What are the indications for radiotherapy in Merkel cell carcinoma post-operative non-head and neck cases?

Postoperative Radiotherapy Indications for Non-Head and Neck Merkel Cell Carcinoma

Adjuvant radiotherapy to the primary site is generally recommended for all postoperative non-head and neck Merkel cell carcinoma cases except for small (<1 cm) widely excised tumors without adverse risk factors. 1

Primary Site Radiation Indications

Observation may be reasonable only for:

• Primary lesions <1 cm that have been widely excised 1
• AND no lymphovascular invasion present 1
• AND no immunosuppression 1
• AND negative surgical margins 1

All other cases require adjuvant radiotherapy to the primary site, particularly:

• Microscopic or grossly positive margins 1
• Presence of lymphovascular invasion 1
• Immunosuppressed patients 1
• Primary tumors ≥1 cm 1

Radiation Dosing for Primary Site

The dose depends on surgical margin status 1, 2:

• Negative margins: 50-56 Gy 1, 2
• Microscopic positive margins: 56-60 Gy 1, 2
• Gross positive or unresectable: 60-66 Gy 1, 2

Regional Nodal Basin Radiation Indications

For Clinically Node-Negative Disease After Negative SLNB

For extremity and torso locations:

• Observation of regional nodal basins is appropriate after negative SLNB 1, 2
• Radiation therapy is given to the primary site only in most instances 1, 2

If SLNB not performed or unsuccessful:

• Consider irradiating nodal beds for subclinical disease at 46-50 Gy 1, 2

For Positive SLNB

Most patients should undergo completion lymph node dissection and/or radiation therapy 1:

• Microscopic N+ on SLNB in axilla or groin: 50 Gy 1, 2
• After lymph node dissection in axilla or groin: 50-54 Gy 1, 2

Adjuvant RT after lymph node dissection is indicated for:

• Multiple involved nodes 1
• Presence of extracapsular extension 1

Adjuvant RT after lymph node dissection is NOT indicated for:

• Low tumor burden on SLNB 1

For Clinically Evident Lymphadenopathy

• Clinically evident adenopathy: 60-66 Gy 1, 2

Critical Technical Considerations

Timing is essential:

• Expeditious initiation of adjuvant RT after surgery is critical, as delays are associated with worse outcomes 1, 2
• Do not pursue extensive surgery to achieve clear margins if it will significantly delay adjuvant RT 2

Radiation technique:

• All doses delivered at 2 Gy per fraction using standard fractionation 1, 2
• Bolus used to achieve adequate skin dose 1, 2
• Wide margins (5 cm) around the primary site when possible 1, 2

Evidence Supporting These Recommendations

The evidence strongly supports adjuvant radiation for non-head and neck sites. A single-institution study of 171 patients demonstrated that RT was associated with improved 3-year local control (91.2% vs 76.9%), locoregional control (79.5% vs 59.1%), and disease-free survival (57.0% vs 30.2%) 3. Importantly, patients with negative margins still had significant improvements in 3-year local control with RT (90.1% vs 75.4%) 3. However, a more recent 2024 study specifically examining low-risk pathologic stage I MCC found that for non-head and neck locations (extremities and trunk), no local recurrences were observed in patients managed with surgery alone, suggesting PORT may not be indicated for this very select low-risk subset 4.

Common Pitfalls to Avoid

• Do not delay RT for extensive reconstruction that could obscure the radiation target area 2
• Do not withhold RT based solely on negative margins in non-head and neck sites, as RT improves outcomes regardless of margin status 3
• Do not irradiate regional nodal basins after negative SLNB in extremity/torso locations unless SLNB was not performed 1, 2
• Do not use adjuvant chemotherapy alone for local disease, as it does not improve outcomes 1