NCCN Flash Updates: NCCN Guidelines^® and NCCN Compendium^® Updated for Smoking Cessation and More

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), and the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) for Smoking Cessation. These NCCN Guidelines^® are currently available as Version 1.2021.

New link to the Summary of Updates in the Guidelines:
NCCN Guidelines for Smoking Cessation

• Initial evaluation (SC-1)
  • Footnote b modified: Recommendations in this guideline apply to cessation of cigarette all combustible tobacco smoking products. Patients with cancer should be encouraged to discontinue the use of all combustible tobacco products (eg, cigarettes, cigars, hookah) and smokeless tobacco products.
  • Footnote d modified: Smoking status of all tobacco products, including e-cigarettes, should be documented in the patient health record and assessment should be repeated at every visit.
• Current smokers and those who have smoked within last 30 days (SC-2)
  • Nicotine dependence
    • First two bullets combined: How much do you currently smoke or use nicotine products (eg, cigarettes, pipes, cigars, e-cigarettes) per day?
    • Third bullet modified: How soon do you smoke after you wake up in the morning? (ie, within 5 minutes 30 minutes)
  • Footnote g added: Time to first use is utilized to determine short-acting NRT dose. See Discussion.
• General approach to smoking cessation for patients with cancer and survivors (SC-5)
  • Footnote s modified: Combination NRT or varenicline are the preferred pharmacotherapy options. However, varenicline + NRT, bupropion ± NRT, or varenicline + bupropion may be appropriate for select patients. See SC-F.
  • Footnote z modified: Varenicline can be used for as long as needed to maintain abstinence. up to 1 year for continued abstinence.
• Principles of Alternative Approaches to Smoking Cessation (SC-A)
  • Under e-cigarettes, fourth bullet modified: Thus, patients should be counseled toward the use of evidence-based smoking cessation methods. However, if long-term abstinence with e-cigarettes is maintained, continue counseling and redirect to evidence-based methods in the event of relapse.
• Principles of Behavioral Strategies (SC-E, 3 of 3)
  • Bullet modified: At a minimum, Brief advice of about 3 minutes by physicians and other health care providers is associated with a small but important increase in smoking abstinence rates. Research suggests that Longer, more frequent sessions (eg, 10–30 minutes) with trained counselors is associated with higher abstinence rates. The maximum benefit is with more time in intensive and sustained counseling. (eg, 10-30 minutes per session)
  • Reference added: Park ER, Perez GK, Regan S, et al. Effect of sustained smoking cessation counseling and provision of medication vs shorter-term counseling and medication advice on smoking abstinence in patients recently diagnosed with cancer: A randomized clinical trial. JAMA 2020;324:1406-1418.
• Principles of Smoking Cessation Pharmacotherapy
  • Other recommended regimens, option added: Varenicline + NRT (SC-F, 1 of 3)
  • Footnote c added: Any form of NRT or combination NRT (nicotine patch + short-acting NRT) may be used. Studies evaluating the efficacy of varenicline combined with NRT utilized the nicotine patch. (Koegelenberg CF, et al. JAMA 2014;312:155-161.) (SC-F, 1 of 3)
  • Standard Dose/Administration (SC-F, 2 of 3)
    • Combination NRT, short-acting NRT dose modified: 2 or 4 mg; 2 mg preferred if time to first cigarette is >30 minutes after waking; or 4 mg preferred if time to first cigarette is ≤30 minutes after waking.
  • Varenicline, bullets added:
    • If severe renal impairment (estimated creatinine clearance <30 mL/min): Begin with 0.5 mg once daily and titrate to 0.5 mg twice daily 
    • For patients with end-stage renal disease undergoing hemodialysis, 0.5 mg maximum daily, if tolerated
  • Bupropion, bullets added:
    • Renal impairment
    • Hepatic insufficiency impairment: Maximum dose 150 mg every other day for moderate/severe hepatic impairment (Child-Pugh score 7-15); For mild hepatic impairment (Child-Pugh score 5 to 6), consider reducing the dose and/or frequency adjustment.

NCCN has published updates to the NCCN Guidelines and the NCCN Compendium^® for Prostate Cancer. These NCCN Guidelines are currently available as Version 2.2021.

