NCCN CLINICAL PRACTICE GUIDELINES IN ONCOLOGY Adult Cancer Pain, Version 3.2019 Robert A. Swarm, MD1,*; Judith A. Paice, PhD, RN2,*; Doralina L. Anghelescu, MD3,*; Madhuri Are, MD4; Justine Yang Bruce, MD5; Sorin Buga, MD6,*; Marcin Chwistek, MD7,*; Charles Cleeland, PhD8; David Craig, PharmD9,*; Ellin Gafford, MD10; Heather Greenlee, PhD, ND11,*; Eric Hansen, MD12; Arif H. Kamal, MD, MBA, MHS13; Mihir M. Kamdar, MD14; Susan LeGrand, MD15; Sean Mackey, MD, PhD16; M. Rachel McDowell, MSN, ACNP-BC17; Natalie Moryl, MD18,*; Lisle M. Nabell, MD19; Suzanne Nesbit, PharmD, BCPS20; Nina O’Connor, MD21; Michael W. Rabow, MD22,*; Elizabeth Rickerson, MD23; Rebecca Shatsky, MD24; Jill Sindt, MD25,*; Susan G. Urba, MD26; Jeanie M. Youngwerth, MD27,*; Lydia J. Hammond, MBA28,*; and Lisa A. Gurski, PhD28,* ABSTRACT NCCN CATEGORIES OF EVIDENCE AND CONSENSUS Category 1: Based upon high-level evidence, there is uni- In recent years, the NCCN Clinical Practice Guidelines in Oncology form NCCN consensus that the intervention is appropriate. (NCCN Guidelines) for Adult Cancer Pain have undergone substantial Category 2A: Based upon lower-level evidence, there is uniform revisions focusing on the appropriate and safe prescription of opioid NCCN consensus that the intervention is appropriate. analgesics, optimization of nonopioid analgesics and adjuvant medica- Category 2B: Based upon lower-level evidence, there is NCCN tions, and integration of nonpharmacologic methods of cancer pain consensus that the intervention is appropriate. management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic Category 3: Based upon any level of evidence, there is major interventions, nonpharmacologic interventions, and treatment of specific NCCN disagreement that the intervention is appropriate. cancer pain syndromes. The complete version of the NCCN Guidelines All recommendations are category 2A unless otherwise for Adult Cancer Pain addresses additional aspects of this topic, including noted. pathophysiologic classification of cancer pain syndromes, comprehen- sive pain assessment, management of pain crisis, ongoing care for cancer Clinical trials: NCCN believes that the best management of pain, pain in cancer survivors, and specialty consultations. any patient with cancer is in a clinical trial. Participation in J Natl Compr Canc Netw 2019;17(8):977–1007 clinical trials is especially encouraged. doi: 10.6004/jnccn.2019.0038 PLEASE NOTE The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use, or application and dis- claims any responsibility for their application or use in any way. 1Siteman Cancer Center at Barnes-Jewish Hospital and Washington University The complete NCCN Guidelines for Adult Cancer Pain are not School of Medicine; 2Robert H. Lurie Comprehensive Cancer Center of printed in this issue of JNCCN but can be accessed online at Northwestern University; 3St. Jude Children’s Research Hospital/The University NCCN.org. of Tennessee Health Science Center; 4Fred & Pamela Buffett Cancer Center; 5University of Wisconsin Carbone Cancer Center; 6City of Hope National © National Comprehensive Cancer Network, Inc. 2019. All Medical Center; 7Fox Chase Cancer Center; 8The University of Texas MD rights reserved. The NCCN Guidelines and the illustrations Anderson Cancer Center; 9Moffitt Cancer Center; 10The Ohio State University herein may not be reproduced in any form without the express Comprehensive Cancer Center - James Cancer Hospital and Solove Research written permission of NCCN. Institute; 11Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; 12Roswell Park Comprehensive Cancer Center; 13Duke Cancer Disclosures for the NCCN Adult Cancer Pain Panel Institute; 14Massachusetts General Hospital Cancer Center; 15Case At the beginning of each NCCN Guidelines Panel meeting, Comprehensive Cancer Center/University Hospitals Seidman Cancer Center fl and Cleveland Clinic Taussig Cancer Institute; 16Stanford Cancer Institute; panel members review all potential con icts of interest. NCCN, in 17Vanderbilt-Ingram Cancer Center; 18Memorial Sloan Kettering Cancer Center; keeping with its commitment to public transparency, publishes 19O’Neal Comprehensive Cancer Center at UAB; 20The Sidney Kimmel these disclosures for panel members, staff, and NCCN itself. Comprehensive Cancer Center at Johns Hopkins; 21Abramson Cancer Center at Individual disclosures for the NCCN Adult Cancer Pain Panel the University of Pennsylvania; 22UCSF Helen Diller Family Comprehensive members can be found on