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derm.squamous-cell-carcinoma-skin.core.v1PRODUCTION
derm.squamous-cell-carcinoma-skin.core.v1

Cutaneous squamous cell carcinoma

dermatologysubacutechronicadult
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Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Frame cSCC as the second most common cutaneous malignancy and the leading cause of NMSC mortality — most cures are achieved by simple local therapy, but a definable high-risk subset (Brigham T2b/T3, organ-transplant, PNI, deep invasion) drives meaningful nodal and death risk and requires Mohs / margin-assessed excision ± adjuvant RT and frequently checkpoint immunotherapy for advanced disease. The dermatology engine owns recognition / biopsy / risk stratification / definitive local therapy / cemiplimab-pembrolizumab systemic ladder; routes only bona-fide distant metastatic / unresectable head-and-neck disease to multidisciplinary care.

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derm-owned scope set; sibling routes (BCC, AK-NMSC, melanoma) noted

Patient inputs (12)

Solid-organ-transplant recipients have 65-100x elevated cSCC incidence, more aggressive course, and benefit from immunosuppression reduction/switch + nicotinamide chemoprevention (NCCN cSCC 2025; ONTRAC PMID 26488693)

Subtype (keratoacanthoma-like / verrucous / invasive nodular / ulcerative / desmoplastic / Marjolin) + anatomic site (H/M/L zone) drive both biopsy approach and risk stratification (NCCN cSCC 2025)

Perineural invasion (named-nerve pain, paraesthesia, motor deficit) is NCCN high-risk; PNI subhazard 3.6 for disease-specific death (NCCN cSCC 2025; Karia PMID 23677079)

Palpable regional lymph nodes change staging and trigger imaging + nodal management; ear/temple site subhazard 3.8 nodal / 5.9 death (Karia PMID 23677079)

Diameter is the strongest single Brigham/NCCN risk factor — ≥2 cm subhazard 7.0 for nodal-metastasis, 15.9 for disease-specific death (Karia JAMA Dermatol 2013 PMID 23677079)

Invasion beyond subcutaneous fat / thickness >6 mm is NCCN high-risk and Brigham T2b/T3 (subhazard 9.3 nodal / 13.0 death) (Karia PMID 23677079)

Poorly differentiated / desmoplastic histology is NCCN high-risk; poor differentiation subhazard 6.1 nodal / 6.7 death (Karia PMID 23677079)

Recurrent disease and tumour arising in previously irradiated skin are NCCN high-risk regardless of other features (NCCN cSCC 2025)

CT/MRI for PNI / orbital / bone invasion; US or CT of regional nodes for high-risk primary; CT chest-abdomen-pelvis for suspected distant metastasis (NCCN cSCC 2025)

Baseline before cemiplimab / pembrolizumab; CLL screen in patients with lymphocytosis (CLL + cSCC = particularly aggressive course) (NCCN cSCC 2025)

Baseline + on-treatment for checkpoint-inhibitor immune-hepatitis surveillance (EMPOWER-CSCC-1 PMID 29863979; KEYNOTE-629 PMID 32673170)

Race-free eGFR (CKD-EPI 2021) for renal-dose context with iodinated-contrast staging imaging and as a baseline for transplant-recipient management (NCCN cSCC 2025; Inker NEJM 2021)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateninglocally_advanced_or_metastatic_cscc
    cSCC not amenable to curative surgery or radiation, regional nodal disease beyond surgical control, or distant metastasis (NCCN cSCC 2025; EMPOWER-CSCC-1 PMID 29863979)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningsevere_checkpoint_inhibitor_irae
    Grade 3-4 immune-related adverse event on cemiplimab / pembrolizumab (colitis / hepatitis / pneumonitis / myocarditis / endocrine crisis) (EMPOWER-CSCC-1 PMID 29863979; KEYNOTE-629 PMID 32673170)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereperineural_invasion_named_nerve
    Symptoms or imaging consistent with perineural invasion of a named nerve (pain, paraesthesia, motor weakness, facial palsy) (NCCN cSCC 2025; Karia PMID 23677079)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveretransplant_recipient_high_risk_cscc
    Solid-organ-transplant recipient with high-risk or recurrent cSCC (NCCN cSCC 2025; ONTRAC PMID 26488693)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverevery_high_risk_brigham_t2b_t3
    Brigham T2b (2 risk factors) or T3 (3+ risk factors) cSCC: ≥2 of diameter ≥2 cm, poor differentiation, PNI ≥0.1 mm, invasion beyond fat (Karia PMID 23677079; NCCN cSCC 2025)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveremarjolin_ulcer_cscc_in_chronic_scar_or_wound
    New cSCC arising in a chronic scar, burn, ulcer, or wound (Marjolin ulcer) (NCCN cSCC 2025)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepalpable_regional_node_in_cscc
    Palpable regional lymph nodes in a patient with current or prior cSCC (NCCN cSCC 2025; Karia PMID 23677079)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

