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Martini A , Jia R , Ferket BS , Waingankar N , Plimack ER , Crabb SJ , Harshman LC , Yu EY , Powles T , Rosenberg JE , Pal SK , Vaishampayan UN , Necchi A , Wiklund NP , Mehrazin R , Mazumdar M , Sfakianos JP , Galsky MD
Tumor downstaging as an intermediate endpoint to assess the activity of neoadjuvant systemic therapy in patients with muscle-invasive bladder cancer
Cancer. 2019 Sep 15;125(18) :3155-3163
PMID: 31150110    PMCID: PMC6859003    URL: https://www.ncbi.nlm.nih.gov/pubmed/31150110
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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.
Notes
1097-0142 Martini, Alberto Orcid: 0000-0003-1272-7154 Jia, Rachel Ferket, Bart S Waingankar, Nikhil Orcid: 0000-0003-4703-0074 Plimack, Elizabeth R Crabb, Simon J Orcid: 0000-0003-3521-9064 Harshman, Lauren C Orcid: 0000-0002-7636-1588 Yu, Evan Y Powles, Thomas Rosenberg, Jonathan E Pal, Sumanta K Orcid: 0000-0002-1712-0848 Vaishampayan, Ulka N Orcid: 0000-0001-5800-4571 Necchi, Andrea Orcid: 0000-0002-3007-2756 Wiklund, N Peter Mehrazin, Reza Mazumdar, Madhu Sfakianos, John P Galsky, Matthew D P30 CA022453/CA/NCI NIH HHS/United States P30 CA008748/CA/NCI NIH HHS/United States Journal Article United States Cancer. 2019 Sep 15;125(18):3155-3163. doi: 10.1002/cncr.32169. Epub 2019 May 31.