PRRT—Pushing the Limits and New Directions

Peptide receptor radionuclide therapy (PRRT) plus chemotherapy is termed PRCRT, a new therapeutic concept that is being tested. A number of small studies have shown that PRCRT is effective in prolonging progression-free survival (PFS) in patients with metastatic gastroenterohepatic neuroendocrine tumors (NETs) with poor prognosis. For example, at a median follow-up of 36 months, 52 patients with spatially discordant FDG-PET avid NETs treated with PRCRT (PRRT + 5-fluorouracil [5-FU]) demonstrated a PFS of 48 months (compared with 5-14 months when treated with chemotherapy alone), with 2% of the patients showing a complete anatomic response, 28% a partial response, 68% stable disease, and only 2% progression.1 Moreover, Dr Richard Baum, a leading nuclear medicine physician from Germany, provided several cases that demonstrate the efficacy of PRCRT. One case was of a 53-year-old man with metastatic rectal NET, Ki-67 40%, with persistent extensive liver disease despite 6 cycles of carboplatin-etoposide chemotherapy. After subsequent treatment with 4 induction cycles of 177Lu-DOTATATE with concomitant radiosensitizing chemotherapy (5-FU), a restaging scan at 3 months showed marked partial response in the liver disease and stable findings in presacral and perirectal disease. Therapy was continued with PRRT + CAPTEM (capecitabine + temozolomide), resulting in resolution of liver metastases at 9 months post-PRCRT, and overall survival of nearly 6.5 years. Several other cases were presented showing similar dramatic results.

PRIT (PRRT + immunotherapy) is also a promising therapeutic approach in patients with NETs. Dr Baum coined the term AERIT (Adaptive EndoRadioImmunotherapy) for this therapeutic approach. While not tested in NETs, there have been a few promising cases in prostate cancer. Testing PRIT in NETs will be a top research priority.

Results from the combination of neoadjuvant PRRT in patients with inoperable NETs, as well as adjuvant PRRT following surgery for NETs, were described. The first report of neoadjuvant PRRT in a NET with subsequent successful complete surgical resection was described. Pancreatic endocrine tumors are among the most common NETs of the abdomen, and many of them are already advanced and difficult to treat at diagnosis. Dr Baum described a report of an initially inoperable malignant pancreatic endocrine tumor in a 33-year-old woman who received neoadjuvant PRRT as first-line treatment, which resulted in a significant downstaging of the tumor and allowed its subsequent complete surgical removal in a Whipple procedure.2 Follow-up at 10 years revealed complete remission.

Similarly, a recent study of more than 700 patients with pancreatic or small intestinal NETs showed that adjuvant PRRT administered after surgery resulted in significantly longer overall survival compared with those who underwent surgery without adjuvant PRRT (P <.001 for both tumor types).3


  1. Kashyap R, et al. Eur J Nucl Med Mol Imaging. 2015;42:176-185.
  2. Kaemmerer D, et al. World J Gastroenterol. 2009;15:5867-5870.
  3. Kaemmerer D, et al. Abstracts of the 14th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease; March 8-10, 2017; Barcelona, Spain.

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