Myometrial Invasion Because access to the lymphatic system increases as cancer invades into the outer one-half of the myometrium, increasing depth of invasion is associated with increasing likelihood of extrauterine spread and recurrence (153,155,175). The association of depth of myometrial invasion with extrauterine disease and lymph node metastases was reported (175). Of patients without demonstrable myometrial invasion, only 1% had pelvic lymph node metastasis, compared with patients with outer one-third myometrial invasion who had 25% pelvic and 17% aortic lymph node metastases. Deep myometrial invasion (>50% for all stages; ≥66% for stage I) is the strongest predictor of hematogenous recurrence (176). Survival decreases with increasing depth of myometrial invasion. In general, patients with noninvasive or superficially invasive tumors have an 80% to 90% 5-year survival rate, whereas those with deeply invasive tumors have a 60% survival rate. The most sensitive indicator of the effect of myometrial invasion on survival is distance from the tumor–myometrial junction to the uterine serosa. Patients with tumors that are less than 5 mm from the serosal surface are at much higher risk for recurrence and death than those with tumors greater than 5 mm from the serosal surface (177,178).
Lymph–vascular space invasion (LVSI) appears to be an independent risk factor for recurrence and death from all types of endometrial cancer (178–181). The overall incidence of LVSI in early endometrial cancer is about 15%, although it increases with increasing tumor grade and depth of myometrial invasion. One study reported LVSI in 2% of grade 1 tumors and 5% of superficially invasive tumors, compared with 42% of grade 3 tumors and 70% of deeply invasive tumors (180). LVSI was demonstrated to be a strong predictor of lymphatic dissemination and lymphatic recurrence (182). Another study reported deaths in 26.7% of patients with clinical stage I disease who had LVSI, compared with 9.1% of those without LVSI (183). Likewise, an 83% 5year survival rate was reported for patients without demonstrable LVSI, compared with a 64.5% survival rate for those in whom LVSI was present (181). Using multivariate analysis, only depth of myometrial invasion, DNA ploidy, and vascular invasion–associated changes correlated significantly with survival of patients with stage I endometrial adenocarcinomas in another report (165).
The location of the tumor within the uterus is important. Involvement of the uterine isthmus, cervix, or both is associated with an increased risk for extrauterine disease, lymph node metastasis, and recurrence. Cervical stromal invasion was a strong predictor of lymphatic dissemination and lymphatic recurrence, especially for pelvic lymph nodes (182). One study reported that if the fundus of the uterus alone was involved with tumor, there was a 13% recurrence rate, whereas if the lower uterine segment or cervix was involved with occult tumor, there was a 44% recurrence rate (151). A subsequent GOG study found that tumor involvement of the isthmus or cervix without evidence of extrauterine disease was associated with a 16% recurrence rate and a relative risk of 1.6 (132). Patients with cervical involvement tended to have higher-grade, larger, and more deeply invasive tumors, undoubtedly contributing to the increased risk for recurrence.