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Outcomes for Metastatic Colorectal Cancer Based on Microsatellite Instability: Results from the South Australian Metastatic Colorectal Cancer Registry

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Abstract

Background

Microsatellite instability (MSI) is the molecular marker for DNA mismatch repair deficiency (dMMR) in colorectal cancer (CRC) and has been associated with better survival outcomes in early stage disease. In metastatic CRC (mCRC), outcomes for patients with MSI are less clear. There is evolving evidence that treatment pathways for MSI CRC should include programmed-death 1 (PD-1) antibodies.

Objective

An analysis was performed to explore the impact of MSI status on overall survival (OS) in mCRC.

Patients and methods

South Australian Metastatic CRC Registry data were analysed to assess patient characteristics and survival outcomes, comparing patients with MSI CRC with those whose tumours were microsatellite stable (MSS). Kaplan–Meier survival analysis was used to assess OS. Cox regression analysis was undertaken to assess the independence of MSI as a prognostic factor.

Results

Of 4359 patients registered on the database, 598 (14%) had been tested for, and 62 (10.1%) of these patients had, demonstrable MSI. There were significantly higher rates of right-sided primary (p < 0.001), poorly differentiated pathology (p = 0.002), and BRAF V600E mutation (p < 0.001) in the MSI group. The MSI group were also less likely to receive chemotherapy (p < 0.001) or to have liver surgery, but more likely to be diagnosed at an early stage. The median overall survival was 9.5 months for those with MSI CRC versus 21.3 months for MSS CRC patients (p = 0.052). Cox regression analysis indicated that MSI was not an independent predictor of OS. Independent predictors of better OS included having liver surgery for metastasis, having chemotherapy, and being initially diagnosed at an early stage.

Conclusions

Only 14% of patients with mCRC were tested for MSI, and 1 in 10 were found to be MSI high. The clinical characteristics of MSI mCRC are in keeping with those previously reported. MSI in this population-based registry was associated with a numerically lower survival which did not attain statistical significance.

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Authors and Affiliations

  1. Department of Medical Oncology, The Queen Elizabeth Hospital, TQEH Woodville Road, Woodville, South Australia, 5011, Australia

    Li Chia Chong, Amanda Rose Townsend, Joanne Young, Jennifer E. Hardingham & Timothy Jay Price

  2. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia

    Amanda Rose Townsend, Joanne Young, Jennifer E. Hardingham & Timothy Jay Price

  3. Department of Medical Oncology, Flinders Medical Centre and Flinders University, Adelaide, SA, Australia

    Amitesh Roy & Christos Karapetis

  4. Department of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia

    Cynthia Piantadosi & Robert Padbury

  5. Epidemiology, University of South Australia, Adelaide, SA, Australia

    David Roder

  6. Department of Surgery, The Queen Elizabeth Hospital, Adelaide, SA, Australia

    Guy Maddern

  7. Department of Surgery, Royal Adelaide Hospital, Adelaide, SA, Australia

    James Moore

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  1. Li Chia Chong
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  2. Amanda Rose Townsend
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  3. Joanne Young
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  6. Jennifer E. Hardingham
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  9. Robert Padbury
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  10. Guy Maddern
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  11. James Moore
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  12. Timothy Jay Price
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Corresponding author

Correspondence to Timothy Jay Price.

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Funding

No external funding was used in the preparation of this manuscript.

Conflict of Interest

Li Chia Chong, Amanda Rose Townsend, Joanne Young, Amitesh Roy, Cynthia Piantadosi, Jennifer E Hardingham, David Roder, Christos Karapetis, Robert Padbury, Guy Maddern, James Moore, and Timothy Jay Price declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Chong, L.C., Townsend, A.R., Young, J. et al. Outcomes for Metastatic Colorectal Cancer Based on Microsatellite Instability: Results from the South Australian Metastatic Colorectal Cancer Registry. Targ Oncol 14, 85–91 (2019). https://doi.org/10.1007/s11523-018-0615-9

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  • DOI: https://doi.org/10.1007/s11523-018-0615-9

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