A recent review by Drs. Jill Sindt and Shane Brogan of the University of Utah School of Medicine detailed the current status of a number of interventional techniques for the treatment of cancer-related pain: intrathecal drug delivery, vertebral augmentation, neurolytic plexus blocks, and image-guided percutaneous tumor ablation.¹ The primary algorithm for the treatment of cancer pain in use today is a 3-step “analgesic ladder” developed by the World Health Organization (WHO). Non-opioid analgesics comprise the first step on the ladder; if pain persists, clinicians are advised to move onto the second step, which consists of non-opioids in combination with weak opioids. The third and final step consists of strong opioids plus non-opioids. Yet evidence from a 2007 systematic review of the medical literature shows that this approach to cancer pain management may be insufficient. Results showed that pain was prevalent in 64% of patients with metastatic, advanced or terminal cancer; 59% of patients undergoing cancer treatment; and 33% of patients who completed curative treatment. More than one-third of cancer patients who reported pain rated it as moderate or severe, suggesting that additional modalities may be warranted when conventional medications do not provide sufficient control.² Due to these unmet needs, interventional techniques have been suggested as a “fourth step” in the WHO analgesic ladder.³

Intrathecal drug delivery

In intrathecal drug delivery (IDD), analgesics are delivered directly to the cerebral spinal fluid using an implanted device or, less commonly, an external pump. Opioids, with or without adjunctive agents, comprise the drug class most frequently used in this technique. In circumventing the general circulation, intrathecal drug delivery allows for smaller drug doses and a better side effect profile than systemic modes of drug delivery, while resulting in more effective analgesia. “Multiple studies have demonstrated the success of IDD, reporting improved pain control, increased survival, fewer side effects, reduced opioid use, and potentially lower cost (for long-surviving patients) as compared with treatment with systemic opioids,” Sindt and Brogan stated in their paper. 

Vertebral augmentation

Vertebral augmentation is a modality for treating vertebral compression fractures, a frequent complication of multiple myeloma, breast, prostate, renal cell, thyroid, and lung cancers. Vertebroplasty and kyphoplasty are the two vertebral augmentation techniques presently in use. In vertebroplasty, the bone cement polymethyl methacrylate (PMMA) is percutaneously injected into the vertebral body. Kyphoplasty is an extension of vertebroplasty that involves an extra step: the use of an inflatable balloon to restore vertebral body height prior to injection. “Several studies and reviews on the use of vertebral augmentation for painful cancer associated VCFs have been published in the last 10 years. These studies consistently demonstrate improvements in pain and function with a low incidence of adverse effects,” wrote the authors.

Neurolytic plexus blocks

Neurolytic plexus blocks, commonly targeting the celiac plexus, superior hypogastric plexus, or ganglion impar, are used to palliate cancer-related visceral pain by blocking the transmission of nociceptive signals from the viscera to the brain. The usual neurolytic agents employed are alcohol and phenol. Pain relief may last for several months, after which the procedure may be repeated. The authors stated, “Numerous case series, meta-analyses, and randomized controlled trials report favorable outcomes with celiac plexus neurolysis. Improvement in pain scores and reduced opioid consumption have been reported in most published reports, and some articles have demonstrated improved survival and quality of life.” The literature supporting other targets are more limited, but case reports and case series report positive results.

Image-guided percutaneous tumor ablation

Image-guided percutaneous tumor ablation is a technique used to treat the painful bone metastases that are common sequelae of cancer. Although external beam radiation therapy is the standard of care for patients with cancer who present with localized bone pain, it provides inadequate analgesia in 20-30% of those treated. In image-guided percutaneous tumor ablation, percutaneous image-guided methods are used to deliver ablative materials or devices into the lesions. Radiofrequency ablation, the technique with the most published evidence, employs a high-frequency, alternating current to cause cell death via heat, while cryoablation utilizes pressurized argon to cause cell death via rapid tissue cooling. Both techniques have been demonstrated in the literature to be efficacious, although radiofrequency ablation has been more extensively studied.

Better collaboration needed between pain specialists and oncologists

In an email interview with Clinical Pain Advisor, Laura Hanson Textor, ACNS-BC, RNC, an advanced practice registered nurse at the Midwest Neuroscience Institute, Kansas City, MO, noted that interventional procedures are not commonly used to their full potential in everyday clinical practice. “Pain specialists have the knowledge base to safely prescribe opioids as well as perform procedures such as nerve destruction or intrathecal pumps that can be very beneficial. Unfortunately, it is almost a widespread epidemic that oncologists will not refer patients to specialists for help. To my knowledge, this phenomenon is not understood though commonly discussed in pain management circles.” Yet she also noted that interest in the use of non-pharmaceutical options is growing. “As the societal issues of drug abuse continue to dominate the conversation, prescribers become more and more reluctant to aggressively provide medications. So, newer methods for controlling pain, along with interest in older neurosurgical approaches, are looked at more favorably. In my practice, many patients have asked why they were allowed to suffer so long when there were options other than pain pills.”

References

1. Sindt JE, Brogan SE. Interventional Treatments of Cancer Pain. Anesthesiol Clin. 2016;34(2):317-339. doi:10.1016/j.anclin.2016.01.004.

2. Everdingen M van den B, Rijke J de, Kessels AG, Schouten HC, Kleef M van, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007;18(9):1437-1449. doi:10.1093/annonc/mdm056.

3. Miguel R. Interventional treatment of cancer pain: the fourth step in the World Health Organization analgesic ladder? Cancer Control J Moffitt Cancer Cent. 2000;7(2):149-156.