8.2 Radiotherapy for basal cell carcinoma

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Unless stated otherwise, tumour stage is according to the American Joint Committee on Cancer (AJCC) cancer staging manual 8th edition [1] and Union for International Cancer Control (UICC) TNM classification of malignant tumours 8th edition.[2]

Background

Radiotherapy (RT) has been used for treating basal cell carcinoma (BCC) for over a century. It is an efficacious alternative treatment for primary untreated BCC in a minority of patients when surgery is disadvantageous:

  • when surgery is not feasible (e.g. in patients unfit for surgery, including those with significant coagulation risk)
  • when the patient declines surgery
  • when surgery will cause cosmetic or functional morbidity unacceptable to the patient (e.g. nasectomy, loss of function of lips or eyelids, large tissue deficits, multiple lesions).

Radiotherapy is also used in the management of metastatic BCC.

Unlike topical therapies, RT is not limited to certain BCC histological subtypes.[3]

The availability of new office-based portable systems is increasing the availability of RT for BCC.[4][5]
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Evidence

Systematic review evidence

In which patients with basal cell carcinoma does a radiotherapy modality achieve equal or better outcomes than conventional surgery?

A systematic review was undertaken to evaluate in which patients with basal cell carcinoma a radiotherapy modality achieves equal or better outcomes than conventional surgery.

The search strategy, inclusion and exclusion criteria, and quality assessment are described in detail in the Technical report.

Twenty studies were identified that assessed outcomes in patients treated with RT for BCC and met the inclusion criteria,[6][7][8][9][10][11][12][13][14][15][3][16][17][18][19][20][21][22][23][24] including five representing level III-2 evidence [11][21][22][23][24] and 15 level IV.[14][3][17][19][20][8][9][7][12][13][15][16][18][6][10]

There were no randomised controlled trials. Three prospective studies were identified,[10][20][13] and the remainder were retrospective studies. All studies were at high risk of bias.

Participants were mainly patients for whom surgery was unsuitable. Many different RT techniques were used, including different types of external-beam radiotherapy (EBRT) and brachytherapy.

Survival

Seven studies reported survival outcomes in patients treated with EBRT or brachytherapy.[14][8][11][12][19][6]

Four studies[14][9][11][6] reported overall survival rates, which ranged from 61% after 1 year follow-up, to 97% after 5 years follow-up.

Six studies[14][9][11][12][19] reported disease-free survival, which ranged from 57% after 13 months follow-up to 90% after 5 years follow-up.

Response rates

Four studies reported response rates for patients with BCC treated with RT or brachytherapy. Three reported complete response rates greater than 95% following treatment by EBRT or brachytherapy, in a combined total of 231 patients, with follow-up ranging from 3 months to 4 years.[14][20][13] Another small study[18] reported a complete response rate of 97.9% for those treated with 40 Gy radiotherapy, and 88.9% response rate for those treated with 50 Gy (n=9).

Recurrence rates

Nine studies reported recurrence or relapse rates for patients treated by EBRT or brachytherapy.[14][17][11][21][7][23][25][10][24]

Recurrence rates ranged from 2% to 10% in a combined total of 2987 patients, with a follow-up of up to 5 years.

A single study[24] reported comparative recurrence rates in patients treated by surgery, adjuvant RT, or RT alone. After a median follow-up of 33 months, patients treated by surgery alone (n=244) had a recurrence rate of 5.3%. The recurrence rate rose to 10% in those treated by surgery and RT (n=20), and to 20% in those treated by RT alone (n=19).[24]

Recurrence can occur at any time after RT, but 88–90% of recurrences were reported to occur within the first 5 years.[26][27] Among patients treated with a curative dose, reported 5-year recurrence rates were approximately 5%.[14][3][17][11][21][7][23][25][10][24]

Control

Five studies reported control rates for patients treated with EBRT or brachytherapy only.[14][20][21][22][6]

Control rates at 5 years and 10 years post treatment were greater than 85% across all studies (reported for 974 patients).

Toxicity

Six studies[20][7][13][16][18][10] reported acute toxicity outcomes. Approximately 75% or more of patient reported grade 0 or 1 acute toxicities, in a cumulative total of 503 patients.

