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Radiation Oncology Factoids > Endometrial carcinoma > Flashcards

Endometrial carcinoma Flashcards

1
Q

What is the incidence of endometrial cancer in the United States?

A

Endometrial cancer is the most common gyn malignancy in the United States, with an incidence of ∼44,000 cases/yr annually. It is the 2nd most common
cause of gyn cancer deaths.

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2
Q

What are the 2 forms of endometrial cancer?

A

Forms of endometrial cancer:

  1. Type I: endometrioid, 70%–80% of cases, estrogen related
  2. Type II: nonendometrioid, typically papillary serous or clear cell, high grade, not estrogen related, aggressive clinical course
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3
Q

What are the The Cancer Genome Atlas molecular categories of endometrial cancer?

A
  1. POLE (ultramutated)
  2. Micro-satellite instability (MSI) (hypermutated)
  3. Copy-number low (endometrioid)
  4. Copy-number high (Serous-like)
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4
Q

What are the risk factors for endometrial cancer?

A

Risk factors for endometrial cancer:

  1. Exogenous unopposed estrogen
  2. Endogenous estrogen (obesity, functional ovarian tumors, late menopause, nulliparity, chronic anovulation/polycystic ovarian syndrome)
  3. Tamoxifen
  4. Advancing age (75% postmenopausal)
  5. Hereditary (HNPCC); 27%–71% lifetime risk of endometrial cancer
  6. Family Hx
  7. HTN
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5
Q

What are protective factors for endometrial cancer?

A

Protective factors for endometrial cancer include combination oral contraceptives and physical activity.

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6
Q

What is the most common clinical presentation of endometrial cancer?

A

Endometrial cancer presents with abnl vaginal bleeding in 90% cases.

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7
Q

What % of postmenopausal women with abnl vaginal bleeding have endometrial cancer?

A

Only 5%–20% of postmenopausal women with abnl vaginal bleeding have endometrial cancer

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8
Q

What are the 3 layers of the uterine wall?

A

The 3 layers of the uterine wall are the endometrium, myometrium, and serosa.

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9
Q

What is the primary lymphatic drainage of the uterus?

A

The primary lymphatic drainage of the cervix and lower uterine segment is to
the pelvic LNs (parametrial, internal and external iliacs, obturator, common iliac, presacral). The fundus has direct drainage to the para-aortic nodes. The round ligament can drain directly to the inguinal nodes

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10
Q

What % of endometrial cancer pts with positive pelvic LNs will also harbor Dz in the P-A LNs? What is the chance of P-A nodal involvement if pelvic nodes are negative?

A

33%–50% of pts with pelvic LN involvement also have involvement of the P-A nodes. Isolated P-A nodal involvement with negative pelvic LNs is detected in ∼1% of surgically staged cases, though the rate may be higher when dissection is extended above the IMA to the perirenal nodes, especially on the left where direct route of spread might occur.

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11
Q

What determines the grade of endometrial tumors?

A

The grade of endometrial tumors depends on the glandular component:
Grade I: ≤5% nonsquamous solid growth pattern
Grade II: 6%–50% nonsquamous solid growth pattern
Grade III: >50% nonsquamous solid growth pattern

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12
Q

What is the risk of LN involvement by DOI and grade per Gynecologic Oncology Group’s GOG 33?

A

According to GOG 33, the risk of LN involvement is <5% for tumors limited to the endometrium (all grades) and 5%–10% for tumors invading the inner
and middle 3rd of the myometrium (all grades). For tumors invading the outer 3rd of the myometrium, the risk is 10% for grade 1, 20% for grade 2, and 35%
for grade 3. Note: imaging of Pelvis was not obtained in these pts. (Creasman WT et al., Cancer 1987)

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13
Q

What % of pts with +LVSI had Pelvic and P-A node involvement in GOG 33?

A

In pts with +LVSI, 27% had +pelvic LNs and 19% had +P-A LNs.

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14
Q

What are the most aggressive histologies of epithelial endometrial cancer?

A

The most aggressive histologies of endometrial cancer are serous, clear cell, and squamous cell variants (i.e., Adenosquamous).

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15
Q

What % of endometrial cancers are adenocarcinomas?

