Endometrial

• Age:

  • 50 - 60 years
  • peak: post menopausal
• True / false: endometrial cancer is the most common gynaecological malignancy

  • true: endometrial cancer is the most common gynaecological malignancy
• Epidemiology:

  • ethnicity: caucasian
  • fifth most common leading cancer in women
  • most common gynaecological malignancy
• Etiology:

  • high cumulative exposure to estrogen
  • low levels of progesterone
  • early menarche
  • late menopause
  • obesity
  • nulliparity
  • Lynch syndrome (HNPCC) → more aggressive treatment
• Natural history:

  • begins in endometrium
  • slow developing disease
  • abnormal vaginal bleeding
• True / False: adenocarcinoma is the most common type of endometrial cancer - also known as endometrioid cancer

  • true
• Presentation:

  • most are asymptomatic - detected by cytologic screening or speculum examination
  • unusual bleeding (after menopause or intermenstrual)
  • if locally advanced: mass or heaviness in pelvic area, urinary symptoms, unintended weight loss
• Diagnostic tests:

  • history and physical
  • menstruation, pregnancy, hormone replacement
  • pelvic + rectal exam, swollen lymph nodes
  • lab tests
  • CA - 125 tumour marker → pre dispose to invasive / extra uterine disease
  • biopsy
  • endometrial biopsy + hysteroscopy
  • dilation + curettage (endometrial biopsy too small, inconclusive results, endometrial hyperplasia)
  • imaging
  • transvaginal ultrasound → spread into myometrium (depth)
  • cystoscopy + proctoscopy → bladder and rectal mets
  • PET → mets
  • MRI → extent into uterine wall, mets, recurrence
• Prognostic Indicators:

  • histology
  • serous + clear cell = poor prognosis
  • depth of myometrial invasion
  • lymphovascular space involvement (LVSI)
  • cancer cells invade blood vessels / lymph channels
• Routes of Spread:

  • local extension → preferred
  • vagina
  • myometrium
  • cervix
  • hematogenous → less common for early stage
  • liver, lungs, bone, brain (rare)
  • lymphatic → more common: pelvic + para aortic
• Lymphatics:

  • fundus of uterus
  • superficial inguinal nodes → external iliac → common iliac → para aortic → cisterna chyli → thoracic duct
  • can also go directly to para aortic nodes
  • body of uterus
  • para cervical → internal iliac → common iliac → para aortic → cisterna chyli → thoracic duct
  • sacral nodes → common iliac → para aortic → cisterna chyli → thoracic duct
  • middle and lower body of uterus
  • obturator nodes → external iliac → common iliac → para aortic → cisterna chyli → thoracic duct
• If pelvic nodes are involved → chance of para aortic involvement is around 60%
• Pathology:

  • type I = common: 90%
  • estrogen responsive
  • younger, obese, perimenopausal
  • low grade tumours
  • most common subtype: adenocarcinoma
  • micro satellite instability + PTEN mutations
  • type II = uncommon: 10%
  • high grade (serous, clear cell histology) → deep myometrial invasion, pelvic and para aortic spread, extra uterine spread
  • older women
  • p53 mutations
• Subtypes:

  • common: adenocarcinoma
  • less common
  • clear cell
  • squamous cell
  • more aggressive → spread rapidly and widely in abdominal cavity, increased incidence of extra uterine disease
  • serous
  • clear cell
  • carcinosarcoma
• True / False: squamous cell carcinoma is the most common type of endometrial cancer

  • false: adenocarcinomas are the most common type of endometrial cancer
• Staging FIGO:

  • 1A: < 1 / 2 myometrium
  • 1B: > 1 / 2 myometrium
  • 2: cervical stroma
  • 3A: into ovary, outer uterus surface, fallopian tubes, supporting ligaments
  • 3B: into vagina and or parametrium
  • 3C1: pelvic lymph nodes
  • 3C2: para aortic lymph nodes
  • 4A: bladder and bowel mucosa
  • 4B: distant organs or non regional lymph nodes
  • peritoneum, lungs, liver, bones
• N staging:

