Dr. Michael Cookson, who presented via teleconference, took the stance that radical cystectomy is the best treatment option for this patient. He notes that radical cystectomy with lymphadenectomy remains the gold standard treatment, with 5-year survival directly related to the pathologic stage and nodal status. He notes that there are four important points of comparison between radical cystectomy and trimodal therapy (TMT): oncologic outcomes, morbidity, guidelines, and cost.
- Oncologic outcomes – experiences over the last two decades have demonstrated that long-term survival for patients with organ-confined disease at the time of radical cystectomy is excellent (upwards of 80% at 15-year follow). Based on results of SWOG 8710, neoadjuvant chemotherapy (NAC) followed by radical cystectomy improved median survival vs radical cystectomy alone (77 vs 46 months)1. Radical cystectomy must be associated with a thorough lymph node dissection according to Dr. Cookson, demonstrating the impact of lymph node density in the following table:
Dr. Cookson notes that there are no randomized comparisons between radical cystectomy and TMT – this is a “RCT data free zone” he notes. In a propensity-matched comparative analysis from the NCDB comparing patients undergoing radical cystectomy vs chemoradiation, Ritch et al.2 found that chemoradiation therapy was associated with decreased mortality at year 1 (HR 0.84, 95%CI 0.74-0.96), but at 2 years (HR 1.4, 95%CI 1.2-1.6) and 3 years onward (HR 1.5, 95%CI 1.2-1.8) chemoradiation therapy was associated with increased mortality. Furthermore, the 5-year OS was greater for radical cystectomy than for chemoradiation (38% vs 30%, p = 0.004). This was subsequently reiterated in a follow-up NCDB study.
- (i) Morbidity – certainly, Dr. Cookson notes that radical cystectomy is associated with high rates of morbidity, as complications may be as high as 40-80%. Several studies have suggested that 1 in 4 patients undergoing radical cystectomy are readmitted and that complication rates are higher for those >75 years of age. A study from Vanderbilt collected prospective data on 753 consecutive patients undergoing radical cystectomy and noted that the readmission rate was 20% <30 days after surgery and 11% for days 30-903. The mortality rates for the same time periods was 2% and 5%, respectively. Regarding the comparison of open and robotic cystectomy, Dr. Cookson notes that the robotic approach may be advantageous for decreased blood loss, transfusion, and possibly for the length of stay, but generally morbidity is comparable between the two approaches.
- (ii) Guidelines – Dr. Cookson highlights that the AUA/ASCO/ASTRO/SUO guidelines strongly advocates that “clinicians should offer radical cystectomy with bilateral pelvic lymph node dissection for surgical eligible patients with resectable non-metastatic (M0) muscle-invasive bladder cancer (Grade B) 4. These recommendations are essentially echoed by the EAU.
- (iii) Cost – A recent publication from Williams et al.5 compared costs between radical cystectomy and TMT. There were 3,200 patients in the SEER-Medicare that met inclusion criteria, and 687 patients (in each group) were propensity score matched. Those who underwent TMT had significantly decreased OS (HR 1.49, 95%CI 1.31-1.69) and CCS (HR 1.55, 95%CI 1.32-1.83). There were no differences in costs at 30 days, however median total costs were significantly higher with TMT than with radical cystectomy at 90 days ($80,174 vs $69,181; median difference, $8964) and at 180 days ($179,891 vs $107,017; median difference). When the authors extrapolated these figures to the total US population, there was $335 million in excess spending for TMT compared with the less costly radical cystectomy.
- Radical cystectomy remains the treatment of choice for most patients with muscle-invasive disease
- Radical cystectomy is associated with significant but acceptable morbidity and has superior oncologic outcomes compared to TMT, particularly for those followed for more than two years
- Radical cystectomy is supported by all of the major oncologic guidelines and appears to be more cost-effective than TMT
- TMT remains an option for those who refuse treatment or are unfit for radical cystectomy
Presented by: Michael Cookson, MD, MMHC, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA
- Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349(9):859-866.
- Ritch CR, Balise R, Prakash NS, et al. Propensity matched comparative analysis of survival following chemoradiation or radical cystectomy for muscle-invasive bladder cancer. BJU Int 2018 May; 121(5):745-751.
- Stimson CJ, Chang SS, Barocas DA, et al. Early and late perioperative outcomes following radical cystectomy: 90-day readmissions, morbidity and mortality in a contemporary series. J Urol 2010 Oct;184(4):1296-1300.
- Chang SS, Bochner BH, Chou R, et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO Guideline. J Urol 2017 Sep;198(3):552-559.
- Williams SB, Shan Y, Jazzar U, et al. Comparing survival outcomes and costs associated with radical cystectomy and trimodal therapy for older adults with muscle-invasive bladder cancer. JAMA Surg 2018 Oct 1;153(10):881-889.
Opposing Debate: Trimodality Therapy is the Best Option for Muscle-Invasive Bladder Cancer