Background: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in plasma markers during PRRT can help identify patients with unfavorable outcomes. Methods: A monocentric retrospective analysis of 141 patients with NET undergoing PRRT with [177Lu]Lu-DOTATOC was conducted. Changes in laboratory parameters were calculated by dividing the values determined immediately before each cycle of PRRT by the pretherapeutic value. Patients with low vs. high PFS were compared with the Wilcoxon rank-sum test. Results: Progression, relapse, or death after PRRT was observed in 103/141 patients. Patients with low PFS showed a significant relative ALP increase before the third (p = 0.014) and fourth (p = 0.039) cycles of PRRT. Kaplan–Meier analysis revealed a median PFS of 24.3 months (95% CI, 20.7–27.8 months) in patients with decreasing ALP values (Δ > 10%) during treatment, 12.5 months (95% CI, 9.2–15.8 months) in patients with increasing ALP values (Δ > 10%), and 17.7 months (95% CI, 13.6–21.8 months) with stable ALP values (Δ ± 10%). Conclusions: Based on these exploratory data, a rise in plasma ALP might indicate disease progression and should be interpreted cautiously during therapy.
