Outcome of Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Mayo Clinic Experience

Zhaohui Jin, Cristobal T. Sanhueza, Benny Johnson, David M. Nagorney, David Larson, Kristin C. Mara, William C. Harmsen, Thomas Christopher Smyrk, Axel F Grothey, Joleen M Hubbard

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Deficiencies in the DNA mismatch repair system cause errors during DNA replication, which in turn give rise to microsatellite instability (MSI). The impact of MSI on survival in metastatic colorectal cancer (mCRC) is unclear. This cohort study aims to investigate the prognostic and predictive value of MSI in mCRC prior to the immune therapy era. Materials and Methods: A total of 75 MSI-high (MSI-H) mCRC patients (pts) and 75 matched (age, gender, disease sidedness, metachronous/synchronous) microsatellite-stable (MSS) mCRC pts were identified from 1,268 mCRC pts who had MSI/mismatch repair test results at Mayo Clinic Rochester between January 1992 and July 2016. A retrospective review was conducted by using data from electronic medical records. Statistical analyses utilized the Kaplan-Meier method, log-rank test, and Cox proportional hazards models. Results: The MSS group was well matched to the MSI-H group based on age, gender, location, and chronicity of metastatic disease. MSI-H mCRC pts had earlier disease recurrence (median time from initial diagnosis to metastatic disease diagnosis, MSI-H group 12.9 vs. MSS group 20.9 months, p =.034). Median overall survival (OS) was 28.1 and 37.4 months for MSI-H and MSS pts, respectively (p =.99). In total, 94.7% of MSI-H pts and 98.7% of MSS pts had fluoropyrimidine-based chemotherapy for metastatic disease, and there was no difference in OS between these two groups (32.3 vs. 37.4 months, p =.91). Forty-three MSI-H and thirty-nine MSS pts had metastasectomy and/or ablation of metastases (p =.51) with longer median OS compared with pts without metastasectomy (MSI-H: 82.0 vs. 13.9, p <.001; MSS: 69.9 vs. 19.7, p <.001). Age <65 years, BRAF wild type, and metastasectomy were associated with better OS in univariate analysis. Only metastasectomy remained statistically significant in multivariate analysis (p <.001). Conclusion: In mCRC, patients with MSI-H tumors have similar, but numerically shorter, median overall survival compared with those with MSS tumors. In both groups, metastasectomy and ablation of metastatic disease should be considered to optimize OS. Implications for Practice: This study clearly demonstrated the survival benefits that aggressive metastasectomy provides in selected microsatellite instability-high metastatic colorectal cancer patients. This could be meaningful practice-changing information that has been long awaited.

Original languageEnglish (US)
Pages (from-to)1083-1091
Number of pages9
JournalOncologist
Volume23
Issue number9
DOIs
StatePublished - Sep 1 2018

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Microsatellite Instability
DNA Mismatch Repair
Colorectal Neoplasms
Metastasectomy
Microsatellite Repeats
Survival
Electronic Health Records
Kaplan-Meier Estimate
DNA Replication
Proportional Hazards Models

Keywords

  • High microsatellite instability
  • Metastasectomy
  • Metastatic colorectal cancer
  • Microsatellite-stable

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Outcome of Mismatch Repair-Deficient Metastatic Colorectal Cancer : The Mayo Clinic Experience. / Jin, Zhaohui; Sanhueza, Cristobal T.; Johnson, Benny; Nagorney, David M.; Larson, David; Mara, Kristin C.; Harmsen, William C.; Smyrk, Thomas Christopher; Grothey, Axel F; Hubbard, Joleen M.

In: Oncologist, Vol. 23, No. 9, 01.09.2018, p. 1083-1091.

Research output: Contribution to journalArticle

Jin, Z, Sanhueza, CT, Johnson, B, Nagorney, DM, Larson, D, Mara, KC, Harmsen, WC, Smyrk, TC, Grothey, AF & Hubbard, JM 2018, 'Outcome of Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Mayo Clinic Experience', Oncologist, vol. 23, no. 9, pp. 1083-1091. https://doi.org/10.1634/theoncologist.2017-0289
Jin, Zhaohui ; Sanhueza, Cristobal T. ; Johnson, Benny ; Nagorney, David M. ; Larson, David ; Mara, Kristin C. ; Harmsen, William C. ; Smyrk, Thomas Christopher ; Grothey, Axel F ; Hubbard, Joleen M. / Outcome of Mismatch Repair-Deficient Metastatic Colorectal Cancer : The Mayo Clinic Experience. In: Oncologist. 2018 ; Vol. 23, No. 9. pp. 1083-1091.
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AU - Jin, Zhaohui

AU - Sanhueza, Cristobal T.

AU - Johnson, Benny

AU - Nagorney, David M.

AU - Larson, David

AU - Mara, Kristin C.

AU - Harmsen, William C.

AU - Smyrk, Thomas Christopher

AU - Grothey, Axel F

AU - Hubbard, Joleen M

PY - 2018/9/1

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N2 - Background: Deficiencies in the DNA mismatch repair system cause errors during DNA replication, which in turn give rise to microsatellite instability (MSI). The impact of MSI on survival in metastatic colorectal cancer (mCRC) is unclear. This cohort study aims to investigate the prognostic and predictive value of MSI in mCRC prior to the immune therapy era. Materials and Methods: A total of 75 MSI-high (MSI-H) mCRC patients (pts) and 75 matched (age, gender, disease sidedness, metachronous/synchronous) microsatellite-stable (MSS) mCRC pts were identified from 1,268 mCRC pts who had MSI/mismatch repair test results at Mayo Clinic Rochester between January 1992 and July 2016. A retrospective review was conducted by using data from electronic medical records. Statistical analyses utilized the Kaplan-Meier method, log-rank test, and Cox proportional hazards models. Results: The MSS group was well matched to the MSI-H group based on age, gender, location, and chronicity of metastatic disease. MSI-H mCRC pts had earlier disease recurrence (median time from initial diagnosis to metastatic disease diagnosis, MSI-H group 12.9 vs. MSS group 20.9 months, p =.034). Median overall survival (OS) was 28.1 and 37.4 months for MSI-H and MSS pts, respectively (p =.99). In total, 94.7% of MSI-H pts and 98.7% of MSS pts had fluoropyrimidine-based chemotherapy for metastatic disease, and there was no difference in OS between these two groups (32.3 vs. 37.4 months, p =.91). Forty-three MSI-H and thirty-nine MSS pts had metastasectomy and/or ablation of metastases (p =.51) with longer median OS compared with pts without metastasectomy (MSI-H: 82.0 vs. 13.9, p <.001; MSS: 69.9 vs. 19.7, p <.001). Age <65 years, BRAF wild type, and metastasectomy were associated with better OS in univariate analysis. Only metastasectomy remained statistically significant in multivariate analysis (p <.001). Conclusion: In mCRC, patients with MSI-H tumors have similar, but numerically shorter, median overall survival compared with those with MSS tumors. In both groups, metastasectomy and ablation of metastatic disease should be considered to optimize OS. Implications for Practice: This study clearly demonstrated the survival benefits that aggressive metastasectomy provides in selected microsatellite instability-high metastatic colorectal cancer patients. This could be meaningful practice-changing information that has been long awaited.

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