Prospective evaluation of a preoperative biomarker panel for prediction of upstaging at radical cystectomy

Shahrokh F. Shariat, Niccolo Passoni, Aditya Bagrodia, Varun Rachakonda, Evanguelos Xylinas, Brian Robinson, Payal Kapur, Arthur I Sagalowsky, Yair Lotan

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Objectives To prospectively test whether a panel of biomarkers could identify patients with organ-confined disease likely to be upstaged at radical cystectomy (RC), as retrospective studies have found that cell-cycle- and proliferation-related biomarkers can help improve prognostic accuracy after RC. Patients and Methods We prospectively performed p53, p21, p27, Ki67, and cyclin E1 immunohistochemical staining on transurethral resection of the bladder (TURB) specimens from 87 patients treated with RC for organ-confined urothelial carcinoma of the bladder (UCB). The number of altered biomarkers was categorised as 'favourable' (≤2 altered markers) or 'unfavourable' (>2). Results Expression of p53, p21, p27, cyclin E1, and Ki67 were altered in 61 (70%), 19 (22%), 26 (30%), four (5%), and 70 (80%) patients, respectively. The median number of positive markers was two. In all, 47 (54%) patients were upstaged when T-stage was considered alone and 49 (56%) when T- and/or N-stage were considered both as upstaging. In multivariable analyses that adjusted for the effects of age, clinical stage, concomitant carcinoma in situ, and time from TURB to RC, an 'unfavourable' biomarker score was independently associated with T-stage upstaging (hazard ratio [HR] 3.3, P = 0.024) but not T- and/or N-stage upstaging (HR 2.76, P = 0.06). Addition of p27, number of positive markers, and biomarker score each increased the discrimination of a base model for prediction of T-stage upstaging (5%, 6%, and 5%, respectively) and T- and/or N-stage upstaging (4%, 6%, and 3%, respectively). Conclusions Cell-cycle- and proliferation-related markers in the TURB specimen improve the prediction of upstaging at RC. Such a marker panel may help identify patients with non-muscle-invasive UCB who are clinically under-staged needing RC and patients with muscle-invasive UCB who are likely to be non-organ-confined thereby potentially benefiting from neoadjuvant chemotherapy.

Original languageEnglish (US)
Pages (from-to)70-76
Number of pages7
JournalBJU International
Volume113
Issue number1
DOIs
StatePublished - Jan 2014

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Cystectomy
Biomarkers
Urinary Bladder
Cyclins
Carcinoma
Cell Cycle
Cell Proliferation
Carcinoma in Situ
Retrospective Studies
Staining and Labeling
Drug Therapy
Muscles

Keywords

  • biomarkers
  • bladder cancer
  • prognosis
  • prospective
  • upstaging

ASJC Scopus subject areas

  • Urology

Cite this

Prospective evaluation of a preoperative biomarker panel for prediction of upstaging at radical cystectomy. / Shariat, Shahrokh F.; Passoni, Niccolo; Bagrodia, Aditya; Rachakonda, Varun; Xylinas, Evanguelos; Robinson, Brian; Kapur, Payal; Sagalowsky, Arthur I; Lotan, Yair.

In: BJU International, Vol. 113, No. 1, 01.2014, p. 70-76.

Research output: Contribution to journalArticle

Shariat, Shahrokh F. ; Passoni, Niccolo ; Bagrodia, Aditya ; Rachakonda, Varun ; Xylinas, Evanguelos ; Robinson, Brian ; Kapur, Payal ; Sagalowsky, Arthur I ; Lotan, Yair. / Prospective evaluation of a preoperative biomarker panel for prediction of upstaging at radical cystectomy. In: BJU International. 2014 ; Vol. 113, No. 1. pp. 70-76.
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abstract = "Objectives To prospectively test whether a panel of biomarkers could identify patients with organ-confined disease likely to be upstaged at radical cystectomy (RC), as retrospective studies have found that cell-cycle- and proliferation-related biomarkers can help improve prognostic accuracy after RC. Patients and Methods We prospectively performed p53, p21, p27, Ki67, and cyclin E1 immunohistochemical staining on transurethral resection of the bladder (TURB) specimens from 87 patients treated with RC for organ-confined urothelial carcinoma of the bladder (UCB). The number of altered biomarkers was categorised as 'favourable' (≤2 altered markers) or 'unfavourable' (>2). Results Expression of p53, p21, p27, cyclin E1, and Ki67 were altered in 61 (70{\%}), 19 (22{\%}), 26 (30{\%}), four (5{\%}), and 70 (80{\%}) patients, respectively. The median number of positive markers was two. In all, 47 (54{\%}) patients were upstaged when T-stage was considered alone and 49 (56{\%}) when T- and/or N-stage were considered both as upstaging. In multivariable analyses that adjusted for the effects of age, clinical stage, concomitant carcinoma in situ, and time from TURB to RC, an 'unfavourable' biomarker score was independently associated with T-stage upstaging (hazard ratio [HR] 3.3, P = 0.024) but not T- and/or N-stage upstaging (HR 2.76, P = 0.06). Addition of p27, number of positive markers, and biomarker score each increased the discrimination of a base model for prediction of T-stage upstaging (5{\%}, 6{\%}, and 5{\%}, respectively) and T- and/or N-stage upstaging (4{\%}, 6{\%}, and 3{\%}, respectively). Conclusions Cell-cycle- and proliferation-related markers in the TURB specimen improve the prediction of upstaging at RC. Such a marker panel may help identify patients with non-muscle-invasive UCB who are clinically under-staged needing RC and patients with muscle-invasive UCB who are likely to be non-organ-confined thereby potentially benefiting from neoadjuvant chemotherapy.",
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T1 - Prospective evaluation of a preoperative biomarker panel for prediction of upstaging at radical cystectomy

