Molecular Classification May be a Significant Predictor of Survival in Recurrent Endometrial Cancer

Molecular classification appears to be a significant predictor of survival for patients with recurrent endometrial cancer, with investigators noting variability in recurrence patterns by molecular subtype, according to findings from a study published in Gynecologic Oncology.

Investigators identified a median time to first recurrence of 16 months (95% CI, 12-20) overall, with patients who had mismatch repair deficient (MMRd) disease exhibiting the lowest median at 13 months (95% CI, 5-21). Additionally, several patterns of recurrence were observed between different molecular subgroups. MMRd tumors were found to have more locoregional recurrence whereas those with abnormal p53 status (p53abn) were most likely to experience abdominal recurrence (P = .042). Median survival following disease recurrence was highest among those whose tumors were MMRd at 43 months (95% CI, 11-76) vs 39 months (95% CI, 21-57) for tumors with no specific molecular profile (NSMP) and 10 months (95% CI, 7-13) in p53abn tumors (P = .001).

“Our results further highlight the different intrinsic tumor biologies among the molecular subgroups and their prognostic importance even in recurrent endometrial cancer,” investigators wrote.

The retrospective cohort study included 594 patients with molecularly classified endometrial cancer who received their primary treatment between 2004 to 2015. In total, 38 tumors were POLE mutant, 199 were MMRd, 86 were p53abn, and 271 with NSMP. In total, 58% of patients did not receive adjuvant therapy, 15% were treated with adjuvant radiotherapy, 7% received chemotherapy, 18% received chemoradiation, and a single patient received endocrine therapy.

In the population of 101 patients with recurrent disease, the median age of recurrence was 71 years, and the mean body mass index was 30 kg/m2. Sixty-eight patients underwent minimally invasive surgery as the approach for primary surgery staging, and 64 patients received a lymphadenectomy; a mean number of 34 lymph nodes were removed per patient. Among those who recurred, most patients had grade 3 tumors (54%) and lymphovascular space invasion (56%). Fifty-four patients in the MMRd group, 50% of the POLE-mutant group, 44% of the NSMP group, and 27% of the p53abn group had FICO stage I disease at primary diagnosis. Most patients whose disease recurred underwent adjuvant treatment (68%).

Seventeen percent of the total patient population experienced disease recurrence during a median follow-up of 54 months, including patients with a POLE mutation (5%), MMRd (17%), p53abn (35%), and NSMP (13%; P <.001). In particular, 2 POLE-mutant tumors had hotspot mutations: c.857C > G, p.P286R and c.1376C > T, p.S459F.

The mean recurrence-free survival was 110 months (95% CI, 103-117). The best survival was observed in the POLE-mutant group (144 months; 95% CI, 130-159), followed by NSMP (113 months; 95% CI, 102-124), MMRd (107 months; 95% CI, 94-120), and p53abn (80 months; 95% CI, 64-95) groups. Moreover, several factors were significantly associated with a high risk of recurrence, including FIGO stage of I or more (HR, 2.17 to 24.17; 95% CI, 1.12-42.06), adjuvant treatment (HR, 1.82; 95% CI, 1.22-2.71), and p53 abnormality (HR, 3.04; 95% CI, 1.87-4.94).

During the studies, investigators reported 31 locoregional, 30 abdominal, and 40 distant recurrences. In particular, locoregional recurrence was observed in 46% of those in the MMRd group, 20% of the p53abn group, and 28% of the NSMP group (P = .111). Moreover, abdominal recurrences were most common in the p53abn group (43%) followed by the MMRd group (18%) and NSMP group (31%; P = .131).

A total of 87 patients were treated for recurrent disease, with most patients receiving chemotherapy and radiotherapy. During follow-up, 69 patients died, including 1 patient who with a POLE mutation, 19 with MMRd tumors, 25 whose tumors were p53abn, and 24 with NSMP. The median survival following recurrence across all subgroups was 23 months (95% CI, 6-50), with the best survival noted in the MMRd group at 43 months, followed by NSMP at 39 months, p53abn at 10 months, and POLE mutations at 6 months.

Reference

Siegenthaler F, Lindemann K, Epstein E, et al. Time to first recurrence, pattern of recurrence, and survival after recurrence in endometrial cancer according to the molecular classification. 2022;165(2):230-238. doi:10.1016/j.ygyno.2022.02.024