97 Practicing knowledge translation: building awareness and assessing barriers and facilitators to provincial implementation of the proactive molecular risk classifier for endometrial cancer (ProMisE)

Prestley, N.; Woo, Mi Jung; Talhouk, Aline; McAlpine, Jessica N.

doi:10.1136/ijgc-2020-igcs.88

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“…Two clinical trials are in progress, 26,27 with a third trial in development 59 . Knowledge translation initiatives for clinicians have demonstrated early success, 60 and this communicates that POLE mut ECs represent a unique subgroup in which the usual pathological prognostic factors and risk stratification systems appear not to be as relevant. We are now working with patient partners to develop material that we hope will further improve dissemination and uptake.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta‐analysis

McAlpine

Chiu

Nout

et al. 2021

Cancer

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BACKGROUND Endometrial cancers (ECs) with somatic mutations in DNA polymerase epsilon (POLE) are characterized by unfavorable pathological features, which prompt adjuvant treatment. Paradoxically, women with POLE‐mutated EC have outstanding clinical outcomes, and this raises concerns of overtreatment. The authors investigated whether favorable outcomes were independent of treatment. METHODS A PubMed search for POLE and endometrial was restricted to articles published between March 1, 2012, and March 1, 2018, that provided individual patient data (IPD), adjuvant treatment, and survival. Following the Preferred Reporting Items for Systematic Review and Meta‐Analysis (PRISMA) reporting guidelines for IPD, the authors used univariate and multivariate one‐stage meta‐analyses with mixed effects Cox models (random effects for study cohorts) to infer the associations of treatment, traditional prognostic factors, and outcome, which was defined as the time from first diagnosis to any adverse event (progression/recurrence or death from EC). RESULTS Three hundred fifty‐nine women with POLE‐mutated EC were identified; 294 (82%) had pathogenic mutations. Worse outcomes were demonstrated in patients with nonpathogenic POLE mutations (hazard ratio, 3.42; 95% confidence interval, 1.47‐7.58; log‐rank P < .01). Except for stage (P < .01), traditional prognosticators were not associated with progression/recurrence or death from disease. Adverse events were rare (11 progressions/recurrences and 3 disease‐specific deaths). Salvage rates in patients who experienced recurrence were high and sustained, with 8 of 11 alive without evidence of disease (range, 5.5‐14.2 years). Adjuvant treatment was not associated with outcome. CONCLUSIONS Clinical outcomes for ECs with pathogenic POLE mutations are not associated with most traditional risk parameters, and patients do not appear to benefit from adjuvant therapy. The observed low rates of recurrence/progression and the high and sustained salvage rates raise the possibility of safely de‐escalating treatment for these patients. LAY SUMMARY Ten percent of all endometrial cancers have mutations in the DNA repair gene DNA polymerase epsilon (POLE). Women who have endometrial cancers with true POLE mutations experience almost no recurrences or deaths from their cancer even when their tumors appear to have very unfavorable characteristics. Additional therapy (radiation and chemotherapy) does not appear to improve outcomes for women with POLE‐mutated endometrial cancer, and this supports the move to less therapy and less associated toxicity. Diligent classification of endometrial cancers by molecular features provides valuable information to inform prognosis and to direct treatment/no treatment.

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Section: Discussionmentioning

confidence: 99%