{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:44:05Z","timestamp":1782809045717,"version":"3.54.5"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Systemic inflammatory biomarkers have emerged as potential prognostic indicators in metastatic colorectal cancer (mCRC). However, the prognostic robustness of inflammatory indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR), and Glasgow Prognostic Score (GPS) remains incompletely characterized. In this study, we aimed to evaluate the prognostic significance of NLR, PLR, CRP, CAR, and GPS for progression-free survival in metastatic colorectal cancer in a cohort of patients from Romania. Materials and Methods: This retrospective observational study included 148 patients diagnosed with mCRC. Inflammatory biomarkers were determined from baseline laboratory parameters. Progression-free survival (PFS) was the primary endpoint. Statistical analyses included correlation testing, Kaplan\u2013Meier survival analysis, Cox proportional hazards regression, Firth penalized Cox regression, restricted cubic spline modeling, time-dependent receiver operating characteristic (ROC) analysis, LASSO penalized regression, multiple imputation, and parsimonious multivariable Cox models adjusted for major clinicopathologic confounders. Results: Median PFS was 21 months (95% CI 19\u201324). In univariable Cox analyses, elevated NLR (HR 1.98, 95% CI 1.11\u20133.51, p = 0.020), PLR (HR 1.89, 95% CI 1.25\u20132.85, p = 0.002), CRP (HR 1.45, 95% CI 1.15\u20131.83, p = 0.002), and CAR (HR 1.44, 95% CI 1.05\u20131.98, p = 0.022) were associated with shorter PFS. Restricted cubic spline analysis demonstrated a significant nonlinear association between NLR and PFS (p = 0.0025). After multiple imputation, NLR remained associated with shorter PFS (HR 2.04, 95% CI 1.13\u20133.68, p = 0.018). However, in a multivariable model adjusted for major clinicopathologic confounders, this association was not retained (HR 1.41, 95% CI 0.81\u20132.43, p = 0.221) and time-dependent ROC analyses demonstrated its limited discriminatory performance. Conclusions: Although some inflammatory markers were associated with shorter PFS in univariable analyses, the prognostic effect of NLR was attenuated after adjustment and was not consistently confirmed across all analyses.<\/jats:p>","DOI":"10.3390\/medicina62071259","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:58:04Z","timestamp":1782799084000},"page":"1259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Inflammatory Biomarkers as Prognostic Indicators in Metastatic Colorectal Cancer: A Retrospective Study"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7650-7798","authenticated-orcid":false,"given":"Diana-Ioana","family":"Panaite","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona-Ruxandra","family":"Volovat","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalina","family":"Ostafe","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cezara-Ioana","family":"Litcanu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian-Constantin","family":"Volovat","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Luiza","family":"Baean","sequence":"additional","affiliation":[{"name":"Faculty of Midwifery and Nursing, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4718-392X","authenticated-orcid":false,"given":"Ingrid-Andrada","family":"Vasilache","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biological Sciences, \u2018\u0218tefan cel Mare\u2019 University, 720229 Suceava, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1582-0135","authenticated-orcid":false,"given":"Constantin","family":"Volovat","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101174","DOI":"10.1016\/j.tranon.2021.101174","article-title":"Global colorectal cancer burden in 2020 and projections to 2040","volume":"14","author":"Xi","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_2","first-page":"998","article-title":"Colorectal Cancer Epidemiology: Recent trends and Impact on Outcomes","volume":"22","author":"Baidoun","year":"2020","journal-title":"Curr. Drug Targets"},{"key":"ref_3","unstructured":"Dominguez, O.H., Yilmaz, S., and Steele, S. (2023). Stage IV Colorectal Cancer Management and Treatment. J. Clin. 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