillus Calmette-Guerin (BCG) within 24 months before study inclusion.

The random allocation in the experimental vs. control group was the following:  40 mg/40 mL of intravesical MMC three times a week for 2 weeks without preceding biopsy. Tumour response was visually evaluated by flexible cystoscopy 4 to 8 weeks after the final instillation and registered in real time in the experimental arm. TURBT or office biopsy and tumour fulguration were performed in patients with incomplete response only. Conversely, in the control arm, standard care with TURBT or office biopsy and tumour fulguration followed by adjuvant instillation treatment according to histological findings was delivered. Of note, MMC for Ta LG tumours and BCG for Ta HG tumours was the pre-defined adjuvant intravesical regimens following resection.

The primary endpoint was the number of patients receiving TURBT or office biopsy w/o tumour fulguration within the first 2 years after randomisation.

Secondary endpoints were recurrence-free survival (RFS) in both groups and serious adverse events in the sole intervention group.

The scheme of follow-up was tailored on the Danish Association of Urology Guidelines which assume for Ta LG cystoscopy at 4 months, and in case of no recurrence, cystoscopy is repeated after 8 months and ultimately annually. For Ta HG cystoscopy and urine cytology, every 4 months until 2 recurrence-free years had passed. Additional follow-up is then carried out similarly to Ta LG.

In total, 120 patients were included with median follow-up of 34 (range, 26-45) months. Significantly fewer patients in the intervention group than in the control group required a procedure during 2 years of follow-up. In particular, there was a net 29% difference in the patients who entirely avoided any surgical procedures over the follow-up between the intervention and control group. Moreover, 26 patients in the intervention group and 47 patients in the control group required a TURBT: (45%; 95% CI, 0.32 to 0.58) vs. (77%; 95% CI, 0.65 to 0.87; P=.001). More importantly, there was no difference in the number of patients requiring a procedure because of subsequent recurrences between groups: 37 patients in the intervention group (64%; 95% CI, 50 to 76) and 35 patients in the control group (57%; 95% CI, 44 to 70; P= .5).

The 12-month RFS was 36% (95% CI, 24 to 50) in the intervention group and 43% (95% CI, 30 to 56) in the control group. No significant statistical difference between groups was observed. This was also true when sub-grouping by tumour grade at baseline. Moreover, there were no differences regarding the number of recurrences at first follow-up (28% vs. 21%) and the tumour focality detected among the recurrent cases. In the intervention group, a complete responder to the chemoresection regimen was a surrogate for subsequent fewer number of recurrences.

The authors stated in the discussion section that no serious adverse events at long term follow-up were registered. Major limitations of the DaBlaCa-13 include the relatively small sample size and the lack of reporting of short- and mid-term non-serious complications in the interventional arm. This precludes the possibility to argue regarding the safety and tolerability of the chemoresection approach and administration of adjuvant BCG to the sole Ta HG patients included in the control group. Of note, these were only n=4 patients, but yet reproducibility of the recurrence results on a larger and more heterogeneous cohort of NMIBC might offer different findings.

The DaBlaCa-13 is the most updated RCT generating a high level of evidence supporting the adoption of chemoresection also for HG Ta NMIBC.  Hopefully this will lead to more multicentre, international trials on this topic.