Treatment of Squamous Cell Carcinoma In Situ on the Foot with Topical 5-Fluorouracil
Topical 5-fluorouracil 5% cream is a reasonable treatment option for squamous cell carcinoma in situ (SCC in situ/Bowen's disease) on the foot, particularly when the lesion is large or when surgical healing would be problematic, but photodynamic therapy (PDT) and surgical excision remain superior options when feasible. 1
Treatment Protocol
Apply 5-FU 5% cream using the following regimen:
- Once daily for 1 week, then twice daily for 3 weeks 1
- Repeat the course if needed based on clinical response
- Treatment duration ≥4 weeks is associated with significantly better outcomes (93.2% clearance) compared to shorter durations 2
Expected Efficacy
The foot represents a "poor healing site" where 5-FU performs relatively well compared to surgical alternatives:
- Complete response rates: 67-96% depending on lesion characteristics 1, 3
- For lesions <2 cm: 88.9% clearance rate 2
- For lesions ≥2 cm: 60% clearance rate (significantly lower, P=0.051) 2
- Long-term data shows only 8% recurrence rate at 17-month follow-up 1
Positioning in Treatment Algorithm
According to British Association of Dermatologists guidelines, for SCC in situ on the foot (classified as "poor healing site"):
For small lesions (<2 cm):
- 5-FU scores as "generally good choice" (score: 2) 1
- Comparable to imiquimod and cryotherapy
- PDT remains superior (score: 5, "probably treatment of choice")
For large lesions on poor healing sites:
- 5-FU scores as "generally fair choice" (score: 3) 1
- More practical than surgery for large lesions at poor healing sites 1
- PDT scores highest (score: 6, "probably treatment of choice")
Critical Factors Affecting Success
Lesion size is the most important predictor:
- Larger tumors have 2.40 times higher odds of treatment failure (P=0.037) 2
- Each additional week of treatment reduces failure odds by 74% (OR: 0.26, P=0.007) 2
Hyperkeratotic lesions may fail due to poor drug penetration 1. Consider:
- Pretreatment with keratolytic agents
- Laser ablation of stratum corneum before 5-FU application 1
- Occlusive dressings to enhance penetration 1
Comparative Performance
5-FU is less effective than PDT but not significantly different from cryotherapy:
- 5-FU: 83% complete response at 3 months vs. PDT: 93% vs. cryotherapy: 86% 1
- At 12 months: 5-FU 48% clearance vs. PDT 82% clearance 1
- Strength of recommendation: B (level of evidence 1+) 1
Important Caveats
This applies ONLY to SCC in situ (Bowen's disease), NOT invasive SCC:
- FDA approval is for actinic keratoses and superficial basal cell carcinoma 4
- Topical 5-FU is NOT recommended for invasive cutaneous SCC 5
- Biopsy confirmation of in situ disease is essential before treatment
Immunosuppression does NOT affect outcomes:
- No significant difference in clearance rates for immunosuppressed patients 2
- 5-FU can be used safely in organ transplant recipients 6
When to Avoid 5-FU on the Foot
Consider alternative treatments when:
- Lesion diameter >2 cm (consider PDT or excision)
- Significant hyperkeratosis present (poor penetration)
- Patient unable to comply with 4+ week treatment course
- Invasive SCC suspected or confirmed (requires surgery)
Combination Therapy Option
If 5-FU monotherapy fails, combination with imiquimod may salvage treatment 7, though recent data suggests imiquimod alone has higher recurrence rates than 5-FU for SCC in situ 8.