Nerve block may provide relief for pancreatic cancer pain

Neurolytic splanchnic nerve block (SNB) appears effective for pain control in patients with moderate-to-severe pain due to unresectable pancreatic cancer, a study has shown.

“Pain arising from pancreatic cancer can be severe and strongly impact quality of life (QoL) … Due to difficulty in early diagnosis and poor prognosis, palliative care, including adequate pain relief and QoL improvement, has become an increasingly important and integral element of pancreatic cancer treatment,” said the researchers.

Although widely used for managing cancer pain, opioids are confounded by issues such as insufficient pain relief, adverse reactions, and intolerance. [Support Care Cancer 2006;14:1086-1093] “Therefore, alternative nonopioid cancer pain treatment options are actively advocated by international consensus … In current clinical practice, neurolysis is often used as salvage therapy when pain control is inadequate with analgesics,” they continued.

Given the role of the splanchnic nerve in pancreatic cancer pain, [Clin Gastroenterol Hepatol 2006;4:1479-1482] the researchers sought to determine whether neurolytic SNB can favourably provide pain relief in this patient group. Ninety-six patients were randomized 1:1 to receive neurolytic SNB (absolute alcohol) or a sham injection (normal saline). Participants received opioid therapy and were followed for 8 months or until death. [Anesthesiology 2021;135:686-698]

For the first 3 months, pain relief was greater with neurolytic SNB vs sham, with the largest effect seen at month 1 (mean VAS* score, 2.8 vs 3.5; p_adjusted<0.001). Albeit small, an improvement that manifests early on during treatment implies that neurolytic SNB provides quicker pain reduction, said the researchers.

The effect gradually waned from month 4 (mean VAS score, 3.1 vs 3.4; p_adjusted=0.12) and was sustained through month 8 (mean VAS score, 3.3 vs 3.5; p_adjusted>0.99). Despite the decline, the similar values between arms imply that “our block technique was effective,” they said.

Daily oral dose of morphine equivalent was lower in the neurolytic SNB vs the sham group over the first 5 months (p_adjusted<0.001 for each month), with the largest effect seen during month 1 (71.0 vs 162.3 mg). The effect declined by month 6 (165.0 vs 206.2 mg; p_adjusted=0.136).

“[T]he analgesic benefit of neurolysis … lasted for almost the whole follow-up period. [This suggests] that neurolysis was an efficacious alternative that may play a crucial role in patients with moderate-to-severe pain conditions,” they said.

Can nerve blocks prolong survival?

However, median survival was shorter with neurolytic SNB vs sham (102.5 vs 151.0 days; hazard ratio [HR], 1.56; p=0.036). Further stratification showed significantly shorter median survival with neurolytic SNB vs sham in stage IV (69.0 vs 146.0 days; HR, 1.94; p=0.001) but not stage III patients (197.0 vs 169.0 days; HR, 1.08; p=0.809).

“[W]e believe disturbances in the autonomic nervous system play a major role in the impact of neurolysis on survival,” they said. This is so because ablation of the celiac plexus may induce sympathetic disorders and unopposed parasympathetic activity. [Gastrointest Endosc 2015; 82:46-56.e2]

The incidences of exhaustion (52 percent) and lethargy (56 percent) with neurolytic SNB may also be attributed to reduced sympathetic excitability, which may consequently accelerate death. “However, this hypothesis cannot explain the different mortality rates according to tumour node metastasis stages,” said the researchers.

Given the paucity of data that can shed light on the link between sympathetic disorders of the visceral nerve and life expectancy, it would be challenging to ascertain whether neurolysis prolongs or cuts survival short in pancreatic cancer.

“More clinical trials are needed to verify these findings and clarify the relationship between neurolysis and survival,” said the researchers. The clinical utility of neurolytic SNB in this setting should also be further elucidated. “Consequently, we expect our findings to have considerable implications for clinical practice.”