title: Revisiting Milan cervical cancer study: Do the original findings hold in the era of chemotherapy?
abstract: BACKGROUND
  The primary treatment of early stage cervical carcinoma (IB-IIA) is either surgery or radiation therapy based on the pivotal Milan randomized study published twenty years ago. In the presence of high-risk features, the gold standard treatment is concurrent chemotherapy and radiation therapy (CRT) whether it is the in the postoperative or the definitive setting. Using the National Cancer Data Base (NCDB), the goal of our study is to compare the outcomes of surgery and radiation therapy in the chemotherapy era.
  
  
  METHODS
  Between 2004 and 2013, 5478 patients diagnosed with early stage cervical cancer were divided into 2 groups based on their primary treatment: non-surgical (n=1980) and surgical groups (n=3498). The distribution of patient/tumor characteristics and treatment variables with their relation to overall survival and proportional regression models were assessed to investigate the superiority of one approach over the other. Propensity score analysis adjusted for imbalance of covariates to create a well-matched-patient cohort.
  
  
  RESULTS
  At 46months median follow-up, the 5-year overall survival was similar between both groups (73·8% vs. 75.7%; p=0.619) after applying propensity score analysis. On multivariate analysis, high Charlson comorbidity score, stage IIA disease, larger tumor size, positive lymph nodes and high-grade disease were significant predictors of poor outcome while older age and treatment approach were not.
  
  
  CONCLUSIONS
  Our analysis suggests that surgery (followed by adjuvant RT or CRT) and definitive radiotherapy (with or without chemotherapy) result in equivalent survival. Prospective studies are warranted to establish this paradigm in the chemotherapy era.
authors.affiliation: Department of Radiation Oncology, Rutgers, The State University of New Jersey, Cancer Institute of New Jersey, Floor G-2 Level, One Robert Wood Johnson Place, New Brunswick,NJ 08901, United States.
authors.forename: W
authors.initials: W
authors.lastname: Ross Green
authors.affiliation: Department of Radiation Oncology, Rutgers, The State University of New Jersey, Cancer Institute of New Jersey, Floor G-2 Level, One Robert Wood Johnson Place, New Brunswick,NJ 08901, United States.
authors.forename: Lara
authors.initials: L
authors.lastname: Hathout
authors.affiliation: Department of Radiation Oncology, Rutgers, The State University of New Jersey, Cancer Institute of New Jersey, Floor G-2 Level, One Robert Wood Johnson Place, New Brunswick,NJ 08901, United States.
authors.forename: Atif J
authors.initials: AJ
authors.lastname: Khan
authors.affiliation: Department of Radiation Oncology, Henry Ford Hospital-Wayne State University, 2799 West Grand Boulevard, Detroit, MI 48202, United States.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Elshaikh
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 300 Halket St, Pittsburgh, PA 15213, United States.
authors.forename: Sushil
authors.initials: S
authors.lastname: Beriwal
authors.affiliation: Department of Radiation Oncology, Loyola University, 2160 S. First Ave, Maywood, IL 60153, United States.
authors.forename: William
authors.initials: W
authors.lastname: Small
authors.affiliation: Department of Radiation Oncology, Rutgers, The State University of New Jersey, Cancer Institute of New Jersey, Floor G-2 Level, One Robert Wood Johnson Place, New Brunswick,NJ 08901, United States; Department of Radiation Oncology, Rutgers, The State University of New Jersey, New Jersey Medical School, 150 Bergen St A1122, Newark, NJ 07103-2496, United States. Electronic address: omar.mahmoud@rutgers.edu.
authors.forename: Omar
authors.initials: O
authors.lastname: Mahmoud
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D057216:Propensity Score; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
keywords: Adjuvant chemoradiotherapy; Definitive chemoradiotherapy; Early stage cervical cancer