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 1.2023.

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

General

• "Abuse" and "addiction" have been removed from the Guideline in all appropriate instances and changed to misuse or substance use disorders.
• Terminologies have been modified to be more inclusive of all sexual and gender identities.

PAIN-1

Principles of Cancer Pain Management

• General Principles
  • Bullet 2 revised: Pain management is an essential part of oncologic management and contributes to overall function and quality of life.
  • Bullet 4 revised: Aninterdisciplinarymultidisciplinary team is optimal (See PAIN-L); consider early referral to a palliative care provider.
  • Bullet 6 revised: Provide accessible educational material to improve pain assessment, pain management, and the safe use of opioid medicationsanalgesics based on the patient’s identified needs.
    • Sub-bullet modified: Involve patients in developing treatment plans and setting meaningful, realistic expectations and measurable goals to include patient values and preferences.
• Assessment
  • Bullet 2 revised: ...and any special issues for the patient relevant to pain treatment and access to care.
• Management/Intervention
  • Number 4 modified: Aberrant drug taking (avoid aberrant drug taking) Aberrant behavior (monitor for aberrant drug-use behavior)

PAIN-2

Assessment

• Comprehensive pain assessment
  • Bullet added: Estimated trajectory of pain
• Pathway added for pain not related to cancer or cancer treatment with referral or coordination with appropriate pain provider or program.

PAIN-3

Management of Pain in Opioid-Naive Patients

• General Principles
  • Bullet 2 revised: Select the most appropriate medicationanalgesic regimen based on the pain diagnosis, comorbid conditions, safety, and potential drug interactions, estimated trajectory of pain, medication availability, and expense/financial toxicity (Also for PAIN-4)
  • Bullet 7 revised: Optimize integrative interventions and multidisciplinary care (See PAIN-L) (Also for PAIN-4)

• Moderate/Severe Pain
  • The following bullets have been reordered and modified:
    • Morphine 5 mg (solution) or immediate release (IR) 7.5 mg (1/2 tablet) (1/2 of a 15 mg tablet),when appropriate
    • Hydromorphone 2 mg PO
    • Oxycodone IR 2.5–5 mg with or without acetaminophen 325 mg
    • Hydrocodone 5 mg with acetaminophen 325 mg
  • Bullet 4 revised: If 4 or moremultiple doses of short-acting opioid are consistently needed per day, consider addition or increase in dose of a long-acting opioid based on the total daily dose (Also for PAIN-4)

PAIN-3A

• Footnote added: See Non-Opioid Analgesic (Nonsteroidal Anti-Inflammatory Drugs [NSAIDS] and Acetaminophen) Prescribing (PAIN-E)

PAIN-4

• Moderate/Severe Pain
  • Bullet 3 revised: Titrate short-acting opioid (may require dose increase of 30%–50% or more30%–100%)
• Severe Pain/Pain Crisis
  • Text modified: For acute, severe pain or pain crisis, consider hospital or inpatient hospice admission to rapidly titrate analgesic and quickly achieve patient-specific goals for comfort and function

PAIN-5

Management of Pain Crisis

• Revised: Oral analgesics - immediate release
• Footnote added: Preference of oral or IV/subcutaneous route of delivery may differ based on the location of care.

PAIN-6

Ongoing Care

• Bullet 5: Ensure continuity of care during transition between sites of care
  • Sub-bullet added: Ensure adequate access and supply of analgesics

PAIN-A 1 of 2

• Table 2: The Faces Pain Rating Scale - Revised
  • Reference updated

PAIN-B 1 of 3

Comprehensive Pain Assessment

• Bullet 2 revised: Individualized pain treatment is based on the etiology and characteristics of pain, pain trajectory, the patient's clinical condition, and patient-centered goals of care.
• Pain experience (continued)
  • Sub-bullet 4, diamond 1 revised: Meaning and consequences of pain for patient and family/caregiver including patient experience of medical or other trauma

PAIN-B 2 of 3

• Psychosocial Support
  • Risk factors for undertreatment of pain
    • Sub-bullet revised: People who are older, female, or historically marginalized; Geriatric, minority, or female patients; communication barriers; history of substance abuseuse disorders; neuropathic pain; cultural factors
    • Footnote added: On this page, the term "female" refers to sex assigned at birth based on the availability of data in this population. However, it is important to note that transgender individuals may also be at risk of undertreatment of pain.

