This case study describes a 65-year-old post-menopausal woman presenting with abnormal uterine bleeding who was diagnosed with endometrial adenocarcinoma. After surgical staging and pathology confirming Grade 3 endometrioid adenocarcinoma with myometrial invasion and lymphovascular space invasion, the patient is a candidate for vaginal brachytherapy based on her risk factors and the PORTEC-2 trial results showing vaginal brachytherapy alone is equivalent to external beam radiation for intermediate-high risk early stage endometrial cancer. Close follow up is recommended given her negative prognostic indicators.

1. Case Study: Endometrial
Cancer
Ali Bagheri M.D
Assistant Professor in Radiation Oncology
Director of Brachytherapy Services at Ahvaz Golestan Hospital
Ahvaz Jundishapur University of Medical Sciences

2. 65y old post-menopausal women with AUB
• Hx: AUB from 6m ago, Not married, Menopause age: 60y, HTN, FHx:
Negative, DHx: Atenolol
• Phys Ex: Obese, Otherwise normal
• What % of postmenopausal women with AUB have endometrial
cancer?
• Endometrial cancer presents with AUB in 90% cases but only 5%–20% of
postmenopausal women with AUB have endometrial cancer.

3. What are the risk factors for endometrial
cancer?
• Exogenous unopposed estrogen
• Endogenous estrogen (obesity, functional ovarian tumors, late
menopause, nulliparity, chronic anovulation/polycystic ovarian
syndrome)
• Tamoxifen
• Advancing age (75% post menopausal)
• Hereditary (HNPCC); 27%–71% life time risk of endometrial cancer
• Positive family Hx

4. What are protective factors for endometrial
cancer?
• Protective factors for endometrial cancer include combination oral
contraceptives and physical activity.

5. Workup?
• CBC: NL
• PAP smear: Atypical glandular cells
• Endometrial Bx: Endometroid
Adenocarcinoma
• D&C is recommended if endometrial
Bx is nondiagnostic.
• CXR: NL
• Pelvic MRI: No LAP
• To establish the origin of the tumor
(endocervical vs. endometrial) and
assess local disease extent.

6. What are the 2 forms of endometrial cancer?
• Type I: Endometrioid, 70%–80% of cases, estrogen related
• Type II: Non-endometrioid, typically papillary serous or clear cell, high
grade, not estrogen related, aggressive clinical course

7. Next step?
• Surgical staging:
• Vertical incision/or laparoscopy
• Peritoneal washing/cytology (controversial)
• Exploration of all peritoneal surfaces with Bx of any lesions
• Total abdominal hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO)
• Uterus bivalved in operating room
• Omental Bx (omentectomy for uterine papillary serous carcinoma / clear cell
carcinoma)
• Pelvic/Para-aortic LN sampling vs. dissection

8. TAH vs. Modified radical hysterectomy
vs. Radical hysterectomy
• TAH removes the uterus and a small rim of vaginal cuff.
• Modified radical hysterectomy:
• Removal of uterus and 1–2cm of vaginal cuff
• Wide excision of parametrial and paravaginal tissues (including median one-
half of cardinal and uterosacral ligaments)
• Ligation of uterine artery at ureter
• Radical hysterectomy:
• Resection of uterus and upper vagina
• Dissection of paravaginal and parametrial tissues to pelvic sidewalls
• Ligation of uterine artery at its origin at internal iliac artery

9. What are the indications for Para-aortic nodal
sampling?
• Gross Para-Aortic disease
• Positive Pelvic LAP
• Gross adnexal mass or peritoneal disease
• More than 1/3 myometrial invasion
• High-grade histology

10. Pathology
• Endometroid Adenocarcinoma
• Tumor size= 2cm
• 25% myometrial invasion
• Cervix: Normal
• Grade 3
• LVSI +
• Pelvic LN assessment: 12/12 Negative

11. What are the indications for pelvic or para-
aortic lymph node dissection?
• Pelvic lymphadenectomy may not be indicated in women with
disease clinically confined to the uterus.
• The ASTEC (A Study in the Treatment of Endometrial Carcinoma)
trial randomized 1,408 pts with endometrial cancer that was clinically
confined to the uterus to standard Sx (TAH + BSO, peritoneal washing,
palpation of P-A nodes) vs. standard Sx + pelvic lymphadenectomy.
• There was no benefit to pelvic lymphadenectomy in terms of OS or RFS;
however pts had increased morbidity.

