{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:55:39Z","timestamp":1781762139680,"version":"3.54.5"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Mismatch repair\u2013deficient tumors exhibit high sensitivity to immune checkpoint inhibitors. While \u201cwatch and wait\u201d organ preservation strategies following clinical complete response are increasingly established in rectal cancer, their application to non-rectal malignancies remains experimental. This report summarizes emerging evidence regarding non-operative management, specifically recent pivotal data on tumor-agnostic responses, and contextualizes these findings through a representative case of MSH6-deficient upper tract urothelial carcinoma. Recent prospective data suggest early substantial clinical complete response rates in selected non-rectal mismatch repair\u2013deficient tumors (approximately 65%), enabling initial non-operative management in selected patients. We present a case of high-grade upper tract urothelial carcinoma in a patient with Muir\u2013Torr\u00e9 syndrome treated with definitive pembrolizumab. The patient achieved a deep clinical response characterized by complete metabolic and endoscopic resolution, with no evidence of invasive carcinoma on biopsy, resulting in successful kidney preservation without surgery. Immunotherapy-based organ preservation may represent a viable strategy for highly selected patients with mismatch repair deficiency. This approach offers a potential selective alternative to immediate radical nephroureterectomy in deep responders, provided that strict and intensive surveillance protocols are feasible.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1784811","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:34:14Z","timestamp":1781760854000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Kidney preservation using immune checkpoint inhibitors in Muir\u2013Torr\u00e9 syndrome-associated upper tract urothelial carcinoma, with literature review"],"prefix":"10.3389","volume":"17","author":[{"given":"Majd","family":"Hanna","sequence":"first","affiliation":[{"name":"Cancer Center, Emek Medical Center","place":["Afula, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Bar-Sela","sequence":"additional","affiliation":[{"name":"Cancer Center, Emek Medical Center","place":["Afula, Israel"]},{"name":"Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology","place":["Haifa, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(05)70465-4","article-title":"Muir-torre syndrome","volume":"6","author":"Ponti","year":"2005","journal-title":"Lancet Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/NRC3878","article-title":"Milestones of lynch syndrome: 1895-2015","volume":"15","author":"Lynch","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/GUTJNL-2017-314057","article-title":"Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database","volume":"67","author":"M\u00f8ller","year":"2018","journal-title":"Gut"},{"key":"B4","doi-asserted-by":"crossref","DOI":"10.21037\/tau-22-882","article-title":"Oncologic outcomes following radical nephroureterectomy for upper tract urothelial carcinoma: a literature review","volume":"12","author":"Grob","year":"2023","journal-title":"Transl Androl Urol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/J.EURURO.2010.06.029","article-title":"Changes in renal function following nephroureterectomy may affect the use of perioperative chemotherapy","volume":"58","author":"Kaag","year":"2010","journal-title":"Eur Urol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1097\/01.SLA.0000141194.27992.32","article-title":"Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results","volume":"240","author":"Habr-Gama","year":"2004","journal-title":"Ann Surg"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/JCO.19.02105","article-title":"Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability\/ mismatch repair\u2013deficient cancer: Results from the phase II KEYNOTE-158 study","volume":"38","author":"Marabelle","year":"2020","journal-title":"J Clin Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA2201445","article-title":"PD-1 blockade in mismatch repair\u2013deficient, locally advanced rectal cancer","volume":"386","author":"Cercek","year":"2022","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1007\/S00262-025-04223-9","article-title":"Biology and evolving management of resectable dMMR\/MSI-H cancers: current status and future perspectives","volume":"74","author":"Tanegashima","year":"2025","journal-title":"Cancer Immunol Immunother"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA2404512","article-title":"Nonoperative management of mismatch repair\u2013deficient tumors","volume":"392","author":"Cercek","year":"2025","journal-title":"N Engl J Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.564714","article-title":"Complete pathological response to neoadjuvant pembrolizumab in a patient with chemoresistant upper urinary tract urothelial carcinoma: a case report","volume":"10","author":"Ikarashi","year":"2020","journal-title":"Front Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/S41591-020-0805-8","article-title":"Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers","volume":"26","author":"Chalabi","year":"2020","journal-title":"Nat Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1784811\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:34:16Z","timestamp":1781760856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1784811\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":13,"alternative-id":["10.3389\/fimmu.2026.1784811"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1784811","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]},"article-number":"1784811"}}