Personalized Management of Pheochromocytoma and Paraganglioma

. 2021 Jun 19;43(2):199–239. doi: 10.1210/endrev/bnab019

Practical tip/synthesis (applies to all clusters):
• Whenever possible, surgery is the therapy of choice. • Details in terms of surgery, surgery in (oligo-)metastatic disease and alpha-adrenoceptor blockade are described under “Personalized Management: Molecular Cluster 1” subsection “Treatment.” • Figure 4 summarizes a therapy flow-chart which suggests a potential sequence of therapy for the practicing physician, including dosing. • All suggestions in terms of therapy and the sequencing of therapy are described in detail under “Personalized Management: Molecular Cluster 1” subsection “Treatment” and apply to all clusters. • For rapidly progressive PPGLs, the recommended first-line therapy is chemotherapy (CVD scheme) and for slowly to moderately progressive PPGLs, the recommended first-line therapy is radionuclide therapy—either with [¹³¹I]-MIBG or PRRT—depending on tumor uptake and location (1). • Systemic therapy approaches which might be specifically effective in kinase signaling cluster 2–related PCCs are [¹³¹I]MIBG therapy, kinase signaling pathway inhibitors such as TKIs (cabozantinib, sunitinib, LOXO-292, lenvatinib, axitinib, etc.), and PI3K/AKT/mTORC1 and RAS/RAF/MEK/ERK inhibitors (Figs. 2, 3).

Practical tip/synthesis (applies to all clusters):

• Whenever possible, surgery is the therapy of choice.
• Details in terms of surgery, surgery in (oligo-)metastatic disease and alpha-adrenoceptor blockade are described under “Personalized Management: Molecular Cluster 1” subsection “Treatment.”
• Figure 4 summarizes a therapy flow-chart which suggests a potential sequence of therapy for the practicing physician, including dosing.
• All suggestions in terms of therapy and the sequencing of therapy are described in detail under “Personalized Management: Molecular Cluster 1” subsection “Treatment” and apply to all clusters.
• For rapidly progressive PPGLs, the recommended first-line therapy is chemotherapy (CVD scheme) and for slowly to moderately progressive PPGLs, the recommended first-line therapy is radionuclide therapy—either with [¹³¹I]-MIBG or PRRT—depending on tumor uptake and location (1).
• Systemic therapy approaches which might be specifically effective in kinase signaling cluster 2–related PCCs are [¹³¹I]MIBG therapy, kinase signaling pathway inhibitors such as TKIs (cabozantinib, sunitinib, LOXO-292, lenvatinib, axitinib, etc.), and PI3K/AKT/mTORC1 and RAS/RAF/MEK/ERK inhibitors (Figs. 2, 3).