Endometrial cancer

Shaukat Khanum Memorial Cancer Hospital and Research Centre
Iqra Yasin
Endometrial Cancer
Fellow Gynecologic Oncology
SKMCH & RC, Lahore

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Outline
 Epidemiology
 Risk / Protective factors
 Classification
 Clinical presentation
 Diagnosis
 Staging
 Treatment (NCCN)
 Follow up
 Prognosis
 Recurrent disease
 Summary
 References

Epidemiology
 Most common cancer of female genital tract in
developed countries
 Sixth most common cancer in women worldwide
(4th in USA)
 Worldwide incidence: 380,000 / year (2018)
 US incidence estimated (2021): 66,570 new
cases
 US mortality estimated (2021): 12,940 deaths
Colombo N, Creutzberg C, Amant F, Bosse T, Gonzalez-Martin A, Ledermann J, Marth C, Nout R, Querleu D, Mirza MR, Sessa C; ESMO-ESGO-ESTRO
Endometrial Consensus Conference Working Group. ESMO-ESGOESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-
up†. Ann Oncol. 2016 Jan;27(1):16-41. doi: 10.1093/annonc/mdv484.

Epidemiology
 Age-adjusted incidence
Henley SJ, Ward EM, Scott S, et al. Annual report to the nation on the status of cancer. I. National cancer statistics. Cancer 2020; 126: 2225-49.

Risk factors
 Obesity
 Lifetime risk
 3 %  3-fold increase
 50 % increased risk /
5 units increase in BMI
Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L. Body-mass index and risk of 22
specific cancers: a population-based cohort study of 5・24 million UK adults. Lancet 2014; 384: 755-65.

Risk factors
 Metabolic Syndrome (DM, HTN, PCOS)
 Old age
 Median age: 63 years
 > 90 % cases after 50 years
 Reproductive factors
 Early menarche, late menopause, nulliparity
 Endogenous / Exogenous estrogens
 Tamoxifen (x 2 risk)

Risk factors
 Familial
 Lynch syndrome (HNPCC)
 3 % of endometrial CA overall
 9 % of endometrial CA < 50 years of age
 Median age: 48-53 years
 Lifetime risk: 40 - 60%
 Cowden Syndrome
 AD mutation PTEN gene
 Lifetime risk: 25 - 30 %

Risk factors

Protective factors
 OCPs (30-40 % reduced risk)
 IUD (mirena)
 Pregnancy

Classification
Type I Type II
80 - 90 % cases 10 - 20 % cases
Villoglandular,
mucinous,
adenosquamous
Serous
Clear cell
Carcinosarcoma
Early diagnosis Late diagnosis
Good prognosis
• 5-yr OS: 85 %
• 5-yr PFS: 80 %
Poor prognosis
• 5-yr OS: 45 – 55 %
• 5-yr PFS: 36 – 46 %
Inactivation of PTEN (80 %)
MMR deficiency (20 %)
Others: KRAS, CTNNB
P53,
CDK2NA inactivation,
ERBB (overexpression)
Pre-invasive condition / Hyperplasia Atrophy
Hyper estrogenism No association

Molecular classification
 Ultra-mutated (POLE subgroup)
 Hypermutated (MSI-H subgroup)
 Low copy number (MSS subgroup)
 High copy number (p53 mutation)

Molecular classification

Clinical Presentation
 Abnormal uterine bleeding (90 % cases)
 Abdominal pain / distension

Diagnosis
 Endometrial biopsy
 Office based
 Fractional D&C
 Hysteroscopic guided D&C
 Imaging
 MRI Pelvis with IV contrast (origin, local extent)
 CT chest /abdomen/pelvis with IV contrast (to rule out
metastases in high grade and incompletely staged
endometrial cancer)
 CA 125 (extent of disease, prognostic value, response)

Staging

Treatment
 Surgery: mainstay of initial management
 Surgical staging
 Visual inspection
 Cytology (peritoneal), recommended
 TH + BSO + LN assessment (standard option)
 Fertility preserving surgery (option for early-stage
diseases)