New link to the Summary of Updates in the Guidelines:
NCCN Guidelines for Prostate Cancer

Principles of ADT (PROS-G, pages 1-5)

• ADT for clinically localized (N0, M0) disease, added relugolix as an option before, during, and/or after radiation.
• ADT for regional (N1, M0) disease:
  • Modified: EBRT and neoadjuvant, concurrent, and/or adjuvant LHRH agonist or LHRH antagonist degarelix with abiraterone.
  • Modified: Options for ADT alone or with abiraterone are.
  • Modified: LHRH antagonist, Degarelix (category 2B) or relugolix
  • Modified: Degarelix LHRH antagonist (as above) plus abiraterone
• ADT for pN1 disease, removed (category 2B for LHRH antagonist).
• ADT for M0 PSA persistence/recurrence after RP or EBRT, M0 EBRT PSA persistence/recurrence, TRUS-biopsy negative or M0 PSA persistence/recurrence after progression on salvage EBRT: added relugolix
• ADT for metastatic castration-naïve disease:
  • Modified: LHRH antagonist Degarelix plus docetaxel
  • Modified: LHRH antagonist (as above) Degarelix plus abiraterone, enzalutamide, or apalutamide
• Secondary hormone therapy for M0 or M1 CRPC, modified: Androgen receptor activation and autocrine/paracrine androgen synthesis are potential mechanisms of recurrence of prostate cancer during ADT (CRPC). Thus, castrate levels of testosterone (<50 ng/dL) should be maintained by continuing LHRH agonist or degarelix antagonist while additional therapies are applied.
• ADT for patients on observation who require treatment and those with life expectancy ≤5 years, modified: Treatment for patients who progressed on observation of localized disease is LHRH agonist or antagonist (category 2B for LHRH antagonist) or orchiectomy.
• Optimal ADT:
  • Added:
    • Relugolix has not been adequately studied in combination with potent androgen receptors inhibitors such as enzalutamide, apalutamide, darolutamide, or abiraterone acetate, nor has it been studied in combination with docetaxel or cabazitaxel chemotherapy. Potential drug interactions include induction of cytochrome P450 enzymes and reduced concentration and efficacy of relugolix with enzalutamide or apalutamide and cardiac QTc interactions with abiraterone. Further studies of relugolix dosing and drug interactions with commonly used agents in advanced prostate cancer are needed to ensure patient safety and proper dosing.
    • Data are limited on long-term compliance of oral relugolix and the potential effects on optimal ADT. Ongoing monitoring for sustained suppression of testosterone (less than 50ng/dL) can be considered, and relugolix may not be a preferred agent if patient compliance is uncertain.

Previous updates to the NCCN Guidelines for Prostate Cancer can be found in the UPDATES section of the current version.

NCCN has published updates to the NCCN Guidelines, the NCCN Compendium, the NCCN Imaging AUC™, and the NCCN Radiation Therapy Compendium™, for Merkel Cell Carcinoma. These NCCN Guidelines are currently available as Version 1.2021.

New link to the Summary of Updates in the Guidelines:
NCCN Guidelines for Merkel Cell Carcinoma

