Figure 3: 56-year-old woman with breast cancer (breast cancer cell...
Updated TNM Staging System For SCLC Offers Better Predictive Power
Photo Credit: Mohammed Haneefa Nizamudeen
Researchers recently validated the ninth edition of the TNM staging system for SCLC, finding improved accuracy and predictive power.
The tumor-node-metastasis (TNM) staging system plays a critical role in the prognostic assessment and treatment decisions for lung cancer. Guidelines recommend treatment modalities for patients with small-cell lung cancer (SCLC), which accounts for approximately 10% of the global incidence of lung cancer, based on the TNM classification.
The ninth edition of the TNM staging system (TNM-9) of lung cancer was presented at the 2023 World Conference on Lung Cancer, but there remained a need for proper external validation of the staging system. Previously, researchers validated the TNM-9 using data from the Surveillance, Epidemiology, and End Results (SEER) database from patients with non-small cell lung cancer who underwent lung resection. However, limited by flaws in the SEERS database, researchers could not further differentiate between N2a and N2b classifications.
To address this, and externally validate the TNM-9, researchers examined multicenter data from patients with limited-stage SCLC. The findings were reported in Lung Cancer.
The multicenter study included 408 patients diagnosed with limited-stage SCLC from 2004 to 2021 who underwent lung resection. The majority (86.8%) of patients were men. Most of the cohort (65.7%) were aged 65 or younger; 34.3% were older than 65 years. Surgical approaches included lobectomy (80.4%), sublobectomy (7.8%), and pneumonectomy (11.8%).
Researchers found that the TNM-9 staging system had improved distinguishing ability versus the eighth edition. These findings were observed across all stage groups that were compared (all P<0.05):
Additionally, the TNM-9 demonstrated better predictive power and accuracy for the overall survival (OS) of patients with SCLC compared with the eighth edition:
"Our external validation demonstrates that the ninth edition of pathological TNM staging for limited-stage SCLC is reasonable and valid based on a multicenter study," investigators wrote. "The ninth edition has better prognostic accuracy than the eighth edition."
Study Finds Declining SCLC Incidence, But Stagnant Survival Rates
SEER data show that small cell lung cancer (SCLS) incidence has steadily declined due to reduced smoking rates, but survival outcomes have seen only minimal improvement, underscoring the need for more effective treatments.
The incidence of small cell lung cancer (SCLC) has steadily declined in the US over the past 2 decades, largely due to reduced smoking rates, but survival outcomes remain largely unchanged, according to a new study published in Cancer Medicine.1
The analysis, which examined data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020, highlights both the progress in cancer prevention and the urgent need for more effective treatment options.
Despite the implementation of CT lung screening in 2013, most patients already had distant metastatic disease at the time of diagnosis.Image credit: Dragana Gordic – stock.Adobe.Com
The researchers found that the age-adjusted incidence rate of SCLC decreased by an average of 3% per year, from 9 per 100,000 people in 2000, to 4.6 in 2020. This decline was consistent across all demographic groups, including different races, sexes, and age categories. Incidence-based mortality rates also decreased, from 6.6 per 100,000 in 2005, to 3.5 in 2020. However, while fewer people are being diagnosed with SCLC, survival rates have shown only minor improvements. The 1-year relative survival rate increased slightly from 33.1% in 2000 to 35.3% in 2019, while the 1-year observed survival rose from 32.4% to 34.5% over the same period.
"Since SCLC almost always occurs in smokers, the decrease in smoking prevalence in the United States, predominately driven by implantation of smoking-related policies is likely responsible for this notable decline," the authors said.
SCLC is a particularly aggressive form of lung cancer, with nearly 60% of patients presenting with metastatic disease at diagnosis.2 For years, platinum-etoposide chemotherapy has been the standard treatment, offering strong initial responses but limited long-term survival.3 More recently, the addition of immune checkpoint inhibitors (ICIs) such as atezolizumab and durvalumab has provided some improvement in extensive-stage SCLC, yet their impact on long-term survival remains modest.1
They also examined the impact of lung cancer screening efforts, particularly the implementation of low-dose computed tomography (CT) scans for high-risk individuals. While screening has led to earlier detection of non–small cell lung cancer, its effectiveness for SCLC is less clear due to the rapid progression of the disease. Despite the implementation of CT lung screening in 2013, most patients (55.9%) in the study already had distant metastatic disease at the time of diagnosis.4,1 According to the authors, this indicates that annual CT screening may not be the most effective tool for detecting SCLC early, as the cancer's aggressive progression and high likelihood of metastasizing within a year may outpace the 1-year screening interval.
At the same time, the study found a slight increase in the diagnosis of localized SCLC and a corresponding decline in metastatic cases over time, particularly after 2013. While the trend was slow before 2013—potentially due to the growing use of diagnostic CT scans—the more noticeable shift afterward suggests that screening may be helping detect some cases at an earlier stage.
"Moreover, advancements in radiation techniques, early-stage at diagnosis with screening CT scans, may have improved survival for patients with limited-stage disease," the study authors added. "Population-based studies to assess the survival benefit of improved cancer care, enhanced radiation techniques and the introduction of immunotherapy are lacking."
The study's limitations include the retrospective nature of SEER data, which does not capture detailed treatment regimens or emerging therapies in real time. Additionally, data before 2004 lacked complete staging information, limiting some analyses.
