Clinicopathologic characteristics and outcomes of endometrial Cancer patients with mismatch repair deficiency in the era of universal Lynch syndrome screening

Carr, Caitlin; Son, Ji; Yao, Meng; Priyadarshini, Anju; Marquard, Jessica; Vargas, Roberto; Michener, Chad M.; AlHilli, Mariam M.

doi:10.1016/j.ygyno.2020.09.039

Cited by 9 publications

(10 citation statements)

References 34 publications

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“…Subsequent studies have identified MMR status as a potential important prognostic biomarker including our previous report from OSUCCC [11]. Our group, as well as others, has reported that patients with MMR deficiency, specifically MLH1 methylated tumors, have higher rates of recurrence [11, 21]. This remained consistent in this updated/expanded cohort.…”

Section: Discussionsupporting

confidence: 80%

“…With the increasing evidence of poorer outcomes in MMR deficient EC there are several phase III clinical trials evaluating the use of immunotherapy in the upfront/ adjuvant setting (NCT03981796, NCT03914612, NCT04214067). Previous reports have noted the excellent response rates in the recurrent setting and thus we suspect immune therapy in the frontline setting may be beneficial 21 . Our data establishes the crucial importance of sequencing treatment as 11/20 recurrent EC deaths with MMR defects did not receive therapy at the time of recurrence.…”

Section: Discussionmentioning

confidence: 74%

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Endometrial Cancer: Who Lives, Who Dies, Can We Improve Their Story?

et al. 2021

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Background. Endometrial cancer (EC) is the most common gynecologic cancer in the United States. The objective of this cohort study was characterize the clinical and pathologic features that are associated with endometrial cancerspecific death for women cared for at a single NCIdesignated comprehensive cancer center. Patients and Methods. This is a retrospective cohort from 2014-2017 including all women who had a hysterectomy for EC. Charts were reviewed for clinical and pathologic data, focusing on survival outcomes. Results. 771 EC patients underwent hysterectomy with 760 informative for outcomes. Seventy-six (10%) deaths were related to their EC; 62 women died from recurrent EC. Non-endometrioid histology and advanced stage were predictors of recurrence and EC death. Among patients with endometrioid ECs, mismatch repair status was significantly associated with EC specific survival (RR=4.8, 95% CI 2.3-10.3; p<0.0001). Most EC patients who recurred died of their disease 62/83 (74.7%). Nearly half of the patients that recurred (27/62) had no additional therapy at the time of recurrence. Overall survival was significantly longer for those women who had additional treatment at the time of recurrence; however the improvement in overall survival with therapy at recurrence was largely attributable to effects in those women who were adjuvant therapy naïve. Conclusions. While there is benefit of treatment at the time of recurrence for treatment-naïve women; only about half of patients were able to receive therapy. There is an urgent need for continued efforts for more effective EC therapy in both the front-line and recurrent setting as well as early identification of cancer diagnosis and recurrence. The Oncologist 2021;9999:• •

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 74%

Endometrial Cancer: Who Lives, Who Dies, Can We Improve Their Story?

et al. 2021

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“…Thus, the prognostic role of MMR proficiency can be distorted by this approach. It is likely that MMR proficient tumors were heterogeneous in earlier studies based on the identification of MMR deficiency alone [5][6][7][8][9][10][11], which could explain the inconsistent findings on the association of MMR status with patient outcome.…”

Section: Discussionmentioning

confidence: 99%

“…MMR deficiency is reported to predict the presence of high-risk features of the disease, including old age, advanced stage, and uterine risk factors [5][6][7][8][9][10]. However, no consistent association between MMR and poor outcome has been found, although three studies have reported an association with either poor recurrence-free survival [7,11] or progression-free survival [8] in univariable analyses. We found that MLH1 methylated carcinomas predict diminished disease-specific survival even after controlling for confounders [9].…”

Section: Introductionmentioning

confidence: 99%

“…Abbreviations: CI, confidence interval; HR, hazard ratio; MMR-D, mismatch repair deficient; NSMP, no specific molecular profile. 1 Grade 1-2 endometrioid carcinoma; 2 grade 3 endometrioid and nonendometrioid carcinoma;3 data missing for 1 patient; 4 data missing for 12 patients; 5 data missing for 16 patients;6 data missing for 4 patients;7 data missing for 3 patients;8 data missing for 8 patients.…”

