{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T14:58:13Z","timestamp":1774277893018,"version":"3.50.1"},"reference-count":18,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Outcomes with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) are influenced by tumor burden, disease kinetics, and host factors. We evaluated the relative prognostic impact of metastatic pattern, laboratory markers, and prostate-specific antigen (PSA) dynamics in a real-world cohort. Methods: We retrospectively analyzed 72 patients with mCRPC treated with enzalutamide. Progression-Free Survival (PFS) and Overall Survival (OS) were estimated using the Kaplan\u2013Meier method. Multivariate Cox proportional hazards models were utilized to identify independent predictors of survival, incorporating clinical variables (visceral metastases, bone tumor burden), kinetic parameters (Time to Castration Resistance [TTCR], Time to PSA Nadir [TTN]), and host factors (Charlson Comorbidity Index [CCI], Eastern Cooperative Oncology Group Performance Status (ECOG PS), Systemic Immune-Inflammation Index [SII], HALP score). Results: Visceral metastasis was a dominant predictor of poor outcomes, increasing the risk of death by 4.0-fold (HR: 4.05; 95% CI: 1.84\u20138.89; p &lt; 0.001). A high skeletal tumor burden (\u22655 bone lesions) was identified as a critical threshold, associated with a 5.5-fold increase in mortality risk (HR: 5.53; p &lt; 0.001). Delays in initiating enzalutamide significantly compromised survival, with each 1-month delay increasing the risk of death by 7.3% (HR: 1.07; p = 0.003). While early PSA decline (\u226550% at 3 months) did not independently predict OS, a prolonged TTN (&gt;12 months) was associated with superior survival. Notably, host-related factors, including age, CCI, and ECOG PS, were not found to be significantly associated with survival outcomes in this specific dataset. Conclusions: Our preliminary findings suggest that survival in real-world mCRPC patients treated with enzalutamide may be influenced predominantly by intrinsic tumor biology\u2014specifically anatomical extent and resistance kinetics\u2014rather than host frailty or comorbidity burden. However, given the retrospective and single-center nature of this study, these findings should be considered hypothesis-generating and require validation in larger, multi-center cohorts. Host-related variables (including age and CCI) were evaluated but were not retained as independent predictors in the final multivariable model. Early initiation of therapy and monitoring of kinetic markers like TTN and TTCR offer superior prognostic stratification compared to static baseline characteristics.<\/jats:p>","DOI":"10.3390\/diagnostics16060950","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:53:34Z","timestamp":1774274014000},"page":"950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Tumor Biology and Host Factors in mCRPC: The Prognostic Value of \u2018Time to Castration Resistance\u2019, Systemic Inflammation, and Comorbidity Burden in Patients Treated with Enzalutamide"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8575-5477","authenticated-orcid":false,"given":"Seda","family":"Sali","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, University of Health Sciences, Bursa City Education and Research Hospital, Bursa 16250, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2918-2592","authenticated-orcid":false,"given":"Arife","family":"Ula\u015f","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University of Health Sciences, Bursa City Education and Research Hospital, Bursa 16250, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8217-3471","authenticated-orcid":false,"given":"Sibel","family":"Oyucu Orhan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University of Health Sciences, Bursa City Education and Research Hospital, Bursa 16250, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6626-0409","authenticated-orcid":false,"given":"Sevgi","family":"Top\u00e7u","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tepecik Training and Research Hospital, \u0130zmir 35120, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muharrem","family":"Ko\u00e7ar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University of Health Sciences, Bursa City Education and Research Hospital, Bursa 16250, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2079-3350","authenticated-orcid":false,"given":"M\u00fcrsel","family":"Sali","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, School of Medicine, Bursa Uluda\u011f University, Bursa 16059, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7537-1699","authenticated-orcid":false,"given":"Birol","family":"Ocak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Bursa Y\u00fcksek \u0130htisas Training and Research Hospital, Bursa 16310, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3931-0191","authenticated-orcid":false,"given":"Adem","family":"Delig\u00f6n\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, School of Medicine, Bursa Uluda\u011f University, Bursa 16059, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9732-5340","authenticated-orcid":false,"given":"T\u00fcrkkan","family":"Evrensel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, School of Medicine, Bursa Uluda\u011f University, Bursa 16059, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erdem","family":"\u00c7ubuk\u00e7u","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, School of Medicine, Bursa Uluda\u011f University, Bursa 16059, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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