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Re: Transurethral Surgery and Twice-daily Radiation Plus Paclitaxel-Cisplatin or Fluorouracil-Cisplatin with Selective Bladder Preservation and Adjuvant Chemotherapy for Patients with Muscle Invasive Bladder Cancer (RTOG 0233): A Randomised Multicentre Phase 2 Trial

European Urology, 6, 65, pages 1221 - 1222


Mitin T, Hunt D, Shipley WU, et al.
Lancet Oncol 2013;14:863–72
Expert's summary:
In a randomized phase 2 trial, two chemotherapeutic regimens were compared before cisplatin-based chemoradiotherapy and adjuvant chemotherapy for muscle-invasive urothelial cancer of the bladder. Induction chemoradiotherapy with paclitaxel plus cisplatin, followed by cisplatin consolidation chemoradiotherapy and adjuvant chemotherapy with cisplatin, gemcitabine, and paclitaxel, was completed by 67%, whereas in the group that received 5-fluorouracil (5-FU) plus cisplatin induction chemoradiotherapy, 53% completed the entire protocol. When the tumor was stage T1 or worse after induction chemoradiotherapy, cystectomy was recommended. T1 or worse disease after induction was present in 2 of 45 patients that completed the induction chemoradiotherapy in the paclitaxel group and in 5 of 45 patients in the 5-FU group. Overall survival and retained-bladder survival was similar for both groups after a median follow up of 5 yr. Grade 3–4 toxicity was slightly more frequent in the paclitaxel group (35%) versus the 5-FU group (19%), and more patients discontinued treatment due to toxicity in the paclitaxel group (13%) compared with the 5-FU group (6%).
Expert's comments:
This study illustrated continued interest in chemoradiotherapy regimens for muscle-invasive bladder cancer management. The good 5-yr overall survival data can be partly explained by the >90% T2-staged tumors in their population. Of note is the fact that although the recommendation of cystectomy after induction chemoradiotherapy for persistent T1 or worse bladder cancer was relatively low (7 of 90 patients, 8%), the 5-yr bladder retention rate was highest in the 5-FU group (71%), indicating that around 20% required cystectomy after consolidation radiotherapy. Also of note is the observation that of 93 patients enrolled in the study, only 58% completed induction, consolidation chemoradiotherapy, and adjuvant chemotherapy.

Muscle-invasive bladder cancer is classically treated by radical cystectomy. A meta-analysis containing 439 patients from three randomized studies showed a slight benefit of radiotherapy plus cystectomy compared with radiotherapy alone [1] . In these trials, no chemotherapy treatment was included. Despite the fact that several trials address the use of chemoradiotherapy in bladder cancer [2] , no randomized trial data are available in a comparison of chemoradiotherapy and cystectomy. Several radiosensitizing chemotherapeutic modalities have been studied. Cisplatin is widely considered a potent radiosensitizer and has been combined with several other agents.

Mitin et al. present data from a randomized phase 2 study comparing two cisplatin-based chemotherapy combinations. Similar to the data presented by James et al. [3] on mitomycin–5-FU chemoradiotherapy, the majority of cases had cT2 disease. This does not necessarily indicate that chemoradiotherapy cannot be considered effective in larger bladder cancers; understaging in bladder cancer is common. A substantial number of patients in both studies will have had undetected extravesical disease and still respond favorable to the chemotherapy regimens. The 5-yr overall survival rate for the two regimens presented by Mitin et al. (>70%) was considerably higher than that reported by James et al. (48%) [3] . The fact that the latter study contained more cT3 disease may account for this difference. Another important difference between the two studies was the use of a primary tumor evaluation after induction chemoradiotherapy. In the BC2001 study [3] , only three patients (0.8%) underwent early cystectomy before protocol treatment was completed, whereas in the RTOG 0233 study reported by Mitin et al., seven patients (8%) underwent early cystectomy for not obtaining at least less than T1 disease after induction chemoradiotherapy.

Selection of patients for chemoradiotherapy regimens requires a multistep, multidisciplinary approach in which close collaboration between medical oncology, radiotherapy, and urology is required. The role of urologists starts with a thorough transurethral resection of the bladder (TURB), since several studies now indicate that a radical TURB predicts a more favorable prognosis after chemoradiotherapy [4] . Clearly, the not infrequent toxicity of the chemoradiotherapy and the need for close bladder surveillance after treatment, considering the 1 in 5 requirement of later salvage cystectomy, warrant the involvement of urologists in these strategies.

Conflicts of interest

The author has nothing to disclose.

References

  • [1] M.D. Shelley, T.J. Wilt, J. Barber, M.D. Mason. A meta-analysis of randomised trials suggests a survival benefit for combined radiotherapy and radical cystectomy compared with radical radiotherapy for invasive bladder cancer: are these data relevant to modern practice?. Clin Oncol (R Coll Radiol). 2004;16:166-171 Crossref
  • [2] G.A. Plataniotis, R.G. Dale. Radio-chemotherapy for bladder cancer: contribution of chemotherapy on local control. World J Radiol. 2013;5:267-274 Crossref
  • [3] N.D. James, S.A. Hussain, E. Hall, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012;366:1477-1488 Crossref
  • [4] J.J. Coen, J.J. Paly, A. Niemierko, et al. Nomograms predicting response to therapy and outcomes after bladder-preserving trimodality therapy for muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys. 2013;86:311-316 Crossref

Footnotes

Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands

lowast Department of Urology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.