Expert opinion: radiotherapy for basal cell carcinoma

Summary

Basal cell carcinoma (BCC), the most common form of skin cancer, is frequently treated with radiotherapy as a curative alternative to surgery. Various radiotherapy modalities, including orthovoltage x‑rays, Grenz-ray therapy (soft x‑rays), electron beams, megavoltage photons, and high-dose-rate (HDR) brachytherapy, offer tailored approaches based on tumor depth, anatomical location, and patient-specific factors. Both conventional fractionation and hypofractionation, particularly for selected patients and smaller tumors, are standard of care. Orthovoltage x‑rays, Grenz-ray (soft x‑rays) therapies, and brachytherapy are especially valuable for treating superficial lesions and tumors located in sensitive anatomical sites such as regions of the ear, eye, or nose. Treatment planning must balance tumor control with cosmetic and functional outcomes. Guidelines from Germany (S2k guideline) and the USA (ASTRO) emphasize evidence-based dosing and modality selection for optimizing therapeutic efficacy and minimizing toxicity [1, 2]. In this guideline review from the German Society of Radiation Oncology (DEGRO) Dermatooncology Working Group, the current role of radiotherapy in the management of BCC is summarized.

Introduction

Basal cell carcinoma (BCC) is the most prevalent form of non-melanoma skin cancer, accounting for approximately 80% of all cases of skin cancer worldwide [3]. It primarily arises from chronic ultraviolet radiation exposure, with the incidence rising steadily in aging populations [3]. While surgical excision remains the gold standard for treatment, radiotherapy serves as the best alternative, especially in patients unsuitable for surgery due to comorbidities or tumor location [1, 4]. Radiotherapy achieves excellent local control rates with favorable cosmetic outcomes, particularly in anatomically complex regions such as the face, nose, eyelids, and ears [5–7]. Postoperative radiotherapy can be recommended in patients with close or positive margins that cannot be corrected surgically due to excessive morbidity or the potential for adverse cosmetic sequelae. It is also suggested for patients who have had a relapse after previous surgery and for those with bone or muscle involvement or perineural growth around a named nerve [1, 2].

Radiotherapy for BCC includes multiple modalities, each characterized by unique radiophysical properties that influence tissue penetration and dose distribution. The choice of modality and fractionation schedule depends on tumor thickness, anatomical location, and patient factors [9, 10].

Clinical guidelines, including the German S2k guideline and the American Society for Radiation Oncology (ASTRO) recommendations, provide evidence-based frameworks for dosing and treatment planning [1, 2]. This review synthesizes current radiotherapy modalities and dosimetric strategies for BCC, highlighting the balance between tumor eradication and preservation of function and cosmesis.

Radiobiological effects of radiotherapy

Basel cell carcinoma, being a slow-growing epithelial tumor with low mitotic activity, shows high radiosensitivity due to inefficient DNA repair mechanisms Fractionated radiotherapy exploits the differential repair capacities of tumor and normal tissues, allowing normal cells to recover while progressively damaging tumor clonogens.

The standard fractionation scheme of 2 Gy per fraction over 6–7 weeks maximizes the therapeutic ratio by minimizing late toxicity to surrounding skin and subcutaneous structures. Hypofractionated regimens deliver larger doses per fraction over fewer sessions. They require experience and caution at sensitive sites due to the increased risk of late effects such as fibrosis or necrosis [8].

Current radiotherapeutic modalities

Radiotherapy for BCC employs several modalities tailored to tumor characteristics and anatomical considerations (Table 1, Fig. 1a,b). Taken together, conventionally fractionated radiotherapy regimens should aim at a biologically equivalent dose (BED₁₀) for gross disease of 70–93.5 Gy, while a BED₁₀ of 56–88 Gy is advised for hypofractionated regimens. For postoperative radiotherapy, a BED₁₀ of 59.5–79.2 Gy for normofractionated regimens and a BED₁₀ of 56–70.2 Gy for hypofractionated regimens is recommended. Hypofractionated external beam regimens and high-dose-rate (HDR) brachytherapy offer excellent alternatives for patients unable to commit to prolonged treatment schedules. Generally, a margin of 5–10 mm around the tumor, depending on size and subtype, is recommended for definition of the clinical target volume [11].

Table 1.

Radiation dose and modalities in basal cell carcinoma (BCC) treatment

Modality	Indication	Typical total dose (Gy)	Fractionation	Tumor thickness	Notes
Orthovoltage x‑rays (50–300 kV)	Superficial BCC, cosmetically sensitive sites	60–70	Daily 2 Gy per fraction, 6–7 weeks or hypofractionated	≤ 5 mm	Good dose conformity; risk of skin necrosis if overdosed
Grenz-ray (“soft x‑ray”) therapy (10–20 kV)	Very superficial BCC	30–40	3–5 Gy per fraction, 5–10 fractions, 2–3 per week	< 2 mm	Very limited penetration; risk of underdosage of thicker tumors
Electron beam therapy	Deeper BCC lesions	60–66	Daily 2 Gy per fraction, 6–7 weeks	Up to 20 mm	Allows dose customization; requires bolus for surface dose
HDR brachytherapy	Irregular surfaces, patients unable to attend long schedules	40–50	2.5–4–Gy per fraction, 8–10 fractions, twice daily, or once every 2–3 days with mold/flap	Variable	High precision; suitable for complex sites
Hypofractionation (any modality)	Optimal for selected, e.g., elderly, patients with smaller lesions	30–40	Larger fraction sizes (3–8 Gy), fewer fractions, 2–3 per week	Variable	Some risk of late toxicity—fibrosis/cosmesis

Fig. 1.

