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PostOperative Radiation for Endometrial Cancer

The standard treatment is surgery (TAH-BSO and node dissection.) If the pathology report reveals deep invasion, high grade tumor, vascular invasion, or spread beyond the uterus, then post operative radiation is generally recommended. See review article  and graphs. PostOp radiation is of most benefit to patients with deeply invading tumors or high grade cancers (see graph and graph here.) Numerous studies show that postOp radiation (external or vaginal cuff) will lower the risk of a vaginal cuff relapse and possibly increase survival (see here). PostOp vaginal cuff HDR radiation may be as effective as postOp external beam radiation (see here).

     see NCCN Guidelines  advice on postOp radiation for stage I or stage II , stage IIIa, advanced stage III/IV or the use of chemotherapy.

 
Disease Stage and Extent PostOp Therapy
Stage IA or IB, Grade 1, 2 nothing
Stage IC or IIA or Grade 3 Pelvic XRT (45-50Gy)
Stage IIB Pelvic XRT + Implant
Stage III Pelvic XRT + ParaAortic Node XRT or Abdom XRT
Stage IV Possible Pelvic and Abdominal XRT

Rose. NEJM 1996;335:

GOG 99 Study of PostOperative Radiation
The study randomized patients between surgery alone or surgery followed by radiation. The results at 2 years showed that postOp radiation patients had better relapse-free survival (96% versus 87%) but no significant improvement in survival (97% versus 95%.) They grouped patients into high risk (defined below) or low risk and found that postOp radiation improved the relapse free survival at 36 months in the high risk group (88% versus 74%) but not in the low risk group (97% versus 95%) This would suggest that only the high risk group receive postOp radiation)
 

 Risk Factors:
     - vascular space invasion
     - outer third myometrial invasion
     - grade 2 or 3
 High Risk Patient:
     - 1 risk factor and age 70y
     - 2 risk factors and age 50 - 70y
     - 3 risk factors, any age

 
High Risk from GOG would include: FIGO surgical stage IB/IC/IIA/IIB with pathologic review documenting 2 or more of the following: Grade 3 disease, Greater than one-third myometrial invasion, Cervical stromal invasion ,Vascular space invasion, Clear cell/papillary serous histology. The GOG-156 randomizes these patients between postOp pelvic radiation and chemotherapy (adriamycin + Platinol.)

Other chemotherapy drugs useful with a 30-35% response rate include: adriamycin, cisplatin, carboplatin and taxol. The new RTOG 99-05/GOG 0194 in high risk patients is comparing XRT (5040cGy) versus XRT + chemoRx (cisplatin 50mg/m2 d1, d28 then 4 more cycles of Cisplatin/Taxol) high risk requires:  grade 2,3 with myometrial invasion > 50% (IC, IIA) or grade 2,3 with stromal invasion of the cervix (IIB)

 

A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. GOG-99

Keys HM,  Gynecol Oncol. 2004 Mar;92(3):744-51

BACKGROUND: Despite their low risk for recurrence, many women with endometrial adenocarcinoma receive postoperative radiation therapy (RT). This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics (FIGO) stages IB, IC, and II (occult disease). METHODS: Four hundred forty-eight consenting patients with "intermediate risk" endometrial adenocarcinoma were randomized after surgery to either no additional therapy (NAT) or whole pelvic radiation therapy (RT). They were followed to determine toxicity, date and location of recurrence, and overall survival.

A high intermediate risk (HIR) subgroup of patients was defined as those with:
(1) moderate to poorly differentiated tumor, presence of lymphovascular invasion, and outer third myometrial invasion;
(2) age 50 or greater with any two risk factors listed above; or
(3) age of at least 70 with any risk factor listed above.

All other eligible participants were considered to be in a low intermediate risk (LIR) subgroup. RESULTS: Three hundred ninety-two women met all eligibility requirements (202 NAT, 190 RT). Median follow-up was 69 months. In the entire study population, there were 44 recurrences and 66 deaths (32 disease or treatment-related deaths), and the estimated 2-year cumulative incidence of recurrence (CIR) was 12% in the NAT arm and 3% in the RT arm (relative hazard (RH): 0.42; P=0.007). The treatment difference was particularly evident among the HIR subgroup (2-year CIR in NAT versus RT: 26% versus 6%; RH=0.42). Overall, radiation had a substantial impact on pelvic and vaginal recurrences (18 in NAT and 3 in RT). The estimated 4-year survival was 86% in the NAT arm and 92% for the RT arm, not significantly different (RH: 0.86; P=0.557). CONCLUSIONS: Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition.