Abstract
BACKGROUND: Many patients with cancer experience pain related to their disease. Opioids are commonly used for moderate-to-severe cancer-related pain but carry significant side effects that may worsen quality of life. Buprenorphine, a partial mu opioid receptor (MOR) agonist, is increasingly used for the management of cancer-related pain. Although well studied as a treatment for opioid use disorder, its role in managing cancer pain is less understood. METHODS: We aim to systematically gather, assess, and summarize prior studies on the impact of buprenorphine upon cancer-related pain. Cochrane CENTRAL, OVID Medline, EMBASE, EBSCO, and Web of Science will be searched in September 2025 for any studies available to date. Studies involving buprenorphine as an intervention upon cancer-related pain will be included where pain outcomes are measured at two or more timepoints using a validated scale. Exclusions apply to case studies/series with fewer than five subjects, qualitative studies, conference abstracts, review articles, research protocols, studies solely focused on post-operative pain, and studies not available in English translation. After final selection, study type classification, and data extraction, a quality assessment will be conducted using the Cochrane ROB 2 tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for cohort and case-control studies. The summarized data will be evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. DISCUSSION: The primary objective is to fill a knowledge gap by summarizing literature on buprenorphine for cancer pain management, including a broad range of study designs, drug formulations, and dosing. This systematic review aims to provide a comprehensive understanding of buprenorphine's efficacy and safety in cancer pain management, which could inform clinical practice and future research directions. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered in PROSPERO (CRD42022383591).