NCCN Flash Updates: NCCN Guidelines and NCCN Templates Updated

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), and the NCCN Radiation Therapy Compendium™, for Basal Cell Carcinoma. These NCCN Guidelines^® are currently available as Version 1.2022.

Link to the NCCN Guidelines: 
Basal Cell Carcinoma v1.2022

• Clinical Presentation, Workup, and Risk Status (BCC-1)
  • Clinical Presentation
    • Footnote e revised: For rare cases that present with regional or distant metastatic disease at diagnosis, treat as nodal or distant metastases pathway on BCC-4. Imaging modality and targeted area should be at the discretion of the treating team based on the suspected extent of disease (ie, local, regional, metastatic).
    • Footnote g added: Imaging modality and targeted area should be at the discretion of the treating team based on the suspected extent of disease (ie, local, regional, metastatic). Histologic confirmation is often sufficient to diagnose local recurrence, but MRI can be considered to assess extent of local disease. For nodal or distant metastasis, histologic analysis and/or CT imaging can be employed for confirmation and to gauge extent of disease.
• Treatment for Local, Low-Risk Basal Cell Skin Cancer (BCC-2)
  • Category header revised: Local low-risk basal cell skin cancer.
  • Primary Treatment of Local low-risk basal cell skin cancer
    • First option, Curettage and electrodesiccation (C&E):
      • First bullet revised: Excluding terminal hair-bearing areas, such as the scalp, pubic and axillary regions, and beard area in men males.
      • Second bullet revised: If adipose reached, tumor appears to extend beyond the dermis, surgical excision should generally be performed rather than C&E.
    • Second option revised: Standard excision with 4-mm clinical margins and postoperative margin assessment. Tissue rearrangement (eg, flap reconstruction, extensive undermining) should not be undertaken until clear margins are identified and (second intention healing, linear repair, or skin graft are acceptable).
    • Additional Treatment of Local low-risk basal cell skin cancer
      • Following positive margins, option revised: Mohs micrographic surgery or resection with CCPDMA other forms of peripheral and deep en face margin assessment (PDEMA). (Also page BCC-3)
  • Footnote k revised: Excision with complete circumferential peripheral and deep margin assessment (CCPDMA) PDEMA with permanent section analysis or intraoperative frozen section analysis is an alternative to Mohs micrographic surgery. See Principles of PDEMA Technique (SCC-G). (Also page BCC-3A)
  • Footnotes removed:
    • Closures like adjacent tissue transfers, in which significant tissue rearrangement occurs, should not be performed until clear margins are verified. (Also page BCC-3A)
    • RT is often reserved for patients older than 60 years because of concerns about long term sequelae. (Also pages BCC-3A and BCC-4)
  • Footnotes added:
    • Footnote i: In patients with superficial basal cell skin cancer, therapies such as topical imiquimod, topical 5-fluorouracil, photodynamic therapy, or cryotherapy may be considered, though cure rates are approximately 10% lower than surgical treatment modalities. Jansen MHE, et al. J Invest Dermatol 2018;138:527-533. Drew BA, et al. Dermatol Surg 2017;43:1423-1430.
    • Footnote l: For tumors on cheeks, forehead, scalp, neck, and pretibia that are <6 mm in depth and confined to the dermis, C&E may be considered as an alternative primary treatment option if Mohs, resection with PDEMA, and standard excision are not feasible due to patient comorbidities. See Risk Factors for Recurrence (BCC-B).
• Treatment for Local, High-Risk Basal Cell Skin Cancer (BCC-3)
  • Category header revised: Local high-risk basal cell skin cancer.
    • Primary Treatment:
      • First option revised: Mohs micrographic surgery or resection with CCPDMA other forms of PDEMA.
      • Second option revised: Standard excision with wider surgical margins and postoperative margin assessment and with second intention healing, linear repair, or delayed repair skin graft.