page 1007. (The most recent version Cancer Center; 23Dana-Farber/Brigham and Women’s Cancer Center; 24UC San of these guidelines and accompanying disclosures are available Diego Moores Cancer Center; 25Huntsman Cancer Institute at the University of at NCCN.org.) Utah; 26University of Michigan Rogel Cancer Center; 27University of Colorado Cancer Center; and 28National Comprehensive Cancer Network The complete and most recent version of these guidelines is available free of charge at NCCN.org. *Discussion Writing Committee Member JNCCN.org | Volume 17 Issue 8 | August 2019 977 NCCN GUIDELINES® Adult Cancer Pain, Version 3.2019 Overview the use of opioids to patients with cancer in the setting of Pain is one of the most common symptoms associated the United States opioid epidemic.10,11 with cancer. Pain is defined by the International Asso- Goals of pain management are to optimize pain ciation for the Study of Pain as an unpleasant sensory treatment outcomes in 5 dimensions, frequently referred and emotional experience associated with actual or to as the “5As” of pain management outcomes (the “4As” potential tissue damage, or described in relation to such originally proposed by Passik and Weinreb12 were later damage.1 Cancer pain or cancer-related pain distin- amended to include “affect”): guishes pain experienced by patients with cancer from ○ Analgesia: optimize analgesia (pain relief) that experienced by patients without malignancies. A ○ Activities: optimize activities of daily living (psychosocial meta-analysis revealed that pain was reported in 59% functioning) of patients undergoing cancer treatment, in 64% of ○ Adverse effects: minimize adverse events patients with advanced disease, and in 33% of patients ○ Aberrant drug taking: avoid aberrant drug taking after curative treatment.2 Inaddition,thisisoneof (addiction-related outcomes) thesymptomspatientsfearmost.Unrelievedpain ○ Affect: relationship between pain and mood denies patients comfort and greatly affects their ac- tivities, motivation, interactions with family and friends, The importance of relieving pain and the availability ff and overall quality of life.3 Evidence is mounting in oncology of e ective therapies make it imperative that health that quality of life and survival are linked to early and ef- care providers be adept at cancer pain assessment 13–15 fective palliative care, including pain management.4–9 Al- and treatment. This requires familiarity with the though improvements have been observed, undertreatment pathogenesis of cancer pain, pain assessment tech- of pain remains an issue in a significant subset of patients niques, and common barriers to the delivery of ap- with cancer and this issue may be exacerbated by the propriate analgesia. Providers should be familiar with inappropriate application of recommendations against pertinent pharmacologic, anesthetic, neurosurgical, and 978 © JNCCN—Journal of the National Comprehensive Cancer Network | Volume 17 Issue 8 | August 2019 Adult Cancer Pain, Version 3.2019 NCCN GUIDELINES® behavioral interventions for treating cancer pain, as well as result, they provide dosing guidelines for opioids, nonopioid complementary approaches such as physical/occupational analgesics, and adjuvant analgesics. They also provide therapy. specific suggestions for titration and rotation of opi- The most widely accepted algorithm for the treat- oids, escalation of opioid dosage, management of ment of cancer pain was developed by the WHO.16,17 It opioid adverse effects, and when and how to proceed to suggests that patients with pain be started on acet- other techniques/interventions for the management of aminophen or a nonsteroidal anti-inflammatory drug cancer pain. (NSAID). If this is not sufficient, therapy should be escalated to a “weak opioid” such as codeine and Management of Adult Cancer Pain subsequently to a “strong opioid” such as morphine. For management of cancer-related pain in adults, the Although this algorithm has served as an excellent algorithm distinguishes 3 levels of pain intensity based teaching tool, the management of cancer pain is consid- on a 0 to 10 numerical value obtained using a numerical erably more complex than this 3-tiered “cancer pain lad- or pictorial rating scale (with 0 being no pain to 10 being der” suggests. the worst pain). The 3 levels of pain intensity referred to These NCCN Clinical Practice Guidelines in Oncol- in the algorithm are mild pain (1–3); moderate pain (4–7); ogy (NCCN Guidelines) for Adult Cancer