A

75%–80% of endometrial cancers are adenocarcinomas.

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16
Q

According to the American College of Obstetricians and Gynecologists (ACOG), should women be screened for endometrial cancer?

A

According to the ACOG, there is no appropriate cost-effective screening test for endometrial cancer.

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17
Q

Per the NCCN (2018), what is the workup for endometrial cancer?

A

NCCN endometrial cancer workup: H&P, CBC, PAP smear, endometrial Bx, and CXR. If extrauterine Dz is suspected, consider CA125, MRI/CT/PET, cystoscopy, and sigmoidoscopy

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18
Q

What are the sensitivity and specificity of an endometrial Bx?

A

Endometrial Bx has 90%–98% sensitivity and 85% specificity.

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19
Q

When is D&C recommended?

A

D&C is recommended if endometrial Bx is nondiagnostic.

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20
Q

What is involved in the surgical staging of pts with endometrial carcinoma?

A

Surgical staging for endometrial cancer:

  1. Vertical incision/or laparoscopy
  2. Peritoneal washing/cytology (controversial)
  3. Exploration of all peritoneal surfaces with Bx of any lesions
  4. Total abdominal hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO)
  5. Uterus bivalved in operating room
  6. Omental Bx (omentectomy for uterine papillary serous carcinoma [UPSC]/clear cell carcinoma [CCC])
  7. Pelvic/P-A LN sampling vs. dissection
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21
Q

During the surgical staging procedure for endometrial cancer, what features are indications for P-A nodal sampling? Appx what % of pts have these features?

A

P-A sampling should take place in endometrial cancer pts with the following:

  1. Gross P-A Dz
  2. Positive Pelvic
  3. Gross adnexal mass or peritoneal Dz
  4. More than 1/3 myometrial invasion
  5. High-grade histology

∼25% of pts have these features, but they account for 98% of all positive P-A LNs.

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22
Q

What is the AJCC 8th edition (2017)/FIGO (2009) pathologic staging for endometrial cancer?

A

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
Note: Endocervical glandular involvement only is considered AJCC T1 and FIGO stage I.
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 of 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
*LN micro mets >0.2 mm and <2 mm are considered N1mi and N2mi respectively.

Stage M1/IVB: DMs

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23
Q

What is the primary Tx modality for endometrial cancer?

A

Sg is the primary Tx modality for endometrial cancer

24
Q

What is resected in a TAH?

A

TAH removes the uterus and a small rim of vaginal cuff.

25
Q

What is resected in a modified radical hysterectomy?

A

Modified radical hysterectomy:

  1. Removal of uterus and 1–2 cm of vaginal cuff
  2. Wide excision of parametrial and paravaginal tissues (including median one-half of cardinal and uterosacral ligaments)
  3. Ligation of uterine artery at ureter
26
Q

What is resected in a radical hysterectomy?

A

Radical hysterectomy:

  1. Resection of uterus and upper vagina
  2. Dissection of paravaginal and parametrial tissues to pelvic sidewalls
  3. Ligation of uterine artery at its origin at internal iliac artery
27
Q

Pelvic and P-A lymphadenectomy is recommended in which pts with endometrial cancer?

A

Although controversial, LNs are commonly assessed at the time of initial Sg for endometrial cancer. Pelvic lymphadenectomy may not be indicated in
women with Dz 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 Sg (TAH + BSO, peritoneal washing, palpation of P-A nodes) vs. standard Sg + pelvic lymphadenectomy. Those at intermediate or high risk for recurrence (independent of nodal status) were further randomized to rcv pelvic RT or not. There was no benefit to pelvic lymphadenectomy in terms of OS or RFS; however pts had increased morbidity. (ASTEC Study Group et al., Lancet 2009)

28
Q

What is the risk of lymphedema following Sg for uterine malignancies?

A

According to an MSKCC retrospective review of 1,289 pts, the rate of lymphedema at a median f/u of 3 yrs was 1.2%. When ≥10 LNs were removed, the rate of symptomatic lymphedema was 3.4%. (Abu-Rustum NR
et al., Gyn Oncol 2006)

29
Q

What are considered negative prognostic factors for endometrial cancer?