TREATMENToptionalDrives dose adjustment
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Recommended regimen

cSCC — risk-directed treatment ladder (NCCN cSCC 2025; Brigham staging; EMPOWER-CSCC-1; KEYNOTE-629)
axis: cscc_risk_directed_ladderstep 1 - Step 1 — Low-risk cSCC and SCC in situ (Bowen): local therapy (dermatology-owned)
Selected step "Step 1 — Low-risk cSCC and SCC in situ (Bowen): local therapy (dermatology-owned)" — NCCN low-risk cSCC (trunk/extremity <2 cm, well-defined, primary, immunocompetent, well-differentiated, no PNI) OR SCC in situ (Bowen)
  • standard_surgical_excision_4_to_6mm_margin
    first line
    definitive_surgery
    triggers: biopsy_confirmed_low_risk_cscc
    NCCN cSCC 2025 — standard excision with 4-6 mm clinical margins achieves ~95% cure in low-risk primary cSCC; 6 mm preferred for tumours 1-2 cm.
  • electrodesiccation_and_curettage
    second line
    destructive_procedure
    triggers: low_risk_small_well_differentiated_cscc, not_terminal_hair_bearing
    NCCN cSCC 2025 — ED&C for low-risk small cSCC on non-terminal-hair-bearing skin; avoid on scalp / beard area and any high-risk feature.
  • fluorouracil
    first line
    topical_antimetabolite
    5% cream • topical • BID x 2-4 weeks (in situ) (max: per tolerance)
    triggers: scc_in_situ_bowen, patient_declines_surgery
    NCCN cSCC 2025 — topical 5-FU 5% for SCC in situ (Bowen) only; not for invasive cSCC; expect erosion / inflammation.
    rxcui 4492
  • imiquimod
    first line
    topical_immune_response_modifier
    5% cream • topical • 5x/week x 12-16 weeks (in situ) (max: per tolerance)
    triggers: scc_in_situ_bowen, cosmetically_sensitive_site, patient_declines_surgery
    NCCN cSCC 2025 — topical imiquimod 5% for SCC in situ (Bowen) only; not for invasive cSCC; brisk inflammation expected.
    rxcui 59943
  • photodynamic_therapy
    second line
    photodynamic_therapy
    triggers: scc_in_situ_bowen, large_field_disease
    NCCN cSCC 2025 — PDT (ALA / MAL) for SCC in situ and AK field; not for invasive cSCC.
  • cryosurgery
    second line
    destructive_procedure
    triggers: scc_in_situ_small_well_demarcated, surgery_declined
    NCCN cSCC 2025 — cryosurgery is an option for selected small SCC in situ when surgery is declined / unfeasible.

outpatient playbook — drug actions (6)

  1. 1. standard surgical excision 4-6 mm margin (low-risk) OR Mohs micrographic surgery (high-risk)
    4-6 mm clinical margin standard excision; Mohs to clear margins • surgical • single definitive procedure
    trigger: Biopsy-confirmed cSCC, risk tier assigned (NCCN cSCC 2025)
    Risk-directed local therapy is curative for the great majority of cSCC
  2. 2. 5-fluorouracil 5% (SCC in situ only) OR imiquimod 5% (SCC in situ only)
    rxcui 4492
    5% cream • topical • 5-FU BID x 2-4 wk; imiquimod 5x/wk x 12-16 wk
    trigger: SCC in situ (Bowen) where surgery declined / not preferred (NCCN cSCC 2025)
    Topical option for in situ only — NOT for invasive cSCC; lower clearance than surgery
  3. 3. adjuvant radiotherapy for PNI / positive margin / very-high-risk
    per radiation oncology • external beam • standard fractionation
    trigger: PNI of named nerve, positive deep margin where re-excision unfeasible, very-high-risk Brigham T2b/T3 (NCCN cSCC 2025; Karia PMID 23677079)
    Adjuvant RT improves local control in PNI, positive-margin, and very-high-risk disease
  4. 4. cemiplimab 350 mg IV q3wk (locally advanced / metastatic, first-line)
    rxcui 2058826
    350 mg • IV • q3wk
    trigger: Locally advanced / unresectable / metastatic cSCC (EMPOWER-CSCC-1 PMID 29863979)
    Cemiplimab ORR ~47%; FDA-approved first-line for advanced cSCC
  5. 5. pembrolizumab 200 mg IV q3wk (alternative for advanced disease)
    rxcui 1547545
    200 mg • IV • q3wk
    trigger: Locally advanced or recurrent/metastatic cSCC (KEYNOTE-629 PMID 32673170 / 34293460)
    Pembrolizumab LA ORR 50.0%, R/M ORR 35.2%; alternative anti-PD-1 option
  6. 6. nicotinamide 500 mg PO BID (chemoprevention; high-risk patients)
    rxcui 7405
    500 mg • PO • BID
    trigger: Multiple prior NMSC / transplant / dense actinic field (ONTRAC PMID 26488693)
    Reduces new NMSC ~23% at 12 mo; safe, OTC

