Treatment/Prognosis

Question 1

What is the primary Tx modality for endometrial cancer?

Answer 1

Surgery is the primary Tx modality for endometrial cancer.

Question 2

What is resected in a TAH?

Answer 2

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

Question 3

What is resected in a modified radical hysterectomy?

Answer 3

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

Question 4

What is resected in a radical hysterectomy?

Answer 4

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

Question 5

Are Recurrences easily salvagable?

Answer 5

• 12/13 patients in GOG 99 in the NAT arm were treated with salvage radiotherapy – crude observations noted 5 of these thirteen died of endometrial cancer.
• Salvage rate may not be as high as those commonly quoted.
• > 70% results are typically quoted.
• Most studies do not support this even in isolated vaginal recurrences.
• Survival typically range around 40 – 50 %.
• Poorer outcomes in non-vaginal pelvic recurrences.
• Petignat et al. Gynecol Oncol 2006; 101:445 risk of toxicity:
  
  • 22 isolated vaginal recurrences
  • 18 EBRT + HDR, 4 HDR alone
  • Median follow-up 32 month
  • 18% grade 3-4 GI toxicity
  • 50% grade 3 vaginal sequelae

Question 6

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

Answer 6

According to an MSKCC retrospective review of 1,289 pts, the rate of lymphedema at a median follow-up 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)

Question 7

What are considered negative prognostic factors for endometrial cancer?

Answer 7

Big Ones:

1. LVSI
2. Age > 60 yrs
3. Grade 3/ nonendometrioid histology
4. Deep myometrial invasion

Others:

5. Tumor size
6. Lower uterine segment involvement
7. Anemia
8. Poor Karnofsky performance status

Question 8

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

Answer 8

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, pelvic RT is considered.

Question 9

What adj therapy is indicated for completely surgically staged endometrial cancers that invade less than half of the myometrium?

Answer 9

Endometrial cancers that invade less than half of the myometrium could be observed or treated with adj vaginal cuff brachytherapy.

1. Stage 1A G1 Observe
2. 1A Grade 2-3 offer Brachytherapy
3. If the tumor is grade 3 with adverse risk factors, pelvic RT should be considered.
4. If the tumor is incompletely surgically staged and grade 1– 2, consider observation or vaginal brachytherapy +/– RT.
5. Endocervical glandular involvement favors the use of vaginal brachytherapy.

Question 10

What adj therapy is indicated for completely surgically staged endometrial cancers that invade half or more of the myometrium?

Answer 10

Endometrial cancers that invade half or more of the myometrium can be observed or treated with adj vaginal cuff brachytherapy.

1. 1B G1-2 Vaginal Brachy
2. If grade 3 or any grade with adverse prognostic factors, whole pelvic RT +/– brachytherapy should be considered.
3. If the tumor is incompletely surgically staged, consider pelvic RT + vaginal brachytherapy. For incompletely staged grade 3 tumors, consider chemo as well.
4. Endocervical glandular involvement favors the use of vaginal brachytherapy.

Question 11

What adj therapy is indicated for completely surgically staged, stage II endometrial cancer?

Answer 11

Adj pelvic RT and vaginal brachytherapy is indicated for endometrial cancers that invade the cervical stroma. If grade 3, consider chemo.

Question 12

What adj therapy is indicated for completely surgically staged, stage III endometrial cancer?

Answer 12

Adj chemo +/– RT should be given for stage III endometrial cancer. RT in addition to chemo is needed if there is gross residual Dz or unresectable Dz.

Question 13

Treatment algorithm for NCCN

Answer 13

Risk factors: age>60, LVSI, tumor>2cm, +cervical gland, ↑grade

Question 14

Key Question #1: Which patients with endometrioid endometrial cancer require no additional therapy after hysterectomy?

Answer 14

Following TAH+/- LND, no RT is reasonable:

1) no residual disease in the hysterectomy specimen despite positive biopsy (Grade: strong recommendation, low-quality evidence)
2) grade 1 or 2 cancers with either no invasion or less than50% myometrial invasion, especially when no other high-risk features are present (Grade: strong recommendation, high-quality evidence).

Patients with the following pathologic features may be reasonably treated with or without vaginal brachytherapy 1) grade 3 cancers without myometrial invasion (Grade: strong recommendation, low-quality evidence) or 2) grade 1 or 2 cancers with less than 50% myometrial invasion and higher risk features such as age greater than 60 and/or lymphovascular space invasion (Grade: strong recommendation, moderate-quality evidence).

