{"entity":{"id":"paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019","kind":"paper","name":"Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade","aka":[],"tldr":"Three in a hundred prostate cancers have a broken proofreading system, and in the men who did, immunotherapy worked and kept working.","summary":"In a case series, 1,551 tumours from 1,346 men with prostate cancer were prospectively analysed with a targeted sequencing assay between January 2015 and January 2018, with tumour mutation burden and MSIsensor score calculated and mutational signature analysis and mismatch repair immunohistochemistry performed in selected cases. Among the 1,033 men whose tumours were of adequate quality for MSIsensor analysis, 32, 3.1%, had microsatellite instability-high or mismatch repair-deficient prostate cancer: 23 with high MSIsensor scores and a further 9 with indeterminate scores but other evidence of deficient repair. Seven of the 32, 21.9%, had a pathogenic germline mutation in a Lynch syndrome-associated gene. Of the 6 men with more than one tumour analysed, 2 displayed an acquired microsatellite instability-high phenotype later in the disease course. Eleven men with microsatellite instability-high or mismatch repair-deficient castration-resistant disease received anti-PD-1 or anti-PD-L1 therapy: 6, 54.5%, had a PSA decline of more than half, 4 of them with radiographic responses, and 5 of the 6 responders were still on therapy at up to 89 weeks.","asOf":"2026-09-25","links":[{"label":"Abida et al., JAMA Oncol 2019: microsatellite instability in 1,033 assessable prostate tumours and response to checkpoint blockade","url":"https://doi.org/10.1001/jamaoncol.2018.5801"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30589920/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["cgp","checkpoint-inhibitor"],"targets":["msh2","msh6","mlh1","pms2","mmr","pd1"],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":["mismatch-repair-msi","pd1-checkpoint","cancer-immunity-cycle"],"terms":["msi","lynch-syndrome","tumour-agnostic","germline-vs-somatic","psa50"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2018.5801","pmid":"30589920","authors":"Abida W, Cheng ML, Armenia J, et al.","paperType":"observational","findings":["Microsatellite instability-high or mismatch repair-deficient disease in 32 of 1,033 men, 3.1%.","A pathogenic germline Lynch syndrome variant in 7 of the 32, 21.9%.","The phenotype was acquired during the disease course in 2 of 6 men with serial tumours.","PSA decline over 50% in 6 of 11 treated men, with 5 still on therapy at up to 89 weeks."],"whatItMeans":"It is the argument for sequencing every man with advanced prostate cancer rather than only the ones who look high risk: the phenotype is uncommon, it is invisible clinically, it opens the only durable immunotherapy route in this disease, and in one man in five it also identifies Lynch syndrome in the family.","caveats":["A single-centre case series with 11 treated men, so the response rate has wide uncertainty.","Not all microsatellite instability-high men responded, and the mechanisms of resistance were not defined.","Because the phenotype can be acquired, a negative result on an old sample does not settle the question."],"changedPractice":true,"participants":1033},"route":"/key-papers/paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"},{"id":"mlh1","kind":"target","name":"MLH1","route":"/targets/mlh1/"},{"id":"msh2","kind":"target","name":"MSH2","route":"/targets/msh2/"},{"id":"msh6","kind":"target","name":"MSH6","route":"/targets/msh6/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pms2","kind":"target","name":"PMS2","route":"/targets/pms2/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"pathway":[{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"cancer-immunity-cycle","kind":"pathway","name":"The cancer-immunity cycle","route":"/pathways/cancer-immunity-cycle/"}],"term":[{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"lynch-syndrome","kind":"term","name":"Lynch syndrome","route":"/terms/lynch-syndrome/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"psa50","kind":"term","name":"PSA50 / PSA90 response","route":"/terms/psa50/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}],"biomarker":[{"id":"dmmr-ihc","kind":"biomarker","name":"dMMR (mismatch repair deficiency by IHC)","route":"/biomarkers/dmmr-ihc/"},{"id":"msi-high","kind":"biomarker","name":"MSI-high (microsatellite instability by PCR or sequencing)","route":"/biomarkers/msi-high/"}]}}