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Persistent hyperkeratotic firm and often tender plaque or nodule on chronically UV-exposed skin (NCCN cSCC 2025); Rapidly growing crateriform nodule with central keratin plug (keratoacanthoma-like cSCC variant) (NCCN cSCC 2025); Non-healing chronic ulcer, or new lesion arising in a burn / scar / chronic wound (Marjolin ulcer) — high-risk cSCC entry (NCCN cSCC 2025).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Cutaneous squamous cell carcinoma** (derm.squamous-cell-carcinoma-skin.core.v1).
Phenotype framing: Terminal differential with named pivots: cSCC vs actinic keratosis (rough hyperkeratotic macule WITHOUT firm/tender base — route derm.actinic-keratosis-nmsc.core.v1; cumulative AK->SCC risk) vs SCC in situ / Bowen (well-demarcated erythematous scaly patch, no invasion pivot) vs basal cell carcinoma (pearly translucent + arborising vessels + rolled border — route derm.basal-cell-carcinoma.core.v1; basosquamous is the hybrid) vs keratoacanthoma (rapidly growing crateriform nodule that may spontaneously regress — but a subset are well-differentiated SCC; treat as cSCC unless certain) vs hypertrophic AK (intermediate; low threshold for biopsy) vs verrucous carcinoma (slow-growing exophytic cauliflower-like; underdiagnosed) vs amelanotic melanoma (asymmetric / rapidly growing pink-red lesion — route derm.melanoma.core.v1) vs Merkel-cell carcinoma (rapidly growing red-purple nodule in elderly / immunosuppressed — high-yield biopsy + MDT). Marjolin in a chronic scar / burn / wound is cSCC until proven otherwise.
Scope: Frame cSCC as the second most common cutaneous malignancy and the leading cause of NMSC mortality — most cures are achieved by simple local therapy, but a definable high-risk subset (Brigham T2b/T3, organ-transplant, PNI, deep invasion) drives meaningful nodal and death risk and requires Mohs / margin-assessed excision ± adjuvant RT and frequently checkpoint immunotherapy for advanced disease. The dermatology engine owns recognition / biopsy / risk stratification / definitive local therapy / cemiplimab-pembrolizumab systemic ladder; routes only bona-fide distant metastatic / unresectable head-and-neck disease to multidisciplinary care.

No severity triggers fired against current inputs.

Plan

Regimen axis: **cSCC — risk-directed treatment ladder (NCCN cSCC 2025; Brigham staging; EMPOWER-CSCC-1; KEYNOTE-629)** — step "Step 1 — Low-risk cSCC and SCC in situ (Bowen): local therapy (dermatology-owned)".
1. standard_surgical_excision_4_to_6mm_margin (definitive_surgery, first line) — NCCN cSCC 2025 — standard excision with 4-6 mm clinical margins achieves ~95% cure in low-risk primary cSCC; 6 mm preferred for tumours 1-2 cm.
2. electrodesiccation_and_curettage (destructive_procedure, second line) — NCCN cSCC 2025 — ED&C for low-risk small cSCC on non-terminal-hair-bearing skin; avoid on scalp / beard area and any high-risk feature.
3. fluorouracil 5% cream topical BID x 2-4 weeks (in situ)  (topical_antimetabolite, first line) — NCCN cSCC 2025 — topical 5-FU 5% for SCC in situ (Bowen) only; not for invasive cSCC; expect erosion / inflammation.
4. imiquimod 5% cream topical 5x/week x 12-16 weeks (in situ) (topical_immune_response_modifier, first line) — NCCN cSCC 2025 — topical imiquimod 5% for SCC in situ (Bowen) only; not for invasive cSCC; brisk inflammation expected.
5. photodynamic_therapy (photodynamic_therapy, second line) — NCCN cSCC 2025 — PDT (ALA / MAL) for SCC in situ and AK field; not for invasive cSCC.
6. cryosurgery (destructive_procedure, second line) — NCCN cSCC 2025 — cryosurgery is an option for selected small SCC in situ when surgery is declined / unfeasible.

