High-risk endometrial cancer subgroups: candidates for target-based adjuvant therapy

To identify patients with endometrial cancer at risk for hematogenous, lymphatic, or peritoneal recurrence (or combinations of them) who might potentially benefit from target-based therapies.

During a 13-year period, 915 patients had endometrial cancer managed with hysterectomy and standard adjuvant therapy. On the basis of our previous regression analyses, depth of myometrial invasion predicted the risk for hematogenous recurrence; positive lymph nodes and cervical stromal invasion predicted lymphatic recurrence; stage IV disease or combination of nonendometrioid histology, cervical stromal invasion, positive lymph nodes, and positive peritoneal cytology was predictive of peritoneal recurrence. Median follow-up was 66 months.

Applying the above criteria to the population of 915 patients, 24% were considered at risk for hematogenous recurrence, 18% for lymphatic recurrence, and 16% for peritoneal recurrence. The respective relapse rates at 5 years were 28% for patients who were at risk for hematogenous recurrence, 31% for lymphatic recurrence, and 42% for peritoneal recurrence. This contrasted with less than a 5% recurrence rate in the corresponding subgroups not at risk for relapse (P < 0.001). Collectively, of the 915 patients, 324 (35%) were considered at risk for recurrence in one or more of the above three sites. Overall, 89% of all recurrences were identified in this at-risk group. Importantly, 46% of the patients considered at risk subsequently had recurrence in one or more of the three sites, compared with only 2% of patients not at risk for relapse (P < 0.001).

Patients at risk for relapse had a 46% probability of experiencing recurrence within 5 years despite management with standard therapy. New target-based algorithms for the 35% of endometrial cancer patients deemed at risk should be incorporated in the development of future prospective multimodality clinical trials predicated on site(s) of recurrence.