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Multicenter Study
. 2021 Nov;128(5):607-614.
doi: 10.1111/bju.15434. Epub 2021 May 18.

Optimal pathological response after neoadjuvant chemotherapy for muscle-invasive bladder cancer: results from a global, multicentre collaboration

Praful Ravi  1 , Gregory R Pond  2 , Leonidas N Diamantopoulos  3   4 , Christopher Su  5 , Ajjai Alva  5 , Rohit K Jain  6 , William P Skelton 4th  6 , Sumati Gupta  7 , Jonathan D Tward  7 , Kathleen M Olson  8 , Parminder Singh  8 , Camilla M Grunewald  9 , Guenter Niegisch  9 , Jae-Lyun Lee  10 , Andrea Gallina  11 , Marco Bandini  11 , Andrea Necchi  12 , Matthew Mossanen  1   13 , Bradley A McGregor  1 , Catherine Curran  1 , Petros Grivas  3 , Guru P Sonpavde  1
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Free article
Multicenter Study

Optimal pathological response after neoadjuvant chemotherapy for muscle-invasive bladder cancer: results from a global, multicentre collaboration

Praful Ravi et al. BJU Int. 2021 Nov.
Free article

Abstract

Objectives: To evaluate outcomes of patients achieving a post-treatment pathological stage of <ypT2N0 at radical cystectomy (RC) following neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) to identify an optimal definition of pathological response.

Patients and methods: Patients from 10 international centres who underwent NAC for cT2-4aN0-1 MIBC and achieved <ypT2N0 disease at RC were included. The primary outcome was time to recurrence, either local or distant. Kaplan-Meier and Cox proportional hazards regression were used to evaluate associations between clinicopathological variables and outcomes.

Results: A total of 625 patients were included. The median age was 66 years and 80% were male. Gemcitabine and cisplatin (GC, 56%) and methotrexate, vinblastine, doxorubicin and cisplatin (MVAC)/dose-dense (dd)MVAC (32%) were the most common NAC regimens. ypT0, pure ypTis, ypTa ±ypTis and ypT1 ± ypTis were attained in 58.1%, 20.0%, 7.6% and 14.2% of patients, respectively. The cumulative incidence of recurrence at 5 years was 9%, 16%, 29% and 30%, respectively. Pathological stage was prognostic for recurrence, with ypTa ± Tis (hazard ratio [HR] 3.20, 95% confidence interval [CI] 1.40-7.30) and ypT1 ± Tis disease (HR 4.03, 95% CI 2.13-7.63) associated with a significantly higher recurrence risk. Pure ypTis (HR 1.66, 95% CI 0.82-3.38) and the type of NAC regimen (ddMVAC: HR 1.59, 95% CI 0.55-4.56; MVAC: HR 1.18, 9%% CI 0.25-5.54; reference: GC) were not associated with recurrence.

Conclusion: We propose that optimal pathological response after NAC be defined as attainment of ypT0N0/ypTisN0 at RC. Patients with ypTaN0 or ypT1N0 disease (with or without Tis) at RC displayed a significantly higher risk of recurrence and may be candidates for trials investigating adjuvant therapy.

Keywords: #BladderCancer; #blcsm; bladder cancer; neoadjuvant chemotherapy; pathological response; recurrence.

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