title: Role of diffusion-weighted magnetic resonance imaging in predicting sensitivity to chemoradiotherapy in muscle-invasive bladder cancer.
abstract: OBJECTIVE
  In chemoradiation (CRT)-based bladder-sparing approaches for muscle invasive bladder cancer (MIBC), patients who respond favorably to induction CRT enjoy the benefits of bladder preservation, whereas nonresponders do not. Thus, accurate prediction of CRT sensitivity would optimize patient selection for bladder-sparing protocols. Diffusion-weighted MRI (DW-MRI) is a functional imaging technique that quantifies the diffusion of water molecules in a noninvasive manner. We investigated whether DW-MRI predicts CRT sensitivity of MIBC.
  
  
  METHODS
  The study cohort consisted of 23 MIBC patients (cT2/T3 = 7/16) who underwent induction CRT consisting of radiotherapy to the small pelvis (40 Gy) with two cycles of cisplatin (20 mg/day for 5 days), followed by partial or radical cystectomy. All patients underwent DW-MRI before the initiation of treatment. Associations of apparent diffusion coefficient (ADC) values with CRT sensitivity were analyzed. The proliferative potential of MIBC was also assessed by analyzing the Ki-67 labeling index (LI) in pretherapeutic biopsy specimens.
  
  
  RESULTS
  Thirteen patients (57%) achieved pathologic complete response (pCR) to CRT. These CRT-sensitive MIBCs showed significantly lower ADC values (median, 0.63 × 10(-3) mm(2)/s; range, 0.43-0.77) than CRT-resistant (no pCR) MIBCs (median, 0.84 × 10(-3) mm(2)/s; range, 0.69-1.09; p = 0.0003). Multivariate analysis identified ADC value as the only significant and independent predictor of CRT sensitivity (p < 0.0001; odds ratio per 0.001 ×10(-3) mm(2)/s increase, 1.03; 95% confidence interval, 1.01-1.08). With a cutoff ADC value at 0.74 × 10(-3) mm(2)/s, sensitivity/specificity/accuracy in predicting CRT sensitivity was 92/90/91%. Ki-67 LI was significantly higher in CRT-sensitive MIBCs (p = 0.0005) and significantly and inversely correlated with ADC values (ρ = -0.67, p = 0.0007).
  
  
  CONCLUSIONS
  DW-MRI is a potential biomarker for predicting CRT sensitivity in MIBC. DW-MRI may be useful to optimize patient selection for CRT-based bladder-sparing approaches.
authors.affiliation: Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yoshida
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Koga
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Chikako
authors.initials: C
authors.lastname: Ishii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hajime
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Komai
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Saito
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Masuda
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujii
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kihara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D002278:Carcinoma in Situ / Q000737:chemistry / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000627:therapeutic use; D015653:Cystectomy / Q000379:methods; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D019008:Drug Resistance, Neoplasm; D005242:Fecal Incontinence / Q000209:etiology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D059351:Organ Sparing Treatments / Q000379:methods; D018579:Patient Selection; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D012007:Rectum / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000601:surgery / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D019394:Ki-67 Antigen; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin