J Toh1,2,3, P H Chapuis1,3,4, L Bokey5,4, C Chan6,7, K J Spring2,8, O F Dent1,3,4. 1. Department of Colorectal Surgery, University of Sydney, Sydney, New South Wales, Australia. 2. Medical Oncology Group, Ingham Institute of Applied Medical Research, University of Sydney, Sydney, New South Wales, Australia. 3. Discipline of Surgery, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. 4. School of Medicine, Western Sydney University, Sydney, New South Wales, Australia. 5. Departments of Colorectal Surgery and Surgery, Liverpool Hospital, University of Sydney, Sydney, New South Wales, Australia. 6. Division of Anatomical Pathology, Concord Hospital, University of Sydney, Sydney, New South Wales, Australia. 7. Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. 8. Centre for Oncology, Education and Research Translation, South West Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
Abstract
BACKGROUND: Despite an extensive literature suggesting that high microsatellite instability (MSI-H) enhances survival and protects against recurrence after colorectal cancer resection, such effects remain controversial as many studies show only a weak bivariate association or no multivariable association with outcome. This study examined the relationship between MSI status and colorectal cancer outcomes with adjustment for death from other causes as a competing risk. METHODS: A hospital database of patients following colorectal cancer resection was interrogated for clinical, operative, pathology, adjuvant therapy and follow-up information. MSI-H status was determined by immunohistochemistry for mismatch repair protein deficiency. The cumulative incidence of recurrence and colorectal cancer-specific death was evaluated by competing risks methods. RESULTS: Among 1009 patients who had a resection between August 2002 and December 2008, and were followed to at least December 2013, there were 114 (11·3 per cent) with MSI-H (72·8 per cent aged at least 70 years; 63·2 per cent women). After potentially curative resection, with adjustment for non-colorectal cancer death as a competing risk and adjustment for 22 clinical, operative and pathological variables, there was no association between MSI-H and recurrence (hazard ratio (HR) 0·81, 95 per cent c.i. 0·42 to 1·57) or colorectal cancer-specific death (HR 0·73, 0·39 to 1·35) in this patient population. For palliative resections, there was no association between MSI-H and colorectal cancer-specific death (HR 0·65, 0·21 to 2·04). MSI-H was associated with non-colorectal cancer death after both curative (HR 1·55, 1·04 to 2·30) and palliative (HR 3·80, 1·32 to 11·00) resections. CONCLUSION: Microsatellite instability status was not an independent prognostic variable in these patients.
BACKGROUND: Despite an extensive literature suggesting that high microsatellite instability (MSI-H) enhances survival and protects against recurrence after colorectal cancer resection, such effects remain controversial as many studies show only a weak bivariate association or no multivariable association with outcome. This study examined the relationship between MSI status and colorectal cancer outcomes with adjustment for death from other causes as a competing risk. METHODS: A hospital database of patients following colorectal cancer resection was interrogated for clinical, operative, pathology, adjuvant therapy and follow-up information. MSI-H status was determined by immunohistochemistry for mismatch repair protein deficiency. The cumulative incidence of recurrence and colorectal cancer-specific death was evaluated by competing risks methods. RESULTS: Among 1009 patients who had a resection between August 2002 and December 2008, and were followed to at least December 2013, there were 114 (11·3 per cent) with MSI-H (72·8 per cent aged at least 70 years; 63·2 per cent women). After potentially curative resection, with adjustment for non-colorectal cancer death as a competing risk and adjustment for 22 clinical, operative and pathological variables, there was no association between MSI-H and recurrence (hazard ratio (HR) 0·81, 95 per cent c.i. 0·42 to 1·57) or colorectal cancer-specific death (HR 0·73, 0·39 to 1·35) in this patient population. For palliative resections, there was no association between MSI-H and colorectal cancer-specific death (HR 0·65, 0·21 to 2·04). MSI-H was associated with non-colorectal cancer death after both curative (HR 1·55, 1·04 to 2·30) and palliative (HR 3·80, 1·32 to 11·00) resections. CONCLUSION: Microsatellite instability status was not an independent prognostic variable in these patients.
Authors: James W T Toh; Stephanie H Lim; Scott MacKenzie; Paul de Souza; Les Bokey; Pierre Chapuis; Kevin J Spring Journal: Cells Date: 2020-02-12 Impact factor: 6.600