Setting playbook (outpatient) — Recognise cSCC, biopsy to confirm, assign NCCN risk tier + Brigham T-stage, deliver risk-directed local therapy (Mohs / excision / ED&C / topical for in situ / adjuvant RT) or checkpoint-inhibitor systemic ladder for advanced disease, coordinate with transplant team for SOT recipients, deliver chemoprevention, and establish intensified lifelong skin surveillance (NCCN cSCC 2025; Karia PMID 23677079; EMPOWER-CSCC-1 PMID 29863979; KEYNOTE-629 PMID 32673170)
7. standard surgical excision 4-6 mm margin (low-risk) OR Mohs micrographic surgery (high-risk) 4-6 mm clinical margin standard excision; Mohs to clear margins surgical single definitive procedure — Biopsy-confirmed cSCC, risk tier assigned (NCCN cSCC 2025) (Risk-directed local therapy is curative for the great majority of cSCC)
8. 5-fluorouracil 5% (SCC in situ only) OR imiquimod 5% (SCC in situ only) 5% cream topical 5-FU BID x 2-4 wk; imiquimod 5x/wk x 12-16 wk — SCC in situ (Bowen) where surgery declined / not preferred (NCCN cSCC 2025) (Topical option for in situ only — NOT for invasive cSCC; lower clearance than surgery)
9. adjuvant radiotherapy for PNI / positive margin / very-high-risk per radiation oncology external beam standard fractionation — PNI of named nerve, positive deep margin where re-excision unfeasible, very-high-risk Brigham T2b/T3 (NCCN cSCC 2025; Karia PMID 23677079) (Adjuvant RT improves local control in PNI, positive-margin, and very-high-risk disease)
10. cemiplimab 350 mg IV q3wk (locally advanced / metastatic, first-line) 350 mg IV q3wk — Locally advanced / unresectable / metastatic cSCC (EMPOWER-CSCC-1 PMID 29863979) (Cemiplimab ORR ~47%; FDA-approved first-line for advanced cSCC)
11. pembrolizumab 200 mg IV q3wk (alternative for advanced disease) 200 mg IV q3wk — Locally advanced or recurrent/metastatic cSCC (KEYNOTE-629 PMID 32673170 / 34293460) (Pembrolizumab LA ORR 50.0%, R/M ORR 35.2%; alternative anti-PD-1 option)
12. nicotinamide 500 mg PO BID (chemoprevention; high-risk patients) 500 mg PO BID — Multiple prior NMSC / transplant / dense actinic field (ONTRAC PMID 26488693) (Reduces new NMSC ~23% at 12 mo; safe, OTC)

Non-pharmacologic actions:
- Diagnostic shave or punch biopsy to dermis; full-thickness for suspected Marjolin / desmoplastic / deep cSCC (NCCN cSCC 2025)
- Electrodesiccation-and-curettage for selected low-risk small well-differentiated cSCC on non-hair-bearing skin (NCCN cSCC 2025)
- Definitive radiotherapy for non-surgical candidates (NCCN cSCC 2025)
- Multidisciplinary tumour-board referral for locally advanced / PNI / nodal / metastatic disease and for any transplant-recipient with high-risk disease
- Transplant-team coordination for immunosuppression reduction / mTOR-inhibitor switch in SOT recipients with recurrent or multiple cSCC
- Photoprotection + skin self-examination + nicotinamide chemoprevention counselling for high-risk patients (NCCN cSCC 2025; ONTRAC PMID 26488693)
- Route to derm.actinic-keratosis-nmsc.core.v1 for ongoing field-therapy of surrounding AK (NCCN cSCC 2025)