  • Additional Treatment, following Positive margins, first option revised: Mohs micrographic surgery or resection with CCPDMA other forms of PDEMA, if feasible or Standard re-excision if CCPDMA PDEMA not feasible.
•  Footnotes (BCC-3A)
  • Footnotes revised:
    • Footnote l: For tumors on cheeks, forehead, scalp, neck, and pretibia that are <6 mm in depth and confined to the dermis, C&E may be considered as an alternative primary treatment option if Mohs micrographic surgery, resection with CCPDMA PDEMA, and standard excision are not feasible due to patient comorbidities. See Risk Factors for Recurrence (BCC-B).
    • Footnote m: For complicated cases (eg, locally advanced, where high chance of surgical cure is in question), consider multidisciplinary consultation...
    • Footnote q: There are conflicting data about the value of adjuvant RT following margin-negative surgical excision, particularly after Mohs surgery.
  • Footnotes removed:
    • When Mohs micrographic surgery with margin assessment is being performed and the preoperative biopsy is considered insufficient for providing all the staging information required to properly treat the tumor, submission of the central specimen for vertical paraffin-embedded permanent sections or documentation of staging parameters in Mohs report is recommended.
    • Negative margins unachievable by Mohs micrographic surgery or more extensive surgical procedures.
• Follow-up and Recurrence or Advanced Disease (BCC-4)
  • Recurrence or Advanced Disease
    • Nodal or distant metastases pathway revised: Primary or recurrent Nnodal or distant metastases
      • Option following Primary or recurrent nodal metastases revised: Multidisciplinary consultation to consider one or more of the following options: Surgery or If surgery is not feasible then RT or systemic therapy.
        • Bullet added: Cemiplimab-rwlc
      • Pathway added: Distant metastases
        • Following Distant metastases pathway, options added: Multidisciplinary consultation to consider: Systemic therapy, HHI, Vismodegib, Cemiplimab-rwlc or RT or surgery for limited metastatic disease or Palliation and best supportive care.
  • Footnote s added: Cemiplimab-rwlc is recommended for patients with locally advanced or mBCC previously treated with an HHI or for whom an HHI is not appropriate.
  • Footnote t added: Under highly selective circumstances, in the context of multidisciplinary consultation, resection of limited metastases can be considered.
• Principles of Pathology (BCC-A)
  • Principles of Biopsy Reporting, second bullet revised: Clinical information to be submitted on biopsy requisition includes patient demographics, clinical diameter of lesion, anatomic location, and prior treatment of lesion. Additional helpful features to include are clinical diameter of lesion, and risk factors such as immunosuppression, and history of RT, or solid organ transplantation.
  • Principles of Excision Reporting
    • Third bullet revised: Minimal reporting elements to be reported for all surgical specimens include histologic subtype of basal cell carcinoma (BCC), invasion of tumor beyond deep reticular dermis, presence or absence of perineural invasion (if involving nerve below dermis or if largest nerve involved is >0.1 mm in caliber) and angiolymphatic invasion, and peripheral and deep margin status.
    • Fourth bullet revised: For Mohs excisions, reporting of these elements is also encouraged. As depth of invasion (in mm) may not be reliably ascertained on Mohs specimens, anatomic level of invasion can be reported. Submission of a central section of tissue at the area of deepest invasion for permanent section evaluation may be considered to evaluate and document high-risk features that were questionable or ambiguous on Mohs sections. Since depth of invasion (in mm) may not be ascertained on tangentially cut Mohs specimens, anatomic level of invasion should be reported. Frozen or permanent section analysis of the clinical tumor specimen may be undertaken if needed for complete reporting of features associated with poor prognosis.
