Neuroendocrine tumors (NETs) can be classified as either poorly differentiated, aggressive neuroendocrine carcinomas (NECs) that have a high propensity for distant metastatic spread or well-differentiated, slow growing NETs with good long-term prognoses. NECs of the gynecologic tract comprise 2% of cervical cancers. Well-differentiated NETs of the gynecologic tract, such as primary ovarian carcinoid tumors, comprise less than 0.1% of ovarian neoplasms and 5% of carcinoid tumors overall. In recent years, an increased incidence in the diagnosis of NETs of the gynecologic tract has been observed in clinical investigations.
Currently, limited data are available to guide clinicians on the diagnosis and treatment on NETs, making management especially challenging. The Society of Gynecologic Oncology Clinical Practice Committee requested that my colleagues and I develop a clinical document on NETs of the gynecologic tract. Published in the July 2011 issue of Gynecologic Oncology, our study sought to provide a comprehensive review of NETs and a platform from which clinicians can select the most appropriate treatment options.
Managing Neuroendocrine Tumors
For most cases of NETs of the gynecologic tract, a multimodality, individualized therapeutic approach is recommended. Treatments largely depend upon extent of the disease and the primary organ of involvement. NECs usually arise from the cervix, and a management algorithm has been created that separates NECs on the basis of early- or late-stage tumors. The algorithm presented in our paper stresses that surgical resection with radical hysterectomy and lymphadenectomy for early-stage NECs of the cervix is appropriate and should be followed by adjuvant chemotherapy with etoposide and cisplatin. Surgery may be required to identify a cervical cancer as an NEC cell type. For advanced-stage NEC, etoposide and platinum in combination with pelvic radiation is recommended.
“The clinical outcome for highly aggressive NECs is greatly different from that of well-differentiated NETs.”
For well-differentiated NETs, such as carcinoid tumors of the ovary, surgical management is recommended. This can include debulking of tumor implants. NETs tend to have a good long-term prognosis, but it’s important to recognize that repeat surgeries may be required in this patient population. These tumors can express somatostatin receptors and are therefore eligible for octreotide scans, which can help determine if somatostatin will be useful in disease management.
Learning From Research on NETs
Research on NETs of the gynecologic tract will draw from the increasing experience with these tumors that occur more commonly. For example, NECs are made up of small- and large-cell carcinomas, which occur more frequently in the lung. Clinical research continues to build upon the results of treating small-cell lung cancer and the development of novel therapies for these tumor types. NETs of the ovary are usually carcinoid tumors, which more often occur as gastrointestinal (GI) carcinoids. A growing interest exists in looking at molecular determinants and targeted therapeutics. Vascular endothelial growth factor and mammalian target of rapamycin inhibitors have shown promise in treating GI carcinoids.
As we wait for more data for this area of medicine to emerge, physicians should keep in mind that NETs represent a wide spectrum of malignancies. Indeed, the clinical outcome for highly aggressive NECs is greatly different from that of well-differentiated NETs. The hope is that the information provided in our Gynecologic Oncology report will be helpful to practitioners as they approach these challenging tumor types.
Readings & Resources (click to view)
Gardner G, Reidy-Lagunes D, Gehrig P. Neuroendocrine tumors of the gynecologic tract: a Society of Gynecologic Oncology (SGO) clinical document. Gynecol Oncol. 2011;122:190-198.
Alexander M, Cope N, Renninson J. Relationship between endometriosis, endometrioid adenocarcinoma, gliomatosis peritonei, and carcinoid tumor in a patient with recurrent ovarian teratoma. Int J Gynecol Pathol. 2011;30:151-157.
Embry J, Kelly M, Post M, Spillman M. Large cell neuroendocrine carcinoma of the cervix: prognostic factors and survival advantage with platinum chemotherapy. 2011;120:444-448.
Frumovitz M, Etchepareborda M, Sun C, et al. Primary malignant melanoma of the vagina. Obstet Gynecol. 2010;116:1358-1365.
Onda T, Yoshikawa H. Neoadjuvant chemotherapy for advanced ovarian cancer: overview of outcomes and unanswered questions. Expert Rev Anticancer Ther. 2011;11:1055-1069.