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NCCN Flash Updates: NCCN Guidelines Updated for Adult Cancer Pain

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Adult Cancer Pain. These NCCN Guidelines^® are currently available as Version 1.2025.

Link directly to the Updates section of the NCCN Guidelines: Adult Cancer Pain

Global

• Transmucosal fentanyl removed due to discontinuation of production.

PAIN-1

• Principles of Cancer Pain Management
  • Pain Definition modified: Pain is defined by the International Association for the Study of Pain (IASP) as an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. Acute cancer pain in adults is a sudden-onset pain directly related to diagnostic procedures, cancer treatments (eg, surgery, radiation therapy, chemotherapy), or rapid tumor growth affecting surrounding tissues or organs. It is characterized by an intense sensation and is typically short-lived, resolving within 3 months as the underlying cause is treated or subsides. Chronic cancer pain in adults is a persistent or recurrent pain lasting more than 3 months. IASP defines chronic cancer-related pain as chronic pain caused by the primary cancer itself, or metastases (chronic cancer pain) or its treatment (chronic post-cancer treatment pain).
• General Principles
  • Bullet 2 revised: Survival ishas been linked to symptom control and...
  • Bullet 4 modified: A multidisciplinary team is optimal (PAIN-L); consider early referral to palliative care (NCCN Guidelines for Palliative Care) and psychological/social/spiritual services (NCCN Guidelines for Distress Management) and/or interventional pain management teams (PAIN-M).
  • Bullet 5 revised: Provide/refer for psychosocial/spiritual support, including emotional and informational support, and coping skills training, and other nonpharmacologic therapies (PAIN-C) (PAIN-D).
  • Bullet 7, sub-bullet added: Take steps to improve disparities in access to effective pain evaluation and care.
• Assessment
  • Bullet 2 modified: The patient's self-report of pain is the primary source for pain assessment, therefore routinely quantify and document pain intensity, location and quality as characterized by the patient (whenever possible). Include patient reporting of breakthrough pain, treatments used and their impact on pain, adverse effects of treatments, satisfaction with pain relief,...
  • Bullet 3 revised: If necessaryWhenever possible, get additional information from caregiver regarding pain and impact on function.
• Management/Intervention
  • Bullet 4 modified: For acute, severe pain or pain crisis, consider urgent evaluation and hospital or inpatient hospice admission.

PAIN-3

• Management of Pain in Opioid-Naïve Patients
  • General Principles
    • Bullet 3 modified: Analgesic regimen may include an opioids.... (Also for PAIN-4)
    • Bullet 5 modified: Provide psychosocial/spiritual support (PAIN-C). (Also for PAIN-4)
    • Bullet 7 modified: Optimize integrative interventions (PAIN-D), interventional strategies (PAIN-M), and multidisciplinary care (PAIN-L). (Also for PAIN-4)
  • Moderate/Severe Pain
    • Sub-bullet added: Buprenorphine is an option (5 mcg/hr transdermal patch every 7 days or buccal film 75 mcg 1–2 times/day) for patients with consistent pain, and who may be more sensitive to full agonist opioid side effects (eg, constipation, confusion, respiratory depression, etc)

PAIN-3A

• Footnote added: Buprenorphine can take hours to take effect. Treat severe pain with immediate release opioids.

PAIN-A 2 of 2

• Pain Assessment in the Nonverbal Patient
  • Bullet 4, link updated to IASP website for Patient Assessment in Dementia

PAIN-B 2 of 3

• Comprehensive Pain Assessment
  • Sub-bullet 4, first diamond revised: Patient, environmental, and social factors as identified by a detailed patient evaluation and/or screening tools at initiation of care (eg, NIDA Single-Question Screening Test, SOAPP-R, ORT, CAGE-AID) and monitoring of ongoing analgesic use (eg, COMM) (Specific screening tools have not been validated in the setting of cancer care) (PAIN-G, 6 of 21). These screening tools may help identify risks for SUD but not for risk of diversion.
    • Reference added: Smith PC, Schmidt SM, Allensworth-Davies D, Saitz R. A Single-Question Screening Test for Drug Use in Primary Care. Arch Intern Med 2010;170:1155–1160.
    • Reference removed: Meltzer EC, Rybin D, Saitz R, et al. Identifying prescription opioid use disorder in primary care: diagnostic characteristics of the current opioid misuse measure (COMM). Pain 2011;152:397-402.

PAIN-C

• Section header modified: Psychosocial/Spiritual Support

PAIN-D

• Section header modified: Non-Pharmacologic and Integrative Interventions
  • Text modified: Consider integrative interventions alone or in conjunction with pharmacologic interventions as needed.
  • Text modified: Pain likely to be relieved or function improved with cognitive, spiritual, physical, or interventional nutritional modalities

PAIN-E 1 of 2

• NSAIDs
  • Bullet 5 revised: Consider topical NSAID for peripheral joint pain due to reduced systemic absorption - diclofenac gel 1% 4 times/day; diclofenac solution 2% 4 times/day; or diclofenac patch 1.3% 1–2 patches/day

PAIN-E 2 of 2

• Reference updated: Antman EM, Bennett JS, Daugherty A, et al. Use of nonsteroidal antiinflammatory drugs: an update for clinicians. A scientific statement from the American Heart Association. Circulation 2007;115:1634-1642. Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med 2016;375:2519-29.