    • Footnote 3 added: Morgan FC, Ruiz ES, Karia PS, et al. Brigham and Women's Hospital tumor classification system for basal cell carcinoma identifies patients with risk of metastasis and death. J Am Acad Dermatol 2021;85:582-587.
• Stratification to Determine Treatment Options for Local BCC Based on Risk Factors for Recurrence (BCC-B)
  • High Risk, Location/size, third row revised: "Mask areas” of face (central face, eyelids, eyebrows, periorbital, nose, lips [cutaneous and vermilion], chin, mandible, preauricular and postauricular skin/sulci, temple, and ear), genitalia, hands, and feet Head, neck, hands, feet, pretibia, and anogenital (any size).
  • Footnote 3 revised: This area constitutes high risk based on location, independent of size. Narrow excision margins due to anatomic and functional constraints are associated with increased recurrence rates with standard histologic processing. Complete margin assessment such as with Mohs micrographic surgery/CCPDMA or PDEMA is recommended for optimal tumor clearance and maximal tissue conservation...
• Principles of Treatment (BCC-C)
  • Second bullet revised: Surgical approaches often offer the most effective and efficient means for accomplishing cure, but considerations of function, cosmesis, and patient preference, and performance status may lead to choosing RT as primary treatment in order to achieve optimal overall results.
  • Fifth bullet revised: When Mohs micrographic surgery with margin assessment is being performed and the preoperative biopsy is considered insufficient for providing all the staging information required to properly treat the tumor, submission of the central specimen for vertical paraffin-embedded permanent sections or documentation of staging parameters in Mohs report is recommended.
• Principles of Radiation Therapy (BCC-D)
  • General Principles
    • New bullet added: Isotope-based brachytherapy can be an effective treatment for certain sites of disease, particularly on the head and neck.
    • Fifth bullet revised: There are insufficient long-term efficacy and safety data to support the routine use of radioisotope or electronic surface brachytherapy.
• Principles of Systemic Therapy(BCC-E)
  • Approach
    • First bullet revised: Systemic therapy may be considered for locally advanced laBCC and mBCC…
    • Fourth bullet, Systemic therapy options include:
      • First bullet revised:HHIs (ie, vismodegib, sonidegib).
        • First sub-bullet revised: Due to frequency of intolerable side effects associated with hedgehog pathway inhibitors HHIs...
        • Second sub-bullet revised: Hedgehog pathway inhibitors HHIs may be considered for diffuse BCC formation (eg, Gorlin syndrome The approach for patients with diffuse BCC formation (eg, Gorlin syndrome, or other genetic forms of multiple BCC), hedgehog pathway inhibitors may be considered. Hedgehog pathway inhibitors HHIs are not approved for Gorlin syndrome; however, they are effective based on a randomized controlled trial.
        • Third sub-bullet revised: Current FDA-approved hedgehog pathway inhibitors HHIs include vismodegib and sonidegib. Vismodegib is FDA approved for the treatment of adults with mBCC or with laBCC that has recurred following surgery, or those who are not candidates for surgery or and who are not candidates for RT. Sonidegib is FDA approved for the treatment of adults patients with laBCC that has recurred following surgery or RT, or those who are not candidates for surgery or RT. Sonidegib is not FDA approved for the treatment of adults with mBCC.
      • Second bullet revised: Cemiplimab-rwlc is recommended for patients with laBCC or mBCC previously treated with an hedgehog pathway inhibitor HHI or for whom an HHI is not appropriate.
  • Footnote 1 added: Dummer R, Guminksi A, Gutzmer R, et al. Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II randomized, double-blind BOLT study. Br J Dermatol 2020;182:1369-1378.
  • Footnote 2 added: Tang JY, et al. Inhibition of the hedgehog pathway in patients with basal-cell nevus syndrome: final results from the multicenter, randomized, double-blind, placebo controlled, phase 2 trial. Lancet Oncol 2016;17:1720-1731.