PAIN-C

Psychosocial Support

• Support
  • Bullet 7 revised: Inform patient and family/caregiver of continued partnershipthat there is always something else that can be done to try to adequately manage pain and other noxious symptoms
• Skills Training
  • Bullet 2 revised: Members of the team may include: oncologist, nurse, palliative care clinician, integrative medicine clinician...

PAIN-D

Integrative Interventions

• Cognitive modalities
  • Moved to first bullet: Cognitive behavioral therapy (CBT), cognitive restructuring

PAIN-E 1 of 2

Non-Opioid Analgesic (Nonsteroidal Anti-Inflammatory Drugs [NSAIDS] and Acetaminophen) Prescribing

• Acetaminophen
  • Bullet 1 revised: For chronic administration or use in older adults, consider limiting the maximum daily dose to 3 g/day or less due to concerns for hepatic toxicity.
• NSAIDs
  • Bullet 1: See PAIN-E 2 of 2 link added
    • Sub-bullet 1 revised: NSAID use should be coordinated with other oncologic therapies.If an NSAID is determined to be of analgesic benefit, use should be coordinated with other oncologic therapies to avoid unintended risk of adverse effects.
  • Bullet 4, sub-bullet 1 revised: Ibuprofen, 400–800 mg four times daily (daily maximum = 3200 mg)
  • Bullet 5 revised: Consider topical NSAID for peripheral joint pain due to reduced systemic absorption - diclofenac gel 1% 4 times/day; or diclofenac patch 180 mg1.3% 1–2 patches/day

PAIN-F 2 of 2

Adjuvant Analgesics for Neuropathic Pain

• Antidepressants
  • Bullet 3, sub-bullet added: TCAs should be used with caution in older adults due to increased risk for falls, confusion, and anticholinergic adverse effects.
• Topical Agents
  • Topical agent examples, sub-bullet added: Topical NSAIDs - See PAIN-E 1 of 2

PAIN-G

Opioid Principles, Prescribing, Initiation, Titration, Maintenance, and Safety

• Landing page added, pages have been reorganized

PAIN-G 1 of 18

• General Principles
  • Bullet 1 revised: Periodically Review prescription drug monitoring program (PDMP) databases as appropriate based on clinical necessity and regulatory requirements.
  • Bullet 2 revised: Consider Documentationof opioid and controlled substance agreement as appropriate per regulatory requirements.
  • Bullet 14 revised: Use caution when combining opioid medications with other medications that have a sedating effect (eg, benzodiazepines) due to increased risk for sedation and respiratory depression

PAIN-G 2 of 18

• Principles of Maintenance Opioid Therapy
  • Bullet 2, sub-bullet 1 revised: ....depending on expected pain natural history trajectory.
  • Bullet 5 revised: Breakthrough pain (pain that fails to be controlled or “breaks through” a regimen of regularly scheduled opioid analgesic) may require additional doses of opioid analgesicfor pain not relieved by regular schedule of long-acting (eg, extended-release) opioid analgesic.
  • Bullet 7, sub-bullet 1 removed: Data do not support a specific transmucosal fentanyl dose equianalgesic to other opioids or between different transmucosal formulations
  • Bullet 7, sub-bullet 2 revised: Always Initiate transmucosal fentanyl with lowest dose in chosen formulation and titrate to effect. (See specific transmucosal prescribing information for appropriate dosing intervals and initial dosing recommendations).

PAIN-G 3 of 18

• Principles of Opioid Dose Reduction
  • Bullet 1 revised: Consider opioid dose reduction by 10%5% to 20% when: possible; situations that may warrant dose reduction include:
    • Link added: https://www.cms.gov/About-CMS/Story-Page/CDCs-Tapering-Guidance.pdf
  • Bullet 2, sub-bullet 1: Link to PAIN-H 3 of 3 added
  • Bullet 3 removed: If pain is worsened with increasing dose, consider opioid-induced hyperalgesia; opioid dose reduction or rotation with attention to other pain therapies may be indicated.
  • Bullet added: Review expected trajectory of pain and goals of care/pain management when considering opioid dose reduction.

