Vol.:(0123456789) Targeted Oncology https://doi.org/10.1007/s11523-019-00640-w LETTER TO THE EDITOR Authors’ Reply to Yu: “Outcomes for Metastatic Colorectal Cancer Based on Microsatellite Instability: Results from the South Australian Metastatic Colorectal Cancer Registry” Li Chia Chong 1  · Christos Karapetis 2  · Amitesh Roy 2  · Robert Padbury 3  · Timothy J. Price 1,4 © Springer Nature Switzerland AG 2019 In response to the comments by Yu [1], as noted, only 14% of patients had microsatellite instability (MSI) results avail- able or performed and this refects the defned subgroup ana- lysed here. However, we would like to clarify that this was done as part of standard care and not retrospectively. One of our aims was to highlight the low level of testing and the need for this to change as it becomes clinically relevant in metastatic colorectal cancer (mCRC). We do agree with Yu regarding the limitations of the study given the retrospective nature of a population-based registry and the small sample of patients with MSI mCRC available. As described in our paper [2], historically, MSI testing was not performed rou- tinely in South Australia for patients with mCRC and we also commented that clinical and familial history may well have led to testing introducing potential selection bias. The study by Goldstein et al. [3] as described by Yu does add useful information in regard to the poor prognostic characteristics of MSI mCRC. A low median overall sur- vival was also reported as potentially driven by the 30% of patients with the BRAF V600E mutation. Importantly, our analysis is quite diferent. Goldstein et al. [3] did not include microsatellite-stable patients; therefore, comparison of overall survival can only be made with historical controls. Furthermore, the patients are a mixture of stages with only 47% mCRC, whereas our analysis only included patients with mCRC. We agree that a subset analysis of patients with Lynch syndrome would be informative; however, the number of patients was too small (in particular the BRAF mutant group) to undertake any additional subset analysis, and fam- ily history is not recorded in our registry. Although polymerase chain reaction testing or next- generation sequencing could be performed to determine MSI status, there is a very low discordance [4] between an immunohistochemical assessment of mismatch repair genes vs. formal testing of MSI, hence this is generally accepted as one option for standard of care, as is the case in South Australia. Routine polymerase chain reaction testing/next- generation sequencing is often not feasible because of the cost and time required. Last, we agree that there is a change in the landscape of treatment for patients with MSI mCRC with signifcant sur- vival outcomes reported in later lines of therapy with single- agent or combination immunotherapy as demonstrated in the Checkmate-142 study [5]. However, we feel it is premature to recommend changes to frst-line chemotherapy in the continuum of care for patients with MSI mCRC while we await outcomes from KEYNOTE-177, the frst-line trial of chemotherapy vs. pembrolizumab [6]. Compliance with Ethical Standards Funding No external funding was used in the preparation of this letter. Conflict of interest Li Chia Chong, Christos Karapetis, Amitesh Roy, Robert Padbury, and Timothy J. Price have no conficts of interest that are directly relevant to the contents of this letter. References 1. Yu C. Comment on: “Outcomes for metastatic colorectal can- cer based on microsatellite instability: results from the South * Timothy J. Price Timothy.Price@sa.gov.au 1 Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville, SA, Australia 2 Department of Medical Oncology, Flinders Medical Centre, Flinders University, Adelaide, SA, Australia 3 Department of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia 4 Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia