title: Gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive transitional and squamous cell carcinoma of the bladder: effect on survival and bladder preservation.
abstract: BACKGROUND
  Despite aggressive local therapy, patients with locally advanced bladder cancer have a significant risk of distant metastases. This study evaluated the role of neoadjuvant combination chemotherapy with gemcitabine/cisplatin (GC) in improving the outcome of this group of patients over radical cystectomy alone.
  
  
  METHODS
  A total of 114 patients with newly diagnosed bladder cancer (T3-4, N0-2, M0) were randomized to radical cystectomy alone or initial 3 cycles of GC, then managed according to response. Patients who achieved complete response completed 6 cycles of GC followed by local radiation therapy (RT) only. If tumors were downstaged to T1, complete transurethral resection was done, followed by 3 cycles of GC and then RT. Patients with partial response underwent radical cystectomy followed by 3 cycles of GC. Patients with stable disease or disease progression underwent radical cystectomy.
  
  
  RESULTS
  The overall response rate to GC was 55.1%, and complete response was achieved in 28.6%. The 3-year overall survival (OS) was 51.9% versus 51.2% in the chemotherapy and surgery arms, respectively (P = .399). The 3-year disease-free survival was 31.8% in the chemotherapy arm and 45.1% in the surgery arm (P = .06). Bladder preservation was achieved in 22.5% of patients in the neoadjuvant arm. OS was 78% in responding patients and 100% in patients with complete response.
  
  
  CONCLUSIONS
  Neoadjuvant GC did not improve survival in locally advanced bladder cancer over radical cystectomy alone. However, bladder preservation was feasible, and OS in responding patients was impressive. Therefore, predictive models to select patients are needed. This is the largest prospective study of squamous cell carcinoma and transitional cell carcinoma using neoadjuvant GC.
authors.affiliation: National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: Hussein M
authors.initials: HM
authors.lastname: Khaled
authors.affiliation: National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Shafik
authors.affiliation: National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: M S
authors.initials: MS
authors.lastname: Zabhloul
authors.affiliation: Urology and Nephrology Center, Mansoura, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: Ghoneim
authors.affiliation: Menia Oncology Center, Menia, Egypt.
authors.forename: R A
authors.initials: RA
authors.lastname: Saber
authors.affiliation: National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: Manie
authors.affiliation: Urology and Nephrology Center, Mansoura, Egypt.
authors.forename: H A
authors.initials: HA
authors.lastname: Enein
authors.affiliation: National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: H A
authors.initials: HA
authors.lastname: Megeed
authors.affiliation: National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: O
authors.initials: O
authors.lastname: Mansur
authors.affiliation: Urology and Nephrology Center, Mansoura, Egypt.
authors.forename: M E
authors.initials: ME
authors.lastname: Sherbini
authors.affiliation: Menia Oncology Center, Menia, Egypt.
authors.forename: T Z
authors.initials: TZ
authors.lastname: Mahran
authors.affiliation: National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: M E
authors.initials: ME
authors.lastname: Kalawee
authors.affiliation: National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: A
authors.initials: A
authors.lastname: Badran
authors.affiliation: National Cancer Institute, Cairo University, Giza, Egypt. Electronic address: safaanci@yahoo.com.
authors.forename: Safaa M
authors.initials: SM
authors.lastname: Ramadan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000601:surgery; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000601:surgery; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D015653:Cystectomy; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Bladder cancer; Bladder preservation; Bladder squamous cell carcinoma; Muscle invasive; Neoadjuvant GC