title: Effective treatment of stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy.
abstract: OBJECTIVE
  Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC.
  
  
  METHODS
  This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using 226Ra or 137Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using 192Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy.
  
  
  RESULTS
  The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94% (18 patients). The 5-year actuarial OS for Stage I UPSC patients treated with HDR vaginal apex brachytherapy and chemotherapy who underwent complete surgical staging was 100% (15 patients). The 5-year actuarial OS for the 20 Stage I UPSC patients treated with combinations of pre- and postoperative LDR brachytherapy and postop WART was 65%. None of the 6 surgically staged UPSC patients treated with LDR radiation and WART/WPRT developed recurrent disease. For patients with FIGO Stage IA, IB, and IC UPSC who underwent complete surgical staging, the 5-year actuarial DFS by depth of myometrial invasion was 100, 71, and 40%, respectively (p = 0.006). The overall salvage rate for local and distant recurrence was 0%. Complications following HDR vaginal apex brachytherapy included only Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicity in 16% of patients. However, complications from patients treated with WART/WPRT, and/or LDR brachytherapy, included RTOG grade 3 and 4 toxicity in 15% of patients.
  
  
  CONCLUSIONS
  Patients with UPSC should undergo complete surgical staging, and completely surgically staged FIGO Stage I UPSC patients can be effectively and safely treated with HDR vaginal apex brachytherapy and chemotherapy. Both OS and DFS of patients with UPSC are dependent on depth of myometrial invasion. The salvage rate for both local and distant UPSC recurrences is extremely poor. Complications from HDR vaginal apex brachytherapy were minimal.
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Turner
authors.forename: J P
authors.initials: JP
authors.lastname: Knisely
authors.forename: B M
authors.initials: BM
authors.lastname: Kacinski
authors.forename: B G
authors.initials: BG
authors.lastname: Haffty
authors.forename: A A
authors.initials: AA
authors.lastname: Gumbs
authors.forename: K B
authors.initials: KB
authors.lastname: Roberts
authors.forename: A H
authors.initials: AH
authors.lastname: Frank
authors.forename: R E
authors.initials: RE
authors.lastname: Peschel
authors.forename: T J
authors.initials: TJ
authors.lastname: Rutherford
authors.forename: B
authors.initials: B
authors.lastname: Edraki
authors.forename: E I
authors.initials: EI
authors.lastname: Kohorn
authors.forename: S K
authors.initials: SK
authors.lastname: Chambers
authors.forename: P E
authors.initials: PE
authors.lastname: Schwartz
authors.forename: L D
authors.initials: LD
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001918:Brachytherapy; D017024:Chemotherapy, Adjuvant; D018283:Cystadenocarcinoma, Papillary / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016879:Salvage Therapy; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*