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Review
. 2023 Dec 15;12(24):7715.
doi: 10.3390/jcm12247715.

Extrapulmonary Neuroendocrine Carcinomas: Current Management and Future Perspectives

Sara Stumpo  1 , Maria Giovanna Formelli  1 , Irene Persano  2 , Elena Parlagreco  2 , Eleonora Lauricella  3 , Maria Grazia Rodriquenz  4 , Luigi Pio Guerrera  5   6 , Ina Valeria Zurlo  7 , Davide Campana  1   8 , Maria Pia Brizzi  9 , Mauro Cives  3   10 , Anna La Salvia  11 , Giuseppe Lamberti  1   7
Affiliations
Review

Extrapulmonary Neuroendocrine Carcinomas: Current Management and Future Perspectives

Sara Stumpo et al. J Clin Med. .

Abstract

Neuroendocrine carcinomas (NECs) are poorly differentiated and highly aggressive epithelial neuroendocrine neoplasms. The most common primary site is the lung, but they may arise in every organ. Approximately 37% of extrapulmonary NECs (EP-NECs) occur in the gastroenteropancreatic (GEP) tract, followed by the genitourinary (GU) system and gynecological tract. As a result of their rarity, there is scant evidence to guide treatment recommendations, and a multidisciplinary approach is essential for the management of such patients. Platinum-based chemotherapy currently represents the standard of care for EP-NECs of any site, mirroring the management of small-cell lung cancer (SCLC), but further approaches are still under investigation. Indeed, ongoing trials evaluating targeted therapies, immune checkpoint inhibitors (ICIs), and radionuclide therapy could provide potentially breakthrough therapeutic options. Given the relative dearth of evidence-based literature on these orphan diseases, the aim of this review is to provide an overview of the pathology and current treatment options, as well as to shed light on the most pressing unmet needs in the field.

Keywords: chemotherapy; extrapulmonary neuroendocrine carcinomas; gastroenteropancreatic tract; genitourinary tract; gynecologic tract.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proposed clinical management algorithm for GEP-NEC. CHT: chemotherapy. RT: radiotherapy.
Figure 2
Figure 2
Proposed clinical management algorithm for cervical NECs based on FIGO staging system (2018). EP: etoposide + cisplatin or carboplatin. Cisplatin (60–80 mg/m2 on day 1 every 3 weeks) or carboplatin (area under the curve of 5 mg/mL/min on day 1 every 3 weeks) + etoposide (100–120 mg/m2 on day 1–3 every 3 weeks). RT: 40–45 Gy external beam radiation ± 40–45 Gy vaginal brachytherapy. * Brain evaluation in cases of symptoms or suspected metastases.
Figure 3
Figure 3
Proposed clinical management algorithm of endometrial NECs. For locally advanced disease, radical surgery could be considered in selected cases (dashed line).
Figure 4
Figure 4
Proposed clinical management algorithm of ovarian NECs.
Figure 5
Figure 5
Proposed clinical management algorithm of urinary bladder NECs.
See this image and copyright information in PMC

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