Understanding Lung Carcinoid Tumors: Current Practices and Future Directions in Specialist Centers

Table of Contents

• Introduction: What Are Lung Carcinoid Tumors?
• How the Research Was Conducted
• Detailed Survey Results: Current Practices
• What This Means for Patients
• Study Limitations
• Recommendations for Patients
• Source Information

Introduction: What Are Lung Carcinoid Tumors?

Lung carcinoid tumors are a rare type of neuroendocrine tumor that originates from specialized cells in the bronchopulmonary tract. These uncommon tumors represent only 1-3% of all lung cancers but account for approximately 30% of all neuroendocrine tumors throughout the body. Over recent years, doctors have observed an increase in diagnoses of both typical and atypical lung carcinoids, likely due to improved detection methods and greater awareness among medical professionals.

The World Health Organization classification system now recognizes three main categories of lung carcinoids. The most recent classification includes a subgroup with atypical morphology that has a higher mitotic count (more than 10 cell divisions per 2mm²) and/or higher Ki67 labeling index (greater than 30%), which indicates more rapidly dividing cells. This distinction is clinically important because despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50-70%, significantly lower than the approximately 90% survival rate for typical carcinoids.

Patients with lung carcinoids often present with symptoms including cough, hemoptysis (coughing up blood), or recurrent respiratory infections. However, a significant minority of these tumors are discovered incidentally during imaging studies for unrelated conditions. Compared to other lung cancers, patients with lung neuroendocrine tumors are typically diagnosed at a younger age, show a slight female predominance, and may express somatostatin receptors that can be targeted with specific treatments.

How the Research Was Conducted

To address the lack of consensus in clinical management decisions for lung carcinoid tumors, the European Neuroendocrine Tumor Society (ENETS) initiated a comprehensive survey among expert centers. The ENETS Lung NET Task Force, established in July 2021, brought together a diverse team of international experts including surgeons, medical oncologists, pathologists, molecular biologists, endocrinologists, radiologists, nuclear medicine physicians, and gastroenterologists.

The survey development process involved multiple stages. First, task force members identified key areas of uncertainty in early-stage disease management during initial meetings. Questions were then developed by two lead investigators and subsequently reviewed and validated by all task force members during three additional meetings. The final survey encompassed various aspects including diagnostic workup processes, surgical interventions, use of adjuvant treatments, and follow-up protocols.

The research team invited 65 centers with neuroendocrine tumor expertise to participate in the survey. These included ENETS or EURACAN-G6 Centres of Excellence (CoEs) or centers with ENETS Advisory Board and Executive Committee members. Each institution was requested to provide a single response, preferably completed by their multidisciplinary tumor board. The survey distribution occurred from March to August 2022, with all responses collected within this timeframe.

The survey data was carefully cleaned and prepared for analysis. Researchers conducted descriptive analysis on the qualitative data, presenting findings as frequency counts and corresponding percentages. Agreement among respondents was defined as concordance of at least 75% of answers. Answers indicating "I don't know" were included in the analysis to provide a complete picture of clinical uncertainty areas.

Detailed Survey Results: Current Practices

Thirty-four experts from 20 specialized lung neuroendocrine tumor centers responded to the survey. The majority of responders were medical oncologists (29.4%), followed by gastroenterologists (20.5%) and endocrinologists (20.5%). Most centers reported handling more than 25 lung NET cases per year (50%), indicating substantial experience with these rare tumors.

Diagnostic Approaches: For a peripheral lung NET incidentally detected by CT scan, almost all investigators (94%) indicated that the imaging of choice would be a somatostatin receptor PET/CT scan, followed by abdominal CT scan (71%) and [18F]FDG PET/CT scan (29%). For patients with centrally located lung NET presenting with symptoms, the majority (88%) recommended somatostatin receptor PET/CT scan, followed by thoracic and upper abdominal CT scan with contrast medium (77%) and [18F]FDG PET/CT scan (50%).

Surgical Decision-Making: The survey revealed significant variation in surgical approaches. When presented with a clinical case of a confirmed carcinoid tumor, responses included "don't know" (35%), segmentectomy with lymphadenectomy (32%), and wide wedge resection (15%). For complex cases requiring difficult decisions, most specialists (67%) indicated they would avoid pneumonectomy and prefer lung parenchyma-saving procedures like sleeve resection combined with lymphadenectomy.

Multidisciplinary Care Gaps: A concerning finding was that 24 centers (70.6%) reported lacking dedicated multidisciplinary tumor boards specifically for lung neuroendocrine tumor patients. Surgery was the specialty acting as the first point of contact in 65% of cases, with pulmonology second (53%).

Adjuvant Treatment Preferences: The majority of centers (69%) would not usually propose adjuvant therapy after complete excision of a primary lung carcinoid tumor with negative scans. When adjuvant treatment was considered, responses varied based on tumor characteristics:

• For node-positive typical carcinoid: 14 centers would never recommend adjuvant treatment, 2 would sometimes, and 1 would often
• For node-negative atypical carcinoid: 14 centers would never recommend, 2 would sometimes, and 1 would often
• For node-positive atypical carcinoid: 9 would never, 9 would sometimes, 1 would often, and 1 would always recommend adjuvant treatment

When adjuvant therapy was recommended, nearly half of specialists indicated preference for systemic treatment without radiotherapy. Somatostatin analogues (42%) and temozolomide-based chemotherapy (29%) were the most common recommendations. No specialists voted for adjuvant platinum-etoposide chemotherapy.

