Treatment Regimens for Metastatic Malignant Phyllodes Tumor
For metastatic malignant phyllodes tumors, surgical resection or local ablative therapy of metastatic lesions should be prioritized when feasible, followed by systemic chemotherapy with doxorubicin-ifosfamide (AI) regimen as the first-line option if surgery is not possible or disease progresses. 1
Primary Treatment Approach: Surgery First
Surgery or other local ablative approaches for metastatic disease should be considered as the initial treatment strategy given the relatively indolent nature of these tumors compared to other sarcomas. 1 This recommendation comes from the 2025 UK guidelines for soft tissue sarcomas, which specifically address malignant phyllodes tumors as a distinct entity within breast sarcomas. 1
When to Consider Metastasectomy:
- Oligometastatic disease (limited number of metastases, typically lung) 2, 3
- Adequate performance status to tolerate surgery 3
- Technically resectable lesions with acceptable morbidity 3
- Slow disease progression suggesting indolent biology 1
Systemic Chemotherapy Regimens
When surgery is not feasible or after progression, systemic chemotherapy should follow soft tissue sarcoma treatment paradigms. 1
First-Line: Doxorubicin-Ifosfamide (AI)
The AI regimen demonstrates the longest progression-free survival among chemotherapy options and should be the preferred first-line systemic therapy. 2
- Progression-free survival: 9.10 months (95% CI: 5.03,14.2) 2
- Multiple case reports demonstrate complete responses with AI therapy 4, 3
- One study showed complete radiologic response after 3 AI cycles 5
- Another case achieved complete remission of lung metastases maintained for 3 years post-treatment 3
Second-Line Options:
Other ifosfamide-containing regimens (without anthracyclines):
Other anthracycline regimens (without ifosfamide):
- PFS: 3.65 months (95% CI: 1.17,7.90) 2
- Doxorubicin monotherapy has been used with variable responses 5
Gemcitabine-based regimens:
Alternative Combination Regimen:
Nab-paclitaxel, cisplatin, and liposomal doxorubicin (biweekly for 12 cycles):
- One case report demonstrated complete regression of lung metastases 6
- Acceptable toxicity profile 6
- Consider when standard AI is contraindicated or after progression 6
Treatment Algorithm
Assess resectability of metastatic lesions - If oligometastatic and technically feasible, proceed with surgical resection or ablation 1, 3
If unresectable or after metastasectomy with residual disease, initiate systemic chemotherapy:
Upon progression on AI:
Third-line and beyond:
Re-evaluate for surgical options at any point if disease becomes oligometastatic or resectable 1
Role of Radiotherapy in Metastatic Disease
Radiotherapy can be used for palliation of symptomatic metastases or in combination with chemotherapy for oligometastatic disease. 6
- One case demonstrated successful use of accelerated hypofractionated radiotherapy to chest wall combined with chemotherapy 6
- Consider for locoregional control when metastases are limited 6
Critical Clinical Pitfalls
Do not use endocrine therapy - Despite 58% containing ER and 75% containing PR, hormonal therapy has no proven efficacy in phyllodes tumors 7
Avoid treating as epithelial breast cancer - Phyllodes tumors require sarcoma-directed therapy, not breast cancer regimens 1
Do not delay chemotherapy indefinitely - While surgery is preferred when feasible, median overall survival is only 10.7 months (95% CI: 8.67,16.5), necessitating prompt systemic therapy for unresectable disease 2
Lung is the most common metastatic site - Always obtain chest imaging for staging and surveillance 5, 4, 3
Prognosis and Expectations
Metastatic malignant phyllodes tumors carry a poor prognosis with median overall survival of approximately 10.7 months. 2 However, aggressive multimodal treatment including surgery when possible and AI chemotherapy can achieve durable complete responses in select cases. 4, 3, 6