EAU 2019: Active Surveillance - Case-Based Debate: No Evidence of Disease after Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer: 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

Dr. Solsona presented the option of active surveillance for patients with clinical stage T2-T4a and complete response after chemotherapy (clinical stage T0). A study using the National Cancer Database (NCDB) analyzing 19,404 unselected patients with clinical stage T2-T4a N0M0 disease who underwent either radical cystectomy or maximal TURBT + chemotherapy demonstrated that the overall survival was slightly better in the radical cystectomy group (36.2% vs. 32.9%, p<0.0001, with a HR of 1.02 (95% CI 1.01-1.3)¹. In a meta-analysis including 18 studies and 518 patients comparing TURBT with chemotherapy to radical cystectomy, it was shown that the 5-year overall survival was 61% in the TURBT+ chemotherapy arm with cancer specific survival of 72% and 61.5% patients being cystectomy free². Data from other centers demonstrated similar favorable outcomes for this specific treatment strategy. Additionally, in a SWOG (S0219) phase 2 trial including 74 patients with clinical stage T2-T4a disease, all patients were given neoadjuvant chemotherapy for 3 weeks. Out of the 34 patients reaching clinical stage T0 disease, 10 underwent radical cystectomy and 24 patients remained on observation. The 2-year overall survival rate was similar between the groups (70% in the radical cystectomy group compared to 76% in the observation group)³.

There is also data comparing TURBT + chemotherapy to trimodal therapy in patients reaching clinical stage T0 disease after chemotherapy + TURBT or after trimodal therapy. These data showed at least comparable results between both modalities, as can be seen in table 1, with a disease specific survival ranging between 80.8%-93% in the TURBT+ Chemotherapy group compared to 76.6%-85% in the trimodal therapy group.

Table 1 – Comparison of studies analyzing trimodal therapy and TURBT + Chemotherapy:

EAU 2019 TURB C vs TMT

Dr. Solsona concluded that this data is robust enough to show that active surveillance is the best approach for patients with clinical stage T2-T4a that have received chemotherapy and have reached a clinical stage T0 disease.

References:

1. Audenet F et al. Effectiveness of Transurethral Resection plus Systemic Chemotherapy as Definitive Treatment for Muscle Invasive Bladder Cancer in Population Level Data. J Urol. 2018 Nov;200(5):996-1004. doi: 10.1016/j.juro.2018.06.001. Epub 2018 Jun 4
2. Moran GW, Li G, Robins DJ, Matulay JT, McKiernan JM, Anderson CB. Systematic Review and Meta-Analysis on the Efficacy of Chemotherapy with Transurethral Resection of Bladder Tumors as Definitive Therapy for Muscle Invasive Bladder Cancer. Bladder Cancer. 2017;3(4):245-258. Published 2017 Oct 27. doi:10.3233/BLC-170134
3. deVere White RW, Katz MH, Steinberg GD. The case for neoadjuvant chemotherapy and cystectomy for muscle invasive bladder cancer. J Urol. 2009 May;181(5):1994-7. doi: 10.1016/j.juro.2009.02.052. Epub 2009 Mar 14.

Presented by: Eduardo Solsona, MD, PhD, Department of Urology, Instituto Valenciano de Oncologia, Valencia, 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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