Monday 23 December 2013

Opiates, Surgery and Prostate Cancer

My son, George, showed no fear when it came to the surgical treatment of his osteosarcoma. He had multiple major operations, some lasting more than 12  hours, in which his bones were moved from one place to the next, tissues cut out from one place and refashioned and repurposed elsewhere. With a tumour in his jaw, the surgeons at St George's Hospital in London worked absolute miracles. And, in the end, it wasn't the tumour in the jaw that killed him, but the metastatic spread to the pelvis and elsewhere. To this day I am astounded at the courage my son showed in facing those long, complex operations, but he had every confidence in Nick Hyde and the maxillofacial team at St Georges. And for George the thing that made it bearable was that there was something definitive about surgery - it lead to the physical removal of the tumour assuming that the margins were clear. In this he was not alone, many cancer patients would rather opt for a surgical option rather than rounds of toxic chemotherapy or being blasted with radiotherapy.

However, it is becoming increasingly clear that surgery itself could well be contributing to the metastatic spread of disease, no matter how good the surgeon or how clear the margins are. It is not the surgery itself that seems to be at issue, but the use of opiate-based pain relief (morphine, fentanyl and so on). It's a topic that I have covered a number of times on this site already:

The culprit is the mu-Opioid Receptor (MOR) pathway that is the main target of the opiate-based pain-killers and which cause increased levels of tumour growth and metastases. We know this from epidemiological studies (looking at what happened to cancer patients after surgery based on what pain relief they had), from studies in animals and from studies in the test tube. The effect is likely due to a number of factors, including the fact that the opiates increase angiogenesis, cause immune suppression and activate a number of pro-cancer pathways.

Another epidemiological study has just been published which looks at the rate of disease progression and overall mortality in prostate cancer patients who have had a radical prostatectomy. The study, 'Association between neuraxial analgesia, cancer progression, and mortality after radical prostatectomy: a large, retrospective matched cohort study' has been published in the British Journal of Anaesthesia. The authors used a large sample of patients, matched for age, surgical year, pathological stage, Gleason scores, and presence of lymph node disease and type of anaesthesia - those treated with neuraxial anaesthesia (which has lower use of opiates) and general anaesthesia (using the 'normal' amount of opiate-based pain relief).

The results are clear and in line with the previous studies I have written about. Increased use of opiates is associated with increased risk of disease progression and higher overall mortality.

The question we need to be asking ourselves now is not whether opiates in surgery are risky for cancer patients, the evidence is there in plain sight. The question we need to be asking now is how can we ensure that clinical practice changes and changes soon? One step in the right direction is the clinical trial being run by Dr Patrice Forget in breast cancer patients:

But at the same time, if I was a cancer patient about to have surgery I know that I would be wanting to speak to my surgical team and pointing them in the direction of these various results. At the very least I would be wanting to explore the use of methylnaltrexone if there is no option but opiate-based pain relief.