Abstract
PurposeOpioids reduce cancer-related pain but an association with shorter survival is variably reported. Aim: To investigate the relationship between pain, analgesics, cancer and survival within the European Palliative Care Cancer Symptom (EPCCS) study to help inform clinical decision making.MethodsSecondary analysis of the international prospective, longitudinal EPCCS study which included 1739 adults with advanced, incurable cancer receiving palliative care. In this secondary analysis, for all participants with date of death or last follow up, a multilevel Weibull survival analysis examined whether pain, analgesics, and other relevant variables are associated with time to death.ResultsDate of death or last follow-up was available for 1404 patients (mean age 65.7 [SD:12.3];men 50%). Secondary analysis of this group showed the mean survival from baseline was 46.5 (SD:1.5) weeks (95% CI:43.6–49.3). Pain was reported by 76%; 60% were taking opioids, 51% non-opioid analgesics and 24% co-analgesics. Opioid-use was associated with decreased survival in the multivariable model (HR = 1.59 (95% CI:1.38–1.84), p < 0.001). An exploratory subgroup analysis of those with C-reactive protein (CRP) measures (n = 219) indicated higher CRP was associated with poorer survival (p = 0.001). In this model, the strength of relationship between survival and opioid-use weakened (p = 0.029).ConclusionOpioid-use and survival were associated; this relationship weakened in a small sensitivity-testing subgroup analysis adjusting for CRP. Thus, the observed relationship between survival and opioid-use may partly be due to tumour-related inflammation. Larger studies, measuring disease activity, are needed to confirm this finding to more accurately judge the benefits and risks of opioids in advanced progressive disease.
Highlights
[1] Pain might be associated with a poorer prognosis, but the evidence is mixed. [2,3,4,5,6] Opioids, used to reduce pain, [7] might reduce immunity and survival, which might limit their use and increase suffering. [8,9,10,11,12,13] A systematic review showed that, findings from individual studies were variable, opioids tended not to affect survival in the last days to weeks of life, but there was a possible association with shorter survival with longer term opioid-use
[14] The findings of this systematic review are supported by subsequent publications. [13, 15,16,17] Retrospective studies in patients in the last weeks of life have shown no statistically significant effect of opioids on survival
Patients with aggressive or advanced disease are likely to have increased pain and shorter survival, confounding an independent association between opioids and survival. [6, 18,19,20,21,22] Symptomatic patients may have worse Karnofsky Performance Status (KPS), itself an independent predictor of survival. [4, 23,24,25,26] Long-term data exploring the association between pain, opioids and survival are limited, but it is vital to address this concern to more accurately judge the benefits and risks of opioids in advanced progressive disease. [8]
Summary
[8,9,10,11,12,13] A systematic review showed that, findings from individual studies were variable, opioids tended not to affect survival in the last days to weeks of life, but there was a possible association with shorter survival with longer term opioid-use. [13, 17] data to date report an association between opioids and survival in patients with advanced cancer only over months of administration. Patients with aggressive or advanced disease are likely to have increased pain (triggering opioid prescribing) and shorter survival, confounding an independent association between opioids and survival. Pain is common in patients with advanced cancer. [1] Pain might be associated with a poorer prognosis, but the evidence is mixed. [2,3,4,5,6] Opioids, used to reduce pain, [7] might reduce immunity and survival, which might limit their use and increase suffering. [8,9,10,11,12,13] A systematic review showed that, findings from individual studies were variable, opioids tended not to affect survival in the last days to weeks of life, but there was a possible association with shorter survival with longer term opioid-use. [14] These were mostly poor quality studies where the effect of opioids on survival was not the primary outcome. [14] The findings of this systematic review are supported by subsequent publications. [13, 15,16,17] Retrospective studies in patients in the last weeks of life have shown no statistically significant effect of opioids on survival.
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