{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:01:06Z","timestamp":1793228466487,"version":"4.5.0"},"reference-count":27,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Deficient DNA mismatch repair (dMMR) and microsatellite instability-high (MSI-H) status, which sensitizes tumors to immune checkpoint inhibitors (ICIs), is three times more common with upper tract urothelial carcinoma (UTUC) than with bladder cancer. However, data on ICI efficacy against dMMR\/MSI-H advanced UTUC remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>We retrospectively reviewed records of 24 patients with dMMR\/MSI-H advanced UTUC treated with single-agent ICIs at a single institution (2015-2024). Descriptive statistics and the Kaplan-Meier method for survival outcomes were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Immunohistochemistry confirmed dMMR in 22 (92%) patients, with loss of MSH2 or MSH6 in 15 (68.2%) patients and loss of PMS2 or MLH1 in seven patients (31.8%). Germline mutation testing confirmed Lynch syndrome in 16 (67%) patients. ICI monotherapy was associated with a median progression-free survival (PFS) time of 65.9 months (95% CI, 31.6 months to nonevaluable [NE]). The PFS rates at 12 and 24 months were 95.2% (95% CI, 86.1% to 100.0%) and 78.8% (95% CI, 60.1% to 97.5%), respectively. At a median follow-up duration of 56.9 months (95% CI, 42.2 to 92.2 months), the median overall survival time was not reached (95% CI, 65.9 months to NE). The confirmed overall response rate was 83%, including 16 complete responses. Four (17%) patients were offered surgical consolidation with these pathologic outcomes: ypTaN0, ypT0N0, and ypT1N0 (two patients). Eight patients (33%) experienced grade \u22653 immune-related adverse events, including bullous pemphigoid (n = 3), hepatitis (n = 1), pancytopenia (n = 1), colitis (n = 1), polyendocrinopathy (n = 1), and polyarthritis with sarcoid-like reaction (n = 1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Our hypothesis-generating findings suggest that dMMR\/MSI-H may serve as a biomarker of sensitivity to single-agent ICIs in advanced UTUC. External validation in larger, ideally prospective, studies is needed to confirm the effectiveness and durability of immune checkpoint blockade in this molecular subgroup.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00772","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T19:59:13Z","timestamp":1774900753000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy of Immune Checkpoint Blockade in Advanced Upper Tract Urothelial Cancer With DNA Mismatch Repair Deficiency or Microsatellite Instability"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7960-8614","authenticated-orcid":true,"given":"Mohammad Jad","family":"Moussa","sequence":"first","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"},{"name":"Internal Medicine Residency Program, Department of Medicine, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0923-5610","authenticated-orcid":true,"given":"Alexander Y.","family":"Andreev-Drakhlin","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-0820","authenticated-orcid":true,"given":"Aradhana M.","family":"Venkatesan","sequence":"additional","affiliation":[{"name":"Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surena F.","family":"Matin","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianchun","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3041-8582","authenticated-orcid":true,"given":"Rebecca S.S.","family":"Tidwell","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9007-0621","authenticated-orcid":true,"given":"Amishi Y.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Adriazola","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2490-4453","authenticated-orcid":true,"given":"John K.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6505-8308","authenticated-orcid":true,"given":"Pavlos","family":"Msaouel","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2182-3287","authenticated-orcid":true,"given":"Charles C.","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5559-8060","authenticated-orcid":true,"given":"Nizar M.","family":"Tannir","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6328-9599","authenticated-orcid":true,"given":"Arlene O.","family":"Siefker-Radtke","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9658-2206","authenticated-orcid":true,"given":"Omar","family":"Alhalabi","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1915-4491","authenticated-orcid":true,"given":"Matthew T.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"},{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2023.07.002"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2404512"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12030519"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2024.02.010"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjonc-2024-000335"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2020.08.001"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/bju.12133"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/bju.15324"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.03.013"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30616-2"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00152-2"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613683"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.08.012"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2024.11.012"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312117"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/bco2.113"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010424"},{"key":"e_1_3_8_20_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.16_suppl.4571"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.5_suppl.684"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2024.102198"},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2025.02.023"},{"key":"e_1_3_8_24_2","article-title":"Comprehensive comparison of somatic, germline, and immune cell profiles in upper tract and bladder urothelial carcinoma","author":"Yuen K","unstructured":"Yuen K, Meagher M, Mercer J, et al: Comprehensive comparison of somatic, germline, and immune cell profiles in upper tract and bladder urothelial carcinoma. JCO Precis Oncol 10.1200\/PO-25-00289","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0720-x"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2020.100165"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)02848-4"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.16_suppl.4500"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-25-00772","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T19:59:16Z","timestamp":1774900756000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-25-00772"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1200\/PO-25-00772"],"URL":"https:\/\/doi.org\/10.1200\/po-25-00772","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-27","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2500772"}}