What is the recommended management of metastatic soft‑tissue sarcoma in a pregnant woman, including systemic therapy, surgery, and delivery planning?

Management of Metastatic Soft Tissue Sarcoma in Pregnancy

For metastatic soft tissue sarcoma in pregnancy, single-agent doxorubicin (60–75 mg/m²) administered during the second trimester is the recommended systemic therapy, while avoiding chemotherapy entirely in the first trimester and considering early delivery in the third trimester to initiate full oncologic treatment. 1

Timing-Based Management Algorithm

First Trimester Diagnosis

• Observation until the second trimester is the preferred approach if the clinical situation permits delay. 2
• If urgent treatment is required due to rapidly progressive metastatic disease, discuss pregnancy termination with the patient, as chemotherapy in the first trimester carries significant risk of fetal malformations and pregnancy loss. 1, 3
• All chemotherapy should be avoided during organogenesis (first 12 weeks) due to teratogenic risk. 3

Second Trimester Management

• Single-agent doxorubicin at 60–75 mg/m² is the recommended chemotherapy regimen for metastatic disease requiring urgent systemic treatment. 1, 2
• Avoid combination regimens, particularly doxorubicin plus ifosfamide, despite their use in non-pregnant patients. 1, 2
  • The rationale is threefold: limited safety data for ifosfamide in pregnancy, its significant toxicity profile, and lack of survival advantage over single-agent doxorubicin. 1
  • Critical caveat: A 2022 multi-institutional study found that all four pregnancy losses (100%) occurred in patients receiving both doxorubicin and ifosfamide, with chemotherapy initiated earlier in the second trimester (mean 15.5 weeks vs. 21.3 weeks for live births, p=0.016). 4
• Chemotherapy initiation later in the second trimester (after 20-21 weeks) appears safer based on available evidence. 4
• Surgery for metastatic disease (such as pulmonary metastasectomy) can be performed safely during the second trimester if clinically indicated. 2, 5

Third Trimester Management

• If diagnosis occurs late in the third trimester, strongly consider pre-term delivery followed by initiation of full oncologic therapy rather than administering chemotherapy during this period. 1, 2
• Induction of labor should be planned to allow immediate postpartum initiation of optimal chemotherapy regimens, which may include combination therapy not safe during pregnancy. 1
• For deliveries before 36 weeks, administer antenatal corticosteroids to reduce neonatal respiratory distress syndrome risk. 3

Surgical Considerations

• Wide surgical excision with tumor-free margins remains the standard approach for any resectable disease and can be safely performed during pregnancy. 2, 5
• Approximately 1 cm margins of normal tissue are acceptable; minimal margins are permissible when anatomic barriers (fascia, periosteum) are encountered. 2
• Most cases can be successfully managed with surgery during gestation, with the majority of patients delivering at term. 5
• Surgery should not be delayed due to pregnancy if the primary tumor or oligometastatic disease is resectable. 5

Radiation Therapy

• Radiation therapy must be deferred until after delivery due to fetal toxicity risk, regardless of trimester. 2
• Standard postoperative radiation (50–60 Gy in 1.8–2 Gy fractions) cannot be administered during pregnancy. 2
• This creates a management challenge for high-grade, deep tumors >5 cm that would typically require adjuvant radiation. 2

Delivery Planning

• Plan delivery timing to optimize both maternal oncologic outcomes and fetal maturity. 2, 5
• Mean gestational age at delivery in reported cases is approximately 30-31 weeks when chemotherapy is administered during pregnancy. 4, 5
• Avoid chemotherapy administration within 3 weeks of planned delivery to minimize neonatal myelosuppression risk. 3
• Breastfeeding is contraindicated if chemotherapy continues postpartum. 3

Multidisciplinary Care Requirements

• Immediate referral to a sarcoma reference center is mandatory, even during pregnancy. 2
• The care team must include: sarcoma surgeons, maternal-fetal medicine specialists, neonatologists, pathologists, radiologists, radiation oncologists, and medical oncologists. 2, 3
• Close fetal monitoring with particular attention to cardiac function is required when anthracyclines are administered. 3

Critical Pitfalls to Avoid

1. Do not use combination doxorubicin-ifosfamide regimens during pregnancy despite their standard use outside pregnancy—the fetal demise rate is unacceptably high. 4
2. Do not initiate chemotherapy in early second trimester (before 20 weeks) unless absolutely necessary—later initiation appears safer. 4
3. Do not delay diagnosis with imaging concerns—MRI and ultrasound are safe during pregnancy for diagnostic evaluation. 6
4. Do not assume regular menstruation postpartum indicates preserved fertility—formal fertility assessment is needed. 7
5. Do not forget contraception counseling—effective contraception is required during and for 3-6 months after completing chemotherapy. 3

Postpartum Considerations

• Switch to combination chemotherapy regimens postpartum if clinically indicated, as the survival advantage of combination therapy can be pursued once fetal risk is eliminated. 1
• Delay subsequent pregnancy for at least 12 months after completing therapy. 7
• Women under 35 years have >80% chance of future pregnancy, while those over 35 have significantly reduced fertility. 7