AVOID / contraindication checks:
- Topical 5fu and imiquimod only for scc in situ (NOT for invasive cSCC — lower efficacy and risk of treating only the superficial component of a deeper tumour)
- Edc not on terminal hair bearing sites or high risk disease (deeper follicular extension defeats ED&C on scalp / beard; high risk features mandate Mohs / margin assessed excision)
- Checkpoint inhibitor graft rejection risk in transplant recipients (cemiplimab / pembrolizumab carry significant graft rejection risk in solid organ transplant recipients — decisions must be made jointly with the transplant team; alternative chemoradiotherapy or palliative RT may be preferred)
- Severe irae recognition and emergent management (Grade 3 4 immune colitis / hepatitis / pneumonitis / myocarditis / endocrinopathy on cemiplimab / pembrolizumab  > hold drug, systemic corticosteroids per oncology pathway, multidisciplinary review)
- Slnb not routine in cscc (controversial; not standard NCCN 2025; reserve for very high risk Brigham T2b/T3 at experienced centres on trial / MDT basis)
- Do not shave a pigmented lesion where melanoma is possible (pigmented amelanotic mimic concern  > full thickness biopsy or route derm.melanoma.core.v1)

Monitoring

Regimen monitoring:
- intensified total-body skin exam: q3-6 mo for high-risk in years 1-2, then q6-12 mo lifelong (30-50% second-NMSC risk; much higher in transplant) (NCCN cSCC 2025)
- regional-node exam at each follow-up for high-risk primaries
- cemiplimab / pembrolizumab on-treatment: routine irAE surveillance — skin, thyroid TSH every cycle, hepatitis LFT, colitis symptoms, pneumonitis cough/dyspnoea, hypophysitis, myocarditis (cTn/ECG as indicated) (EMPOWER-CSCC-1 PMID 29863979; KEYNOTE-629 PMID 32673170)
- transplant-recipient coordination: immunosuppression review by transplant team every 3-6 months in patients with active NMSC; monitor graft function on mTOR-inhibitor switch
- photoprotection adherence + skin self-examination habit reinforcement at every visit (NCCN cSCC 2025)

Setting (outpatient) monitoring:
- Intensified total-body skin exam: q3-6 mo high-risk in years 1-2, then q6-12 mo lifelong (NCCN cSCC 2025)
- Regional-node examination at each follow-up for high-risk primaries
- Checkpoint-inhibitor irAE surveillance for patients on cemiplimab / pembrolizumab (EMPOWER-CSCC-1 PMID 29863979; KEYNOTE-629 PMID 32673170)
- Transplant graft function on mTOR-switch and during checkpoint immunotherapy

Follow-up plan: Lifelong derm continuity with emphasis on photoprotection (broad-spectrum SPF ≥30 + sun-protective clothing + behavioural avoidance), structured skin self-examination + regional-node self-check education, AK / field-therapy maintenance (route derm.actinic-keratosis-nmsc.core.v1 for ongoing field treatment), and nicotinamide chemoprevention for transplant recipients / multiple prior NMSC (ONTRAC PMID 26488693). Organ-transplant recipients receive intensified surveillance + transplant-team coordination on immunosuppression. Recurrence at the prior site -> re-biopsy + escalate (Mohs re-excision, adjuvant RT, or systemic therapy if unresectable).
- Close-out criterion: photoprotection + self-exam + field-therapy + chemoprevention + intensified surveillance documented

Monitoring phase: Surveillance is intensified: total-body skin exam every 3-6 months for years 1-2 in high-risk patients, then every 6-12 months lifelong; 30-50% second-NMSC risk overall, much higher in transplant. On cemiplimab / pembrolizumab: routine irAE surveillance (skin, thyroid TSH every cycle, hepatitis LFT, colitis symptoms, pneumonitis cough/dyspnoea, hypophysitis, myocarditis with cTn / ECG as indicated). Adjuvant RT toxicity (mucositis, xerostomia for head-and-neck fields). Regional nodal exam at each follow-up for high-risk primaries.

