Tumor downstaging as an intermediate endpoint to assess the activity of neoadjuvant systemic therapy in patients with muscle‐invasive bladder cancer

Abstract

BACKGROUND: Achieving a pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC) has been associated with improved overall survival (OS). This study was aimed at evaluating the impact of pathologic downstaging (pDS; ie, a pT stage at least 1 stage lower than the pre-NAC cT stage) on the OS of patients with MIBC treated with NAC. METHODS: The Retrospective International Study of Cancers of the Urothelial Tract (RISC) and the National Cancer Database (NCDB) were queried for cT2-4N0M0 patients treated with NAC. A multivariable Cox model including either pDS or pCR was generated. A nested model was built to evaluate the added value of pDS (excluding patients achieving a pCR) to a model including pCR alone. C indices were computed to assess discrimination. NCDB was used for validation. The treatment effect of NAC versus cystectomy alone in achieving pDS was estimated through an inverse probability-weighted regression adjustment. RESULTS: Overall, 189 and 2010 patients from the RISC and NCDB cohorts, respectively, were included; pDS and pCR were achieved by 33% and 35% and by 20% and 15% in RISC and NCDB, respectively. In both data sets, pDS and pCR were associated with better OS and C indices. Adding pDS excluding pCR to the model with pCR fit the data better (likelihood ratio, P = .019 for RISC and P < .001 for NCDB), and it yielded better discrimination (incremental C index, 4.2 for RISC and 1.6 for NCDB). The treatment effect of NAC in achieving pDS was 2.07-fold (P < .001) in comparison with cystectomy alone. CONCLUSIONS: A decrease of at least 1 stage from the cT stage to the pT stage is associated with improved OS in patients with MIBC treated with NAC.

The natural history of untreated muscle‐invasive bladder cancer

“…Yet, these rates still remain unsatisfactory. It has been demonstrated that the administration of neoadjuvant chemotherapy (NAC) improves OS in patients with MIBC . However, this treatment modality is associated with grade 3–4 toxicity in slightly >35% of the recipients and some elderly patients may not be ideal candidates for NAC administration.…”

Traditional Classification and Novel Subtyping Systems for Bladder Cancer

“…Moreover, the traditional classification system can only predict the risk of recurrence and progression of NMIBC but not the risk of MIBC. After radical cystectomy, some muscle invasive bladder cancer patients (MIBCs) benefit from neoadjuvant chemotherapy (NAC), while others do not (14)(15)(16), which cannot be predicted by the traditional classification system. The pathological parameters of the tumor cannot fully reflect the "intrinsic characteristics" of bladder cancer.…”

The role of complete TURBT before radical cystectomy for organ-confined bladder cancer

“…In most studies, downstaging had an important impact on survival, even neoadjuvant chemotherapy was not performed 4,6,20 . In this study, complete TURBT was related to a higher rate of downstaging, which was from T2/T1 to T1/Ta, and downstaging was not signi cantly associated with oncological outcome signi cantly.…”

“…Radical cystectomy (RC) is the standard option for muscle invasive bladder cancer (MIBC) and some high-risk non-muscle invasive bladder cancer (NMIBC). For locally-advanced disease, neoadjuvant chemotherapy is recommended, and downstaging is associated with good prognosis [4][5][6][7][8][9] . For ≤ pT2N0M0 disease, complete TURBT was related to a higher rate of downstaging after RC, and it was associated with good outcomes [10][11][12][13] .…”