SUO 2017: Trimodal Therapy Versus Extirpative Surgery for Bladder Cancer, Who May Benefit

Washington, DC ( There has been growing interest in the role of trimodal therapy (TMT) also known as chemoradiation therapy (CMT) as a primary treatment option for patients with muscle invasive bladder cancer, as an alternative to radical cystectomy (RC). 

Prior institutional studies have demonstrated similar cancer-specific survival outcomes in appropriately selected patients.1 However, population-based analyses have not demonstrated equally favorable outcomes,2,3 but are often significantly limited by the granularity of the data and the inappropriate patient selection.

In this study, the authors utilized the SEER-Medicare dataset to help identify clinical and pathologic features that may predict improved response to TMT. However, it should be noted that, as population-level data, it suffers from the same limitations as other population-level analyses listed above – specifically the lack of knowledge regarding patient candidacy for RC and intent of treatment with TMT.

The authors identified patients diagnosed with non-metastatic urothelial carcinoma of the bladder (65-90 years of age) after transurethral resection (TUR) using Medicare-linked Surveillance, Epidemiology, and End Results data (2004-13). We categorized patients based on treatment following endoscopic debulking (RC vs. TMT, including radiation and systemic chemotherapy). 

  • RC was defined based on CPT codes for the procedure
  • TMT defined by CPT codes for IMRT, CRT or uncategorized radiotherapy
They utilized two TMT definitions –

1) >= 10 XRT cycles and >= 3 Chemo cycles = “Treated group”

2) >=5 XRT cycles and >= 1 chemo cycles = “Intent to Treat group”

They then completed competing risk regression to identify independent predictors of cancer-specific mortality (bladder cancer mortality BCM) using death from other causes as the competing variable.

They identified 6470 patients undergoing TUR followed by either TMT (n=306) or RC (n=5684). TMT was associated with an increased risk of BCM (hazard ratio 1.63, p<0.001), as can be expected as patients were likely not surgical candidates and received suboptimal TMT due to frailty and morbidity. Patient survival was worse when using either definition of TMT. They did however identify 4 patient populations that exhibited superior survival with TMT - patients with pelvic lymphadenopathy (cN+) (>65 years for female, >79 years for male), females with ≥T3 disease and Charlson Index >2, and males >65 years who had both cN+ and ≥T3 disease.

Interestingly, these criteria are in direct conflict with the prior studies regarding TMT as primary therapy. Perhaps, in this study, the authors have identified patients who benefit from salvage TMT in surgically-unfit patients. 

Limitations / Discussion Points:

1. Intent of therapy is never made clear, as it cannot be determined using a population-level study. However, as TMT has traditionally been used in surgically unfit patients as a substandard primary therapy, the presumption should be that these patients were elderly or frail and surgically unfit.

2. This is not a study determining the benefit of TMT as a primary therapy. 


1. Propensity Score Analysis of Radical Cystectomy Versus Bladder-Sparing Trimodal Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic. Kulkarni GS, Hermanns T, Wei Y, Bhindi B, Satkunasivam R, Athanasopoulos P, Bostrom PJ, Kuk C, Li K, Templeton AJ, Sridhar SS, van der Kwast TH, Chung P, Bristow RG, Milosevic M, Warde P, Fleshner NE, Jewett MAS, Bashir S, Zlotta AR. J Clin Oncol. 2017 Jul 10;35(20):2299-2305. doi: 10.1200/JCO.2016.69.2327. Epub 2017 Apr 14.

2. Trimodal Therapy is Inferior to Radical Cystectomy for Muscle-invasive Bladder Cancer using Population-level Data: Is There Evidence in the (Lack of) Details? Kulkarni GS, Klaassen Z. Eur Urol. 2017 Oct;72(4):488-489. doi: 10.1016/j.eururo.2017.04.028. Epub 2017 May 6. No abstract available.

3. Comparative Effectiveness of Trimodal Therapy Versus Radical Cystectomy for Localized Muscle-invasive Urothelial Carcinoma of the Bladder. Eur Urol. 2017 Oct;72(4):483-487. doi: 10.1016/j.eururo.2017.03.038. Epub 2017 Apr 12. Seisen T, Sun M, Trinh QD.

Presented by:  Matthew B. Clements, MD, MS

Co-Authors: Timothy Showalter MD, MPH and Stephen Culp MD, PhD, MS
Affiliation: University of Virginia, Charlottesville, VA

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC