EAU 2021: There Is No Role for Radical Cystectomy in cT0 After Neoadjuvant Chemotherapy

(UroToday.com) At the European Association of Urology 2021 Meeting’s controversies in Onco-Urology session, Dr. Alexandra Masson-Lecomte discussed that there is no role for radical cystectomy in cT0 disease after neoadjuvant chemotherapy.

Dr. Masson-Lecomte noted that up to 5-15% of patients will have T0 disease after TURBT alone, which increases to 25-38% after MVAC after neoadjuvant chemotherapy based an analysis of the Nordic I, Nordic II, SWOG, and MRC trials.¹ More recently, presented at the ASCO GU 2020 meeting, preliminary results from the randomized phase III GETUG/AFU VESPER trial for treatment of muscle-invasive urothelial bladder cancer showed that with dose-dense MVAC, pT0 rates of 42% are attainable.

Dating back to the original neoadjuvant chemotherapy trial by Grossman et al.² we know that survival among patients that achieve a pT0 response is excellent. At five years, 85% of the patients with a pT0 surgical specimen were alive:

Assessing an international cohort of 4,430 patients, Tilki et al.³ compared outcomes in patients with pT0 bladder urothelial carcinoma to those in patients with other stages and assessed the effect of clinical stage on outcome. Among this cohort, 228 (5.1%) had pT0 disease at radical cystectomy, and at a median 48.2 months of follow-up, disease-free and cancer-specific survival in pT0 cases was similar to that in pTa/pTis cases but significantly better than in pT1 or pT2 cases:

In 2018, patients from Memorial Sloan Kettering Cancer Center and Columbia University were pooled to assess whether conservative treatment could be safely implemented in patients who had a complete response to neoadjuvant chemotherapy.⁴ Among 148 patients followed over a median of 55 months (range 5 to 145), the 5-year disease specific survival was 90%, overall survival was 86%, cystectomy-free survival was 76%, and recurrence-free survival was 64%. There were 71 patients (48%) that experienced recurrence in the bladder, including 16 (11%) with muscle invasive disease and 55 (37%) with noninvasive disease. Salvage radical cystectomy prevented cancer specific death in 9 of 12 patients (75%) who underwent cystectomy after muscle invasive relapse and in 13 of 14 (93%) after noninvasive relapse.

The addition of immune checkpoint inhibitor therapy has been tested in the phase 2 trial of gemcitabine, cisplatin, plus nivolumab with selective bladder sparing in patients with muscle-invasive bladder cancer (HCRN GU 16-257):

Among 76 patients in this trial, 31 patients had a clinical complete response with 30 patients opting for no cystectomy but treated with nivolumab for 4 months. There was a 25% local recurrence rate among complete responders, of which six underwent cystectomy (pT0N0 = 1, pTaN0 = 1, pTisN0 = 1, pT2N0 = 2, pT4N1 = 1).

Dr. Masson-Lecomte concluded this presentation with the following take home messages:

• There is synergy between medical and surgical treatment of bladder cancer, whereby surgery does not necessarily mean radical cystectomy, but may also mean extensive TURBT
• pT0 are more and more common with the increasing use of neoadjuvant chemotherapy and perhaps neoadjuvant immunotherapy on the way
• pT0 patients are a population with excellent oncological outcomes for which treatment has to be reinvented, but endoscopic T0 does not necessarily mean pathological T0 and we must incorporate imaging into the algorithm 

Presenter by: Alexandra Masson-Lecomte, MD, PhD, Associate Professor of Urology at Hôpital Saint Louis, Paris, France

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.

References:

1. Lavery HJ, Stensland KD, Niegisch G, et al. Pathological T0 following radical cystectomy with or without neoadjuvant chemotherapy: A useful surrogate. J Urol 2014 Apr;191(4):898-906.
2. 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.
3. Tilki D, Svatek RS, Novara G, et al. Stage pT0 at radical cystectomy confers improved survival: An international study of 4,430 patients. J Urol 2010 Sep;184(3):888-894.
4. Mazza P, Moran GW, Li G, et al. Conservative management following clinical complete response to neoadjuvant chemotherapy of muscle invasive bladder cancer: Contemporary outcomes of a multi-institutional cohort study. J Urol. 2018 Nov;200(5):1005-1013.