Examples of curative radiotherapy for basal cell carcinoma (BCC) as single modality before and 3 months after treatment. a 90-year-old patient with BCC in the corner of the eye after progression under vismodegib and already compromised visual acuity, treated at a linac with 18 × 3 Gy using a flab. b BCC of the tip of the nose before and after 8 × 5 Gy with an energy of 50 kV every 2–3 days

Orthovoltage x‑rays (50–300 kV) are commonly used for superficial BCC lesions, especially those under 5 mm thickness, providing limited tissue penetration and sparing deeper structures [12, 13]. This makes orthovoltage therapy particularly suitable for sensitive areas such as the eyelids, nose, and ears (Fig. 1b). Typical dosing ranges from 60 to 70 Gy delivered in daily 2‑Gy fractions over 6–7 weeks or 30–40 Gy using hypofractionated schedules over 2–4 weeks, aiming to balance effective tumor control and acceptable cosmetic outcomes [12]. Margins around the macroscopic tumor of around 5–10 mm should be used. Careful treatment planning is essential to prevent skin ulceration or necrosis, particularly in areas with thin skin.

Grenz-ray therapy utilizing very low-energy x‑rays (“soft” x‑rays of 10–20 kV) is indicated primarily for very superficial BCCs with penetration depths under 2 mm. Although less commonly used today, it remains a treatment option for selected thin lesions, particularly those located on the face and scalp [14]. Hypofractionated schedules of 30–40 Gy in 5–10 fractions over 2–4 weeks are typically applied. The limited penetration minimizes damage to underlying tissues but restricts use to very superficial tumors.

Electron beam therapy offers precise control over dose depth for lesions up to approximately 2 cm thick, using energies that allow dose customization to tumor thickness. Standard total doses ranging from 60 to 66 Gy with conventional fractionation are considered standard. Hypofractionated treatment regimens, especially for early-stage lesions, may provide high response rates and excellent cosmetic results in selected patients [15]. Custom cutouts and bolus materials are used to conform the dose distribution and secure full surface dose, particularly on irregular surfaces like the nose and ears [15].

A special mention should be made of advanced photon techniques, such as volumetric modulated arc therapy (VMAT) requiring complex 3D planning and flabs (Fig. 1a), which can often be the only therapeutic solution in cases with complex anatomy or multiple lesions, e.g., for total scalp irradiation [16].

Basel cell carcinomas located at anatomical boundaries such as the eyelids, nose tip, or ear demand meticulous treatment planning to preserve function and cosmetic appearance. Adjustments in fraction size or total dose can mitigate risks like eyelid ectropion or cartilage necrosis. Hypofractionated regimens are also often applied in these sensitive sites, but caution is warranted.

High-dose-rate brachytherapy provides high precision in delivering dose to complex surface geometries with reduced exposure of adjacent normal tissues and improved cosmetic outcome [11, 17]. Typical HDR treatment schedules deliver 40–50 Gy in 8–10 fractions twice daily, but other forms of brachytherapy such as molds, flaps, and dedicated applicators can also be used with 3–5 Gy per fraction every 2–3 days [11].

A very important aspect for patient information is that quality of life, encompassing emotions, functioning, social connections, and personal appearance, clearly improves after radiotherapy of patients with early-stage disease after a slight decline during the first 6 weeks after treatment [18].

Recommendation

Radiotherapy is the best upfront alternative to surgery, achieving comparable local control and favorable cosmetic results with 60–70 Gy in conventional fractionation [1, 5]. Postoperative irradiation should be considered for incompletely resected (R1/R2) tumors or gross perineural growth and is likewise appropriate for lesions with skeletal muscle or bony invasion and for recurrent BCCs. Conversely, RT is contraindicated in patients with heightened radiosensitivity due to autoimmune disorders (e.g., lupus erythematosus, scleroderma) or genetic syndromes (notably basal cell nevus syndrome/Gorlin and xeroderma pigmentosum) and is generally discouraged in patients younger than 40 years given the risk of radiation-induced secondary malignancies.

Orthovoltage x‑rays are recommended for superficial lesions less than 5 mm thick, particularly in cosmetically sensitive locations, while electron beam therapy is better suited for slightly deeper tumors up to 2 cm in thickness. Grenz-ray therapy (soft x‑rays) may be considered for very thin superficial lesions where sparing deeper tissue is essential. In certain situations with complex anatomy, other types of radiotherapy (i.e., megavoltage photons, VMAT) may be utilized.

Hypofractionated schedules and HDR brachytherapy represent optimal approaches for elderly or multimorbid patients who may be unable to complete conventionally fractionated treatment. Moreover, HDR brachytherapy offers superior dose conformity for tumors located in anatomically complex or irregular regions. Treatment planning should carefully balance the risks of late toxicity against therapeutic benefit, emphasizing preservation of function and aesthetics.

Conclusion

Radiotherapy offers an effective organ-sparing treatment for BCC, with multiple modalities tailored to tumor depth and location. Both conventional fractionation and hypofractionation are viable approaches, while orthovoltage and Grenz-rays (soft x‑rays) are excellent options for superficial lesions. Brachytherapy is especially advantageous for tumors in challenging anatomical locations. Adherence to guideline-based dosing and modality choice optimizes therapeutic outcomes while minimizing toxicity. Ongoing research continues to refine protocols, aiming to enhance integration with other treatment modalities and improve patient-centered care.

Declarations

Conflict of interest

P. Balermpas, K. Hering, A. Rühle, M. Trommer, K. Elsayad, S. Adeberg, and D. Vordermark declare that they have no competing interests.

Ethical standards

This expert opinion reviews literature without identifiable data from human subjects, so ethics approval is not required.