  • N0(I+): isolated cells in regional lymph nodes < 0.2 mm
  • N1: pelvic nodes
  • mi: 0.2 mm < node < 2 mm
  • a: > 2 mm
  • N2: para aortic nodes +/- positive pelvic nodes
  • mi: 0.2 mm < node < 2 mm
  • a: > 2 mm
• M staging:

  • M1: mets to inguinal lymph nodes, intraperitoneal disease, lung, liver, bone
  • does not include: pelvic nodes, para aortic nodes, vagina, pelvic serous, adnexa
• Grade FIGO:

  • 1: 5% or less solid tumour, well differentiated
  • 2: 6 - 50% solid tumour, moderately differentiated
  • 3: > 50% solid tumour, poorly differentiated
• Lynch syndrome screening:

  • blood test
  • if positive: increased risk for colorectal cancer and endometrial cancer
  • lifetime risk of endometrial cancer (40 - 60%)
  • impacts decision making for treatment → more aggressive treatment
• Surgical staging:

  • total abdominal hysterectomy + bilateral salpingoophorectomy +/- pelvic and para aortic LND +/- omentectomy + peritoneal washing
  • peritoneal washing: salt water to wash peritoneal cavity → water removed and analyzed for cancer
  • if incompletely staged: repeat surgery for staging
• Stage 1A - grade 1, grade 2 (non LVSI) management:

  • surgery + no adjuvant treatment

  Stage 1A - grade 2 (LVSI), grade 3 (adverse risk factors), stage IB - grade 1 and 2:

  • surgery + post op vaginal brachy (60 - 70 Gy / 3 fr, HDR, 0.5 cm depth)
• Stage 1B, grade 3 management:

  • vaginal brachy +/- pelvic RT +/- chemo
  • 1 = 45 - 50 Gy / 20 - 25 fr (if with pelvic RT)
  • 2 = boost for gross disease: brachy up to 75 - 90 total, EBRT up to 60 - 65 total
• Stage 2 management:

  • if grade 1 only + radical hysterectomy, BSO, pelvic LND → observation
  • if uncertain: pelvic RT + vaginal brachy
• Stage 3A, 3B management:

  • Chemo +/- pelvic RT or vaginal brachy +/- hormone therapy

  Stage 3C: para aortic involved → larger fields

  • chemo +/- EBRT and or vaginal brachy +/- hormone therapy
• Stage 4A, 4B management:

  • chemo +/- RT +/- hormone therapy
  • more based on patient individual needs
• Brachy:

  • if EBRT (45 Gy / 20 fr) + brachy boost: 15 Gy / 3 fr → total: 90 Gy
  • if HDR boost only: 35 Gy / 5 fr
• EBRT borders: 4 field

  • AP/PA
  • sup: L4 / L5 (no para aortic) or L5 / S1 (negative lymph nodes - just include external and internal iliac nodes)
  • if para aortic involvement: L1 / L2
  • inf: inferior edge of inferior pubic ramus
  • lat: 1.5 - 2 cm lateral to true pelvis
  • Lat
  • ant: anterior to pubic symphysis
  • post: S2 / S3
  • include:
  • primary tumour, uterus, upper vagina, ovary, perimetric, pelvic lymph nodes
• Acute reactions:

  • skin:
  • erythema = 20
  • dry desquamation = 30
  • moist desquamation = 40
  • bladder:
  • cystitis = 30
  • small bowel:
  • diarrhea = 20
• Chronic reactions:

  • bladder:
  • 65 = volume loss
  • rectum:
  • 60 = proctitis
  • small bowel:
  • 40 = obstruction
• Chemo:

  • single:
  • doxorubicin
  • cisplatin
  • combination:
  • carboplatin + paclitaxel (4 - 6 cycles)
• Hormone therapy:

  • progestins = main type of hormone therapy used (mimic progesterone to balance out estrogen)
  • tamoxifen = prevents estrogen stimulation
  • LHRH = inhibits estrogen production in ovaries
  • aromatase inhibitors = stop estrogen production in adrenal glands and fatty tissues
• Uterine carcinosarcoma is more aggressive and has poorer prognosis