Neuroendocrine carcinoma of the cervix: a systematic review of the literature

Abstract

BackgroundNeuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for this type of malignancy based on controlled trials.MethodsWe performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials describing the management and outcome of women with NECC.ResultsThree thousand five hundred thirty-eight cases of NECC in 112 studies were identified. The pooled proportion of NECC among women with cervical cancer was 2303/163470 (1.41%). Small cell NECC, large cell NECC, and other histological subtypes were identified in 80.4, 12.0, and 7.6% of cases, respectively. Early and late stage disease presentation were evenly distributed with 1463 (50.6%) and 1428 (49.4%) cases, respectively. Tumors expressed synaptophysin (424/538 cases; 79%), neuron-specific enolase (196/285 cases; 69%), chromogranin (323/486 cases; 66%), and CD56 (162/267; 61%). The most common primary treatment was radical surgery combined with chemotherapy either as neoadjuvant or adjuvant chemotherapy, described in 42/48 studies. Radiotherapy-based primary treatment schemes in the form of radiotherapy, radiochemotherapy, or radiotherapy with concomitant or followed by chemotherapy were also commonly used (15/48 studies). There is no standard chemotherapy regimen for NECC, but cisplatin/carboplatin and etoposide (EP) was the most commonly used treatment scheme (24/40 studies). Overall, the prognosis of women with NECC was poor with a mean recurrence-free survival of 16 months and a mean overall survival of 40 months. Immune checkpoint inhibitors and targeted agents were reported as being active in three case reports.ConclusionNECC is a rare variant of cervical cancer with a poor prognosis. Multimodality treatment with radical surgery and neoadjuvant/adjuvant chemotherapy with cisplatin and etoposide with or without radiotherapy is the mainstay of treatment for early stage disease while chemotherapy with cisplatin and etoposide or topotecan, paclitaxel, and bevacizumab is appropriate for women with locally advanced or recurrent NECC. Immune checkpoint inhibitors may be beneficial, but controlled evidence for their efficacy is lacking.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4447-x) contains supplementary material, which is available to authorized users.

Updates and management algorithm for neuroendocrine tumors of the uterine cervix

“…Marker positivity in small-cell neuroendocrine tumors ranges from 33% to 100%. In the latest systematic review published by Tempfer et al ,13 the most frequently observed immunohistochemistry markers were synaptophysin (79%), neuron specific enolase (69%), chromogranin (66%), and CD56 (61%). Synaptophysin and CD56 are the most sensitive neuroendocrine markers, but CD56 lacks specificity.…”

“…In a recently published systematic review that included 3,538 neuroendocrine patients, the most common primary treatment was radical surgery combined with chemotherapy, either as neoadjuvant or adjuvant (40/48 studies) 13. There was no standard chemotherapy regimen but platinum and etoposide was the most commonly used treatment (24/40 studies).…”

“…There is no standard chemotherapy regimen, but due to its pathologic appearances and clinical behaviors similar to small-cell lung cancer, almost all patients with small-cell cervical cancer receive platinum and etoposide as part of their primary therapy 13. For early-stage disease, SGO and GCIG guidelines recommend that patients with complete surgical resection undergo adjuvant chemotherapy 32 41.…”

Role of diagnostic laparoscopy in patients with large cell neuroendocrine carcinoma of the ovary with cancerous peritonitis: case report and review of the literature

“…Therefore, the patient received the chemotherapy with etoposide and cisplatin, although postoperative chemotherapy did not improve the clinical outcome in the present case with carcinomatous peritonitis. Previous reports have shown the possible efficacy of paclitaxel and carboplatin, which can be less toxic than cisplatin in cases of even pure LCNEC of the ovary [9,15,20,27,33,35], as well as in cases of NEC of the uterine cervix [43], suggesting that these chemotherapeutic regimens could be considered in patients with poor performance status and prognosis because of unresectable carcinomatous peritonitis. Taken together, in LCNEC, diagnostic laparoscopy followed by primary debulking surgery or neoadjuvant chemotherapy might be useful in cases without carcinomatous peritonitis, whereas it might also be useful for deciding whether patients should receive less invasive chemotherapy or best supportive care in cases with carcinomatous peritonitis with much poorer outcomes.…”

Rare case of tonsillar and subcutaneous metastasis from neuroendocrine cervical cancer

“…Neuroendocrine cervical carcinoma (NECC) is a rare type of gynecologic malignancy, accounting for only 1–1.5% of all cervical cancers . Since 2014, NECC has been categorized by the World Health Organization as low‐grade and high‐grade neuroendocrine carcinoma .…”