BACKGROUND: Retrospective studies demonstrated that cell cycle-related and proliferation biomarkers add information to standard pathologic tumor features after radical cystectomy (RC). There are no prospective studies validating the clinical utility of markers in bladder cancer. OBJECTIVE: To prospectively determine whether a panel of biomarkers could identify patients with urothelial carcinoma of the bladder (UCB) who were likely to experience disease recurrence or mortality. DESIGN, SETTING, AND PARTICIPANTS: Between January 2007 and January 2012, every patient with high-grade bladder cancer, including 216 patients treated with RC and lymphadenectomy, underwent immunohistochemical staining for tumor protein p53 (Tp53); cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A); cyclin-dependent kinase inhibitor 1B (p27, Kip1); antigen identified by monoclonal antibody Ki-67 (MKI67); and cyclin E1. INTERVENTION: Every patient underwent RC and lymphadenectomy, and marker staining. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox regression analyses tested the ability of the number of altered biomarkers to predict recurrence or cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Pathologic stage among the study population was pT0 (5%), pT1 (35%), pT2 (19%), pT3 (29%), and pT4 (13%); lymphovascular invasion (LVI) was seen in 34%. The median number of removed lymph nodes was 23, and 60 patients had lymph node involvement (LNI). Median follow-up was 20 mo. Expression of p53, p21, p27, cyclin E1, and Ki-67 were altered in 54%, 26%, 46%, 15%, and 75% patients, respectively. In univariable analyses, pT stage, LNI, LVI, perioperative chemotherapy (CTx), margin status, and number of altered biomarkers predicted disease recurrence. In a multivariable model adjusting for pathologic stage, margins, LNI, and adjuvant CTx, only LVI and number of altered biomarkers were independent predictors of recurrence and CSM. The concordance index of a baseline model predicting CSM (including pathologic stage, margins, LVI, LNI, and adjuvant CTx) was 80% and improved to 83% with addition of the number of altered markers. CONCLUSIONS: Molecular markers improve the prediction of recurrence and CSM after RC. They may identify patients who might benefit from additional treatments and closer surveillance after cystectomy.
BACKGROUND: Retrospective studies demonstrated that cell cycle-related and proliferation biomarkers add information to standard pathologic tumor features after radical cystectomy (RC). There are no prospective studies validating the clinical utility of markers in bladder cancer. OBJECTIVE: To prospectively determine whether a panel of biomarkers could identify patients with urothelial carcinoma of the bladder (UCB) who were likely to experience disease recurrence or mortality. DESIGN, SETTING, AND PARTICIPANTS: Between January 2007 and January 2012, every patient with high-grade bladder cancer, including 216 patients treated with RC and lymphadenectomy, underwent immunohistochemical staining for tumor protein p53 (Tp53); cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A); cyclin-dependent kinase inhibitor 1B (p27, Kip1); antigen identified by monoclonal antibody Ki-67 (MKI67); and cyclin E1. INTERVENTION: Every patient underwent RC and lymphadenectomy, and marker staining. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox regression analyses tested the ability of the number of altered biomarkers to predict recurrence or cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Pathologic stage among the study population was pT0 (5%), pT1 (35%), pT2 (19%), pT3 (29%), and pT4 (13%); lymphovascular invasion (LVI) was seen in 34%. The median number of removed lymph nodes was 23, and 60 patients had lymph node involvement (LNI). Median follow-up was 20 mo. Expression of p53, p21, p27, cyclin E1, and Ki-67 were altered in 54%, 26%, 46%, 15%, and 75% patients, respectively. In univariable analyses, pT stage, LNI, LVI, perioperative chemotherapy (CTx), margin status, and number of altered biomarkers predicted disease recurrence. In a multivariable model adjusting for pathologic stage, margins, LNI, and adjuvant CTx, only LVI and number of altered biomarkers were independent predictors of recurrence and CSM. The concordance index of a baseline model predicting CSM (including pathologic stage, margins, LVI, LNI, and adjuvant CTx) was 80% and improved to 83% with addition of the number of altered markers. CONCLUSIONS: Molecular markers improve the prediction of recurrence and CSM after RC. They may identify patients who might benefit from additional treatments and closer surveillance after cystectomy.
Authors: Laura-Maria Krabbe; Aditya Bagrodia; Mary E Westerman; Bishoy A Gayed; Ahmed Q Haddad; Arthur I Sagalowsky; Shahrokh F Shariat; Payal Kapur; Yair Lotan; Vitaly Margulis Journal: World J Urol Date: 2015-05-20 Impact factor: 4.226
Authors: J Y Liu; Q H Zeng; P G Cao; D Xie; F Yang; L Y He; Y B Dai; J J Li; X M Liu; H L Zeng; X J Fan; L Liu; Y X Zhu; L Gong; Y Cheng; J D Zhou; J Hu; H Bo; Z Z Xu; K Cao Journal: Oncogene Date: 2018-04-17 Impact factor: 9.867
Authors: Aditya Bagrodia; Eugene K Cha; John P Sfakianos; Emily C Zabor; Bernard H Bochner; Hikmat A Al-Ahmadie; David B Solit; Jonathan A Coleman; Gopa Iyer; Sasinya N Scott; Ronak Shah; Irina Ostrovnaya; Byron Lee; Neil B Desai; Qinghu Ren; Jonathan E Rosenberg; Guido Dalbagni; Dean F Bajorin; Victor E Reuter; Michael F Berger Journal: J Urol Date: 2016-01-14 Impact factor: 7.450