NCCN has published updates to the NCCN Guidelines, the NCCN Compendium^®, and the NCCN Radiation Therapy Compendium™, for Dermatofibrosarcoma Protuberans. These NCCN Guidelines are currently available as Version 1.2022.

Link to the NCCN Guidelines: 
Dermatofibrosarcoma Protuberans v1.2022

• Clinical Presentation and Workup (DFSP-1)
  • Clinical Presentation
    • Workup, fourth bullet revised: Consider preoperative MRI with contrast for treatment planning if extensive extracutaneous subcutaneous extension or a recurrent tumor is suspected.
  • Footnote b, last sentence removed: Biopsy closures are encouraged to be kept small so as not to distort the anatomy for definitive excision.
  • Footnote d revised: If fibrosarcomatous changes/malignant transformations are is noted found, multidisciplinary consultation for consideration of further treatment and surveillance is recommended. See the NCCN Guidelines for Soft Tissue Sarcoma for multimodal therapy and surveillance considerations. Multidisciplinary consultation is recommended for other high-risk features. (Also page DFSP-2)
• Treatment and Follow-up (DFSP-2)
  • Treatment
    • Header revised: Excision with Mohs micrographic surgery (MMS) or other forms of CCPDMA peripheral and deep en face margin assessment (PDEMA).
  • Revised footnotes
    • Footnote e: The most commonly used form of complete circumferential peripheral and deep margin assessment (CCPDMA) PDEMA is Mohs (MMS). See NCCN Guidelines for Squamous Cell Skin Cancer - Principles of CCPDMA PDEMA Technique. If CCPDMA is unavailable, consider wide excision. Wide undermining is discouraged due to the difficulty of interpreting subsequent re-excisions pathologically and the risk of concealing residual tumor below immobilized tissue. See Principles of Excision (DFSP-B). When anatomic structures at the deep margin (eg, major vessels, nerves, bone) preclude complete histologic evaluation of the marginal surface via Mohs or other forms of PDEMA, Mohs or other forms of PDEMA should be used to evaluate as much of the marginal surface as feasible. Treatment considerations for non-visualized areas may be the subject of multidisciplinary discussion.
    • Footnote g: Consider neoadjuvant imatinib for patients in whom resection with negative margins may result in unacceptable functional or cosmetic outcomes. is not anticipated to achieve negative margins without unacceptable functional or cosmetic outcomes.​ Ugurel S, et al. Clin Cancer Res 2014;20:499-510.
    • Footnote j: For negative margins When Mohs or other forms of PDEMA are utilized, RT is not recommended. When Mohs or other forms of PDEMA are not utilized, consider RT if margins are <1 cm. RT can be considered for treatment of positive margins if not given previously and further resection is not feasible.
    • Footnote k: Tumors lacking the t(17;22) rearrangement may not respond to imatinib. Cytogenetic analysis (molecular or conventional) of a tumor may be useful prior to the institution of imatinib therapy. Navarrete-Dechent C, et al. JAMA Dermatol 2019;155:361-369.
  • Footnote f added: If PDEMA is unavailable, consider wide excision. Wide undermining is discouraged prior to confirmation of clear margins due to the difficulty of interpreting subsequent re-excised margins, and the risk of concealing residual tumor below mobilized tissue. See Principles of Excision (DFSP-B).
• Principles of Pathology (DFSP-A)
  • First bullet revised: Evaluation by a qualified physician with specific expertise in sarcoma/soft tissue pathology or dermatopathology is preferred (if available).
  • Fourth bullet revised: Fibrosarcomatous transformation (FS-DFSP) is reflected by characterized by transition from storiform to a herringbone pattern, with a higher degree of cellularity, cytologic atypia, mitotic activity (>5/10 high-power fields [HPF]), and negative frequent loss of CD34 immunostaining.
  • Sixth bullet revised: Margin control during excision (see Principles of Excision) may require occasionally be aided by H&E sections supplemented by CD34 immunohistochemistry.
  • Footnote 2 revised: FS-DFSP should be noted when present as the metastatic risk is 15%–20% and the patient should be referred to a center with expertise in management of soft tissue sarcomas. as it is associated with a poor prognosis.
• Principles of Excision (DFSP-B)
  • Goal, bullet revised: Every effort should be made to achieve clear surgical margins. Complete histologic surgical margin examination to include review of the entire excised peripheral and deep margin is recommended, whenever possible. Tumor characteristics include long, irregular, subclinical extensions. Debulking Sspecimens from debulking/Mohs all excisions should be examined to identify fibrosarcomatous transformation (FS-DFSP) since this is associated with metastatic potential.
  • Surgical approach, heading revised: Mohs Micrographic Surgery or Other Forms of CCPDMA PDEMA.
    • First bullet revised: See NCCN Guidelines for Squamous Cell Skin Cancer - Principles of CCPDMA PDEMA Technique.
    • Second bullet revised: If CCPDMA Mohs or other forms of PDEMA are unavailable, consider wide excision.
      • First sub-bullet removed: If there is concern that the surgical margins are not completely clear, consider avoiding repair with a flap or other technique, as it may impede monitoring of the site and delay detection of a recurrence. Split-thickness skin grafting (STSG) may be considered.
      • Second sub-bullet removed: It is recommended that any reconstruction involving extensive undermining or tissue movement be avoided or delayed until negative histologic margins are verified to prevent subclinical tumor persistence, particularly inadvertent concealment of residual tumor below repositioned tissue or a repair.
      • New sub-bullet added: Reconstruction should be delayed until clear margins have been verified to avoid the risk of translocating tumor within the resection bed making further margin assessments inaccurate.
• Principles of Radiation Therapy (DFSP-C)
  • General Treatment Information, Adjuvant RT, Negative margins:
  • First sub-bullet revised: When Mohs or other forms of PDEMA are utilized, RT is not recommended.
  • New sub-bullet added: When Mohs or other forms of PDEMA are not utilized, consider RT if margins are <1 cm.

NCCN has published updates to the NCCN Guidelines, the NCCN Compendium, and the NCCN Radiation Therapy Compendium™, for Merkel Cell Carcinoma. These NCCN Guidelines are currently available as Version 1.2022. 