PAIN-F 2 of 2

• Anticonvulsants
  • Sub-bullet 2 modified: Pregabalin- Starting dose 50–75 mg twice a day nightly, increasing to twice a day and then with increasing dose increments...
  • Sub-bullet 3 modified: Consider other anticonvulsant agents, many of which have been shown to have efficacy in non-cancer neuropathic pain. See Table 2 in the Discussion section for Potential Drug-Drug Interactions.
• Antidepressants
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
    • Sub-bullet 2 modified: Venlafaxine ER

PAIN-G 3 of 21

• Principles of Opioid Dose Reduction in Cancer Pain Management
  • This page has been extensively revised

PAIN-G 4 of 21

• Opioids and Risk Evaluation and Mitigation Strategy (REMS)
  • Bullet 1 modified: In 2021, 106,699 drug overdose deaths occurred in the United States, including 80,411 deaths involving opioids.In 2023, 105,007 drug overdose deaths occurred in the United States, including 79,358 deaths involving opioids. ....See CDC Drug Overdose Death Data (December 2022December 2024)

PAIN-G 5 of 21

• Table 1. Glossary of Terms Related to Opioid Misuse
  • Definition added for aberrant drug-related behavior: Behavior that suggests substance misuse, a substance use disorder, or diversion is known as aberrant drug-related behavior.

PAIN-G 6 of 21

• Opioid Risk Mitigation Strategies During Chronic Opioid Use
  • Bullet 2, Risk assessment, sub-bullets revised:
    • Current Opioid Misuse Measure (COMM)
    • NIDA Single-Question Screening Test
• Patients with increased risk for OUD
  • Bullet 6 added: If a patient has both cancer pain and OUD, both conditions should be treated.

PAIN-G 7 of 21

• Urine Drug Testing
  • General Principles
    • Bullet 3 modified: UDT should be strongly considered at baseline...
  • Urine Drug Screen Monitoring in Cancer Pain Management
    • Bullet 1 modified: UDT should be considered as part of a comprehensive safety monitoring program...
    • Bullet 2 modified: Therefore, it is recommended that, for all patients receiving opioids for subacute and/or chronic cancer-related pain, strong consideration be given to UDT prior to initiating opioid therapy...
  • Limitations of Monitoring
    • Bullet 2 modified: More specific mass spectrometry and/or quantitative UDT significantly increases drug costs and...

PAIN-G 10 of 21

• Table 2. Oral and Parenteral Opioid Equivalences and Relative Potency of Drugs as Compared with Morphine Based on Single-Dose Studies
  • Methadone: Link to PAIN-G 17 of 21 added
  • Buprenorphine added to table with link to PAIN-G 14 of 21
• Text box modified: Not recommended for cancer pain
• Footnote c revised: In single-dose administration, 10 mg IV morphine is equivalent to approximately 100 mcg IV fentanyl; however, with repeated(steady-state) fentanyl administrationchronic fentanyl administration,....
• Footnote l revised: Mixed agonists-antagonists have limited usefulnessare not recommended for use in cancer pain;...

PAIN-G 11 of 21

• Case Example of Converting IV Morphine to IV Hydromorphone
  • Number 3, text modified:
    • If patientpain was effectively controlled
    • If dose of IV morphine was ineffective in controlling painIf pain was ineffectively controlled with IV morphine (192 mg/day),...

PAIN-G 13 of 21

• Link updated: See transdermal fentanyl package insertFDA websitefor conversion tables from morphine and other opioids to transdermal fentanyl.

PAIN-G 14 of 21

• Buprenorphine for Cancer Pain
  • Sub-bullet removed: Due to its long-duration of effect, it is best used in patients with stable and predictable opioid requirements.
  • Sub-bullet added: The recommended starting dose of buprenorphine transdermal for opioid-naïve patients is a 5 mcg/hour patch every 7 days or 75 mcg buccal film once or twice a day.
• Buprenorphine for Chronic Pain
  • Bullet 2 modified: In selected cases, buprenorphine use may behas been associated with effectivebetter pain control without precipitating opioid withdrawal in patients with pain and on long-term opioid therapy (when using the correct induction method [ie, low-dose]).
• Buprenorphine for OUD
  • Bullet 2, sub-bullet 1 modified: Patients with OUD may be at higher risk for poorly controlled cancer-associated pain. This is due to higher opioid tolerance and related increased sensitivity to pain.

