ACTAUNIVERSITATIS

UPSALIENSISUPPSALA

2021

Digital Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Medicine 1756

Colon Cancer, Prognosis AfterSurgery

What Are the Risks of Recurrent Disease, and HowDo We Find Those at Risk?

ERIK OSTERMAN

ISSN 1651-6206ISBN 978-91-513-1253-8URN urn:nbn:se:uu:diva-437831

Dissertation presented at Uppsala University to be publicly examined in Rudbecksalen,Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, Saturday, 25 September 2021 at13:00 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination willbe conducted in English. Faculty examiner: Professor Ismail Gögenur (Center for SurgicalScience, Copenhagen university, Copenhagen).

AbstractOsterman, E. 2021. Colon Cancer, Prognosis After Surgery. What Are the Risks of RecurrentDisease, and How Do We Find Those at Risk? (Prognos efter kirurgi för koloncancer. Hur storär recidivrisken och hur hittar vi dem med hög risk). Digital Comprehensive Summaries ofUppsala Dissertations from the Faculty of Medicine 1756. 56 pp. Uppsala: Acta UniversitatisUpsaliensis. ISBN 978-91-513-1253-8.

Colon cancer is the fourth most common cancer worldwide with approximately 1.2 millionyearly cases. Developments in the standard of care have improved prognosis.

In Paper I the recurrence risk was investigated in a national material consisting of 14,325colon cancer patients. Three fourths of stage II patients have a risk of approximately 11%,indicating that adjuvant chemotherapy can marginally improve prognosis. In stage III, one fifthof the patients have such a low risk of recurrence that the addition of a second chemotherapeuticdrug, oxaliplatin with its risk for late toxicity, may be questioned.

In Paper II emerging risk factors were investigated in a thoroughly staged and describedmaterial of 416 colon cancer patients from one county. All emerging risk factors correlatedwith an increased recurrence risk. Adjusting for established risk factors, pN-substage andpostoperative carcinoembryonic antigen (CEA) correlated independently with recurrence.

Paper III investigated the completeness and correctness of recurrences in the SwedishColorectal Cancer registry in 2,893 patients from two counties. In patients operated more than5 years ago 2% of recurrences were not registered.

In Paper IV a nomogram for clinicians was developed using registry data to aid theinterpretation of the recurrence risk and discussion with patients about treatment choices. Itwas validated in Norwegian cancer registry data and performed better than other availablenomograms.

Future investigations of the cohort from paper II are planned with immunohistochemistry,tumour-normal tissue sequencing and biomarkers.

In summary, recurrence rates have decreased since the early 2000s and a large proportion ofpatients can probably be spared some or all adjuvant treatment. Established risk factors describea large part of the risk, but there is room for improvement. The biomarker CEA taken aftersurgery could aid in the selection of patients to receive adjuvant treatment and guide follow-up. Adding other biomarkers might further improve the prediction of recurrence risk, thoughlarger, prospective patient materials are needed.

Keywords: colon cancer, recurrence risk, prediction model, biomarkers

Erik Osterman, Department of Immunology, Genetics and Pathology, Experimental andClinical Oncology, Rudbecklaboratoriet, Uppsala University, SE-751 85 Uppsala, Sweden.

© Erik Osterman 2021

ISSN 1651-6206ISBN 978-91-513-1253-8URN urn:nbn:se:uu:diva-437831 (http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-437831)

Acta Universitatis UpsaliensisDigital Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Medicine 1756

Editor: The Dean of the Faculty of Medicine

A doctoral dissertation from the Faculty of Medicine, UppsalaUniversity, is usually a summary of a number of papers. A fewcopies of the complete dissertation are kept at major Swedishresearch libraries, while the summary alone is distributedinternationally through the series Digital ComprehensiveSummaries of Uppsala Dissertations from the Faculty ofMedicine. (Prior to January, 2005, the series was publishedunder the title “Comprehensive Summaries of UppsalaDissertations from the Faculty of Medicine”.)

Distribution: publications.uu.seurn:nbn:se:uu:diva-437831

ACTAUNIVERSITATIS

UPSALIENSISUPPSALA

2021