title: Long-term single-institute experience with trimodal bladder-preserving therapy with proton beam therapy for muscle-invasive bladder cancer.
abstract: OBJECTIVE
  We retrospectively elucidated the oncological outcomes, prognostic factors and toxicities of proton beam therapy in trimodal bladder-preserving therapy for muscle-invasive bladder cancer at our institution.
  
  
  METHODS
  From 1990 to 2015, 70 patients with cT2-3N0M0 muscle-invasive bladder cancer underwent trimodal bladder-preserving therapy consisting of maximal transurethral resection of the bladder tumor, small pelvis photon irradiation, intra-arterial chemotherapy and proton beam therapy. The overall survival rate, progression-free survival rate, time to progression, predictive factors for progression and toxicities were analyzed. Progression was defined as when muscle-invasive recurrence, distant metastasis or upper urinary tract recurrence was observed.
  
  
  RESULTS
  The patients' median age was 65 (range 36-85) years. The median follow-up period was 3.4 (range 0.6-19.5) years. The 5-year cumulative overall survival rate, progression-free survival rate and time to progression rate were 82%, 77%, and 82%, respectively. In univariate and multivariate analyses, tumor multiplicity and tumor size (≥5 cm) were significant and independent factors associated with progression (hazard ratio 3.5, 95% confidence interval 1.1-12; hazard ratio 5.0, 95% confidence interval 1.3-17; P < 0.05 for all). As for toxicity, 26 (18%) patients had grade 3-4 acute hematologic toxicities and 2 (3%) patients had grade 3 late genitourinary toxicity. No patient had to discontinue the treatment due to acute toxicity.
  
  
  CONCLUSIONS
  Our bladder-preserving therapy with proton beam therapy was well tolerated and achieved a favorable mortality rate. Tumor multiplicity and tumor size were important risk factors for progression. Our findings indicate that this therapy can be an effective treatment option for selected muscle-invasive bladder cancer patients.
authors.affiliation: Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors.forename: Ei-Ichiro
authors.initials: EI
authors.lastname: Takaoka
authors.affiliation: Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors.forename: Jun
authors.initials: J
authors.lastname: Miyazaki
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Ishitsuka
authors.affiliation: Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kanuma
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Takizawa
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
authors.affiliation: Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba nishiuro@md.tsukuba.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishiyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D061766:Proton Therapy / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*
keywords: muscle-invasive bladder cancer; proton beam therapy; toxicity; trimodal bladder-preserving therapy