AccScience Publishing / JCTR / Volume 12 / Issue 4 / DOI: 10.36922/JCTR026220048
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ORIGINAL ARTICLE

The three-month referral threshold as an independent prognostic marker of cancer-specific survival in advanced oncological disease

Anda-Elena Crișan1,2,3 Andrada Nemesis Crișan2,4* Roxana Elena Sicoe2,4 Liliana-Eleonora Semenescu2,5 Oana Ciobănescu3,6 Adina Mitrea3,7
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1 Department of Oncology–Radiotherapy, Emergency Clinical Hospital Craiova, Craiova, Romania
2 Centrul Medical Galaxy Med SRL, Craiova
3 Department of Oncology and Radiotherapy, Faculty of Nursing, University of Medicine and Pharmacy of Craiova, Craiova, Romania
4 Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
5 Department of Oncology, Filantropia Clinical Municipal Hospital, Craiova, Romania
6 Department of Radiotherapy, Craiova County Emergency Clinical Hospital, Craiova, Romania
7 Department of Diabetes, Nutrition and Metabolic Diseases, Filantropia Clinical Municipal Hospital, Craiova, Romania
JCTR 2026, 12(4), 026220048 https://doi.org/10.36922/JCTR026220048
Received: 30 May 2026 | Revised: 7 July 2026 | Accepted: 9 July 2026 | Published online: 24 August 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Background: Guidelines recommend the early integration of palliative care in advanced cancer; however, “earliness” remains heterogeneously defined, with no temporal consensus, and timing studies are vulnerable to immortal-time bias and do not model competing risks. Objective: To evaluate a pre-specified three-month threshold as a prognostic marker of cancer-specific survival (CSS) and as a potential auditable indicator of timely access to palliative care. Methods: A retrospective observational cohort study of 147 consecutive adults with advanced locoregional or metastatic cancer, admitted to a Romanian palliative care center (2018–2022; median follow-up 26 months), was conducted. The six-stratum analytical framework comprised multivariable Cox regression, Fine–Gray models, Grambsch–Therneau coefficients, Imai–Keele–Tingley mediation, restricted mean survival time (RMST) with inverse probability of censoring weighting, and validation through landmark and left-truncation analyses. Results: Fifty-nine patients (40.1%) were referred within the first three months. Referral within three months was independently associated with a reduced risk of cancer-specific death in locoregional disease (adjusted hazard ratio [HR], 0.49; 95% confidence interval, 0.28–0.86) and metastatic disease (HR, 0.58). Fine–Gray models confirmed the association (subdistribution HR 0.52). The RMST benefit was + 18.7 months (locoregional) and + 4.3 months (metastatic), persisting across landmark and truncation analyses. Conclusion: The three-month threshold is independently associated with significantly better CSS and is robust across six analytical approaches. As the design is observational, the findings remain associative and hypothesis-generating. Relevance for patients: The proportion of patients referred within the first three months can be computed from routine documentation and, subject to external validation, could serve as an auditable indicator of access to palliative care.

Graphical abstract
Keywords
Palliative care
Referral timing
Cancer-specific survival
Competing risks
Restricted mean survival time
Immortal-time bias
Statistical mediation
Quality indicators
Funding
The research did not receive external funding from public, commercial, or non-profit sources. The work was conducted as part of the routine clinical activities of Centrul Medical Galaxy Med SRL, Craiova, at no additional cost to patients.
Conflict of interest
The authors declare the absence of any conflict of interest— financial, commercial, professional, or personal—in connection with this research or its publication.
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Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing