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.