Aim/Introduction: Peptide receptor radionuclide therapy (PRRT) represents a cornerstone of treatment regimens for patients with low proliferative neuroendocrine tumors (NETs). However, in patients experiencing somatostatin receptor–positive NET with higher proliferation rates, a value and potential therapeutic benefit of PRRT as part of multimodal treatment approaches and potentially with addition of radiosensitizing agents has not yet been established. Patients and Methods: In this study, 20 patients with histologically confirmed gastroenteropancreatic (GEP) NET with proliferation rates (Ki67) between 15% and 55% were treated either with PRRT only (n = 10) or with a combination therapy (n = 10) comprising PRRT and capecitabine/temozolomide (CAP/TEM) for at least 2 consecutive cycles. Results: Disease control rate in patients treated with PRRT alone was 60% (40% stable disease and 20% partial response). Strikingly, in patients treated with PRRT in combination with radiosensitization (CAP/TEM), the disease control rate was 90% (20% stable disease and 70% partial response). The median progression-free survival in the PRRT only group was 12 months, whereas the median progression-free survival in the PRRT + CAP/TEM group was 26 months and has not been yet reached for all patients in the group during the observation period. The median disease-specific survival for patients with PRRT alone was 51 months, whereas this end point was not yet reached in the PRRT + CAP/TEM group. Moreover, the PRRT + CAP/TEM group showed a significantly higher reduction of SSTR-PET–based metabolic tumor volume and chromogranin A levels compared with the PRRT only group. Importantly, adverse events of all grades did not differ between both groups. Conclusions: PRRT + CAP/TEM represents a highly promising and well-tolerated therapeutic regimen for patients experiencing somatostatin receptor–positive NET with higher (Ki67 ≥ 15%) proliferation rate. Prospective randomized clinical trials are warranted.

Neuroendocrine neoplasms (NENs) represent a rare, heterogeneous group of malignancies. Within this tumor entity, primary renal neuroendocrine tumors (PRNETs) are exceedingly rare, with only 160 cases reported worldwide. Due to the absence of native neuroendocrine cells in the renal parenchyma, their cellular origin remains unclear. Clinical and diagnostic challenges are reflected by the low incidence, non-specific clinical presentation, resemblance to common renal neoplasms, and the need for specialized histopathological diagnostic examination. Here, we present the case of a 61-year-old female with an incidentally diagnosed left-sided PRNET in September 2024. This case highlights the diagnostic complexity of PRNET and, importantly, underscores its genomic heterogeneity. It demonstrates a lack of typical renal cell carcinoma (RCC) or common NEN-associated gene alterations, emphasizing their unique molecular landscape.

Background/Objectives: Cardiac metastases (CM) represent a rare manifestation of neuroendocrine neoplasms (NEN). Detailed clinical characteristics and significance remain understudied. Methods: We retrospectively evaluated 1201 patients with NEN treated at an ENETS Center of Excellence to determine prevalence, clinical features, and outcomes of cardiac metastases. CM were identified in 15 patients (prevalence 1.25%) through multimodal imaging, incorporating somatostatin receptor positron emission tomography/computed tomography (SSTR PET/CT). Metachronous CM occurrence accounted for 93% of cases. Results: The majority of patients showed well-differentiated tumors (G1/G2), with ileum being the most frequent site of origin. Clinical symptoms attributable to CM were observed in 27% of affected patients. Following CM detection, therapeutic management was adjusted in 73% of cases, most frequently by initiating peptide receptor radionuclide therapy (PRRT) n = 8, 53%. Median overall survival (OS) from CM diagnosis was 95 months, with an estimated 5-year survival rate of 77%, with a 5-year OS from NEN diagnosis of 87%. Conclusions: CM in NEN are rare and often clinically silent, with SSTR PET/CT proving essential for detection. While treatment adjustments were frequently observed, particularly with PRRT, OS remained favorable, indicating that the presence of CM in NEN serves as an indicator of metastatic spread rather than a standalone diagnostic determinant of survival. Larger, prospective studies are needed to further validate these findings and to better define the clinical implications of CM in NEN.