12. What is the risk of lymphedema following Sx
for uterine malignancies?
• According to an MSKCC retrospective review of 1,289 patients, the
rate of lymphedema at a median f/u of 3y was 1.2%.
• When ≥10 LNs were removed, the rate of symptomatic lymphedema
was 3.4%.

13. Pathologic Staging
• Stage T1a/IA: limited to
endometrium or less than one-half
of myometrium including
endocervical glandular
involvement.
• Stage T1b/IB: invades half or more
of myometrium
• Stage T2/II: invades connective
tissue of cervix but does not
extend beyond uterus.
• Stage T3a/IIIA: tumor involves
serosa and/or adnexa by direct
extension or mets
• Stage T3b/IIIB: vaginal involvement
or parametrial involvement
• Stage T4/IVA: tumor invades
bladder mucosa (bullous edema is
not sufficient) and/or bowel
mucosa
Stage N0: no regional LN mets
Stage N1/IIIC1: regional LN mets to
pelvic nodes
• Stage N2/IIIC2: regional LN mets to
P-A nodes
• Stage M1/IVB: DMs
Per the AJCC 8th edition (2017) and FIGO (2009), positive cytology no longer alters stage. Endometrial intraepithelial
carcinoma is considered T1. LN micro mets >0.2 mm and <2 mm are considered N1mi or N2mi.

14. Negative prognostic indicators for endometrial
cancer
• LVSI
• Age > 60y
• Grade3/non-endometrioid histology
• Deep myometrial invasion (>50% based on GOG249)
• Tumor size
• Lower uterine segment involvement
• Anemia
• Poor KPS

15. Treatment Options?

16. Intravaginal Brachytherapy
• According to the ABS, for
endometrioid carcinoma of the
endometrium, the proximal 3–5
cm of the vagina (appx one-half)
should be treated.
• For clear cell carcinoma and
papillary serous carcinoma, the
target is the entire vaginal canal.
• Prescription is typically vaginal
surface or 0.5 cm beyond the
vaginal mucosa.

17. HDR dose/fractionation
• 21 Gy (7 Gy × 3) at 0.5 cm depth (PORTEC-2)
• Alternatively 6 Gy × 5 prescribed to the surface can also be used.
• The proximal 1/2 or 4 cm at 2 fx/week is commonly used for
endometrioid histology.

18. PORTEC-2 Trial
• Randomized 427 patients (intermediate and high–risk endometrial cancer):
• Age>60y + inner 1/3 myometrial invasion + grade 3
• Age>60y + outer 2/3 myometrial invasion + grades 1–2
• Invasion of cervical glandular epithelium + grades 1–2
• All patients treated with TAH/BSO without pelvic LND and were randomized to
EBRT (46 Gy) vs. VBT alone (21 Gy/3 fx or 30 Gy).
• At median follow up at 3.8y, VBT was similar to EBRT with respect to 5-yr
outcomes: vaginal relapse (1.8% vs. 1.6%), isolated pelvic relapse (1.5% vs.
0.5%), LRR (5.1% vs. 2.1%), or OS (85% vs. 80%).
• However, there were significantly higher rates of acute grades 1–2 GI toxicity in
the EBRT group.
• The authors concluded that VBT should be standard in intermediate-high–risk
endometrial cancer.

19. What is the RT tolerance of proximal and distal
vagina?
• The RT tolerance of the mucosa of the proximal vagina is 120 Gy and
distal vagina is 98 Gy.

20. Follow up?
• Exam q3–6m for 2–3y, then q6–12m.
• CA125 only if initially elevated.
• Imaging if clinically indicated.