A

Negative prognostic indicators for endometrial cancer:

  1. LVSI
  2. Age >60 yrs
  3. Grade 3/nonendometrioid histology
  4. Deep myometrial invasion (>50% based on GOG 249)
  5. Tumor size
  6. Lower uterine segment involvement
  7. Anemia
  8. Poor KPS
30
Q

What adj therapy is indicated for completely surgically staged endometrial cancers limited to the endometrium?

A

No adj therapy is indicated for endometrial cancers limited to the endometrium, except for grade 3, where vaginal cuff brachytherapy is considered. In grade 3 tumors with adverse risk factors and incomplete
surgical staging, adj therapy should be considered.

31
Q

Which endometrioid endometrial cancers can be treated with vaginal brachytherapy (VBT) alone?

A

Surgically staged pts with true high-intermediate–risk Dz, namely stage IA tumors, grades 2–3 without LVSI; Stage IB tumors, grade 1–2 without LVSI;
and 1B tumors, grade 1–2 with LVSI. Stage 1B grade 3 tumors are controversial as they were not included in the PORTEC randomization, however, in well-staged pts, this may be an acceptable Tx option.

32
Q

Which endometrioid endometrial cancers should be managed with pelvic RT vs VBT?

A
  1. Stage IB, grade 3 or other higher-grade histology with multiple adverse prognostic factors.
  2. Incompletely surgical staging—low LN count, only 1-side sampled, etc. For incompletely staged grade 3 tumors, chemo may be considered as well.
  3. If LVSI is present without LND, strongly consider with whole pelvis (WP) RT.
33
Q

Which clinical situations should VBT be added to pelvic RT?

A

The overall benefit of adding VBT to pelvic RT is currently under question. Several retrospective series have suggested there to be small/negligible benefit. Currently accepted situations include:

  1. Adj pelvic RT and VBT is indicated for endometrial cancers that invade the cervical stroma. If grade 3, consider chemo.
  2. Tumors with the combination of deep myometrial invasion (>50%) and LVSI.
34
Q

When is chemo indicated for endometrial cancer?

A

Adj chemo should be considered for grade 3, nonendometrioid histology (serous and clear cell), and in pts with stage III–IV Dz.

35
Q

Describe the whole pelvic RT field for endometrial cancer. What total doses are typically prescribed?

A 
Borders of the WP RT field for endometrial cancer:
Superior: L4–5 or L5/S1
Inferior: bottom of obturator foramen
Lateral: 1.5–2.0 cm lat to pelvic brim
Anterior: front of pubic symphysis
Posterior: split sacrum to S3
Treat to 45–50.4 Gy.
36
Q

What is the border of an extended RT field for endometrial cancer, and when should extended fields be used?

A

The sup border of an extended RT field for endometrial cancer depends on the upper extend of the para-aortic nodes to be treated. If only pelvic LNs are involved, the upper border can be placed at the level of the renal vessels, or L2–3. In situations where the entire para-aortic LN chain is being treated (for positive P-A LNs), then the upper border should be T10–11 or T11–12.

37
Q

According to the American Brachytherapy Society (ABS), what are the Tx site and depth for vaginal cuff brachytherapy for endometrial cancer?

A

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 CCC,
UPSC, or stage IIIB, the target is the entire vaginal canal up to the urethra. Rx is typically vaginal surface or 0.5 cm beyond the vaginal mucosa. (Small
W, Brachytherapy 2012)

38
Q

What LDR and HDR dose/fractionation schemes are typically used for adj intracavitary RT alone for stage 1 endometrial cancer?

A

For adj intracavitary RT therapy alone, the LDR is 50–60 Gy over 72 hrs (0.7–0.8 Gy/hr). The HDR Rx in PORTEC-2 was 21 Gy (7 Gy × 3) at 0.5 cm
depth; alternatively 6 Gy × 5 prescribed to the surface can also be used. The proximal 1/2 or 4 cm at 2 fx per wk is commonly used for endometrioid histology. (Harkenrider M et al., Brachytherapy 2016)

39
Q

What LDR and HDR dose/fractionation schemes are commonly used for adj intracavitary RT given with WP RT for endometrial cancer?