AU - Shariat, Shahrokh F.

AU - Passoni, Niccolo

AU - Bagrodia, Aditya

AU - Rachakonda, Varun

AU - Xylinas, Evanguelos

AU - Robinson, Brian

AU - Kapur, Payal

AU - Sagalowsky, Arthur I

AU - Lotan, Yair

PY - 2014/1

Y1 - 2014/1

N2 - Objectives To prospectively test whether a panel of biomarkers could identify patients with organ-confined disease likely to be upstaged at radical cystectomy (RC), as retrospective studies have found that cell-cycle- and proliferation-related biomarkers can help improve prognostic accuracy after RC. Patients and Methods We prospectively performed p53, p21, p27, Ki67, and cyclin E1 immunohistochemical staining on transurethral resection of the bladder (TURB) specimens from 87 patients treated with RC for organ-confined urothelial carcinoma of the bladder (UCB). The number of altered biomarkers was categorised as 'favourable' (≤2 altered markers) or 'unfavourable' (>2). Results Expression of p53, p21, p27, cyclin E1, and Ki67 were altered in 61 (70%), 19 (22%), 26 (30%), four (5%), and 70 (80%) patients, respectively. The median number of positive markers was two. In all, 47 (54%) patients were upstaged when T-stage was considered alone and 49 (56%) when T- and/or N-stage were considered both as upstaging. In multivariable analyses that adjusted for the effects of age, clinical stage, concomitant carcinoma in situ, and time from TURB to RC, an 'unfavourable' biomarker score was independently associated with T-stage upstaging (hazard ratio [HR] 3.3, P = 0.024) but not T- and/or N-stage upstaging (HR 2.76, P = 0.06). Addition of p27, number of positive markers, and biomarker score each increased the discrimination of a base model for prediction of T-stage upstaging (5%, 6%, and 5%, respectively) and T- and/or N-stage upstaging (4%, 6%, and 3%, respectively). Conclusions Cell-cycle- and proliferation-related markers in the TURB specimen improve the prediction of upstaging at RC. Such a marker panel may help identify patients with non-muscle-invasive UCB who are clinically under-staged needing RC and patients with muscle-invasive UCB who are likely to be non-organ-confined thereby potentially benefiting from neoadjuvant chemotherapy.

AB - Objectives To prospectively test whether a panel of biomarkers could identify patients with organ-confined disease likely to be upstaged at radical cystectomy (RC), as retrospective studies have found that cell-cycle- and proliferation-related biomarkers can help improve prognostic accuracy after RC. Patients and Methods We prospectively performed p53, p21, p27, Ki67, and cyclin E1 immunohistochemical staining on transurethral resection of the bladder (TURB) specimens from 87 patients treated with RC for organ-confined urothelial carcinoma of the bladder (UCB). The number of altered biomarkers was categorised as 'favourable' (≤2 altered markers) or 'unfavourable' (>2). Results Expression of p53, p21, p27, cyclin E1, and Ki67 were altered in 61 (70%), 19 (22%), 26 (30%), four (5%), and 70 (80%) patients, respectively. The median number of positive markers was two. In all, 47 (54%) patients were upstaged when T-stage was considered alone and 49 (56%) when T- and/or N-stage were considered both as upstaging. In multivariable analyses that adjusted for the effects of age, clinical stage, concomitant carcinoma in situ, and time from TURB to RC, an 'unfavourable' biomarker score was independently associated with T-stage upstaging (hazard ratio [HR] 3.3, P = 0.024) but not T- and/or N-stage upstaging (HR 2.76, P = 0.06). Addition of p27, number of positive markers, and biomarker score each increased the discrimination of a base model for prediction of T-stage upstaging (5%, 6%, and 5%, respectively) and T- and/or N-stage upstaging (4%, 6%, and 3%, respectively). Conclusions Cell-cycle- and proliferation-related markers in the TURB specimen improve the prediction of upstaging at RC. Such a marker panel may help identify patients with non-muscle-invasive UCB who are clinically under-staged needing RC and patients with muscle-invasive UCB who are likely to be non-organ-confined thereby potentially benefiting from neoadjuvant chemotherapy.

KW - biomarkers

KW - bladder cancer

KW - prognosis

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