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confidence: 99%

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Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Molecularly Classified Endometrial Carcinoma

Loukovaara

Pasanen

Bützow

2021

Cancers

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The aggressiveness of mismatch repair (MMR) deficient endometrial carcinomas was examined in a single institution retrospective study. Outcomes were similar for MMR proficient (n = 508) and deficient (n = 287) carcinomas, identified by immunohistochemistry. In accordance with molecular classification based on The Cancer Genome Atlas (TCGA), tumors with abnormal p53 staining or polymerase-ϵ exonuclease domain mutation were excluded from the MMR proficient subgroup, termed as “no specific molecular profile” (NSMP). Compared with NSMP (n = 218), MMR deficiency (n = 191) was associated with poor disease-specific survival (p = 0.001). MMR deficiency was associated with an increased risk of cancer-related death when controlling for confounders (hazard ratio 2.0). In the absence of established clinicopathologic risk factors, MMR deficiency was invariably associated with an increased risk of cancer-related death in univariable analyses (hazard ratios ≥ 2.0). In contrast, outcomes for MMR deficient and NSMP subgroups did not differ when risk factors were present. Lymphatic dissemination was more common (p = 0.008) and the proportion of pelvic relapses was higher (p = 0.029) in the MMR deficient subgroup. Our findings emphasize the need for improved triage to adjuvant therapy and new therapeutic approaches in MMR deficient endometrial carcinomas.

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Stage distribution and prognostic accuracy of the 2023 FIGO (the International Federation of Gynecology & Obstetrics) staging system for endometrial cancer: A retrospective cohort study

Loukovaara,

Pasanen,

Bützow

2024

Intl J Gynecology & Obste

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ObjectiveTo assess the stage distribution and stage‐related disease‐specific survival rates for endometrial cancer using the FIGO (the International Federation of Gynecology & Obstetrics) 2009 and 2023 staging systems. Further, we sought to evaluate the prognostic utility of additional covariates beyond the FIGO 2023 stage.MethodsEndometrial carcinomas were molecularly classified by the Proactive Molecular Risk Classifier for Endometrial Cancer and staged according to FIGO 2009 and 2023 criteria. Disease‐specific survival was calculated as the time from surgery to death from endometrial cancer.ResultsData from 604 patients were analyzed. Median follow‐up time was 81 months. A total of 118 stage shifts (19.5%) occurred between the FIGO 2009 and FIGO 2023 systems, with upshifts accounting for 107 (90.7%) of these changes. Within the FIGO 2023 system, molecular classification resulted in restaging of 69 patients (11.4%). Shifts that could alter adjuvant therapy decisions were identified in 23 patients (3.8%). The FIGO 2023 system effectively categorized endometrial cancers into prognostic subgroups. The FIGO 2023 stage, tumor size, positive peritoneal cytology, and mismatch repair deficiency were associated with disease‐specific survival in a multivariable analysis, whereas age and adjuvant therapy were not.ConclusionThe FIGO 2023 staging system for endometrial cancer appears highly prognostic. Prognostic assessment of the patients can be further enhanced by readily accessible covariates. A stage shift between the FIGO 2009 and 2023 systems occurs in about one‐fifth of patients. The implementation of molecular classification within the FIGO 2023 system bears implications for decisions regarding adjuvant therapy.

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Clinicopathologic characteristics and outcomes of endometrial Cancer patients with mismatch repair deficiency in the era of universal Lynch syndrome screening

Cited by 9 publications

References 34 publications

Endometrial Cancer: Who Lives, Who Dies, Can We Improve Their Story?

Endometrial Cancer: Who Lives, Who Dies, Can We Improve Their Story?

Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Molecularly Classified Endometrial Carcinoma

Stage distribution and prognostic accuracy of the 2023 FIGO (the International Federation of Gynecology & Obstetrics) staging system for endometrial cancer: A retrospective cohort study

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