Only two studies.[12][18] reported late toxicity outcomes. Grade 0 or 1 late toxicity was reported in 78–91% of patients (n=127). There were no cases of necrosis.[12][18]

Cosmetic outcomes

Six studies[3][20][23][13][16][18] reported cosmetic outcomes for patients treated with EBRT or brachytherapy.

Good or excellent outcomes were reported in 62–100% of the 308 patients included.

Cosmetic outcomes for brachytherapy were generally inferior to those reported for EBRT[3][20][23][13][16][18]
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Overview of additional evidence (non-systematic literature review)

Outcomes of RT series and other relevant clinical findings were reported in additional studies that did not meet inclusion criteria.

Control rates

For BCC ≤2cm treated with RT, control rates of 95–99% at 5 years and 93–95% at 10 years have been reported (Table 7).[28][29][26][30][27][31][32][33]
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Table 7. Control rates for BCC treated with radiotherapy, according to AJCC/UICC stage (6th edition)[34][35][36][37][38][39][40][41]
Lesion size T Stage 5 years 10 years
<2cm T1 97% 95%
2–5cm T2 92% 89%
>5cm T3 60% 50%
T4 lesions T4
Note: Staging according to American Joint Committee on Cancer and International Union Against Cancer classification (AJCC/UICC) 6th edition,[42] which was the edition current at the time the cited studies were conducted.


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Basal cell carcinoma of medial canthus

Radiotherapy has comparable control rates to surgery[26] but results in superior tissue conservation.

A small case series reported good cancer outcomes and cosmetic outcomes for high-dose-rate brachytherapy in the treatment of tumours of the medial canthus of the eyelid, the majority of which were BCCs.[43] At median follow-up of 40 months investigators reported a local control rate of 94% and good or excellent cosmetic outcomes in 70% of patients.

Recurrent tumours of the medial canthus require surgical salvage.[44]

Recurrence of basal cell carcinoma following radiotherapy

Recurrent BCC should be treated with excisional surgery, including excision of the irradiated tissues, by a specialistMedical practitioners who through training, experience and peer opinion specialise in the management of keratinocyte cancers surgeon.

Salvage re-irradiation can be considered In some circumstances (e.g. a long disease-free interval[45]) when surgery cannot be performed.[46][47] Surgery may be preferred to re-irradiation, as there is increased risk of more serious late RT-related sequelae (radionecrosis of skin and other underlying tissues).

Residual basal cell carcinoma following radiotherapy

Complete clinical resolution of a BCC following curative radiotherapy can occasionally take up to 4 months.[48] Most small BCC resolve by the time the acute radiation reaction has resolved (4–6 weeks after finishing radiotherapy).[48]

Postoperative radiotherapy for aggressive tumours

Postoperative RT has been reported to increase local control rates for extensive, locally advanced BCCs where complete surgical excision cannot be achieved,[49] and for head-and-neck BCCs with aggressive features on histopathology.[50]

A small case series reported a 5-year cure rate of 55.13% with definitive RT for extensive and recurrent BCC.[49]

Postoperative radiotherapy for residual tumours following incomplete excision

The observed recurrence rate of incompletely excised BCC is approximately 33% on average.[51][52][53][54][55][56][57][58][59][47][60]

Re-excision following incomplete excision of BCC is controversial (Protocol to manage incomplete resected basal cell carcinoma). Approximately two-thirds of incompletely excised BCCs do not recur. Some authors have reported similar rates for salvage of recurrent lesions. However, a Canadian case series of incompletely resected BCCs reported that 6% were eventually not controlled after salvage.[58] Numerically higher rates of recurrence have been reported when the deep margin is involved, compared with a lateral margin, and higher again when both are involved.[57][58]

Following incomplete excision, re-excision surgery is usually performed as complete excisional surgery is more accessible, expedient and convenient, and has optimal cancer outcomes and cosmetic outcomes. However, RT is an option following incomplete excision of primary BCCs when surgery is declined, likely to be associated with unacceptable function and cosmetic outcomes, or is not feasible (e.g. due to comorbidity). Margins added for RT fields depend on tumour size and histology.[61]

Salvage radiotherapy

Control rates after salvage therapy are lower than those for primary treatment and are associated with size of the recurrent tumour, number of recurrences and invasion of skeletal muscle, cartilage or bone.[32]

