title: Impact of histology and surgical approach on survival among women with early-stage, high-grade uterine cancer: An NRG Oncology/Gynecologic Oncology Group ancillary analysis.
abstract: OBJECTIVE
  We sought to analyze the clinicopathologic features, recurrence patterns and survival outcomes of women with high-grade uterine cancer (UC) enrolled on The Gynecologic Oncology Group (GOG) LAP2 trial.
  
  
  METHODS
  This is a post-hoc analysis of LAP-2 patients with grade 3 endometrioid adenocarcinoma (ENDO), uterine serous (USC), clear cell (CC) and carcinosarcoma (CS). Demographics, clinicopathologic features, and recurrence patterns, were compared by histology and surgical approach. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.
  
  
  RESULTS
  Of the 2600 patients enrolled in LAP-2, 753 patients had high-grade UC: 350 had ENDO, 289 had USC, 42 had CC and 72 had CS. Compared with the ENDO cohort, those with other high-grade subtypes were older (p<0.001) and were more likely to have positive peritoneal cytology (p<0.001), positive lymph nodes (p=0.05) and higher disease stage on final pathology (p<0.001). With a median follow-up time of 60months, compared to patients with ENDO, those with USC, CCC and CS subtypes had higher recurrence rates (p<0.001), extra-pelvic recurrences (p<0.001) and poorer PFS (p<0.001) and OS (p<0.001). Those diagnosed with USC and CS experienced the worst survival outcomes (p=0.003). Patterns of recurrence and survival were not different in those staged with LSC vs LAP. On multivariable analysis, age, stage, pelvic washings and Type II histology were independently and adversely associated with survival.
  
  
  CONCLUSIONS
  Women with apparent early-stage, USC and CS histologies have poorer outcomes than women with grade 3 endometrioid adenocarcinoma. Patterns of recurrence and survival were not impacted by surgical approach.
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, United States. Electronic address: afader1@jhmi.edu.
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Fader
authors.affiliation: NRG Oncology/Gynecologic Oncology Group Statisticsl & Data Center, Roswell Park Cancer Institute, Buffalo, NY, United States. Electronic address: james.j.java@gmail.com.
authors.forename: James
authors.initials: J
authors.lastname: Java
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Chicago School of Medicine, Chicago, IL, United States. Electronic address: mtenney@babies.bsd.uchicago.edu.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Tenney
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, United States. Electronic address: RICCIS@ccf.org.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ricci
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Oklahoma, Oklahoma City, OK, United States. Electronic address: camille-gunderson@ouhsc.edu.
authors.forename: Camille C
authors.initials: CC
authors.lastname: Gunderson
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, United States. Electronic address: stemkin1@jhmi.edu.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Temkin
authors.affiliation: Women's Cancer Center of Nevada, Las Vegas, NV, United States. Electronic address: nspirtos@wccenter.com.
authors.forename: Nick
authors.initials: N
authors.lastname: Spirtos
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, United States. Electronic address: christinalkush@gmail.com.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Kushnir
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stony Brook University, Stony Brook, NY, United States. Electronic address: michael.pearl@sbumed.org.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Pearl
authors.affiliation: Division of Gynecologic Oncology, Memorial Sloan-Kettering Cancer Center, New York City, NY, United States. Electronic address: zivanovo@mskcc.org.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zivanovic
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California Medical Center at Irvine; Orange, CA, United States. Electronic address: ktewari@uci.edu.
authors.forename: Krishnansu S
authors.initials: KS
authors.lastname: Tewari
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ohio State Comprehensive Cancer Center; Columbus, OH, United States. Electronic address: omalley.46@osu.edu.
authors.forename: David
authors.initials: D
authors.lastname: O'Malley
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Wisconsin Hospital - Madison; Madison, WI, United States. Electronic address: emharten@wisc.edu.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Hartenbach
authors.affiliation: Division of Gynecologic Oncology; Walter Reed National Military Medical Center; Bethesda, MD, United States. Electronic address: chad.a.hamilton.mil@health.mil.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Hamilton
authors.affiliation: Women's Cancer Center of Nevada, Las Vegas, NV, United States. Electronic address: ngould@wccenter.com.
authors.forename: Natalie S
authors.initials: NS
authors.lastname: Gould
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Oklahoma, Oklahoma City, OK, United States. Electronic address: Robert-Mannel@ouhsc.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.affiliation: Department of Pathology; New York Hospital Queens; Flushing, NY, United States. Electronic address: whr9001@nyp.org.
authors.forename: William
authors.initials: W
authors.lastname: Rodgers
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Oklahoma, Oklahoma City, OK, United States. Electronic address: joan-walker@ouhsc.edu.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D002296:Carcinosarcoma / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007044:Hysterectomy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D010535:Laparoscopy; D007813:Laparotomy; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D015996:Survival Rate; D014594:Uterine Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*
keywords: High-grade uterine cancer; LAP-2 trial; Minimally invasive surgery; Type II uterine cancer; Uterine cancer