title: Clinical implication of surgically treated early-stage cervical cancer with multiple high-risk factors.
abstract: OBJECTIVE
  Presence of high-risk factor in cervical cancer is known to be associated with decreased survival outcomes. However, the significance of multiple high-risk factors in early-stage cervical cancer related to survival outcomes, recurrence patterns, and treatment implications is not well elucidated.
  
  
  METHODS
  A retrospective study was conducted for surgically treated cervical cancer patients (stage IA2-IIB, n=540). Surgical-pathological risk factors were examined and tumors expressing ≥1 high-risk factors (nodal metastasis, parametrial involvement, or positive surgical margin) were eligible for analysis (n=177, 32.8%). Survival analysis was performed based on the number of high-risk factors and the type of adjuvant therapy.
  
  
  RESULTS
  There were 68 cases (38.4%) expressed multiple high-risk factors (2 high-risk factors: n=58, 32.8%; 3 high-risk factors: n=10, 5.6%). Multiple high-risk factors remained an independent prognosticator for decreased survival outcomes after controlling for age, histology, stage, and treatment type (disease-free survival: hazard ratio [HR], 2.34; p=0.002; overall survival: HR, 2.32; p=0.007). Postoperatively, 101 cases (57.1%) received concurrent chemoradiotherapy (CCRT) and 76 cases (42.9%) received radiotherapy (RT) alone. CCRT was beneficial in single high-risk factor cases: HRs for CCRT over RT alone for cumulative risk of locoregional and distant recurrence, 0.27 (p=0.022) and 0.27 (p=0.005), respectively. However, tumor expressing multiple high-risk factors completely offset the benefit of CCRT over RT alone for the risk of distant recurrence: HR for locoregional and distant recurrence, 0.31 (p=0.071) and 0.99 (p=0.980), respectively.
  
  
  CONCLUSIONS
  Special consideration for the significance of multiple high-risk factors merits further investigation in the management of surgically treated early-stage cervical cancer.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Los Angeles County Medical Center, University of Southern California, Los Angeles, CA, USA.; Norris Comprehensive Cancer Center, Los Angeles, CA, USA. koji.matsuo@gmail.com.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mabuchi
authors.affiliation: Department of Gynecology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Okazawa
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Mahiru
authors.initials: M
authors.lastname: Kawano
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Kuroda
authors.affiliation: Department of Gynecology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kamiura
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000328:Adult; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D006801:Humans; D007044:Hysterectomy / Q000379:methods*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000601:surgery*
keywords: Combined Modality Therapy; Neoplasm Recurrence, Local; Retrospective Studies; Risk Factors; Survival Analysis; Uterine Cervical Neoplasms