A

When given in combination with WP RT, LDR doses of 30–40 Gy and HDR doses of 15 Gy (5 Gy × 3) prescribed to the vaginal surface is commonly
used.

40
Q

How are nonbulky vaginal cuff recurrences managed in endometrial cancer pts?

A

For nonbulky vaginal cuff recurrences in pts with no prior RT, a combination of pelvic RT and brachytherapy is typically used. Treat to 45 Gy pelvic RT and assess the response. If the residual is ≤0.5 cm, add
HDR VBT at 7 Gy × 3 to 0.5-cm depth beyond the vaginal mucosa. (Nag S et al., IJROBP 2000)

For endometrial cancer pts with vaginal cuff recurrences that are bulky (>0.5 cm thickness) or in a previously irradiated field, interstitial brachytherapy may be employed (salvage LC ranges from 50%–75%).

41
Q

When do inguinal nodes need to be included in the RT fields for endometrial cancer?

A

In cases with distal vaginal involvement, the entire vagina and inguinal nodes need to be included in EBRT fields.

42
Q

How should inoperable endometrial cancer be treated with RT?

A

Consider pelvic RT to 45 Gy → intracavitary RT boost using 1–3 tandem intrauterine applicators to 6.3 Gy × 3 prescribed to 2-cm depth (serosal surface). If pelvic RT is contraindicated, consider definitive intracavitary RT
alone (7.3 Gy × 5 prescribed to 2-cm depth). (Nag S et al., IJROBP 2000)

43
Q

Describe the design and results of PORTEC-1 (Post Operative Radiation Therapy in Endometrial Carcinoma).

A

In PORTEC-1, 714 pts grade 1 with ≥50% myometrial invasion, grade 2 with any invasion, or grade 3 <50% myometrial invasion underwent TAH/BSO with washings with no lymphadenectomy and were randomized to adj EBRT (46 Gy) vs. observation. EBRT reduced LRR from 14% to 5% at 10 yrs. 74% of LRs were in the vaginal vault. There was no difference in 10-
yr OS. Note that with central pathology review, there was a significant shift from grade 2 to grade 1. (Creutzberg CL et al., Lancet 2000; Scholten AN et
al., IJROBP 2005)

44
Q

Describe the design and results of GOG 99.

A

In GOG 99, 392 endometrial cancer pts with myometrial and/or occult cervical invasion underwent TAH/BSO, pelvic and P-A LN sampling, and peritoneal cytology and then were randomized to observation vs. WP RT (50.4 Gy). Inclusion criteria were revised during the trial to include only high-intermediate–risk pts defined as: (1) age >70 yrs with 1 risk factor (grade 2 or 3, LVI, outer one-third myometrial invasion), (2) age >50 yrs with 2 risk factors, and (3) any age with 3 risk factors. RT improved LR from 12% to 3%. The greatest benefit in LR was in high-intermediate–risk pts from 26% to 6% vs. low-intermediate–risk pts from 6% to 2%. There was no change in OS, but the study was not powered to detect this. Conclusion: Limit pelvic RT to high-intermediate–risk pts. The major flaw of this study is that grade 2 was grouped with grade 3 even though grade 2 Dz tends to behave more similarly to grade 1. (Keys HM et al., Gyn Oncol 2004)

45
Q

Describe the design and results of PORTEC-2.

A

PORTEC-2 randomized 427 pts with intermediate-high–risk endometrial cancer defined as:

  1. Age >60 yrs and inner 1/3 (IA) myometrial invasion and grade 3
  2. Age >60 yrs and outer 2/3 (IB and IC) myometrial invasion and grades 1–2
  3. Invasion of cervical glandular epithelium and grades

1–2 except grade 3 with > 1/2 myometrial invasion. All pts were s/p TAH/BSO without pelvic LND and were randomized to EBRT (46 Gy) vs. VBT alone (21 Gy in 3 fx or 30 Gy). At median f/u at 3.8 yrs, 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. (Nout RA et al., Lancet 2010)

46
Q

What is the strongest predictor for LR, DM, and OS based off the PORTEC studies?