PAIN-G 4 of 18

• Opioids and Risk Evaluation and Mitigation Strategy (REMS)
  • Bullet 1, data updated: Opioids are the principal analgesics for moderate to severe pain, yet opioids pose risks to patients and society. In 20182021, 67,367106,699 drug overdose deaths occurred in the United States, including 46,80280,411 deaths involving opioids.
    • Link updated: CDC Drug Overdose Death Data (December 2022)
  • Bullet 5 revised: ...pain management should be carried out in coordination with an addiction a substance use disorders specialist and consider referral to a pain specialist.

PAIN-G 5 of 18

• Table 1. Glossary of Terms Related to Opioid Misuse
  • Addiction definition removed and replaced with "See Substance use disorders"
  • Abuse and opioid use disorder removed
  • Substance use disorders (including opioid use disorder) added with definition

PAIN-G 6 of 18

• Title modified: Strategies to Maintain Patient Safety and Minimize the Risk of Opioid Misuse and Abuse During Chronic Opioid UseOpioid Risk Mitigation Strategies During Chronic Opioid Use
• Risk Assessment
  • Link updated: The Opioid Risk Tool (ORT)
• Educate
  • Sub-bullet 2 revised: Provide guidance and education about the potential for diversion and misuse of opioids and the addictive potential associated with prescription opioids.
• Risk Mitigation for All Patients Receiving Opioid Analgesics
  • Bullet added: Review PDMP databases as appropriate based on clinical necessity and regulatory requirements.
  • Bullet 2 revised: Consider prescribingDiscuss the role of naloxone for administration by caregivers in the event of respiratory depression and sedation and make available as indicated.
• Text modified: High-risk patients who exhibit one or more opioid misuse and abuse risk factors may benefit from additional education and support services.
  • Bullet 3 revised: Consider referral to interdisciplinarymultidisciplinary team including a specialist for substance use disordersan addiction specialist.

PAIN-G 7 of 18

• Table 2: Parenteral Dose removed for oxymorphone and tramadol
• Footnote d revised and reference added: Long half-life with marked variability(may be between 15–120 hours [Chou R, et al. J Pain 2014;15:321-337]) observe for drug accumulation and adverse effects, especially over first 4–5 days.
• Footnote g revised: Codeine has no analgesic effect unless it is metabolized into morphine by hepatic enzyme CYP2D6 and then to its active metabolite morphine-6-glucuronide by phase II metabolic pathways. (See PAIN-N) Individuals with low CYP2D6 activity may receive no analgesic effect from codeine, but rapid metabolizers may experience toxicity from higher morphine production. Dosage must be monitored for safe limits as it may be available in combination with ASA or acetaminophen. Dose listed refers only to opioid portion.

PAIN-G 9 of 18

• Transdermal Fentanyl
  • Title revised: Special NotesGeneral Comments Regarding Transdermal Fentanyl
  • Text added: Convert or Rotate From Another Opioid to Transdermal Fentanyl, see PAIN-G 10 of 18

PAIN-G 10 of 18

• Link added to package insert for transdermal fentanyl with text: See transdermal fentanyl package insert for conversion tables from morphine and other opioids to transdermal fentanyl.

PAIN-G 12 of 18

• Buprenorphine
  • Regulatory requirements for use of buprenorphine have been revised with DEA regulation changes as of 2023
  • Adding an opioid (full mu-agonist) to treat pain in a patient receiving buprenorphine for OUD
    • Bullets have been reordered and revised
  • Pitfalls of adding buprenorphine to a full opioid agonist
    • Bullet 2 revised: Reduce the risk of opioid withdrawal, according to FDA recommendations, by decreasing the dose of the current opioid to no more than 30 mg/day oral morphine mg equivalents (MME) (immediate-release only) before starting buprenorphine. Those with experience in buprenorphine conversion may recommend other dosing strategies.