Radiotherapy has been reported to increase local control in advanced BCC.[62]

Radiotherapy has been reported to be successful as a salvage treatment for recurrence of BCC post Mohs micrographic surgery.[63]

Following recurrence of BCC after RT managed by salvage surgery, further recurrence rates of 14–18% have been reported.[27][51][64][65]
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Evidence summary and recommendations

Evidence summary Level References
Recurrence and control

Recurrence rate were relatively low (≤10%) across all reported studies, and were comparable for surgery only and RT only. Short-term recurrence rates were variable across studies, and were dependent on patient-related factors. Control rates after approximately 10 years of follow-up were >90% in all studies.

III-2, IV [14], [20], [13], [18], [3], [17], [11], [21], [7], [23], [25], [10], [24], [22], [6]
Survival

Overall survival and disease-free survival were high, but variable across the included studies, ranging from 57% to 97%, depending on follow-up time.

Survival outcomes were likely to have been influenced by patients’ ages, disease characteristics, and comorbidities.

III-2, IV [14], [8], [9], [11], [12], [19], [6]
Toxicity

Substantial acute and late toxicities were reported in <25% of treated patients following RT or brachytherapy.

IV [20], [7], [13], [66], [18], [10], [12]
Cosmetic outcomes and complications

Treatment by RT or brachytherapy resulted in good or excellent cosmetic outcomes in most, if not all patients.

Fewer than half of patients experienced treatment-related complications or side effects. Adverse effects were more pronounced in patients treated with higher RT doses and higher dose per fraction.

III-2, IV [3], [20], [23], [13], [66], [18], [22], [25], [19]
Evidence-based recommendationQuestion mark transparent.png Grade
EBR 8.2.1. Radiotherapy using curative doses can be considered as an alternative to surgical excision in the definitive treatment of basal cell carcinoma if surgery is either declined by the patient or surgery is inappropriate.
D
Consensus-based recommendationQuestion mark transparent.png

CBR 8.2.1. For patients with T3/T4 primary persistent or recurrent basal cell carcinoma, consideration should be given to obtaining an opinion from a radiation oncologist as part of multidisciplinary care.

Practice pointQuestion mark transparent.png

PP 8.2.1. Clinical persistence or progression of a basal cell carcinoma after a standard curative dose of radiotherapy should be confirmed in consultation with the treating radiation oncologist. The lesion should be biopsied and managed with salvage excisional surgery.

Practice pointQuestion mark transparent.png

PP 8.2.2. Patients who have undergone complete excision of basal cell carcinomas should be offered referral to a specialistMedical practitioners who through training, experience and peer opinion specialise in the management of keratinocyte cancers skin cancer clinic (or head and neck clinic) for individual assessment and consideration of postoperative radiotherapy or additional treatment if any of the following are present:

  • bone invasion
  • rapidly growing tumour
  • tumour recurrence (including multifocal recurrence or multiple recurrences)
  • inadequate margins on excision when further surgery is problematic
  • perineural invasion (major and minor nerves)
  • lymphovascular invasion
  • in-transit metastases
  • regional nodal involvement
  • histological subtype associated with poor prognosis (micronodular, infiltrative or metatypicalshowing evidence of squamatisation (descriptor applicable to basaloid tumours and indicating aggressive subtype)).
Key point(s)
  • Radiotherapy can be considered an alternative to re-excision in the management of incompletely excised basal cell carcinoma if further treatment is deemed advisable and re-excision is disadvantageous or not feasible.
  • Radiotherapy can be considered as an alternative to excision surgery as a definitive treatment for T1 and T2 BCC when surgery is difficult due to patient-related factors (e.g. frailty), tumour-related factors (e.g. where tissue conservation or cosmesis is a high priority, such as in BCC of the eyelid), or treatment-related factors (e.g. concurrent anticoagulant therapy).

Notes on the recommendations

Radiotherapy may be considered in some cases when function and/or cosmesis are a high priority, as RT is tissue-conserving when compared with surgery.


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Appendices

Jutta's magnifying glass icon.pngPICO question RT2 View Evidence statement form RT2Evidence statement form RT2

View Systematic review report RT2Systematic review report RT2

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