Link to the NCCN Guidelines: 
Merkel cell Carcinoma v1.2022

• Clinical Presentation, Preliminary Workup, Diagnosis, Additional Workup, and Clinical Findings (MCC-1)
  • Footnote c revised: Imaging is encouraged in most cases of MCC. Imaging is indicated whenever metastatic or unresectable disease is suspected based on H&P findings... (Also page MCC-2A, MCC-3, 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. As immunosuppressed patients are at high risk for recurrence, more frequent follow-up may be indicated. (Also page MCC-4, MCC-5)
• Primary and Adjuvant Treatment of Clinical N0 Disease (MCC-2)
  • Management of the Primary Tumor:
    • Following ≥1 baseline risk factor, category revised: Narrow margin eExcision with individualized margins and multimodal therapy determined from multidisciplinary assessment including radiation oncology.
  • Management of the Draining Nodal Basin:
    • Following SLN negative, second option revised: May consider RT to the nodal basin in high-risk patients at increased risk for a false-negative SLNB.
• Footnotes (MCC-2A)
  • Footnotes revised:
    • Footnote h: Baseline risk factors: larger primary tumor (>2 1 cm); chronic T-cell immunosuppression, HIV, CLL, solid organ transplant; head/neck primary site; lymphovascular invasion present.
    • Footnote j: In the head and neck region, risk of false-negative SLNBs is higher due to aberrant lymph node drainage and frequent presence of multiple SLN basins. If SLNB is not performed or is unsuccessful, consider irradiating nodal beds for subclinical disease. Consider empiric RT to the nodal basin when: 1) the accuracy of SLNB may have been subject to anatomic compromise (lymphoma involved nodes, or history of remote lymph node excision); 2) when the risk of false-negative SLNB is high due to aberrant lymph node drainage and presence of multiple SLN basins (such as in head & neck or midline trunk MCC); or 3) when identified by lymphoscintigraphy in cases of profound immunosuppression (ie, solid organ transplant recipients). See Principles of Radiation Therapy (MCC-B).
    • Footnote l: SLNB is typically performed at this time.
    • Footnote n: Mohs micrographic surgery (MMS) or CCPDMA other forms of peripheral and deep en face margin assessment (PDEMA), using margins similar to WLE [wide local excision] wide local excision (WLE), may be appropriate. See NCCN Guidelines for Squamous Cell Skin Cancer - Principles of CCPDMA PDEMA Technique for description of CCPDMA PDEMA.
    • Footnote s revised: Neoadjuvant/aAdjuvant 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 removed: Consider RT when there is a potential for anatomic (eg, previous history of surgery including WLE), operator, or histologic failure (eg, failure to perform appropriate immunohistochemistry on SLNs) that may lead to a false-negative SLNB. Consider RT in cases of profound immunosuppression.
• Primary and Adjuvant Treatment of Clinical N+ Disease (MCC-3)
  • Clinical N+:
    • Header revised: Clinical N+ (regional MCC).
  • Management of the Draining Nodal Basin, Positive, following M0:
    • Third bullet revised: Clinical trial for neoadjuvant or adjuvant therapy preferred if available.
    • New bullet added: Consider neoadjuvant immunotherapy.
  • Footnote t added: See Principles of Systemic Therapy (MCC-D).
• Treatment of Clinical M1 Disease (MCC-4)
  • Clinical M1:
    • Header revised: Clinical M1 (Disseminated MCC).
  • Footnote v revised: Under highly selective circumstances, in the context of multidisciplinary consultation, resection of oligometastasis limited metastases can be considered. (Also page MCC-5)
• Follow-up, Recurrence, and Treatment (MCC-5)
