title: Surgical treatment and histopathological assessment of advanced cervicovaginal carcinoma: A prospective study and retrospective analysis.
abstract: Standard treatment of advanced cervicovaginal cancer [international federation of gynecology and obstetrics (FIGO) stages II(B), III(A, B), IVA] is (chemo-)radiation excluding the possibility of systematic histopathological assessment of locoregional tumour spread. Laterally extended endopelvic resection (LEER) and therapeutic lymph node dissection (tLND) are novel surgical treatment options for advanced cervicovaginal cancer.
  
  
  
  The therapeutic efficacy of LEER for locally advanced primary and recurrent cervicovaginal cancer was reassessed by an update of the prospective observational trial at the University of Leipzig. LEER specimens were histopathologically analysed for patterns of locoregional tumour spread with particular consideration of morphogenetic cancer fields. Histopathological features associated with malignant ureteral obstruction were evaluated. Clinical (FIGO), pathological (pT) and ontogenetic (oT) tumour staging were compared.
  
  
  
  Eighty-eight patients with locally advanced primary and recurrent cervicovaginal cancer were treated with LEER and tLND. LEER removed all but one tumour with microscopically clear margins (R0). After median follow-up of 40 months (7-191) five-year overall survival rate was 50% (95% confidence interval [CI]: 40-62) for the whole cohort and 46% (95% CI: 34-62) for 51 patients without a curative option from current treatment. The tissue domains of cervicovaginal cancer spread mirrored the derivatives of the morphogenetic fields instrumental for the formation of the lower genital ducts. Periureteral fibrosis accompanying mesometrial invasion, tumour infiltration of the mesureter and infiltration of the ureter itself were identified as histopathological correlates of ureteral obstruction associated with an increasingly worse prognosis. Ontogenetic tumour staging based on morphogenetic cancer fields predicted outcome better than pT and FIGO staging.
  
  
  
  LEER and tLND expand the curative treatment options for advanced cervicovaginal cancer. Histopathological assessment of advanced disease supports the concept of tumour spread within morphogenetic cancer fields, provides insights into the pathomechanism of ureteral obstruction and allows precise tumour staging.
authors.affiliation: Department of Gynaecology, Women's and Children's Centre, University of Leipzig, Leipzig, Germany. Electronic address: michael.hoeckel@uniklinik-leipzig.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Höckel
authors.affiliation: Department of Gynaecology, Women's and Children's Centre, University of Leipzig, Leipzig, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wolf
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hentschel
authors.affiliation: Division of Breast, Gynaecological and Perinatal Pathology, Institute of Pathology, University of Leipzig, Leipzig, Germany.
authors.forename: Lars-Christian
authors.initials: LC
authors.lastname: Horn
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002277:Carcinoma / Q000473:pathology* / Q000601:surgery*; D005260:Female; D006801:Humans; D007422:Intestines / Q000601:surgery; D008197:Lymph Node Excision; D008875:Middle Aged; D009367:Neoplasm Staging; D010502:Perineum / Q000601:surgery; D011183:Postoperative Complications / Q000209:etiology; D011446:Prospective Studies; D019651:Plastic Surgery Procedures; D012189:Retrospective Studies; D016019:Survival Analysis; D014513:Ureter / Q000601:surgery; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000601:surgery*; D014621:Vagina / Q000601:surgery
keywords: Advanced cancer; Cancer fields; Cervical carcinoma; Histopathology; Laterally extended endopelvic resection; Ontogenetic anatomy; Surgical treatment; Tumour staging; Vaginal carcinoma