In studying how successful treatments are for cancer, one of the most important outcomes is the effect on how long treated patients survive. Treatments that do not extend life or, even worse, shorten it are considered poor choices.
Opioids are a mainstay for many forms of cancer-related pain, although for some forms--most notably neuropathic and bone pain related to the cancer--other classes of medications are usually more effective.
Taken together these two statements raise an interesting question: what effect do opioids prescribed for cancer-related pain have on length of survival?
Considering how frequently opioids are used to manage cancer pain, one might think this question has been well studied and settled. A new study shows, however, that the question is still largely unanswered.
The study is a literature review of research on how opioids affect cancer survival.1 Only 20 studies fit the inclusion criteria. Many studies did not primarily examine the effects of opioids on survival, and many were not designed to provide clear comparisons between opioid users and the control populations.
Of the 20 studies, 13 examined survival among patients receiving opioids who were in the last days or weeks of life. All of these studies were considered of low or very low quality and there was little agreement as to the effects of the drugs on survival. In some of the studies, higher doses of opioids were associated with lengthened survival times while others found no such association; some found that the higher doses were associated with shortened survival.
The other 7 studies examined the effects of opioid use in patients who lived for months to years after onset of treatment. Three were of moderate quality while the other 4 were considered to be of low or very low quality.
Six of these studies found associations between reduced survival and opioid use and higher dosages.
This study demonstrates that, as with many other issues about opioid use (eg, whether long-term use is beneficial in chronic pain), the question of their effects on cancer survival is far from settled. If anything, the results indicate that when we prescribe opioids for patients with cancer, especially those who are not in the final stages of life, we may be introducing treatment that could have a detrimental effect on survival.
As the authors note, there are many factors that limit how much we can interpret from the findings of the studies they reviewed. The most obvious are their inconsistent quality and the fact that they were not designed to assess the effects of opioids on outcome.
Also potentially confounding results is the impact of the cancer itself on patients’ pain levels and corresponding need for opioids. Ongoing opioid use and dose escalation might be the result of increased pain levels associated with disease progression that is the cause of reduced survival.
The studies provide little information as to whether different opioids might have different effects on survival. In most of the studies only morphine was used; in those in which different opioids were also used, the data were pooled, making it impossible to differentiate effects.
The article notes that there are multiple mechanisms that might result in reduced survival among opioids users. Opioids can affect the immune system and a number of other physiologic functions that could have an impact on how the body responds to cancer.
There is also the strong possibility that cancer type might affect the magnitude of opioid impact on survival. For example, two studies of patients with advanced prostate cancer found that opioid use was associated with shortened survival. As opioid use can decrease testosterone level, it is possible that this may have played a role.
This study doesn't mean that we should stop using opioids to manage cancer pain. However, we need to be aware that when we do so there may be as yet uncertain effects on survival.
Boland JW, Ziegler L, Boland EG, et al. Is regular systematic opioid analgesia associated with shorter survival in adult patient with cancer? A systematic literature review. Pain. 2015;156:2152-2163.