Clinical Trial Support: An overwhelming majority of experts (91%) believed a prospective randomized study on adjuvant therapy is feasible. Most proposed including patients with node-positive atypical carcinoid following complete or microscopically involved margin resection, with disease-free survival at 3-5 years as the primary endpoint. 85% of experts indicated their ability to participate with up to 10 patients per year in such a trial.

Follow-up Protocols: The survey investigated follow-up practices after surgical resection. For a 75-year-old patient with a typical carcinoid (Ki67<1%, 0 mitoses, negative scans), most specialists (85%) preferred radiological/clinical follow-up rather than additional treatment.

What This Means for Patients

This survey reveals several important implications for patients diagnosed with lung carcinoid tumors. The significant variability in management approaches across expert centers means that where you receive care may substantially influence your treatment plan. This variability underscores the importance of seeking care at centers with specific expertise in neuroendocrine tumors and those that utilize multidisciplinary tumor boards.

Patients should be aware that for typical carcinoids with no lymph node involvement, most experts do not recommend additional treatments after complete surgical removal. However, for higher-risk situations such as atypical carcinoids or those with lymph node involvement, there is considerable disagreement among specialists about whether additional therapy is beneficial. This uncertainty highlights the need for more research and the importance of discussing all options thoroughly with your medical team.

The strong consensus (91%) among experts that clinical trials are feasible and necessary indicates that the medical community recognizes these knowledge gaps and is motivated to address them. Patients may want to inquire about clinical trial opportunities, particularly if they have higher-risk disease features where the benefit of additional treatments remains uncertain.

The finding that 70.6% of centers lack dedicated multidisciplinary tumor boards for lung neuroendocrine tumors suggests that patients should actively seek out centers that offer this comprehensive approach. Multidisciplinary care has been shown to improve outcomes for complex cancers by ensuring all treatment perspectives are considered.

Study Limitations

While this survey provides valuable insights into current practices, several limitations should be considered. The response rate from the 65 invited centers was relatively low, with only 20 centers (34 experts) participating. This may introduce selection bias, as responding centers might have different practices than non-responding centers.

The survey design captured expert opinions rather than objective outcome data. While opinions from specialists are valuable, they may not always align with what the evidence ultimately shows to be most effective. The scenarios presented were hypothetical, and real-world decision-making might differ when facing actual patients with unique circumstances.

The survey primarily included European centers of excellence, which may limit generalizability to other healthcare settings with different resources and practice patterns. Additionally, the small number of respondents in certain specialist categories (only one thoracic surgeon responded) means some perspectives may be underrepresented.

Finally, this survey provides a snapshot in time (2022) of clinical practices, and management approaches continue to evolve as new evidence emerges. The findings represent expert opinion rather than established evidence-based guidelines.

Recommendations for Patients

Based on the survey findings, patients with lung carcinoid tumors should consider the following recommendations:

1. Seek specialized care: Given the variability in management approaches, seek evaluation at centers with specific expertise in neuroendocrine tumors. These centers are more likely to have experience with the nuances of your specific cancer type.
2. Ensure multidisciplinary review: Request that your case be reviewed by a multidisciplinary team including medical oncologists, surgeons, endocrinologists, radiologists, and pathologists with neuroendocrine tumor experience.
3. Discuss all options thoroughly: For higher-risk situations (atypical histology, lymph node involvement), have detailed conversations with your medical team about the potential benefits and limitations of adjuvant therapy, as expert opinions vary significantly.
4. Inquire about clinical trials: Ask your medical team about ongoing clinical trials, particularly if you have higher-risk disease features. Many experts believe trials are feasible and necessary to establish better treatment guidelines.
5. Understand follow-up plans: Discuss a clear, personalized follow-up plan with your medical team, including what imaging will be used and how frequently it will occur.
6. Seek second opinions: Given the lack of consensus on many management aspects, consider seeking second opinions, especially for complex decisions about adjuvant therapy or surgical approach.

Remember that lung carcinoid tumors are generally slower-growing than other lung cancers, which allows time for thorough consideration of treatment options. Don't hesitate to ask questions and ensure you fully understand the reasoning behind your recommended treatment plan.

Source Information

Original Article Title: Clinical management of typical and atypical carcinoids/neuroendocrine tumors in ENETS centres of excellence (CoE): Survey from the ENETS lung NET task force

Authors: Anna Koumarianou, Pier Luigi Filosso, Lisa Bodei, Justo P. Castano, Lynnette Fernandez-Cuesta, Christophe M. Deroose, Matthieu Foll, Clarisse Dromain, Nicholas Simon Reed, Martyn Caplin, Jaume Capdevila, Jenny Falkerby, Antongiulio Faggiano, Andrea Frilling, Enrique Grande, Rodney J. Hicks, Atsuko Kasajima, Beata Kos-Kudla, B. A. Krishna, Eric Lim, Anja Rinke, Simron Singh, Chrissie Thirlwell, Marco Volante, Thomas Walter

Publication: Journal of Neuroendocrinology, 2024;36:e13412

Note: This patient-friendly article is based on peer-reviewed research conducted by leading experts in neuroendocrine tumors and represents the first comprehensive investigation of real-world practice patterns for lung carcinoid management across international specialist centers.