• Clinical Presentation (MCC-1)
  • Preliminary Workup; first bullet revised: Complete skin and lymph node examination.
  • Additional Workup; bullet added after H&P: Complete skin and lymph node examination.
• Footnotes (MCC-1A)
  • Footnote c revised: Imaging is encouraged in most cases of MCC. Imaging is encouraged whenever metastatic or unresectable disease is suspected based on H&P findings. Occult metastatic disease that resulted in upstaging has been detected in 12%–20% of patients presenting without suspicious H&P findings (Singh N, et al. J Am Acad Dermatol 2021;84:330-339). Whole-body PET with fused axial imaging (CT or MR) or chest/abdomen/pelvis CT with contrast, with neck CT if primary tumor on head/neck or brain MRI if clinical suspicion, may be useful to identify and quantify regional and distant metastases. Several studies indicate whole-body PET with fused axial imaging is more sensitive for detecting occult metastatic disease at baseline. Imaging may also be useful to evaluate for the possibility of a skin metastasis from a noncutaneous primary neuroendocrine carcinoma (eg, small cell lung cancer), especially in cases where CK20 is negative. The most reliable staging tool to identify subclinical nodal disease is sentinel lymph node biopsy (SLNB). (George A, et al. Nucl Med Commun 2014;35:282-290; Hawryluk EB, et al. J Am Acad Dermatol 2013;68:592-599; Siva S, et al. J Nucl Med 2013;54:1223-1229.) (Also pages MCC-2A and MCC-3).
  • Footnote d revised: Quantitation of serum Merkel cell polyomavirus (MCPyV) oncoprotein antibodies may be considered as part of initial workup; seronegative patients may have a higher risk of recurrence; in seropositive patients, a rising titer may be an early indicator of recurrence; baseline testing should be performed within 3 months of treatment, because titers are expected to decrease significantly after clinically evident disease is eliminated. (Also page MCC-5)
  • Footnote e added: As immunosuppression in MCC is a risk factor for poor outcomes, immunosuppressive treatments should be minimized as clinically feasible in consultation with the relevant managing physician. (Also page MCC-4)
  • Footnote removed: If clinically indicated, whole-body PET with fused axial imaging (CT or MR) or chest/abdomen/pelvis CT with contrast, with or without neck CT and brain MRI, may be useful to identify and quantify regional and distant metastases. Some studies indicate that whole-body PET with fused axial imaging may be preferred in some clinical circumstances. Imaging may also be useful to evaluate for the possibility of a skin metastasis from a noncutaneous primary neuroendocrine carcinoma (eg, small cell lung cancer), especially in cases where CK20 is negative. (Also pages MCC-3 and MCC-5)
• Primary and Adjuvant Treatment of Clinical N0 Disease (MCC-2)
  • First column revised to: Clinical N0 (local MCC only - no disease beyond the primary).
  • Management of the Primary Tumor pathway and associated footnotes were significantly revised.
• Primary and Adjuvant Treatment of Clinical N+ Disease (MCC-3)
  • Second column added: Imaging studies recommended.
  • Pathway for patients with Positive FNA or core biopsy; M0 revised: Clinical trial for neoadjuvant or adjuvant therapy preferred if available.
  • Pathway for patients with Negative FNA or core biopsy; column added: Radiographic surveillance or excisional biopsy.
  • Footnotes
    • Footnote t revised: Neoadjuvant/adjuvant chemotherapy may be considered in select clinical circumstances; however, available retrospective studies do not suggest survival benefit for neoadjuvant/adjuvant chemotherapy. No data are available to support the adjuvant use of immunotherapy outside of a clinical trial. See Principles of Systemic Therapy (MCC-D).
    • Footnote u added: An open biopsy may be considered to confirm a negative initial FNA or core lymph node biopsy if clinical suspicion remains high.
• Follow-up (MCC-5)
  • Footnote x added: Surveillance imaging is typically via diagnostic CT of chest/abdomen/pelvis with oral and IV contrast; neck CT is often included if primary lesion was on head/neck.
• Principles of Pathology (MCC-A)
  • Last bullet revised: SLNB evaluation for metastatic MCC requires complete microscopic evaluation of the SLN(s). Before determining SLNB negativity, multiple H&E levels (recommend at least 2) including H&E and at least one immunohistochemistry stain should be used to help evaluate for metastatic disease....
• Principles of Radiation Therapy (MCC-B 1 of 2)
  • General Treatment Information-Primary MCC Tumor Site; General Dosing Prescription; sub-bullet revised: In the Palliation: A less protracted fractionation palliative setting, a wide range of fractionation schedules may be used, in the palliative setting, such as including less protracted fractionation schedules such as 30 Gy in 10 fractions, 20 Gy in 4 or 5 fractions, or 8 Gy in 1 fraction.
• Principles of Radiation Therapy (MCC-B 2 of 2)
  • General Treatment Information-Draining Nodal Basin
    • Treatment information; sub-bullet revised: Irradiation of in-transit lymphatics is often not feasible unless recommended only when the primary site is in close proximity to the nodal bed.
    • General Dosing Prescription; sub-bullet revised: In the palliative setting, a wide range of fractionation schedules may be used, including less protracted fractionation schedules ranging from such as 30 Gy in 10 fractions, 20 Gy in 4 or 5 fractions, to or 8 Gy in 1 fraction.
• Principles of Excision (MCC-C)
  • Surgical approaches
    • Sub-bullet added: If adjuvant RT is planned, narrow excision margins are likely sufficient. (See MCC-2)
    • Sub-bullet revised: If adjuvant RT may not be indicated (See MCC-2), Wwide excision with 1- to 2-cm margins to investing fascia of muscle or pericranium when clinically feasible and consistent with reconstruction and radiation goals listed below.
  • Reconstruction
    • Bullet revised: Since RT is often indicated postoperatively, closure should be chosen to allow for expeditious initiation of RT (eg, primary closure, avoiding extensive tissue movement).
• Principles of Systemic Therapy
  • Regional Disease
    • Bullet revised: Neoadjuvant/adjuvant chemotherapy is not routinely recommended for regional disease as survival benefit has not been demonstrated in available retrospective studies, but could be used on a case-by-case basis if clinical judgment dictates. No data are available to support the adjuvant use of immunotherapy outside of a clinical trial.

NCCN has published updates to the NCCN Chemotherapy Order Templates (NCCN Templates^®) for Breast Cancer to reflect the currently published NCCN Guidelines for Breast Cancer v1.2021.

• The following NEW NCCN Templates^® have been published:
  • BRS179a: Dose-Dense AC (DOXOrubicin/Cyclophosphamide) followed by Pertuzumab + Trastuzumab + PACLitaxel - Dose-Dense AC (DOXOrubicin/Cyclophosphamide) Course
  • BRS179b: Dose-Dense AC (DOXOrubicin/Cyclophosphamide) followed by Pertuzumab + Trastuzumab + PACLitaxel - Pertuzumab + Trastuzumab + PACLitaxel Course

For the complete updated versions of the NCCN Guidelines, NCCN Guidelines with NCCN Evidence Blocks™, the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Biomarkers Compendium^®, the NCCN Chemotherapy Order Templates (NCCN Templates^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), please visit NCCN.org.

To view the NCCN Guidelines for Patients^®, please visit NCCN.org/patientguidelines.

Free NCCN Guidelines apps for iPhone, iPad, and Android devices are now available! Visit NCCN.org/apps.

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