  • Footnote removed: As immunosuppressed patients are at high risk for recurrence, more frequent follow-up may be indicated. Immunosuppressive treatments should be minimized as clinically feasible, in consultation with their managing physician.
  • Footnote w added: Patients at high risk of recurrence include those who are immunosuppressed and patients who have positive non-SLN metastases.
• Principles of Radiation Therapy (MCC-B 1 of 2)
  • Following Resection of Primary MCC:
    • Removed: or Consider observation.
  • Footnote removed: Consider observation of the primary site in cases where the primary tumor is small (eg, <1 cm) and widely excised with no other adverse risk factors such as LVI or immunosuppression.
• Principles of Radiation Therapy (MCC-B 2 of 2)
  • SLNB without LN dissection, SLN negative revised: SLN negative - RT not routinely indicated.
  • Footnotes removed:
    • Consider RT when there is a potential for anatomic (eg, previous WLE), operator, or histologic failure (eg, failure to perform appropriate immunohistochemistry on SLNs) that may lead to a false-negative SLNB.
    • In the head and neck region, risk of false-negative SLNB is higher due to aberrant lymphatic drainage and frequent presence of multiple SLN basins. If SLNB is unsuccessful, consider irradiating draining nodal basin for subclinical disease.
    • Consider RT to draining nodal basin identified by lymphoscintigraphy in cases of profound immunosuppression (ie, solid organ transplant recipients).
  • Footnote 3 added: Consider empiric RT to the nodal basin when: 1) the accuracy of SLNB may have been subject to anatomic compromise (lymphoma involved nodes, or history of remote lymph node excision); 2) when the risk of false-negative SLNB is high due to aberrant lymph node drainage and presence of multiple SLN basins (such as in head & neck or midline trunk MCC); or 3) when identified by lymphoscintigraphy in cases of profound immunosuppression (ie, solid organ transplant recipients).
• Principles of Excision (MCC-C)
  • Surgical Approaches:
    • Second sub-bullet revised: If adjuvant RT may not be indicated (See MCC-2), perform wide 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.
    • Third sub-bullet revised: Techniques for more exhaustive histologic margin assessment may be considered (Mohs micrographic surgery, CCPDMA or other forms of PDEMA), provided they do not interfere with SLNB when indicated.
  • Footnote 2 revised: If When Mohs is used being performed and the preoperative biopsy is considered insufficient for providing all the staging information required to properly treat the tumor, submission of the central specimen for vertical paraffin-embedded permanent sections or documentation of staging parameters in Mohs report is recommended.
  • Footnote removed: CCPDMA = complete circumferential peripheral and deep margin assessment.
• Principles of Systemic Therapy (MCC-D)
  • Header revised: Local Disease N0
    • First bullet revised: For primary disease, adjuvant chemotherapy is not recommended.
  • Header revised: Regional Disease N+
    • Bullet removed: For recurrent regional disease, consider pembrolizumab if curative surgery and curative RT are not feasible.
    • Second bullet revised: For regional disease, 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.
    • Options useful in certain circumstances:
      • Option added: Neoadjuvant nivolumab.
    • Bullet added: For recurrent regional disease, consider pembrolizumab if curative surgery and curative RT are not feasible.
  • Header revised: Disseminated Disease M1
    • Preferred interventions, Pembrolizumab: reference 4 added.
  • Reference added: Topalian SL, Bhatia S, Amin A, et al. Neoadjuvant nivolumab for patients with resectable Merkel cell carcinoma in the CheckMate 358 Trial. J Clin Oncol 2020;38:2476-2487.

