The Role of Surgery in High-Grade Neuroendocrine Cancer: Indications for Clinical Practice

Abstract

Pulmonary neuroendocrine tumors (pNET) represent a particular type of malignant lung cancers and can be divided into well-differentiated low-grade NET and poorly-differentiated high-grade NET. Typical and atypical carcinoids belong to the first group while large cell neuroendocrine carcinomas (LCNEC) and small-cell lung cancers (SCLC) belong to the second one. The aim of this mini-review is to focus on the role of surgical therapy for high grade neuroendocrine tumors. SCLC has the worst prognosis among all lung cancer neoplasms: in fact, the two-year survival rate is about 5% and median survival usually ranges between 15 and 20 months. The surgical treatment of SCLC has thus infrequently been judged as a valuable aspect of the therapeutic approach, the gold standard treatment being a combination of platinum-based chemotherapy and radiotherapy. As LCNEC are rare, there is a lack of extensive literature and randomized clinical trials, therefore the curative approach is still controversial. Current treatment guidelines suggest treating LCNEC by surgical resection in non-metastatic stages and recommend adjuvant chemotherapy according to SCLC protocol. Upfront surgery is suggested in early stages (from I to IIB), a multimodality approach is recommended in locally advanced stages (III) while surgery is not recommended in stage IV LCNEC. The rate of surgical resection is quite low, particularly for SCLC, ranging from 1 to 6% in limited diseases; lobectomy with radical lymphadenectomy is considered the gold standard surgical procedure in the case of limited disease SCLC and resectable LCNEC; pneumonectomy, although reported as an effective tool, should be avoided in the light of local and distant recurrence rates.

Development and validation of nomograms to predict survival of neuroendocrine carcinoma in genitourinary system: A population-based retrospective study

“…Stage and grade significantly affect patient prognosis [ 15 – 17 ]. A higher stage or grade usually indicates poorer differentiation, greater malignancy, and tremendous potential for metastasis, which can affect patient survival [ 18 , 19 ]. As a malignant wasting disease, a higher stage or grade of NEC can cause greater consumption, burden, and impact on the body [ 20 ].…”

“…Some scholars have proposed that complete surgical resection is considered to improve prognosis regardless of the NEN histological type, while LND is necessary for complete resection. This view has gradually reached consensus through extensive clinical practice and research [ 19 , 27 ].…”

The survival benefit from surgery on patients with large-cell neuroendocrine carcinoma in the lung: a propensity-score matching study

“…As a classical treatment approach, surgical resection has been proven to be associated with extended survival in patients with neuroendocrine carcinoma [ 6 , 14 , 15 ]. Previous studies focused on small-cell lung cancer and reported that patients with stage I-IIA were more appropriate to receive surgery than those with stage IIb-III [ 5 , 16 ].…”

Survival of small-cell lung cancer patients after surgery: A single-center retrospective cohort study

“…However, with advances in diagnostic and surgical technologies, many researchers have begun challenging the current view of surgery in treating SCLC and have attempted to expand the surgical indications for SCLC. 5–10…”

“…4 However, with advances in diagnostic and surgical technologies, many researchers have begun challenging the current view of surgery in treating SCLC and have attempted to expand the surgical indications for SCLC. [5][6][7][8][9][10] In the present study, we explored the value of surgery in treating SCLC. We identified relevant prognostic factors in the hope of clarifying the significance of surgery in the prognosis of SCLC patients and reassessing its importance in the multi-disciplinary treatment of SCLC.…”