A

Substantial LVSI is the strongest independent prognostic factor for LR, DM, and OS based off pooled analysis of PORTEC 1 and 2. Only EBRT reduced
the risk of pelvic recurrence. (Bosse T et al., Eur J Cancer 2015)

47
Q

Describe the design and results of GOG 122.

A

In GOG 122, 388 pts with endometrial tumors invading beyond the uterus (all histologies) underwent TAH/BSO and surgical staging with <2-cm residual tumor. P-A LNs were allowed, but mets to the chest or SCV nodes
were not allowed. Pts were randomized to whole abdomen irradiation (30 Gy AP/PA +15 Gy boost to pelvic +/– P-A LNs) vs. chemo (doxorubicin/cisplatin q3wks × 8 cycles). At 5 yrs, chemo had improved
stage-adjusted OS (55% vs. 42%) and PFS (38% vs. 50%). Chemo had increased grades 3–4 heme toxicity (88% vs. 14%) and increased GI, cardiac, and neurologic toxicity. (Randall ME et al., JCO 2006)

48
Q

Describe the design of GOG 249.

A

GOG 249 comparing EBRT alone vs. VBT + carbo/taxol in early stage highintermediate–risk pts. Initial reports show similar rates of RFS, PFS, and OS with higher toxicity and poorer QOL in the VB + chemo arm. (59th Annual ASTRO Meeting presentation, 2017)

49
Q

Describe the design and results of the TIME-C trial.

A

Time-C trial compared 3D vs. IMRT for postop endometrial and cervical pts evaluating GU and GI outcomes. Initial reports show improved GI and GU
toxicity with IMRT. (58th Annual ASTRO Meeting presentation, 2016)

50
Q

Describe the design and results of the Nordic Society of Gynaecological Oncology (NSGO)–EORTC trial that evaluated adj RT +/- chemo in high risk
endometrial cancer.

A 
The NSGO–EORTC trial enrolled 367 endometrial cancer pts with surgical stages I–II, positive peritoneal fluid cytology or positive pelvic LNs. Most
had ≥2 risk factors: grade 3, deep myometrial invasion, or DNA nondiploidy. Pts with serous, clear cell, or anaplastic carcinomas were eligible regardless
of risk factors. Pts were randomized to RT vs. RT + chemo (various regimens allowed). RT was pelvic EBRT (44 Gy) +/– VBT. 5-yr PFS favored the RT +
chemo arm (82% vs. 75%). (Hogberg T et al., ASCO 2007 abstract)
51
Q

Which major prospective trials for endometrial cancer are currently forthcoming?

A
  1. PORTEC-3 trial comparing pelvic RT vs. Pelvic RT + chemo in high-risk pts.
  2. PORTEC-4 trial comparing VBT and Observation after Sg in pts with endometrial cancer and high-intermediate–risk features.
  3. GOG 258 trial in stage 3 and 4 pts comparing RT + cisplatin (concurrent) f/b carbo/taxol vs. carbo/taxol alone.
52
Q

What is the RT tolerance of proximal and distal vagina?

A

The RT tolerance of the mucosa of the proximal vagina is 120 Gy and distal vagina is 98 Gy. (Hintz BL et al., IJROBP 1980)

53
Q

At what RT dose does ovarian failure occur?

A

Ovarian failure occurs after 5–10 Gy.

54
Q

At what RT dose does sterilization occur in women?

A

Sterilization in women occurs after 2–3 Gy.

55
Q

What are the expected acute and late RT toxicities associated with RT Tx for endometrial cancer?

A

Acute toxicities: diarrhea, proctitis, abdominal cramps, fatigue, bladder irritation, drop in blood counts, n/v

Late toxicities: vaginal dryness and atrophy, pubic hair loss, vaginal stenosis and fibrosis (recommend vaginal dilators), urethral stricture, fistula formation, SBO, chronic urinary and bowel frequency, and secondary
malignancy.

56
Q

What is the recommended f/u schedule post Tx per NCCN (2018)?

A

Exam q3–6 mos for 2–3 yrs, then q6–12 mos; CA125 only if initially elevated and imaging if clinically indicated.

Radiation Oncology Factoids (44 decks)

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