NCCN has published updates to the NCCN Guidelines, the NCCN Compendium^®, and the NCCN Radiation Therapy Compendium™, for Squamous Cell Skin Cancer. These NCCN Guidelines are currently available as Version 1.2022. 

Link to the NCCN Guidelines: 
Squamous Cell Skin Cancer v1.2022

• Global Changes:
  • Changed "Mohs micrographic surgery (MMS) or other forms of CCPDMA" to "Mohs or other forms of PDEMA."
  • Changed "Complete circumferential peripheral and deep margin assessment (CCPDMA)" to "Peripheral and deep en face margin assessment (PDEMA)."
  • Changed "CCPDMA" to "PDEMA."
  • Changed "MMS" to "Mohs."
• Clinical Presentation, Workup, Diagnosis, and Risk Status (SCC-1)
  • Workup
    • Second sub-bullet under H&P revised: Regional lymph node exam as indicated for suspicion of nodal disease.
  • Footnote e revised: For rare cases that present with distant metastatic disease at diagnosis, treat as distant metastases pathway on SCC-6. Imaging modality and targeted area should be at the discretion of the treating team based on the suspected extent of disease (ie, local, regional, metastatic).
  • Footnote g added: Imaging modality and targeted area should be at the discretion of the treating team based on the suspected extent of disease (ie, local, regional, metastatic). Histologic confirmation is often sufficient to diagnose local recurrence, but MRI can be considered to assess extent of local disease. For nodal or distant metastases, histologic analysis and/or other imaging modalities can be employed for confirmation and to gauge extent of disease.
• Treatment for Local, Low-Risk Squamous Cell Skin Cancer (SCC-2)
  • Primary Treatment
    • Curettage and electrodesiccation (C&E), second bullet revised: If tumor appears to be not confined to skin (penetrates beyond the skin) extend beyond the dermis, surgical excision should generally be performed rather than C&E.
    • Second option revised: Standard excision with 4- to 6-mm clinical margins and postoperative margin assessment. Tissue rearrangement (eg, flap reconstruction, extensive undermining) should not be undertaken until clear margins are identified and (second intention healing, linear repair, or skin graft are acceptable).
    • Option added: Mohs or other forms of peripheral and deep en face margin assessment (PDEMA).
  • Footnotes removed:
    • Closures like adjacent tissue transfers, in which significant tissue rearrangement occurs, are best performed after clear margins are verified. (Also page SCC-3A)
    • RT is often reserved for patients older than 60 years because of concerns about long-term sequelae. (Also page SCC-3A)
  • Footnote j revised: Excision with complete circumferential peripheral and deep margin assessment (CCPDMA) PDEMA with (via permanent section analysis or intraoperative frozen section analysis) is an alternative to MMS Mohs. See Principles of CCPDMA PDEMA Technique (SCC-G). (Also page SCC-3A)
  • Footnote k added: When Mohs is being performed and the preoperative biopsy is considered insufficient for providing all the staging information required to properly treat the tumor, submission of the central specimen for vertical paraffin-embedded permanent sections or documentation of staging parameters in Mohs report is recommended.
• Treatment for Local, High-Risk/Very-High-Risk Squamous Cell Skin Cancer (SCC-3)
  • Primary Treatment
    • Second option revised: Standard excision with wider surgical margins and postoperative margin assessment and second intention healing, linear repair, or delayed repair skin graft.
    • Pathway following Mohs or other forms of PDEMA, Negative margins revised: If extensive perineural, large, or named nerve involvement, or if other high-risk features poor prognostic features: Recommend multidisciplinary consultation and Consider adjuvant RT.
• Footnotes (SCC-3A)
  • Footnotes revised:
    • Footnote k: When MMS Mohs with margin assessment is being performed and the preoperative biopsy is considered insufficient for providing all the staging information required to properly treat the tumor, submission of the central specimen for vertical paraffin-embedded permanent sections or documentation of staging parameters in Mohs report is recommended.
    • Footnote l: For complicated cases, consider multidisciplinary consultation. For locally advanced disease in which curative RT and curative surgery are not feasible, consider treatment with immunotherapy systemic therapy (cemiplimab-rwlc or clinical trial). See Principles of Systemic Therapy (SCC-F).
    • Footnote o: Discuss and consider sentinel lymph node biopsy (SLNB) prior to PDEMA for patients with the very-high-risk CSCCs that are recurrent or have multiple risk factors placing them in very-high-risk group, and have normal exam of draining nodal basin (category 2B). See Stratification to Determine Treatment Options and Follow-up for Local CSCC Based on Risk Factors for Local Recurrence, Metastases, or Death from Disease (SCC-B).
    • Footnote p: If invasion to parotid fascia, superficial parotidectomy is may be indicated.
    • Footnote s: Large nerve involvement is defined by the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th Edition for CSCC of the head and neck as ≥0.1 mm or nerve involvement deeper than the dermis.; mMost nerves deep to the dermis are >0.1 mm.
    • Footnote u: For tumors in cheeks, forehead, scalp, neck, and pretibia that are <6 mm in depth and confined to the dermis…
• Clinical Staging, Preoperative Assessment, and Primary Treatment (SCC-4)
  • Clinical Staging and Preoperative Assessment
    • Option following FNA or core biopsy, Negative revised: Consider re-evaluation: clinical exam, CT with contrast of the nodal basin, repeat FNA, core biopsy, or open lymph node excisional biopsy.
  • Primary Treatment
    • Option following Surgical evaluation revised: Unresectable, inoperable, or not fully incompletely resectable resected disease.
