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Pathologic Downstag...
Pathologic Downstaging Is a Surrogate Marker for Efficacy and Increased Survival Following Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Urothelial Bladder Cancer
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- Rosenblatt, Robert (author)
- Karolinska Institutet
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- Sherif, Amir (author)
- Department of Urology, Karolinska University Hospital-Solna, Stockholm, Sweden
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Rintala, Erkki (author)
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Wahlqvist, Rolf (author)
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- Ullén, Anders (author)
- Karolinska Institutet
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- Nilsson, Sten (author)
- Karolinska Institutet
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- Malmström, Per-Uno (author)
- Uppsala universitet,Urologkirurgi
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(creator_code:org_t)
- Elsevier, 2012
- 2012
- English.
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In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 61:6, s. 1229-1238
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Background: Characterising responders to neoadjuvant chemotherapy (NAC) is important to minimise overtreatment and the unnecessary delay of definitive treatment of urothelial urinary bladder cancer.Objective: To assess the effect of NAC on tumour downstaging and overall survival.Design, setting, and participants: A total of 449 patients from the randomised prospective Nordic Cystectomy Trials 1 and 2 were analysed retrospectively. Eligible patients were defined as T2–T4aNXM0 preoperatively and pT0–pT4aN0−N + M0 postoperatively. The median follow-up time was 5 yr.Intervention: The experimental arm consisted of cisplatin-based NAC; the control arm consisted of cystectomy only.Measurements: The primary outcome was tumour downstaging defined as pathologic TNM less than clinical TNM. Different downstaging thresholds were applied: complete downstaging (CD) (pT0N0), noninvasive downstaging (NID) (pT0/pTis/pTaN0), and organ confinement (OC) (≤pT3aN0). Downstaging rates and nodal status were compared between the study arms using the chi-square test. Secondary outcome was overall survival (OS) stratified by treatment arm, downstaging categories, and clinical stages, analysed by the Kaplan-Meier method. The following covariates were tested as prognostic factors in univariate and multivariate analyses using the Cox regression method: age, sex, clinical stage, pN status, NAC, CD, NID, and OC.Results and limitations: Downstaging rates increased significantly in the NAC arm independent of the downstaging threshold. The impact was more prominent in clinical T3 tumours, with a near threefold increase in CD tumours. The combination of CD and NAC showed an absolute risk reduction of 31.1% in OS at 5 yr compared with CD controls. The combination of NAC and CD revealed a hazard ratio of 0.32 compared with 1.0 for the combination of no NAC and no CD. Limitations were the retrospective approach and uncertain clinical TNM staging.Conclusions: Survival benefits of NAC are reflected in downstaging of the primary tumour. Chemo-induced downstaging might be a potential surrogate marker for OS.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Urinary bladder neoplasms
- Neoadjuvant therapy
Publication and Content Type
- ref (subject category)
- art (subject category)
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