title: Expression of nucleoside transporters and deoxycytidine kinase proteins in muscle invasive urothelial carcinoma of the bladder: correlation with pathological response to neoadjuvant platinum/gemcitabine combination chemotherapy.
abstract: OBJECTIVE
  In pancreatic cancer, deoxycytidine kinase and the human equilibrative nucleoside transporter 1 have been validated as predictive markers for benefit from gemcitabine therapy. Gemcitabine is used with cisplatin or carboplatin as neoadjuvant chemotherapy for muscle invasive urothelial cancer of the bladder before radical cystectomy and patients rendered disease-free at surgery tend to have better outcomes. In this trial we examined if nucleoside transporter or deoxycytidine kinase protein abundance in biopsy specimens before chemotherapy is related to the response to neoadjuvant chemotherapy.
  
  
  METHODS
  A total of 62 consecutive patients undergoing neoadjuvant chemotherapy with platinum/gemcitabine at a single institution were accrued. Initial transurethral resection of bladder tumor specimens and cystectomy specimens were collected, and scored for nucleoside transporter and deoxycytidine kinase expression. Pathological response rates and survival data were collected.
  
  
  RESULTS
  Of the 62 patients 17 (27%) achieved a complete pathological response (pT0) to neoadjuvant chemotherapy. Nucleoside transporter and deoxycytidine kinase protein expression in the transurethral resection of bladder tumor specimens did not predict for pT0 status to neoadjuvant chemotherapy. Median overall survival was not reached for the group achieving pT0 status and was 46 months for those with persistent cancer at definitive surgery (p = 0.07). Median followup for the cohort was 30 months.
  
  
  CONCLUSIONS
  Nucleoside transporter and deoxycytidine kinase expression in transurethral resection of bladder tumor samples do not predict for response to gemcitabine and platinum neoadjuvant chemotherapy. Patients should continue to be offered neoadjuvant chemotherapy before radical cystectomy based on clinical and pathological staging.
authors.affiliation: Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. Electronic address: scott.north@albertahealthservices.ca.
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.affiliation: Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
authors.forename: Faraj
authors.initials: F
authors.lastname: El-Gehani
authors.affiliation: Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Santos
authors.affiliation: Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
authors.forename: Sunita
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.affiliation: Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
authors.forename: Carol E
authors.initials: CE
authors.lastname: Cass
authors.affiliation: Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: Mackey
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003842:Deoxycytidine Kinase / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D033703:Nucleoside Transport Proteins / Q000096:biosynthesis*; D017671:Platinum Compounds / Q000008:administration & dosage; D011237:Predictive Value of Tests; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D033703:Nucleoside Transport Proteins; D017671:Platinum Compounds; D003841:Deoxycytidine; D003842:Deoxycytidine Kinase; D000093542:Gemcitabine
keywords: MVAC; NAC; NT; RC; TURBT; carcinoma; dCK; deoxycytidine kinase; drug therapy; gemcitabine; methotrexate, vinblastine, doxorubicin and cisplatin; neoadjuvant chemotherapy; neoadjuvant therapy; nucleoside transport proteins; nucleoside transporter; radical cystectomy; transitional cell; transurethral resection of bladder tumor