{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:29:29Z","timestamp":1789468169004,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Temporal bone squamous cell carcinoma (TBSCC) is a rare and aggressive malignancy with limited evidence regarding prognostic factors. This systematic review and meta-analysis evaluated the prognostic significance of tumor stage, cervical nodal status, and surgical margin status in patients with TBSCC. Methods: A systematic search of PubMed and Scopus was conducted from database inception to December 29, 2025, in accordance with the PRISMA 2020 statement. Studies reporting hazard ratios (HRs) for overall survival in patients with TBSCC staged according to the modified Pittsburgh classification were included. Pooled HRs were calculated using random-effects models. Results: Thirteen retrospective cohort studies including 801 patients were analyzed. Positive surgical margins were associated with the greatest increase in mortality risk (HR, 4.79, 95% CI, 2.35\u20139.75; p &lt; 0.001), followed by cervical nodal metastasis (HR, 2.81; 95% CI, 1.72\u20134.60; p &lt; 0.001) and advanced tumor stage (T3\u2013T4 vs. T1\u2013T2; HR, 2.39; 95% CI, 1.24\u20134.60; p = 0.009). Sensitivity analyses confirmed the robustness of the pooled estimates. Conclusions: Positive surgical margins, advanced tumor stage, and cervical nodal metastasis were all significantly associated with poorer survival, with positive surgical margins showing the largest pooled association with mortality among the three evaluated factors. Prospective multicenter studies are needed to validate these findings and improve prognostic stratification in this rare malignancy.<\/jats:p>","DOI":"10.3390\/jcm15187143","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:16:48Z","timestamp":1789460208000},"page":"7143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Survival Determinants in Temporal Bone Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"15","author":[{"given":"Martina","family":"Sebastiani","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy"},{"name":"Otorhinolaryngology Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Facheris","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy"},{"name":"Otorhinolaryngology Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5937-8847","authenticated-orcid":false,"given":"Daniele","family":"Bernardeschi","sequence":"additional","affiliation":[{"name":"Service d\u2019Oto-Rhino-Laryngologie, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, AP-HP, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9957-149X","authenticated-orcid":false,"given":"Luca","family":"Canali","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Colombo","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology, Head and Neck Department, Ospedale Nuovo di Legnano, ASST Ovest Milanese, Via Papa Giovanni Paolo II, 20025 Legnano, MI, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4028-7187","authenticated-orcid":false,"given":"Matteo","family":"Di Bari","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology, Head and Neck Department, Ospedale Nuovo di Legnano, ASST Ovest Milanese, Via Papa Giovanni Paolo II, 20025 Legnano, MI, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.anorl.2012.08.003","article-title":"Cancer of the external auditory canal","volume":"130","author":"Ouaz","year":"2013","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s12105-018-0908-4","article-title":"Squamous Cell Carcinoma of the External Auditory Canal and Temporal Bone: An Update","volume":"12","author":"Allanson","year":"2018","journal-title":"Head Neck Pathol."},{"key":"ref_3","first-page":"582","article-title":"Squamous cell carcinoma of the external auditory canal: An evaluation of a staging system","volume":"21","author":"Moody","year":"2000","journal-title":"Am. J. Otol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/01.mlg.0000154744.71184.c7","article-title":"The outcome of radical surgery and postoperative radiotherapy for squamous carcinoma of the temporal bone","volume":"115","author":"Moffat","year":"2005","journal-title":"Laryngoscope"},{"key":"ref_5","first-page":"438","article-title":"Invasion patterns of advanced temporal bone malignancies","volume":"17","author":"Leonetti","year":"1996","journal-title":"Am. J. Otol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cazzador, D., Franz, L., Tealdo, G., Carobbio, A.L.C., Ferraro, M., Mazzoni, A., Marioni, G., and Zanoletti, E. (2023). Survival outcomes in squamous cell carcinoma of the external auditory canal: A systematic review and meta-analysis. J. Clin. Med., 12.","DOI":"10.3390\/jcm12072490"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/lary.24400","article-title":"Temporal