Radiation Oncology: A Question-Based Review

Uterine Sarcoma

Kristin Janson Redmond and Fariba Asrari

image Background

What % of uterine malignancies are sarcomas?

Sarcomas account for ~4% of uterine malignancies.

What are the 3 most common histologic subtypes of uterine sarcoma?

Most common uterine sarcomas (in order of frequency):

1.     Carcinosarcoma, also referred to as malignant mixed mullerian tumor (MMMT)

2.     Leiomyosarcoma (LMS)

3.     Endometrial stromal sarcoma (ESS)

How does uterine sarcoma typically present?

Typical presentation by histologic subtype:

1.     MMM: vaginal bleeding

2.     LMS and ESS: similar Sx and signs as uterine fibroids

What is the incidence of nodal mets?

1.     MMM: 30% (20%–38%), even in clinically early-stage Dz

2.     LMS: 8% (6.6%–9.1%), usually associated with extrauterine Dz

3.     ESS: traditionally thought to be low (A recent study of 831 pts with ESS showed a 10% incidence.)

Note: The nodal mets and response rate to cisplatinum are similar in MMM and endometrial adenocarcinoma.

How does the risk of DM compare between endometrial cancer and uterine sarcoma?

In general, uterine sarcoma has a higher rate of metastatic Dz than endometrial cancer.

What is the most common site of mets in uterine sarcoma?

In uterine sarcoma, the most common site of mets is the lung.

For which histologic subtype of uterine sarcoma is grade most important?

Grade is most important for ESS. Low-grade ESS is a hormone-sensitive low-grade malignancy with an indolent course, whereas high-grade ESS is characterized by an aggressive clinical course that cannot be differentiated from other high-grade uterine sarcomas such as LMS and MMM.

image Workup/Staging

What is the FIGO (2008) staging for uterine sarcoma?

MMM is still staged according to the FIGO system for endometrial adenocarcinoma.

LMS and ESS staging:

1.     Stage I: limited to uterus

2.     Stage IA: <5 cm

3.     Stage IB: >5 cm

4.     Stage II: extends to pelvis

5.     Stage IIA: adnexal involvement

6.     Stage IIB: extends to extrauterine pelvic tissue

7.     Stage III: invades abdominal tissues (not just protruding into abdomen)

8.     Stage IIIA: 1 abdominal site

9.     Stage IIIB: >1 abdominal site

10. Stage IIIC: mets to pelvic LNs, para-aortic (P-A) LNs, or both

11. Stage IVA: invades bladder or rectum

12. Stage IVB: DM

How should the initial workup for uterine sarcoma differ from the workup for endometrial cancer?

The initial workup for uterine sarcoma is identical to the workup for endometrial cancer, but it should include a CT chest b/c of the increased risk of pulmonary mets. There is also anecdotal evidence that PET/CT may be useful.

image Treatment/Prognosis

What is the primary Tx modality for uterine sarcoma?

Uterine sarcoma primary Tx modality: Simple hysterectomy and bilateral salpingo-oophorectomy (BSO) is the mainstay. Ovarian preservation may be considered in young pts with early-stage LMS and ESS. The role of RT, chemo, and HRT is still controversial.

What is the role of LND in the Tx of uterine sarcoma?

Pelvic lymphadenectomy, P-A lymphadenectomy, or both for uterine sarcoma is considered controversial. They usually are recommended in MMM and undifferentiated sarcoma. They usually are not recommended in LMS and ESS without extrauterine Dz.

Is there a benefit to postop pelvic RT for the management of uterine sarcomas?

The role of adj RT remains controversial. The issue has been addressed in at least 1 randomized trial and 2 important retrospective studies. In general, the data suggest an LC benefit for MMM but limited, if any, OS benefit with adj RT. The LC and OS benefits of adj RT in LMS are unclear.

EORTC 55874 (Reed NS, Eur J Cancer 2008) randomized 224 pts with stage I–II high-grade uterine sarcoma (46% LMS, 41% carcinosarcoma, 13% endometrial stromal tumor) s/p total abdominal hysterectomy/BSO, washings (75%), and optional nodal sampling (25%) to either (1) observation or (2) pelvic RT to 50.4 Gy. The results suggest that pelvic RT improves LC but not OS or PFS for MMM; however, there is no benefit for LMS.

A SEER-based study found that adj RT offered survival benefits in pts with early MMM but not in LMS. (Wright JD et al., Am J Obstet Gynecol 2008)

A retrospective series from Mayo included 208 pts with uterine LMS. Pelvic RT had no impact on DSS (p = 0.06), but it was associated with a significant improvement in LR. (Giuntoli R et al., Gyn Onc 2003)

What is the role of whole abdomen irradiation (WAI) in MMM?

GOG 150 is a randomized trial of WAI vs. 3 cycles of cisplatin/ifosfamide/mesna (CIM) as postsurgical therapy in stage I–IV carcinosarcoma of the uterus.

Results: Neither Tx was particularly effective. Vaginal recurrence increased and abdominal recurrence fell in the chemo group. Serious late adverse events increased significantly in the group receiving WAI.

(Wolfson AH et al., Gynecol Oncol 2007)

For which pts with MMM is pelvic irradiation typically indicated?

Pelvic irradiation is typically recommended for MMM with age >60 yrs, deep myometrial involvement, cervical involvement, high mitotic rate, nodal involvement, or residual Dz (micro- or macroscopic).

For which pts with LMS is pelvic irradiation typically indicated?

Although controversial, pelvic irradiation should be considered in pts with uterine LMS with micro- or macroscopic residual Dz, particularly in the context of a clinical trial.

How do the RT fields for uterine sarcoma differ from those used for endometrial carcinoma?

The RT fields are the same for uterine sarcoma and endometrial carcinoma.

Does the prognostic index developed for soft tissue sarcomas apply to uterine sarcomas?

No. The prognostic index for soft tissue sarcomas does not apply to uterine sarcomas.

What is the role for adj chemo in uterine sarcoma?

The role of adj chemo for uterine sarcoma is controversial. Doxorubicin-based regimens appear to be most effective but have not resulted in significant improvements in OS. (Sutton G, Gyn Onc 1996, 2005Edmonson JH, Gyn Onc 2002Long HJ III, Gyn Onc 2005)

image Toxicity

What are the expected acute and late toxicities associated with RT Tx for uterine sarcoma?

1.     Acute toxicities: n/v, diarrhea, mucositis, fatigue, bladder irritation

2.     Late toxicities: vaginal dryness and atrophy, pubic hair loss, vaginal stenosis and fibrosis (recommend vaginal dilators), urethral stricture, fistula formation, SBO