Treatment
 Ovarian preservation in premenopausal women
 Stage IA / IB
 May be safe
 Not associated with increased cancer related mortality
on 16 years follow up
 Criteria: Normal looking ovaries, early-stage disease, no
personal /family history of breast cancer and Lynch
syndrome

Treatment
 Approaches
 Minimal invasive preferred in terms of less post
operative complications and good short term QoL
 Long term outcomes (OS equal)
 LAP2 trail (n=2616, Stage I/II)
 LACE trail and (n=760, stage I)
 RCT by Janda et al
1. Walker JL, Piedmonte MR, Spirtos NM, et al.
Recurrence and survival after random assignment to
laparoscopy versus laparotomy for comprehensive
surgical staging of uterine cancer: Gynecologic
Oncology Group LAP2 study. J Clin Oncol 2012; 30:
695-700.
2. Janda M, Gebski V, Brand A, et al. Quality of life
after total laparoscopic hysterectomy versus total
abdominal hysterectomy for stage I endometrial
cancer (LACE): a randomised trial. Lancet Oncol
2010; 11: 772-80.
3. Janda M, Gebski V, Davies LC, et al. Effect of total
laparoscopic hysterectomy vs total abdominal
hysterectomy on disease-free survival among women
with stage I endometrial cancer: a randomized
clinical trial. JAMA 2017; 317: 1224-33.

Treatment
 Lymph node assessment (prognostic factor may
alter treatment decision)
 PLND +/- Para aortic LND
 Para aortic LN evaluation (high risk tumors)
 Stage IA, grade 1/2 (LN sampling not recommended)

Treatment
 SLN mapping with ultra staging
 Associated with increased LN metastases detection
 Less false negative rate
 Less morbidity vs systemic lymphadenectomy
 99mTc labelled colored dye injected in cervix
 Indocyanine green (ICG) technique

Treatment

NCCN Guidelines

Adjuvant therapy in uterine confined
disease
 Several phase III trails: improved pelvic control but
doesn’t affect OS.
 PORTEC-1 trail
 Aalders’ RCT
 ASTEC/EN.5
 GOG99 trail
 PORTEC-2 trail: (vaginal brachytherapy = EBRT)

NCCN Guidelines
Poor risk factors: Age > 60 years, > 50 % myometrium involvement, LVSI

NCCN Guidelines
Vaginal Brachytherapy: Grade I/II, < 50 % myometrial involvement, no LVSI, microscopic cervical disease

NCCN Guidelines
Response rate : 40 – 60 %
OS 13-29 months

Advanced / Recurrent Disease
 Carboplatin / Paclitaxel (current standard of care:
GOG0209 trail)
 PFS: 13 months
 OS: 37 months
 Carboplatin / Paclitaxel / Bevacizumab (MITO
END-2 trail)
 No additional benefit

 Hormonal therapy (Grade I/2 , ER/PR +)
 Progesterone (Medroxyprogesterone acetate or
Megestrol acetate or IUD)
 Anti-estrogenic (tamoxifen, letrozole)
 2nd/3rd line of therapy (poor performance status)
 27 % response rate (MA + Tamoxifen)
 32 % response rate (Everlimus + Letrozole)

 Targeted therapy
Pembrolizumab:
• KEYNOTE-158:
• Overall response 57 %
• Complete response 16 %
• Partial response 41 %
Pembrolizumab + Lenvatinib : Response rate 40 % (24 months)

Prognosis
5-year survival
Localized 95 %
Regional 69 %
Distant 17 %
Overall 81 %

Summary
 Endometrial cancer is most common female genital tract cancer
 Obesity is strongest risk factor
 Around 80 % cases present at early stage
 Diagnosis done on endometrial biopsy.
 Surgery is mainstay of treatment
 LN assessment important part of surgical staging
 Refinement of adjuvant therapy of early stage is challenging
 Biological understanding, preventive approaches and targeted therapy are crucial to
address raising trend in incidence and associated mortality.

References
 Textbook of Gynecological Oncology (European Society of Gynecological Oncology)
 Berek & Hacker ‘s Gynecologic Oncology (6th edition)
 NCCN guidelines (version 1.2022)

THANK YOU

Endometrial cancer

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