PAIN-G 13 of 18

• Transdermal Buprenorphine Patch for chronic pain
  • Bullet 3 revised: Transdermal patches of 7.5, 10, 15, and 20 mcg/hour are only for use in patients who are opioid-tolerant. Do not exceed 20 mcg/h due to risk of QTc prolongation.
• Table 3. Dose Conversion Guidelines for Daily Oral Morphine Equivalents to Buprenorphine
  • Bullet 2 revised: Other micro dosinglow-dose initiation protocols have been described. Consider consultation with pain management specialist or OUD specialist familiar with buprenorphine initiation.

PAIN-G 14 of 18

• Methadone
  • Text revised and reference added: Due to the unique nature of methadone with a long and variable half-life (may be between 15–120 hours [Chou R, et al. J Pain 2014;15:321-337])
  • Cautions Regarding Oral Methadone Use
    • Bullet 3 revised: If more rapid titration is desired, consult with a pain or palliative care specialist or experienced methadone prescriber.
    • Bullet 3, sub-bullet 1 revised: 5–7 days is the time to steady state, and therefore, marked improvement in the first 2–3 days of methadoneor any significant sedation significant improvement in pain OR immediate resolution of pain prior to the 5th day of methadone may indicate the dose is too high and the patient may be at risk of oversedation or respiratory depression by day 5–7 if the dose is not immediately adjusted.
    • Bullet 5 revised: Electrocardiogram (ECG) should be considered prior to initiation and when methadone doses exceed 30–40 mg/day and again with dose of 100 mg/day and should be performed prior to initiation of methadone in patients who have risk factors for increased QTc, including medications that may lengthen QTc (including some chemotherapies and biologic agents).
      • Sub-bullet removed: Consider ECG when doses exceed 30–40 mg/day and again with dose of 100 mg/day. Obtain follow-up ECGs in patients with risk factors for prolonged QTc after initiation of methadone.(http://www.jpain.org/article/S1526-5900(14)00522-7/fulltext)

PAIN-G 16 of 18

• Bullet 1, text added: (See PAIN-N for pharmacogenetic considerations).

PAIN-H 1 of 3

Management of Opioid Adverse Effects

• Principles of Managing Opioid Adverse Effects
  • Bullet 6 revised: Chronic opioid therapy may depress HPA axis and cause hypogonadism in males and females.
• Constipation
  • Prophylactic medications
    • Sub-bullet modified: Stimulant laxative (eg, senna, 2 tablets daily; FDA recommended maximum 8 tablets per day of senna)

PAIN-H 2 of 3

• Nausea
  • Alternative agents to consider
    • Modified: Olanzapine 2.5–5 mg QHS (every night at bedtime)
    • Added: Mirtazapine
• Delirium
  • Bullet 5 revised: For further information about delirium, including non-pharmacologic management, see NCCN Guidelines for Palliative Care.

PAIN-H 3 of 3

• Respiratory Depression
  • Bullet 1 revised: Sedation oftentypically precedes respiratory depression; therefore, progressive sedation should be noted and adjustments in care should be made.

PAIN-I 1 of 2

Patient and Family/Caregiver Education

• Messages to be conveyed to patient and family/caregiver regarding management of pain
  • Bullet 3 revised: Patients with pain often have other symptoms (eg, anxiety, constipation, nausea, fatigue, insomnia, depression)...
  • Bullet added: Educate patient and families on the processes contributing to their pain.
• Messages to be conveyed to patient and family/caregiver regarding opioid analgesics
  • Bullet 3, sub-bullet 3 revised: Analgesics must be in a secured location, preferably in a locked box and not in a medicine cabinet to avoid danger to others/diversion.

PAIN-K

Management Strategies for Specific Cancer Pain Syndromes

• Bullet added for disease-specific pain: refer to tumor-specific guidelines for details on palliative radiation as applicable.

PAIN-L

Specialty Consultations for Improved Pain Management

• Mental health consultation
  • Bullet 4: Evidence-based treatment modalities
    • Music therapy and yoga/meditation added

PAIN-M

Interventional Strategies

• Interventional consultation
  • Bullet 2, sub-bullet 4 revised: Neurostimulation procedures (ie, spinal cord, dorsal root ganglion, peripheral nerve stimulation) for cancer-related symptoms(ie, peripheral neuropathy, plexitis, neuralgias, complex regional pain syndrome)

ABBR-1

• New section added: Abbreviations

 

 

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