Main Session
Sep 28
SS 04 - GYN 1: Molecular and Precision Medicine for Gynecologic Cancers in Diverse Resource Settings

121 - Impact of MMR Status vs. Clinicopathologic Risk Factors on Locoregional Recurrence in Stage I Endometrioid Endometrial Cancer Treated with Brachytherapy Alone

02:30pm - 02:37pm PT
Room 160

Presenter(s)

Lara Hathout, MD, FRCPC Headshot
Lara Hathout, MD, FRCPC - Rutgers Cancer Institute , New Brunswick, NJ

L. Hathout1, Z. D. Horne2, Z. Sherwani1, E. C. Fields3, S. Beriwal4, E. A. Kidd5, E. W. Leung6, J. P. Chino7, N. K. Taunk8, A. L. Russo9, M. A. A. Dyer10, K. V. Albuquerque11, and S. Damast12; 1Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, NJ, 2Allegheny Health Network Cancer Institute, Department of Radiation Oncology, Pittsburgh, PA, 3Department of Radiation Oncology, Virginia Commonwealth University Health System, Massey Cancer Center, Richmond, VA, 4Allegheny Health Network, Pittsburg, PA, 5Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 6Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 7Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 8Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, 9Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 10Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, 11Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 12Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT

Purpose/Objective(s):

To examine the impact of molecular versus clinicopathologic risk factors associated with locoregional recurrence-free survival (RFS) in patients with stage I endometrioid endometrial cancer (EEC) who underwent surgical lymph node staging and adjuvant vaginal cuff brachytherapy (VBT) alone.

Materials/Methods:

A multi-institutional retrospective cohort study across 11 North American institutions included patients with stage I EEC and known mismatch repair (MMR) status. Sentinel nodal assessment and pelvic lymphadenectomy were performed in 40.5% and in 59.5% of patients, respectively followed by VBT (14-30Gy in 2-6 fractions). Tumors with MSH2, MSH6, MLH1 and/or PMS2 mutations were classified as somatic deficient MMR (sdMMR), while tumors with epigenetic silencing of the MLH1 promoter via hypermethylation were classified as MLH1ph. Lymphovascular invasion (LVSI) was classified as present or absent and was not quantified. Patients were subdivided into high-intermediate risk (HIR) and low-intermediate risk (LIR) groups according to GOG-99 criteria. Locoregional RFS was defined as time from surgery date to date of first recurrence in the pelvis or vagina or last follow-up. Kaplan-Meier analysis, log-rank tests and Cox univariate and multivariate models were used to compare outcomes. Statistical analyses were conducted using statistical software.

Results:

A total of 484 patients were included with a median age of 65 (Interquartile Range (IQR) 59-71). Risk groups were LIR (37.2%), HIR (58.1%), or unknown (4.7%). Approximately one-third were MMR deficient (n=155, 32%) and had LVSI (n=156, 32.2%). After a median follow up of 37.8 months, locoregional RFS was 95.1%. Vaginal and pelvic recurrences occurred in 9 and 12 patients, respectively.

On multivariate analysis, MMR status was the only prognostic factor associated with worse locoregional RFS (p<0.001, HR 6.1, 95% CI 2.3-15.7). Neither stage, age, grade, LVSI, nor risk group were significant. When teasing out MLH1ph and comparing it to pMMR and sdMMR, MLH1ph had significantly decreased locoregional RFS at 3 years. The cumulative incidence of locoregional recurrence was 2%, 7%, and 16% among the pMMR, sdMMR, and MLH1ph patients, respectively. There were significantly more nodal recurrences in the dMMR group compared to the pMMR group (7.8% vs 0.3%, p=0.004, respectively), but no difference in vaginal recurrences (1.8 vs 1.9%, respectively).

Conclusion:

MMR status was the single most important prognostic factor for locoregional RFS among stage I EEC patients treated with adjuvant VBT. Compared to pMMR and sdMMR, MLH1ph was associated with a higher cumulative incidence of locoregional recurrence reaching 16% at 3 years regardless of clinicopathologic risk group.