Melanoma has had a reputation as a disease that is more difficult to control with RT than most other histological types. Therefore, the use of adjuvant radiotherapy (RT) following surgery for locally advanced melanoma has not been accepted as standard management in the same manner as other common cancer types. Numerous retrospective studies have addressed this issue in melanoma, with mixed results as to the benefit of adjuvant RT following therapeutic lymph node dissection. It is likely that selection bias and lack of generalisability have contributed to the variability of results. A randomised controlled trial (RCT) has helped to resolve the uncertainty.
Locoregional tumour recurrence is frequently associated with significant morbidity. However, the role of adjuvant RT must be considered in the era of effective systemic therapy, where longer survival is now possible and late complications of treatment may cause considerable morbidity.
Systematic review evidence
Randomised controlled trial
A single RCT was identified comparing regional lymph node dissection alone with regional lymph node dissection followed by adjuvant RT. A total of 217 patients who had undergone complete cervical, axillary or inguinal lymphadenectomy for metastatic melanoma in the regional lymph node basin were randomised to surgery alone (n=108) versus surgery followed by adjuvant radiotherapy (n=109). The criteria for eligibility included the number of involved nodes (any involved parotid node, two involved nodes in cervical or axilla, three involved nodes in groin), the size of involved nodes (≥3 cm in cervical node, ≥4 cm for axillary or inguinal nodes) and extracapsular extension.
Adjuvant RT consisted of a mildly hypofractionated schedule (48 Gray in 20 fractions). The endpoints were lymph-node basin relapse, overall survival, relapse-free survival, late toxicity and quality of life.
Results were reported at 3 and 5 years. At 3 years there was a significant reduction in lymph node basin relapse (31% vs 19%, p=0.04) but no difference in overall survival or relapse-free survival. At 5 years the cumulative incidence for isolated lymph node basin relapse as a site of first relapse was 8.3% for adjuvant radiotherapy and 23% for surgery alone (p=0.002). There was no difference in overall survival. Quality of life was the same in both groups, but late toxicity was increased in the adjuvant RT arm, particularly in field fibrosis and leg oedema following inguinal treatment.
There were eight retrospective cohort studies identified comparing lymph node dissection alone with adjuvant RT. The endpoints were generally the infield recurrence rates and overall survival. All cohort studies suffered from selection bias, as melanomas with high risk features and considered more likely to suffer locoregional relapse were considered for adjuvant RT. Surgical technique and RT doses and schedules varied between studies. The results varied greatly between studies, with conflicting conclusions regarding both the local control and possible survival benefits of adjuvant RT. As a result of these uncertainties, these retrospective cohort studies were disregarded in this guideline.
Evidence summary and recommendations
|Adjuvant RT following therapeutic lymph node dissection decreased the risk of locoregional recurrence but did not improve survival compared with surgery alone.||II|||
|Adjuvant RT following therapeutic lymph node dissection increased late toxicity, especially soft tissue fibrosis in the treated lymph node basin and leg oedema after groin irradiation.||II|||
|Adjuvant RT following regional lymph node dissection may be considered following histopathological identification of high risk features if potentially effective systemic therapy is not available.||B|
Patients at high risk of locoregional recurrence are also at high risk of distant metastases. The decision to recommend adjuvant RT should be made in a multidisciplinary forum where all options for further local and systemic therapy are addressed. In particular, the role of local treatments including adjuvant RT is changing rapidly as effective systemic therapies become available.
Adjuvant RT may be considered also for (i) positive margins (ii) after therapeutic dissection where further surgical clearance is not feasible (eg parotid) and (iii) further recurrence after surgery.
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