Although it is generally agreed that intracavitary radiation is necessary to achieve adequate local control, the indications for external-beam radiation therapy in the primary treatment of endometrial cancer are less well defined. Patients with cervical involvement and known or suspected extrauterine pelvic spread undoubtedly would benefit from external-beam radiation therapy. Theoretically, external-beam radiation could sterilize microscopic nodal disease and possibly increase the radiation dose to deep myometrial or subserosal uterine disease, which may receive an insufficient dose from intracavitary radiation alone. A correlation between tumor grade and recurrence was noted in several reports. One found that the 5-year progression-free survival rate for medically inoperable patients with clinical stage I disease treated with radiotherapy alone
Patterns of Metastatic Dissemination: Implications for Postoperative and Disease-Based Adjuvant Treatment was 94% for grade 1, 92% for grade 2, and 78% for grade 3 tumors (274). Therefore, patients with grade 3 tumors and a known propensity for deep myometrial invasion and lymph node metastasis may benefit from external-beam therapy.
The decision to treat a patient who has endometrial cancer with radiation alone must involve a careful analysis of the relative risks and benefits of surgery. Although radiation alone can produce excellent survival and local control, it should be considered for definitive treatment only if the operative risk is estimated to exceed the 10% to 15% risk for uterine recurrence that is expected with radiation treatment alone.
Endometrial cancer is commonly diagnosed early in its natural history with approximately 80% of patients presenting with stage I disease. Nevertheless, approximately oneof every threewomen who die of endometrial cancer was considered to have early locoregional disease at primary diagnosis. The majority of treatment failures and the accompanying compromised longevity probably result from the failure to recognize sites of occult extrauterine dissemination at primary diagnosis. Traditional postoperative therapy (modality-based) for high-risk endometrial cancer is external-beam radiotherapy that is frequently supplemented with vaginal brachytherapy (278). This approach improves local control but not survival in early stage disease (135,155,279).
Understanding the different pathways of metastatic dissemination of endometrial cancer and their predictive factors allows the development of an individualized model for target-based therapeutic approaches to the predicted site(s) of failure. The natural history of epithelial corpus cancer includes fourpotential routes of metastasis: (i) contiguous extension (mainly to the vagina), (ii) hematogenous dissemination, (iii) lymphatic embolization, and (iv) exfoliation with intraperitoneal spread. On the basis of regression analysis, independent pathologic risk factors predictive of the four routes of metastatic spread were identified: 1.
Contiguous extension: histologic grade 3 and lymphovascular space invasion are proven predictors of vaginal relapse in stage I endometrial cancer (280).
2.
Hematogenous: deep myometrial invasion is the strongest predictor of hematogenous recurrence (>50% for all stages and ≥66% for stage I) (176,281).
3.
Lymphatic: lymphatic failure is more likely to occur when cervical stroma involvement or positive lymph nodes are present (182).
4.
Peritoneal: predictors of peritoneal relapse are: (i) stage IV disease or (ii) stage II or III disease with twoor more of the following risk factors: cervical invasion, peritoneal cytologic results positive for endometrial cancer, positive lymph nodes, and nonendometrioid histologic findings (195).