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Conversely, selected opioids with atypical pharmacological profiles, including tramadol, nalbuphine, and dezocine, as well as antagonists of opioid receptors such as naloxone, naltrexone, and low\u2010dose naltrexone, exhibit antineoplastic and immunomodulatory properties, frequently mediated through noncanonical pathways such as the opioid growth factor\u2010opioid growth factor receptor axis. Clinical findings remain inconclusive: perioperative opioid administration has been variably associated with an increased risk of recurrence, whereas tramadol use has correlated with improved survival outcomes. Notably, while some reports suggest signs of potential risk, other perioperative studies, including large cohorts and randomized trials, have shown neutral or even favourable associations, underscoring heterogeneity across study designs and tumour biology. 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