Figure 2.

Simplified flow chart of the practical therapy standards in metastatic PPGLs (12). Each metastatic PPGL patient should be discussed in an interdisciplinary endocrine tumor board. Surgery of the primary tumor, of oligometastatic disease or debulking surgery, should always be considered. In the case of slow progression, low tumor burden and oligometastatic disease, active surveillance may be considered. In patients with slow-to-moderate progression, moderate-to-high tumor burden and positivity on SSTR2 or MIBG imaging, radionuclide therapy using either PRRT or MIBG (depending on avidity on molecular imaging) may be applied. For slowly/moderately progressing tumors that are not eligible for PRRT or MIBG, TKIs or temozolomide may be considered as first-line therapies. In the case of rapid progression or high visceral tumor burden, CVD chemotherapy may be applied. In the case of slow-to-moderate progression following radionuclide therapy, TKIs or temozolomide may be considered. In the case of rapid progression and high visceral tumor burden following other systemic therapies, CVD should be considered. Following progression to CVD, TKIs, or temozolomide may be considered. In case of further progression, inclusion in clinical trials may be considered. MIBG, meta-[¹³¹I] iodobenzylguanidine; PRRT, somatostatin receptor-based radionuclide therapy; RFA, radiofrequency ablation; TKI, tyrosine kinase inhibitor.