Diagnostic Utility of Red Flags for Detecting Spinal Malignancies in Patients with Low Back Pain: A Scoping Review

Download PDFsettingsOrder Article Reprints This is an early access version, the complete PDF, HTML, and XML versions will be available soon. Open AccessReview Diagnostic Utility of Red Flags for Detecting Spinal Malignancies in Patients with Low Back Pain: A Scoping Review by Gianluca Notarangelo 1ORCID,Michele Margelli 2ORCID,Giuseppe Giovannico 1ORCID,Francesco Bruno 1ORCID,Claudia Milella 2,Daniel Feller 3,4ORCID,James Dunning 5,6ORCID,Lorenzo Storari 2ORCID,Firas Mourad 7,8,9ORCID andFilippo Maselli 2,10,*ORCID 1 Department of Medicine and Health Science “Vincenzo Tiberio”, University of Molise, c/o Cardarelli Hospital, C/da Tappino, 86100 Campobasso, Italy 2 Department of Human Neurosciences, Sapienza University of Rome, 00185 Rome, Italy 3 Provincial Agency for Health of the Autonomous Province of Trento, 38100 Trento, Italy 4 Department of General Practice, Erasmus MC, University Medical Centre, 3015 CA Rotterdam, The Netherlands 5 American Academy of Manipulative Therapy Fellowship in Orthopaedic Manual Physical Therapy, Montgomery, AL 36104, USA 6 Montgomery Osteopractic Physical Therapy & Acupuncture Clinic, Montgomery, AL 36104, USA 7 Department of Health, LUNEX University of Applied Sciences, Differdange, Luxembourg L-4671, Luxembourg 8 Luxembourg Health & Sport Sciences Research Institute A.s.b.l., Differdange, Luxembourg L-4671, Luxembourg 9 Facoltà Dipartimentale di Medicina e Chirurgia, Università Campus Bio-Medico di Roma, 00128 Roma, Italy 10 Sovrintendenza Sanitaria Regionale Puglia INAIL, 70126 Bari, Italy * Author to whom correspondence should be addressed. J. Clin. Med. 2025, 14(20), 7174; https://doi.org/10.3390/jcm14207174 (registering DOI) Submission received: 28 August 2025 / Revised: 27 September 2025 / Accepted: 6 October 2025 / Published: 11 October 2025 (This article belongs to the Special Issue Musculoskeletal Diagnosis and Treatment: Connecting Gaps to Enhance Patient Care) Downloadkeyboard_arrow_down Versions Notes Abstract Introduction: While low back pain (LBP) is most often associated with musculoskeletal issues, in a minority of cases, it can be caused by serious underlying conditions such as cancer. Recognizing malignancy early remains a major clinical challenge, as the warning signs, known as red flags (RFs), are often vague and inconsistent. Methods: A comprehensive search of six databases (PubMed, Scopus, Google Scholar, Web of Science, Cochrane Library, and SciELO) and grey literature was conducted for studies published from January 1999 to March 2025. Eligible sources included studies describing adult patients with cancer presenting with LBP. Study selection and data extraction were independently performed by two reviewers. Results: We included 70 studies, most of which were case-based, along with reviews and observational research. In these studies, cancer prevalence among patients with LBP ranged from 0.1% to 1.6%, with metastatic disease being the most common finding. A prior history of cancer emerged as the most reliable red flag (specificity up to 0.99), while other signs and symptoms were less consistent. Notably, combining multiple RFs, such as a history of cancer and unexplained weight loss, significantly improved the diagnostic accuracy (LR+ = 10.25 in one study). Conclusions: While current evidence is limited and largely based on case-based studies, some RFs, particularly a history of cancer, show greater diagnostic value. In patients with LBP associated with underlying malignancy, RFs seem to be more useful for ruling in rather than ruling out (i.e., screening) serious pathologies. Most RFs have poor standalone accuracy; however, considering combinations of RFs within the broader clinical context may improve early detection of spinal malignancy in patients with LBP.