Uterine and endometrial cancer are the most common gynecologic cancers. Risk factors include obesity, tamoxifen use, and certain genetic conditions. Diagnosis involves endometrial biopsy. Treatment typically involves hysterectomy with or without radiation or chemotherapy depending on risk factors like tumor grade and stage. New immunotherapies are showing promise for recurrent or advanced disease. Precision medicine approaches are helping to classify subtypes and identify targeted therapies.
1. Uterine and Endometrial
Cancer 101
Jason D. Wright, M.D.
Sol Goldman Associate Professor
Chief, Division of Gynecologic Oncology
Columbia University College of Physicians and Surgeons
4. Epidemiology
• Most common gynecologic cancer diagnosed in women
• Estimated new cases in 2015 61,880
• Estimated deaths in 2015 12,160
• Lifetime risk 1 in 37
6. Epidemiology
•Incidence is highest in Caucasian women
• Lifetime risk of 2.88% compared to 1.69% risk for
African-American women
•African American women are more likely to
have:
• Non-endometrioid, high grade tumors
• More advanced stage of disease
• Nearly 2x the mortality rate
8. Endometrial Hyperplasia
• Proliferation of glands of
irregular size and shape
• Classification:
• Simple
• Complex
• Atypical
• 30-40% risk of cancer
associated with atypical
hyperplasia
• Bleeding
9. Tamoxifen and Endometrial
Cancer
• Selective estrogen receptor modulator (SERM)
• Treatment of breast cancer
• 6.4 to 7.5 fold increased risk
• National Surgical Adjuvant Breast and Bowel Trial B-14
(NASBP)
• 15/1220 patients on Tamoxifen developed uterine CA
• 2/1424 patients on placebo developed uterine cancer
• Breast cancer relapse rate for women treated with
tamoxifen was reduced from 227.8/1000 to 123.5/1000
• No routine screening
10. Obesity and Endometrial Cancer
• Rate of obesity rising rapidly in the U.S.
• Adipose cells (fat cells) secrete estrogen that stimulates the
endometrium
• Projected increase to 42 cases per 100,000 women by the
year 2030
• 55% increase over the 2010 endometrial cancer rates.
14. Lynch Syndrome
•Hereditary nonpolyposis colon cancer (HNPCC)
syndrome
•Autosomal dominant
•Mismatch repair (MMR) genes
•MLH1, MSH2, MSH6, PMS2
•Tumors display microsatellite instability (MSI)
•9% of women <50 yo carriers
Aarnio M, Sankila R, Pukkala E, et al. Int J Cancer 1999;81:214-18.
Lu KH, Schorge JO, Rodabaugh KJ, et al. J Clin Oncol 2007;25:5158-64.
15. Lynch Syndrome
•Risk up to age 70
•Colon cancer 82%
•Endometrial cancer 60%
•Other tumors: ovary, stomach, biliary tract, ureter,
renal, CNS
•Screening Amsterdam criteria and Bethesda criteria
•Diagnosis: IHC, sequencing
16. Lynch Syndrome
• Screening
• Colonoscopy every other year beginning at age 20 and
annually after the age of 35
• Transvaginal sonogram, CA-125 and pelvic exama starting
at age 30.
• Prophylactic Hysterectomy/BSO once childbearing is
complete or after age 35
21. Laparoscopy in Endometrial Cancer
• GOG LAP 2
– Randomized trial (n=2612) patients
• Laparoscopic staging
• Laparotomy
– Outcomes
– Fewer complications (14% vs. 21%)
– Similar intraoperative complications
– Longer operative times (204 vs. 130 min)
– Shorter LOS (> 2 days 52% vs. 94%)
– Less often performed LND (8% vs. 4% not performed)
Walker JL, Piedmonte MR, Spirtos NM, et al. J Clin Oncol 2009;27(32):5331-6.
22. Laparoscopic Surgery
•Recurrence (3 year): 11.4% laparoscopy vs. 10.2%
laparotomy
Walker JL, Piedmonte MR, Spirtos NM, et al. J Clin Oncol 2012;30(7):695-700.
27. Surgery Caveats
•In young women occasionally treated with non-
surgical options (preserve fertility)
•Young women may consider ovarian conservation
•Women with significant underlying medical
problems may require alternative management
• Vaginal hysterectomy
• Radiation therapy
28. What to Do Next: Adjuvant
Therapy
•Low risk
• IA grade 1-2
• IB grade 1
•Intermediate risk
• IA grade 3
• IB grade 2, 3
• II
•High risk
• III/IV
• High risk histologies
No Treatment
Chemotherapy and radiation
? Radiation
29. Study N Inclusion Treatment Locoregional
recurrence
Overall survival
Norwegian
Radium
Hospital
540 Stage I Brachytherapy vs.
Brachytherapy/EBRT
7% vs. 2%
P<0.01
89% vs. 91%
NS
PORTEC-1 715 Stage IB (G2, 3)
Stage IC (G1, 2)
Observation vs.
EBRT
14% vs. 4%
P<0.0001
85% vs. 81%
NS
GOG-99 392 Stage IB, IC
Stage II (occult)
Observation vs.
EBRT
12% vs. 3%
P=0.007
86% vs. 92%
NS
ASTEC 905 Stage IA, IB (G3)
IC, IIA
Observation vs.
EBRT
6% vs. 3%
P=0.02
84% vs. 84%
NS
PORTEC-2 427 IC (G2, 3, >60)
IB (G3, >60)
Stage IIA
Brachytherapy vs.
Pelvic radiation
5% vs. 2%
P=0.42
86% vs. 82%
NS
Radiation for Intermediate Risk
Disease
30. PORTEC
Creutzberg CL, van Putten WLJ, Koper PC, et al. Lancet 2000;355:1404-11.
Control 14%
Radiation 4%
Recurrence Survival
Radiation versus observation
32. Adjuvant Therapy for Stage III
Endometrial Cancer
•Historically whole pelvic radiation
•2000’s importance of chemotherapy recognized
•Combination therapy
33. • N=686
• Stage IB (G3 or LVSI), II, III or
stage I-III (UPSC or CC)
• WPRT vs. WPRT and
chemotherapy (weekly
cisplatin then
carboplatin/paclitaxel x4)
• 5-year OS
• 81.4% combination vs. 76.1% RT
(P=0.03)
• HR=0.70
• Toxicity (>G3)
• 8% combination vs. 5% RT (P=0.24)
PORTEC-3
De Boer S, Powell ME, Mileshkin L, et al. Lancet Oncol 2019;20:1273-85.
34. Recurrent Endometrial Cancer
• Treatment palliative
• Progestational agents classically considered first line
• Variable response to cytotoxic agents
• Surgery rarely indicated
40. Conclusions
•Endometrial cancer has a very favorable prognosis
overall
•Surgery has improved with minimally invasive
options
•Adjuvant therapy remains controversial
•Treatment for recurrent endometrial cancer is
improving