PAIN-G 15 of 21

• Adding an Opioid (full mu-agonist) to Treat Pain in a Patient Receiving Buprenorphine for OUD
  • Bullet 3, sub-bullet 1 modified: In select patients with cancer pain, buprenorphine-naloxone alone may be an effective analgesic. In general, the formulations used for OUD may be used interchangeably. Maintenance doses of buprenorphine as MOUD (medication for treatment of OUD) will not typically be adequate to treat new acute pain, and patients will need an increase in the buprenorphine dosing or an additional full agonist opioid for acute pain.
• Pitfalls of Adding Buprenorphine to a Full Opioid Agonist
  • Bullet 3 modified: Discontinue all around-the-clock and long-acting opioids when initiating buprenorphine. For patients who are maintained on full agonist opioids chronically, these patients can be rotated to buprenorphine while maintaining adequate analgesia. Consider consultation with pain management or palliative care specialist with experience in low-dose initiation techniques.

PAIN-G 16 of 21

• Buprenorphine Buccal Film for Chronic Pain
  • Bullet 2 revised: ....Do not exceed 900 mcg (every 12 hours) due to risk of QTc interval prolongation.
• Transdermal Buprenorphine Patch for Chronic Pain
  • Bullet 2 modified: ....minimal titration interval is 72 hours. Increase buprenorphine patch as needed after 72 hours.
  • Bullet added: If patient is receiving 20 mcg/h patch and requires dose escalation, 20 mcg/h is equal to transdermal fentanyl 25 mcg/h.
• Table 3
  • Bullet 3 modified: Consider consultation with pain management specialist or OUD specialist familiar with buprenorphine initiation and titration.
  • Footnote n added: If there is a need to escalate above 160 mg, consult pain medicine specialist.

PAIN-G 18 of 21

• Convert from Oral Morphine to Oral Methadone
  • Number 3, text modified: Divide the total daily PO methadone dose into 2–42 or 3 daily doses.

PAIN-G 19 of 21

• Mixed-Mechanism Drugs
  • Bullet 1, sub-bullet 2 added: Tramadol decreases the seizure threshold, and has risk of both opioid and serotonin withdrawal even after short-term use (days).
• Non-Opioid Analgesic (given in collaboration with a pain/palliative care specialist)
  • Bullet 2 modified: IV lidocaine infusion may be a useful therapy for refractory pain; however data is limited.

PAIN-G 20 of 21 and PAIN-G 21 of 21

• References have been updated.

PAIN-H 1 of 3

• Management of Opioid Adverse Effects
  • Constipation
    • Text/link added to header: (see also NCCN Guidelines for Palliative Care)
    • Bullet 3, sub-bullet 2 added: If impaction, manual disimpaction may be necessary.

PAIN-H 2 of 3

• Nausea
  • Bullet 4 modified: Consider side effect profile when selecting an antiemetic, as some side effects may be of benefit to other symptoms (eg, metoclopramide for constipation, olanzapine for insomnia and cancer cachexia).
• Delirium
  • Bullet 4 modified: If delirious behavior necessitates medical intervention (eg, behavior causes risk of harm to self or others),...

PAIN-H 3 of 3

• Motor and Cognitive Impairment
  • Bullet 3 modified: Consider evaluation for driving impairment, often done through occupational therapy, neuropsychiatry, or rehabilitation programs.

PAIN-I 1 of 2

• Patient and Family/Caregiver Education
  • Messages to be conveyed to patient and family/caregiver regarding opioid analgesics
    • Bullet 2, sub-bullet 2 added: Offer nasal naloxone if patient has >50 mg MEDDs, is co-prescribed benzodiazepines, or has a history of opioid overdose or OUD.

PAIN-K

• Bone pain without oncologic emergency
  • Sub-bullet 2 modified: Consider bone-modifying agents to prevent additional fractures (eg, bisphosphonates, denosumab).

PAIN-M

• Interventional Consultation
  • Bullet 1, sub-bullet 1 modified: ...anal/rectal/external genitalia with ganglion impar, chest wall with intercostal nerve block)
  • Bullet 1, sub-bullet 3 modified: Desire to avoid or limit systemic opioid administration in the setting of regional pain
  • Bullet 1, sub-bullet 4 added: Regional chronic pain syndromes in patients with cancer

• Bullet 2, sub-bullets modified:
  • Regional nerve blockinfusions (may requires infusion pump for continuous drug administration)
  • Epidural: ...prolonged use beyond several days to a few weeks is limited by concerns for catheter displacement and infection
  • Intrathecal: ...implanted infusion pumps may be costlycost-effective over several months of use,....
  • Percutaneous vertebral augmentation, radiofrequency or ablative procedure, and/or cementoplasty for bone lesions
  • Head and neck: peripheral neurolysis generallypossibly associated with sensory and/or motor deficit
  • For rare cases of refractory pain:
    • Unilateral pain syndromes: consider neuroablative procedures such as cordotomy (depending on availability and surgical expertise)

PAIN-N

• Principles of Pharmacogenetics
  • Bullet 2 revised: (metabolic enzymes, ie, cytochrome P450 [CYP450]CYP P450)
  • Bullet 4 revised: Many commonly prescribed analgesics are metabolized via CYP450 enzymesP450 (CYP) such as...

 

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