Uri Hochberg,1 Pablo Ingelmo,2– 4 Ester Solé,5 Jordi Miró,5,6 Gonzalo Rivera,7,8 Jordi Perez2,3,9 1Pain Institute of the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada; 3Edwards Family Interdisciplinary Centre for Complex Pain, Montreal Children’s Hospital McGill University Health Centre, Montreal, Quebec, Canada; 4Research Institute, McGill University Health Center, Montreal, Quebec, Canada; 5Universitat Rovira i Virgili, Tarragona, Spain; 6Chair in Pediatric Pain, Center for Behavior Assessment (CRAMC), Department of Psychology, Institut d’Investigació Sanitària Pere Virgili, Tarragona, Spain; 7Hospital de Niños Luis Calvo Mackenna, Santiago de Chile, Chile; 8Clínica las Condes, Santiago de Chile, Chile; 9Cancer Pain Clinic, Cedars Cancer Center, McGill University Health Centre, Montreal, Quebec, CanadaCorrespondence: Jordi Perez, Cancer Pain Clinic, Cedars Cancer Centre, Royal Victoria Hospital, McGill University Health Centre, D2-1995, 1001 Boul, Decarie, Montreal, H4A 3J1, Canada, Tel +1 514 934 4502, Fax +1 514 934 8415, Email Jordi.perez@mcgill.caAbstract: Between 10% and 20% of patients with cancer-related pain cannot achieve adequate control following the three-step ladder guidelines by the World Health Organization. Therefore, a “fourth step”, including interventional approaches, has been suggested for those cases. Systematic reviews support the early use of interventional procedures to treat refractory cancer pain, control symptoms and prevent opioid dose escalation. There is strong evidence of the efficacy of celiac plexus or splanchnic neurolysis, vertebroplasty, kyphoplasty and intrathecal drug delivery. Those procedures have been found to be associated with a decrease in the symptom burden and opioid consumption, improved quality of life, and suggested as having a potentially positive impact on survival. Several studies have recommended using specific interventional techniques at earlier stages, possibly even when opioid treatment is first being considered. Conversely, leaving these options as a last analgesic resource might not be advisable since the burden these procedures might impose on too ill patients is significant. The objective of this review was to collect the available evidence published on the use of interventional treatments for refractory cancer pain with a particular interest in comparing early versus late indications. The results of the search demonstrated a very low number and quality of articles particularly addressing this question. This scarce number of evidence precluded performing a systematic analysis. A detailed and narrative description of the potential benefits of integrating interventional techniques into clinical guidelines at the early stages of the disease is provided.Keywords: cancer pain, interventional pain, neurolysis, cement augmentation, intrathecal drug delivery, early, timing