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259 Impact of molecular profile on prognosis and relapse pattern in low and intermediate risk endometrial cancer
  1. Kristina Lindemann1,2,
  2. Wanja Kildal3,
  3. Andreas Kleppe3,4,5,
  4. Kari Anne R. Tobin6,
  5. Manohar Pradhan3,
  6. Maria X. Isaksen3,
  7. Ljjljana vlatkovic3,
  8. Håvard E. Danielsen3,7,
  9. Gunnar B. Kristensen1,3 and
  10. Hanne A. Askautrud3
  1. 1Department of Gynecological Oncology, Division of Cancer Medicine, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
  2. 2Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  3. 3Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway
  4. 4Department of Informatics, University of Oslo, Oslo, Norway
  5. 5Centre for Research-based Innovation Visual Intelligence, UiT The Arctic University of Norway, Tromsø, Norway
  6. 6Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Oslo, Norway
  7. 7Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK


Introduction/Background The role of molecular classification in patients with low/intermediate risk endometrial cancer (EC) is uncertain. Higher precision in diagnostics will inform the unsettled debate on optimal adjuvant treatment.

Methodology We retrospectively included patients referred to The Norwegian Radium Hospital, Oslo, Norway (2006–2017). Patients with low/intermediate risk EC were molecularly classified as pathogenic polymerase epsilon (POLE)-mutated, mismatch repair deficient (MMRd), p53 abnormal, or no specific molecular profile (NSMP). The main outcome was time to recurrence (TTR) and cancer-specific survival (CSS) within the molecular subgroups. We also studied patterns of recurrence in molecular groups.

Results Of 626 patients, 610 could be molecularly classified and only 24 received adjuvant treatment. Molecular subgroup distribution was: 57 patients (9%) with POLE-mutated tumors, 202 (33%) with MMRd tumors, 34 (6%) with p53 abnormal tumors, and 317 (52%) with NSMP tumors. After a median follow-up time of 8.9 years (95% confidence interval (CI): 6.2–12.6 years), there was a statistically significant difference in TTR (p<0.001) and CSS (p<0.001) by molecular groups. Patients with p53 abnormal tumors had poor prognosis with a 5-year cumulative incidence for recurrence of 32.4% (95% CI: 17.6–48.0) and cancer-specific death (CSD) of 29.4% (95% CI: 15.4–44.9). The majority of these recurrences were para-aortic/distant metastases. Patients with POLE mutations had excellent prognosis with a 5-year cumulative incidence for recurrence of 3.5% (95% CI: 0.7–10.7%) and CSD of 0%. In the NSMP group, L1CAM expression was associated with shorter CSS (HR 12.52, 95% CI: 3.53–44.42, p<0.0001) but not TTR (HR 2.7, 95% CI: 0.95–7.7, p=0.053).

Conclusion Large differences in prognosis and localization of recurrence by molecular groups demand a higher precision in diagnostics, also in patients with low and intermediate risk EC. Tailored adjuvant treatment strategies need to consider systemic treatment for patients with p53 abnormal tumors and de-escalation of treatment in patients with POLE mutated tumors.

Disclosures KL: Receipt of grants/research supports: GSK, research funding paid to

Institution; Receipt of honoraria or consultation fees: Advisory board fees: Astra Zeneca, Nycode, GSK, Eisa

GK: Stockholder: Novo Nordic

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