Applications of Platelet-Rich Plasma in Lymphedema

Dear Editor,

We read with great interest the article by Akgül et al. ¹ titled “Applications of Platelet-Rich Plasma in Lymphedema.” The authors concluded that current evidence obtained from in vitro and animal studies pointed out that platelet-rich plasma (PRP) may potentially be used to regenerate injured lymphatic vessels to treat or prevent lymphedema. But, in the same time, they mention that there is no clinical trial regarding the use of PRP in lymphedema treatment. Is there any reason for that?

To answer this question, we performed a thorough search of the literature that resulted in only a few reported cases of PRP application on tumor excision sites. Cancer, that is, breast cancer or melanoma, is the first leading cause of surgical excisions that could lead to the need for lymph node dissection, which may result in lymphedema.

The release of growth factors contained in PRP, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), induces tumor lymphangiogenesis, leading to enhanced rate of nodal metastasis. ² Patients with breast tumors positive for PDGF have a significantly lower response rate to chemotherapy as well as significantly shorter duration of survival. In addition, patients with breast cancer who have elevated plasma PDGF levels have a significantly shorter survival. ³ EGFR (HER) and other members of the ErbB receptor family regulate several cell biology processes, including proliferation, survival, differentiation, and tumorigenesis. ⁴ Transforming growth factor-β ligand is a multifunctional growth factor that regulates various cell behavior, such as cell differentiation, migration, and apoptosis. ⁵ Furthermore, inhibiting angiogenesis pathway has long remained a significant hope for the development of novel, effective, and target-orientated antitumor agents arresting tumor proliferation and metastasis. ⁶ So, the real question is can we proceed to clinical application of PRP and its growth factors on tumor excision sites, that is, after axillary lymph node dissection for breast cancer?

By the time a tumor is established, countless interactions between tumor and stroma have already taken place, making it virtually impossible to dissect out the complex, reciprocal, and changing cause-and-effect relationships responsible for tumor evolution and maintenance. ⁷

Even after a tumor is excised and optimal survival is achieved, we must implement every single evidence-based guideline, while, at the same time, excluding any maneuver, the indication of which has not been established yet.

The role of PRP in patients affected by outcomes of breast tumor resection such as lymphedema deserves further experimental investigation and large-scale prospective randomized clinical trials. The use of novel reversibly switchable in vivo tumor models can elucidate the cause-and-effect chain of processes triggered by acute oncogene activation, providing an indication of the extent to which the tumor cell instructs its microenvironment versus the microenvironment instructing the tumor.