Pattern of recurrence of the molecular subgroups in stage I high-grade endometrial cancer.

Objective: Patterns of recurrence may impact the possibilities for salvage treatment and prognosis of patients with endometrial carcinoma (EC). We evaluated the recurrence rate and distribution pattern of the molecular EC subgroups in patients with stage I high-grade disease without adjuvant treatment and those staged by lymphadenectomy.

Method: 412 high-grade EC from the Danish Gynecological Cancer Database were molecularly profiled and classified into POLE mutant (POLEmut), mismatch repair deficient (MMRd), p53-abnormal (p53abn) or no specific molecular profile (NSMP) EC. Patients with stage II-IV (FIGO 2009) or residual disease after surgery were excluded. Crude and actuarial recurrence rates were calculated.

Results: Stage I high-grade POLEmut and MMRd EC rarely recurred (5-year overall recurrence rate 7 % (95 % CI 3-16) and 6 % (95 % CI 2-22), respectively), also when not receiving adjuvant treatment. Stage I high-grade NSMP and p53abn EC had high recurrence rates (5-year overall recurrence rate 29 % (95 % CI 16-48) and 35 % (95 % CI 27-45), respectively), mostly presenting with abdominal (NSMP EC n = 1 (3.0 %); p53abn EC n = 28 (22.4 %)) or distant recurrences (NSMP EC n = 8 (24.2 %); p53abn EC n = 21 (16.8 %)).

Conclusion: Stage I high-grade EC present more frequently with abdominal and distant recurrences rather than isolated loco-regional recurrences, independently of molecular subgroup. Stage I high-grade POLEmut EC and MMRd EC have a favorable prognosis with few recurrences, even with no adjuvant treatment. Stage I high-grade NSMP and p53abn EC have a high recurrence rate, frequently with abdominal or distant recurrences, underscoring the need to investigate more effective adjuvant systemic treatments for these patients.