EAU 2019: Cystectomy: Case-based Debate No Evidence of Disease after Neoadjuvant Chemotherapy for MIBC: What next?

Barcelona, Spain (UroToday.com) This session began with a case presentation of a 45-year-old man who is a heavy smoker and presented with macroscopic hematuria due to a 3.5 cm mass in the left lateral wall of the bladder. Following a TURBT procedure, he was found to have a transitional cell carcinoma (TCC) high grade (G3) tumor invading the lamina propria and detrusor muscle. No carcinoma in situ (CIS) was found, but lymphovascular invasion was found. He was staged as a T2-3 HG TCC. He underwent a CT scan showing thickness of the left lateral wall of the bladder and normal upper urinary tract. No lymph node enlargement was seen. The patient was treated with neoadjuvant chemotherapy with 3 cycles of Gemcitabine and cisplatin. He underwent a CT scan and TURBT after completion of chemotherapy, and he was found to have a T0 disease with a normal CT scan.

At this point the patient was offered 3 treatment options:
  1. Radical cystectomy
  2. Bladder preservation with chemoradiation
  3. Active surveillance
In this presentation, Dr. Canas discussed the reasons why this patient should undergo radical cystectomy. Currently, radical cystectomy is considered the gold standard treatment for muscle-invasive bladder cancer (T2-T4a, N0M0, and for high-risk non-muscle invasive bladder cancer).

Neoadjuvant chemotherapy with a treatment combination based on cisplatin has been shown to cause a 5-8% absolute increase in overall survival. Additional benefits of neoadjuvant chemotherapy include an increase in the PT0 rate with 20-25% of complete responders1. However, it is important to ask how reliable is the clinical T0 stage, as there is conflicting evidence on the correlation between clinical T0 and pathological T0. In a study assessing 157 patients with clinical T0, a repeat TURBT was done and demonstrated that only 35.7% had pathological T0, with almost 2/3 of patients not demonstrating T0 disease2. Even if the patients are real complete responders with T0 disease, they are still at risk of recurrence and death from bladder cancer. The stage of the disease after surgery is the main prognostic indicator of survival.

In the young patient presented at the beginning of this session, Dr. Canas believes that it is important to stay ontologically safe, thereby extending life expectancy, and try to minimize the adverse effects of surgery.

This can be achieved in several ways:
  1. The results have been shown to be better in high volume centers, therefore it is important these patients get operated by experienced surgeons3.
  2. Incorporation of the Enhanced recovery pathways (ERAS) to improve patient outcomes
  3. Orthotopic diversion – the rate of continent urinary diversion is very variable even at centers of excellence, but young people should be preferred candidates for continent urinary diversion, to maintain their body image.
  4. Discuss the possibility of preserving sexual function. This can be done with preservation of the neurovascular bundles, preservation of the seminal vesicles, and/or prostate sparing procedure. The potential candidates for this approach include young patients with normal sexual function, with organ confined disease, with no tumor in the bladder neck/prostatic urethra, and absence of prostate cancer. This has been incorporated into the European Association of Urology (EAU) guidelines which state that men motivated to preserve their sexual function, preservation of their sexual function should be offered.
Dr. Canas reiterated that radical cystectomy remains the gold standard treatment in muscle-invasive bladder cancer. Clinical stage T0 disease does not always mean pathological T0N0. However, patients who are real complete responders (pathological stage T0) have the best oncological outcomes. Lastly, in young patients, it is important to try and minimize surgical adverse effects by various available strategies and try to preserve sexual function if possible.

References:
1. Rosenblatt R1, Sherif A, Rintala E, Wahlqvist R, Ullén A, Nilsson S, Malmström PU; Nordic Urothelial Cancer Group. Pathologic downstaging is a surrogate marker for efficacy and increased survival following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive urothelial bladder cancer. Eur Urol. 2012 Jun;61(6):1229-38. doi: 10.1016/j.eururo.2011.12.010. Epub 2011 Dec 13.
2. Kukreja et al. Eur Urol Focus 2016
3. Scarberry K, Berger NG, Scarberry KB, Agrawal S, Francis JJ, Yih JM, Gonzalez CM, Abouassaly R.Improved surgical outcomes following radical cystectomy at high-volume centers influence overall survival. Urol Oncol. 2018 Jun;36(6):308.e11-308.e17. doi: 10.1016/j.urolonc.2018.03.007. Epub 2018 Apr 5.

Presented by: Virginia Hernández Cañas, MD, PhD, FEBU, Hospital Universitario Fundación Alcorcón, Madrid, Spain 

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 34th European Association of Urology (EAU 2019) #EAU19, conference in Barcelona, Spain from March 15-19, 2019.
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