Disposition

Current setting: outpatient — Recognise cSCC, biopsy to confirm, assign NCCN risk tier + Brigham T-stage, deliver risk-directed local therapy (Mohs / excision / ED&C / topical for in situ / adjuvant RT) or checkpoint-inhibitor systemic ladder for advanced disease, coordinate with transplant team for SOT recipients, deliver chemoprevention, and establish intensified lifelong skin surveillance (NCCN cSCC 2025; Karia PMID 23677079; EMPOWER-CSCC-1 PMID 29863979; KEYNOTE-629 PMID 32673170)

Disposition criteria:
- Low-risk cSCC fully excised / treated -> intensified surveillance (NCCN cSCC 2025)
- High-risk / very-high-risk cSCC -> Mohs / margin-assessed excision ± adjuvant RT; intensified surveillance
- Locally advanced / metastatic disease -> systemic checkpoint immunotherapy + MDT shared-care
- Transplant recipient -> derm + transplant-team co-management; nicotinamide chemoprevention

Escalation triggers (move to higher acuity):
- Perineural invasion (named-nerve pain / paraesthesia / motor weakness / facial palsy) -> urgent MRI + MDT (NCCN cSCC 2025)
- Palpable regional lymph nodes -> imaging + FNAC / core biopsy and head-and-neck surgical oncology referral
- Locally advanced / unresectable / metastatic disease -> systemic immunotherapy + MDT
- Severe Grade 3-4 checkpoint-inhibitor irAE -> hold drug + systemic corticosteroids per oncology pathway
- Transplant recipient with high-risk / recurrent cSCC -> transplant team for immunosuppression review

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] cSCC not amenable to curative surgery or radiation, regional nodal disease beyond surgical control, or distant metastasis (NCCN cSCC 2025; EMPOWER-CSCC-1 PMID 29863979)
- [LIFE_THREATENING] Grade 3-4 immune-related adverse event on cemiplimab / pembrolizumab (colitis / hepatitis / pneumonitis / myocarditis / endocrine crisis) (EMPOWER-CSCC-1 PMID 29863979; KEYNOTE-629 PMID 32673170)
- [SEVERE] Symptoms or imaging consistent with perineural invasion of a named nerve (pain, paraesthesia, motor weakness, facial palsy) (NCCN cSCC 2025; Karia PMID 23677079)

Citations

- NCCN Squamous Cell Skin Cancer v.1.2025 (NCCN.org) + Brigham T-stage outcomes (Schmults/Karia JAMA Dermatol 2013; PMID 23677079, DOI 10.1001/jamadermatol.2013.2139) + EMPOWER-CSCC-1 cemiplimab in metastatic / locally advanced cSCC (Migden NEJM 2018; PMID 29863979, DOI 10.1056/NEJMoa1805131) + KEYNOTE-629 pembrolizumab in R/M cSCC primary (Grob JCO 2020; PMID 32673170, DOI 10.1200/JCO.19.03054) and combined LA + R/M (Hughes Ann Oncol 2021; PMID 34293460, DOI 10.1016/j.annonc.2021.07.008) + ONTRAC nicotinamide chemoprevention (Chen NEJM 2015; PMID 26488693, DOI 10.1056/NEJMoa1506197) [PMID:23677079](https://pubmed.ncbi.nlm.nih.gov/23677079/)
- Cited evidence (PMID 29863979) [PMID:29863979](https://pubmed.ncbi.nlm.nih.gov/29863979/)
- Cited evidence (PMID 32673170) [PMID:32673170](https://pubmed.ncbi.nlm.nih.gov/32673170/)
- Cited evidence (PMID 34293460) [PMID:34293460](https://pubmed.ncbi.nlm.nih.gov/34293460/)
- Cited evidence (PMID 26488693) [PMID:26488693](https://pubmed.ncbi.nlm.nih.gov/26488693/)

Last reconciled with current guidelines: 2026-05-26.
References
  • NCCN Squamous Cell Skin Cancer v.1.2025 (NCCN.org) + Brigham T-stage outcomes (Schmults/Karia JAMA Dermatol 2013; PMID 23677079, DOI 10.1001/jamadermatol.2013.2139) + EMPOWER-CSCC-1 cemiplimab in metastatic / locally advanced cSCC (Migden NEJM 2018; PMID 29863979, DOI 10.1056/NEJMoa1805131) + KEYNOTE-629 pembrolizumab in R/M cSCC primary (Grob JCO 2020; PMID 32673170, DOI 10.1200/JCO.19.03054) and combined LA + R/M (Hughes Ann Oncol 2021; PMID 34293460, DOI 10.1016/j.annonc.2021.07.008) + ONTRAC nicotinamide chemoprevention (Chen NEJM 2015; PMID 26488693, DOI 10.1056/NEJMoa1506197) — PMID:23677079
  • Cited evidence (PMID 29863979) — PMID:29863979
  • Cited evidence (PMID 32673170) — PMID:32673170
  • Cited evidence (PMID 34293460) — PMID:34293460
  • Cited evidence (PMID 26488693) — PMID:26488693