  • Footnote x 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 (SCC-6)
  • Footnotes revised:
    • Footnote g: Imaging modality and targeted area should be at the discretion of the treating team based on the suspected extent of disease (ie, local, regional, metastatic). Histologic confirmation is often sufficient to diagnose local recurrence, but MRI can be considered to assess extent of local disease. For nodal or distant metastases, histologic analysis and/or CT other imaging modalities can be employed for confirmation and to gauge extent of disease.
    • Footnote ff: Surveillance CT with contrast imaging of regional nodal basin and to evaluate for distant metastatic disease, ideally based on multidisciplinary board recommendation, or as clinically indicated.
  • Footnote gg added: Under highly selective circumstances, in the context of multidisciplinary consultation, resection of limited metastases can be considered.
• Principles of Pathology (SCC-A)
  • Second header revised: Principles of Excision Reporting (including Mohs micrographic excisions)
    • Third bullet revised: Immunohistochemistry may be utilized as needed to help identify lymphovascular or nerve invasion, or to identify single tumor cells or small aggregates few-cell tumor foci.
  • Third header revised: Recommended Elements for Pathology Reporting of Excisional Specimens (including Mohs micrographic excisions).
• Stratification to Determine Treatment Options and Follow-up for Local CSCC Based on Risk Factors for Local Recurrence, Metastases, or Death from Disease (SCC-B 2 of 2)
  • Footnote 1 revised: Risk stratification category assignment should be based on the highest risk factor present. The high-risk group has elevated risk of local recurrence; the very-high-risk group has elevated risk of local recurrence and elevated risk of metastasis.
• Identification and Management of Patients at High-Risk for Multiple Primary CSCCs (SCC-C 2 of 3)
  • First header revised: Treatment of Precancers (Diffuse Actinic Keratoses, Field Cancerization, and CSCC Prophylaxis).
    • Bullet added: Use of nicotinamide may be effective in reducing the development of CSCCs.
    • Second bullet, first sub-bullet revised: Accepted treatment modalities include cryotherapy, topical 5-fluorouracil (5-FU) (preferred) with or without calcipotriol (calcipotriene), topical imiquimod, topical ingenol mebutate topical tirbanibulin, photodynamic therapy (eg, aminolevulinic acid [ALA], porfimer sodium), and C&E...
  • Treatment of Skin Cancers
    • Second bullet revised: In patients who develop multiple adjacent tumors in close proximity, surgical excision of invasive disease sometimes does not include surrounding in situ disease, and tissue rearrangement should be minimized. In situ disease may then be treated with topical approaches similar to actinic keratoses/field cancerization. secondary approaches.
  • Footnote 2 added: The longest duration of prophylaxis against SCC has been demonstrated with 5-FU plus calcipotriol.
  • References updated.
• Identification and Management of Patients at High-Risk for Multiple Primary CSCCs (SCC-C 3 of 3)
  • References updated.
• Principles of Treatment (SCC-D)
  • Bullet removed: Use of nicotinamide may be effective in reducing the development of CSCCs.
• Principles of Radiation Therapy (SCC-E)
  • Bullet added: Isotope-based brachytherapy can be an effective treatment for certain sites of disease, particularly on the head and neck.
  • Last bullet revised: There are insufficient long-term efficacy and safety data to support the routine use of radioisotope or electronic surface brachytherapy.
• Principles of Systemic Therapy (SCC-F 1 of 2)
  • Second header revised: Primary and Recurrent Locally Advanced Disease in Non-Surgical Candidates (See SCC-3)
  • New Regional Disease
    • Third bullet revised: For patients with unresectable, inoperable, or not fully incompletely resectable resected disease inoperable or incompletely resected regional disease, multidisciplinary consultation to consider:
  • Table 1: Systemic Therapy Options for Use with RT
    • Useful in Certain Circumstances, option revised: Carboplatin ± paclitaxel
• Principles of Systemic Therapy for Squamous Cell Skin Cancer (SCC-F 2 of 2)
  • Reference 3 revised: Recent published phase II trial data reported an objective response (OPR) of 44% (95% CI, 32-55), partial response rate (PR) of 31% and complete response rate (CR) of 13% to cemiplimab-rwlc in patients with locally advanced or recurrent CSCC. Data from the phase II KEYNOTE-629 trial, which included patients with recurrent or metastatic CSCC or locally advanced CSCC, reported an OPR of 50% (95% CI, 36-64), a PR of 33%, and a CR of 17%, for patients treated with pembrolizumab. support the efficacy and safety of cemiplimab-rwlc and pembrolizumab in patients with locally advanced, recurrent, and metastatic CSCC. Preliminary data and the clinical experience of NCCN Panel Members suggest that other anti–PD-1 inhibitors may also be effective in this setting.
  • References updated.
• Principles of PDEMA Technique (SCC-G)
  • Header revised: Principles of CCPDMA PDEMA Technique
  • New bullet added: The most commonly used form of PDEMA is Mohs. When anatomic structures at the deep margin (eg, major vessels, nerves, bone) preclude complete histologic evaluation of the marginal surface via Mohs or other forms of PDEMA, Mohs or other forms of PDEMA should be used to evaluate as much of the marginal surface as feasible. Treatment considerations for non-visualized areas may be the subject of multidisciplinary discussion.

NCCN has published updates to the NCCN Chemotherapy Order Templates (NCCN Templates^®) for Chronic Myeloid Leukemia to reflect the currently published NCCN Guidelines for Chronic Myeloid Leukemia v2.2022.

• The following New NCCN Template^® has been published:
  • CML11: Asciminib

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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