US consensus defines adjuvant radiotherapy indications for high-risk node-negative cutaneous SCC

KEY POINTS

• This US-based modified Delphi study brought together 35 multidisciplinary experts, including 15 radiation oncologists, nine dermatologists/Mohs surgeons, seven medical oncologists, three head and neck surgeons, and one surgical oncologist. All participants completed three anonymous survey rounds, with consensus predefined as ≥80% agreement and near-consensus as 70–79%. The objective was to standardize adjuvant radiotherapy (ART) decisions for node-negative cutaneous squamous cell carcinoma (cSCC), including patient selection, treatment volumes, timing, and dose fractionation.
• Unanimous consensus (35/35, 100%) supported ART to the primary tumor bed when gross or microscopically positive surgical margins remain and further surgery is not feasible. Following complete excision with negative margins, ART was supported when the estimated five-year risk of local recurrence was ≥20% (29/35, 83%), while an estimated nodal metastasis risk ≥20% reached near-consensus (27/35, 77%). Lower proposed risk thresholds of 10% or 15% received little support, suggesting a preference for risk-adapted rather than routine postoperative treatment.
• Several anatomical and pathological features strongly favored ART after negative-margin surgery. Consensus was reached for gross cortical bone or marrow invasion (32/35, 91%), skull base invasion (32/35, 91%), and clinical nerve invasion regardless of T stage (31/35, 89%). ART was also supported for tumors with four high-risk factors (35/35, 100%), three high-risk factors (86–94%), or large-caliber perineural invasion ≥0.1 mm plus another risk factor (30/35, 86%). The four predefined risk factors were tumor diameter ≥2 cm, invasion beyond subcutaneous fat, large-caliber perineural invasion, and poor differentiation.
• Individual adverse pathological findings were not considered sufficient to justify ART automatically. Only 13/35 experts (37%) supported treatment for isolated lymphovascular invasion, 9/35 (26%) for isolated small-caliber perineural invasion, and 20/35 (57%) for invasion beyond subcutaneous fat without other adverse factors. Immunosuppression influenced ART decision-making for 30/35 experts (86%), while 27/35 (77%) were more likely to recommend ART in immunosuppressed patients, reflecting concern about aggressive tumor behavior and limited salvage options.
• Response to neoadjuvant immunotherapy was another important consideration. 34/35 experts (97%) supported omitting ART after a pathological complete response, whereas 30/35 (86%) supported ART following pathological nonresponse and 26/35 (74%) favored ART after partial pathological response. No consensus emerged after major pathological response (12/35, 34%). These recommendations represent expert opinion in an evolving treatment setting and do not establish the oncological safety of omitting postoperative RT after immunotherapy.
• Among the 15 radiation oncologists, there was unanimous agreement that the preferred interval for initiating ART was 4–8 weeks after surgery (15/15, 100%), with treatment timing influenced by wound healing and tumor aggressiveness. Nonhealed wounds (29/35, 83%) and exposed bone (30/35, 86%) supported delaying or omitting ART, while ECOG performance status 4 supported omission (32/35, 91%). For primary tumor-bed irradiation, consensus favored 60–66 Gy in 30–33 fractions (15/15, 100%) or 50–55 Gy in 20–22 fractions (13/15, 87%). Hypofractionation using fewer than 20 fractions was considered appropriate in selected circumstances (12/15, 80%), but no specific shorter regimen or clinical scenario reached consensus.
• Elective nodal irradiation remained unresolved. Only 6/15 radiation oncologists (40%) routinely favored ART to draining nodal basins in patients at high risk of nodal metastasis, whereas 9/15 (60%) did not routinely recommend it or considered the decision conditional. For primary tumor-bed RT, IMRT (15/15, 100%) and electrons (14/15, 93%) were considered appropriate, while superficial RT and brachytherapy were generally considered unsuitable for high-stage disease. When treatment involved the skull base or a cranial nerve, consensus supported IMRT (14/15, 93%) and 60–66 Gy in 2-Gy fractions (13/15, 87%). The predominantly academic panel (34/35, 97%) and absence of patient-outcome validation limit generalizability.

CLINICAL TAKEAWAY

SOURCE

International Journal of Radiation Oncology, Biology, Physics