Stage IIIA: Adnexal or Uterine Serosal Involvement with other evidence of extrauterine disease spread and were performed without appropriate multivariate analysis and with patients who were incompletely staged. The GOG studycritically analyzed 1,180 clinical stagesI and II endometrial cancer patients in whom appropriate surgical and pathologic staging was performed (132). Considering only the 697 patients for whom peritoneal cytology status and adequate follow-up were available, 25 (29%) of 86 patients with positive cytology developed recurrence, compared with 64 (10.5%) of 611 patients with negative cytology. They noted that 17 of the 25 recurrences in the positive cytology group were outside the peritoneal cavity.
In contrast to these reports, an equal number of studies found no significant relationship between malignant peritoneal cytology and an increased incidence of disease recurrence in the absence of other risk factors such as extrauterine disease (186–189). Patients with positive peritoneal cytology as the only site of extrauterine disease (i.e., no adnexal or uterine serosal invasion) and without poor prognosticators (i.e., myometrial invasion more than50%, nonendometrioid histologic subtype, grade 3, lymphovascular space invasion, cervical invasion) have a very favorable outcome with an absence of extra-abdominal recurrences (190). These patients have an associated 5-year survival of 98% to 100% even when not treated with adjuvant therapy (148,191,192). On the other hand, patients with positive cytology in addition to poor prognostic factors demonstrate a high rate (47%) of distant extra-abdominal failure and may potentially benefit from systemic chemotherapy. Positive peritoneal cytology seems to have an adverse effect on survival only if the endometrial cancer has spread to the adnexa, peritoneum, or lymph nodes, not if the disease is otherwise confined to the uterus (188,189,191). These considerations led to the omission of cytology as a factor impacting stage in the FIGO 2009 staging criteria.
The following conclusions may be reached regarding the prognostic implications of positive peritoneal cytology: 1.
Positive peritoneal cytology is associated with other known poor prognostic factors.
2.
Positive peritoneal cytology in the absence of other evidence of extrauterine disease or poor prognostic factors has no significant effect on recurrence and survival.
3.
Positive peritoneal cytology, when associated with other poor prognostic factors or extrauterine disease, increases the likelihood for distant as well as intra-abdominal disease recurrence and has a significant adverse effect on survival.
4.
Use of several different therapeutic modalities has not resulted in any proven benefit to patients with endometrial cancer and positive peritoneal cytology.
Most patients with stage IIIA disease have other poor prognostic factors that place them at high risk for recurrence. One series described treatment of all patients with serosal or adnexal invasion (or both) with whole-abdomen radiotherapy. Failures were observed outside the abdomen in 100% of patients with full thickness myometrial invasion or uterine serosal invasion, and in 20% to 25% of cases in the presence of isolated adnexal invasion (132,193). These patients may benefit from postoperative systemic chemotherapy.