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Inverse probability treatment weighting comparison of radical cystectomy to trimodality therapy for cT2-cT4 muscle invasive bladder cancer

  • Alexandre Zlotta,
  • Leslie Ballas,
  • Andrzej Niemierko,
  • Katherine Lajkosz,
  • Cynthia Kuk,
  • Gus Miranda,
  • Michael Drumm,
  • Andrea Mari,
  • Ethan Thio,
  • Neil Fleshner,
  • Girish Kulkarni,
  • Michael Jewett,
  • Rob Bristow,
  • Charles Catton,
  • Padraig Warde,
  • Alejandro Berlin,
  • Srikala Sridhar,
  • Anne Schuckman,
  • Hooman Djaladat,
  • Adam Feldman,
  • Matthew Wszolek,
  • Douglas Dahl,
  • Richard Lee,
  • Philip Saylor,
  • Marc Michaelson,
  • David Miyamoto,
  • Anthony Zietman,
  • William Shipley,
  • Peter Chung,
  • Sia Daneshmand,
  • Jason Efstathiou

Introduction and objective

Prior randomized controlled trials comparing bladder preservation to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) closed due to lack of accrual. Given that none are foreseen, we aimed to compare trimodality therapy (TMT, maximal transurethral resection of bladder tumor followed by concurrent chemoradiation) to radical cystectomy (RC) in weighted cohorts of patients with MIBC who would have been eligible for both procedures and aligned with NRG/RTOG trials’ inclusion criteria (cT2-cT4).


This retrospective analysis included 722 patients with MIBC clinical stage T2-T4N0M0 MIBC urothelial carcinoma of the bladder (440RC/282TMT) who would have been eligible for both RC and TMT, treated at three university centers between 2005-2017 (Massachusetts General Hospital, Boston; Princess Margaret Cancer Centre, Toronto; and University of Southern California, Los Angeles). All patients had solitary tumors <7cm, no or unilateral hydronephrosis, and no extensive/multifocal carcinoma in situ. Differences in survival outcomes by treatment were evaluated using inverse probability treatment weighting (IPTW), a well-established method in balancing out differences between treatment groups. Doubly robust multivariable Cox and competing risk regression models incorporating both stabilized weights and confounders were fit. Five year survival probabilities were estimated.


30% of all MIBC surgical candidates were also candidates for TMT. Age (70.2 vs 71.3) was not significantly different between RC vs TMT. cT2 stage (82.3 vs 90.4%), presence of hydronephrosis (23.0vs9.6%), and use of (neo)-or adjuvant chemotherapy (40.5vs56.4%) were significantly different between RC and TMT. Salvage cystectomy was performed in 38 (13%) patients treated by TMT. Using IPTW, metastasis-free (74.4 vs. 75.2%, p=0.40) and cancer-specific survival (80.5 vs. 83.5%, p=0.07) were not statistically different between RC and TMT whereas overall survival favored TMT (66.5% vs. 73.4%, p=0.007). Outcomes for RC and TMT were not different among centers (p=0.74 and p=0.64, respectively). Pathological stage in the 440 RC was pT2 in 28.2%, pT3-4 in 44.1% and 25.9% node positive. Median number of nodes removed was 39, soft tissue positive margin rate 1.1%, and perioperative mortality 2.5%.


This large contemporary study demonstrates similar oncologic outcomes between RC and TMT for select cT2-cT4 MIBC patients. These patients should be offered the opportunity to discuss various treatment options.