Total pain, opioids, and immune checkpoint inhibitors in the survival of patients with cancer

Experimental and observational studies have shown that opioid analgesics may increase tumor growth, potentially reduce immunotherapy efficacy, and shorten survival. As a result of the lack of clinical data, the current rationale for continuing opioid analgesic treatment is based on animal models, which suggests that physical pain itself may potentially influence cancer growth and exert immunosuppressive effects. Total pain encompasses the various factors that patients may experience during their cancer journey: physical symptoms, social isolation/loneliness, psychological, spiritual/existential, and financial distress. These need to be screened and discussed with patients to help them cope with the treatment and disease. As each issue may affect survival, it is essential to identify them to understand how they might affect the patient's immune system, influence immunotherapy outcomes, and ultimately, survival. The question arises whether a single factor, such as the combination of opioids and immune checkpoint inhibitors, negatively affects treatment outcomes. While there is a risk of fostering opioid phobia, the complex interplay between total pain, quality of life, and the immune system must be considered. Thus, in studies that appropriately investigate the interactions between opioid analgesics and the immune system, it is essential to consider all the distress factors that patients may experience at each stage of their illness.