Question 15

Key Question #2: Which patients with endometrioid endometrial cancer should receive vaginal cuff radiation?

Answer 15

Vaginal cuff brachytherapy is as effective as pelvic radiation therapy at preventing vaginal recurrence for patients

1) grade 1 or 2 cancers with ≥50% myometrial invasion
2) grade 3 tumors with < 50% myometrial invasion (Grade: strong recommendation, moderate-quality evidence).

Vaginal cuff brachytherapy is preferred to pelvic radiation in patients with these risk factors particularly in patients who have had comprehensive nodal assessment (Grade: strong recommendation, low-quality evidence).

Question 16

Key Question #3A: Which women with early stage endometrial cancer should receive postoperative external beam radiation?

Answer 16

Pelvic radiation is an effective means of decreasing pelvic recurrence for early stage patients but has not been proven to improve overall survival.

Patients with 1B 3 cancer or Stage II cervical stroma invasion may benefit from pelvic radiation to reduce the risk of pelvic recurrence (Grade: strong recommendation, high-quality evidence).

1BG1-2 may also benefit from pelvic radiation to reduce pelvic recurrence rates if other risk factors are present such as age >60 years and/or LVSI (Grade: strong recommendation, high-quality evidence).

Question 17

Key Question #3B: Which women with stage III-IVA endometrial cancer should receive postoperative external beam radiation?

Answer 17

Pelvic RT has been shown to improve survival in some settings. The best available evidence at this time suggests that a reasonable option for adjuvant treatment of patients with positive nodes, or involved uterine serosa, ovaries/fallopian tubes, vagina, bladder, or rectum includes external beam radiation therapy as well as adjuvant chemotherapy (Grade: strong recommendation, moderate-quality evidence). Chemotherapy (Grade: weak recommendation, moderate-quality evidence) or radiation therapy alone (Grade: weak recommendation, low-quality evidence) may be considered for some patients based on pathologic risk factors for pelvic recurrence

Question 18

Key Question #4: When should brachytherapy be used in addition to external beam radiation?

Answer 18

Prospective data is lacking to validate the use of vaginal brachytherapy after pelvic radiation and retrospective studies show little conclusive evidence of a benefit, albeit with small patient numbers. Use of vaginal brachytherapy in patients also undergoing pelvic external beam radiation may not generally be warranted, unless risk factors for vaginal recurrence are present (Grade: weak recommendation, low-quality evidence)

The low rate of vaginal recurrence in patients receiving pelvic radiation without brachytherapy leaves little margin for improvement with the addition of brachytherapy. In the pelvic RT arms of PORTEC-1 and 2, the rates of vaginal recurrence were 2.3% and 1.6%, respectively. 3,9 Among patients with deeply invasive grade 3 tumors, which were included in a nonrandomized cohort of patients who received 46 Gy of pelvic radiation, 2% vaginal apex recurrences were reported.22 In the JGOG study 1% of women treated with 45-50 Gy of pelvic radiation developed vaginal recurrence. 18 Several retrospective studies have compared outcomes among patients with endometrial cancer treated with pelvic radiation with and without brachytherapy. Rossi et al23 compared outcomes in patients with stage IIIC endometrial cancer treated with various approaches utilizing SEER data. Their data suggested that the addition of brachytherapy to external beam radiation was associated with superior outcomes in patients coded as having “direct extension.” No data on rate of vaginal recurrence were available and imbalances in clinical or pathologic factors that influence treatment decisions may account for these findings.

Question 19

Key Question #5: How should radiation therapy and chemotherapy be integrated in the management of endometrial cancer?

Answer 19

The best available evidence suggests that concurrent chemoradiation followed by adjuvant chemotherapy is indicated for patients with positive nodes or involved uterine serosa, ovaries/fallopian tubes, vagina, bladder, or rectum (Grade: strong recommendation, moderate-quality evidence).

Alternative sequencing strategies with external beam radiation and chemotherapy are also acceptable (Grade: weak recommendation, low-quality evidence).

Chemotherapy (moderate-quality evidence) or radiation therapy alone (low-quality evidence) may be considered for some patients based on pathologic risk factors for pelvic recurrence.