bone squamous cell carcinoma: Analyzing prognosis with univariate and multivariate models","volume":"124","author":"Zanoletti","year":"2014","journal-title":"Laryngoscope"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_9","unstructured":"Wells, G.A., Shea, B., O\u2019Connell, D., Peterson, J., Welch, V., Losos, M., and Tugwell, P. (2014). The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses, Ottawa Hospital Research Institute. Available online: http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2307\/3001666","article-title":"The combination of estimates from different experiments","volume":"10","author":"Cochran","year":"1954","journal-title":"Biometrics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"key":"ref_12","unstructured":"R Core Team (2024). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1080\/00016489.2025.2534365","article-title":"Factors associated with survival and recurrence of temporal bone squamous cell carcinoma: A single-center clinical study","volume":"145","author":"Chen","year":"2025","journal-title":"Acta Oto-Laryngol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"259","DOI":"10.21053\/ceo.2017.01340","article-title":"Prognostic factors affecting surgical outcomes in squamous cell carcinoma of the external auditory canal","volume":"11","author":"Nam","year":"2018","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1002\/lary.30504","article-title":"Analysis of Prognostic Factors For External Auditory Canal Carcinoma: A 22-Year Experience","volume":"133","author":"Jang","year":"2023","journal-title":"Laryngoscope"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E583","DOI":"10.1002\/lary.28653","article-title":"Primary Advanced Squamous Cell Carcinoma of the Temporal Bone: A Single-Center Clinical Study","volume":"131","author":"Komune","year":"2021","journal-title":"Laryngoscope"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Komune, N., Kuga, R., Hongo, T., Kuga, D., Sato, K., and Nakagawa, T. (2023). Impact of Positive-Margin Resection of External Auditory Canal Squamous Cell Carcinoma. Cancers, 15.","DOI":"10.3390\/cancers15174289"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1097\/MAO.0000000000000265","article-title":"Squamous cell carcinoma of the temporal bone: Clinical outcomes from radical surgery and postoperative radiotherapy","volume":"35","author":"Masterson","year":"2014","journal-title":"Otol. Neurotol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1002\/hed.27111","article-title":"Treatment of advanced squamous cell carcinoma of the external auditory canal: Critical analysis of persistent failures in diagnosis and surgery with a competing-risk model","volume":"44","author":"Mazzoni","year":"2022","journal-title":"Head Neck"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1097\/MAO.0000000000001152","article-title":"The Outcomes of Surgery and Chemoradiotherapy for Temporal Bone Cancer","volume":"37","author":"Morita","year":"2016","journal-title":"Otol. Neurotol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.anl.2025.02.001","article-title":"Treatment outcomes of 73 cases of external auditory canal squamous cell carcinoma: A single-center six-year analysis in Japan","volume":"52","author":"Ooka","year":"2025","journal-title":"Auris Nasus Larynx"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1216","DOI":"10.1002\/lio2.1216","article-title":"Treatment outcome and prognostic factors of external auditory canal squamous cell carcinoma: A retrospective study in a tertiary center","volume":"9","author":"Huang","year":"2024","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e127","DOI":"10.1097\/MAO.0000000000004668","article-title":"Prognostic Value of EZH2 and Ki-67 in Squamous Cell Carcinoma of Ear and Temporal Bone","volume":"47","author":"Li","year":"2026","journal-title":"Otol. Neurotol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"110691","DOI":"10.1016\/j.radonc.2024.110691","article-title":"Development and validation of a nomogram to predict overall survival in patients with External auditory canal cancer","volume":"203","author":"Zhang","year":"2025","journal-title":"Radiother. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5304","DOI":"10.1002\/cam4.5338","article-title":"Clinical outcomes of temporal bone squamous cell carcinoma: A single-institution experience","volume":"12","author":"Zheng","year":"2023","journal-title":"Cancer Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:55:57Z","timestamp":1789462557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":25,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15187143"],"URL":"https:\/\/doi.org\/10.3390\/jcm15187143","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}