References
Grades, Types And Stages Of Lung Neuroendocrine Cancer
Lung neuroendocrine cancers start in the neuroendocrine cells
of the lung. Your healthcare team might call them lung neuroendocrine neoplasms, or lung NENs. This means the same thing as lung neuroendocrine cancer. There are 2 key groups of lung neuroendocrine cancer: lung neuroendocrine tumours (lung NETs, also called carcinoids) lung neuroendocrine carcinomas (lung NECs) There are also different sub-types of: lung NETs - these are typical carcinoid and atypical carcinoid lung NECs - these are small cell and large cell lung NEC A specialist doctor (pathologist) looks at the cancer cells under a microscope. They report how abnormal the cells look (differentiation). And how quickly or slowly the cancer cells are dividing and growing (the grade). This helps to tell them whether you have a NET or a NEC. The stage of a neuroendocrine cancer tells you its size and whether it has spread. The tests and scans you have give information about the type, stage and grade. This helps your doctor decide which treatment you need. Grading and differentiation The pathologist looks at a sample of neuroendocrine cancer cells under a microscope. They look at: how abnormal the cancer cells look – doctors call this differentiation how quickly or slowly they are dividing and growing – this is grading Differentiation Your doctor uses the differentiation to diagnose you with one of the following: a lung neuroendocrine tumour (lung NET) – these are well differentiated cancers a lung neuroendocrine carcinoma (lung NEC) – these are poorly differentiated cancers Grading This is about cell division and growth rate. To describe this, you might hear the terms mitotic rate or Ki67 score or percentage (%). The higher the mitotic rate or Ki67%, the faster the growth. There are 3 grades of neuroendocrine tumours (NETs) – grade 1, 2 and 3: Grade 1 cancers grow slowly. They are low grade. Grade 2 grow at a moderate pace (between 1 and 3). They are intermediate grade. Grade 3 grow rapidly. They are high grade. All neuroendocrine carcinomas (NECs) are grade 3. Types of lung neuroendocrine cancers Lung neuroendocrine tumours (NETs) include: typical carcinoid (TC) atypical carcinoid (AC) Lung neuroendocrine carcinomas (NECs) include: small cell neuroendocrine carcinoma large cell neuroendocrine carcinoma You can also get neuroendocrine cancer cells mixed in a tumour with a different type of cancer. Doctors call this MiNEN or mixed cell carcinoma. Types of lung NET Typical carcinoid (TC) Typical carcinoids are grade 1 cancers. They are slow growing and less likely to spread outside the lungs. The cancer cells look very like normal cells. Doctors also call these well differentiated cancers. Typical carcinoids are also called carcinoid tumours. Around 2 in every 100 lung cancers (around 2%) diagnosed in the UK every year are typical carcinoids. Atypical carcinoid (AC) Atypical carcinoids are grade 2 cancers. They behave somewhere between grade 1 and grade 3 cancers. They usually grow faster than typical carcinoids. And they are more likely to spread. The cancer cells look more abnormal. Doctors also call these moderately differentiated cancers. Atypical carcinoids are also called carcinoid tumours. Fewer than 1 in every 100 lung cancers (1%) diagnosed in the UK every year are atypical carcinoids. Types of lung NEC Small cell lung cancer (SCLC) Small cell lung cancers are grade 3 cancers. They tend to grow quickly and are more likely to spread. The cancer cells look very abnormal. Doctors also call these cancers poorly differentiated cancers. Around 15 out of every 100 lung cancers (around 15 %) diagnosed are this type. It is linked to smoking. SCLC tends to spread quickly early on. Large cell neuroendocrine carcinoma (LCNEC) Large cell neuroendocrine carcinomas are grade 3 cancers. They tend to grow quickly and are more likely to spread. The cancer cells look very abnormal. Doctors also call these cancers poorly differentiated cancers. Around 3 out of every 100 lung cancers (3%) diagnosed in the UK every year are this type. They are linked to smoking. Other terms you might hear Primary and secondary cancer A neuroendocrine cancer that starts in the lung is called a primary lung neuroendocrine cancer. A cancer that spreads to your lung from somewhere else in your body is a secondary lung cancer. Secondary cancers are also called metastases. This is important. The primary cancer tells your doctor which type of treatment you need. The information on this page is about primary lung neuroendocrine cancers. Functioning and non functioning neuroendocrine tumours (NETs) Cancer can disrupt how much hormone the neuroendocrine cells make. It is much more common for NETs to produce abnormal levels of hormone than NECs. Doctors sometimes group NETs depending on whether they make abnormal levels of hormone: Non functioning NETs make and release normal levels of hormone. Functioning NETs make and release abnormal levels of hormone. Most lung neuroendocrine cancers are non functioning. Central and peripheral You might hear or read these terms. They refer to the position of the cancer in your lung. Central lung neuroendocrine cancers start in the bronchi. These are the large airways in the centre of your lungs. Peripheral lung neuroendocrine cancers start in the smaller airways. These are on the edges of the lungs. DIPNECH DIPNECH stands for diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. It's a very rare condition where the neuroendocrine cells of the lung start to grow in an uncontrolled, rapid way. Doctors call this hyperplasia. In some people these cells develop into a typical or atypical carcinoid. Some doctors call DIPNECH a pre cancer. The abnormal cells are all contained within the lining of the lung and have not spread. Stages of lung neuroendocrine cancer The stage of a lung neuroendocrine cancer tells you its size and whether it has spread. There are different ways to stage lung neuroendocrine cancer. You have tests and scans to diagnose a lung neuroendocrine cancer. These give some information about the stage of the cancer. Sometimes it's not possible to be certain about the stage until after surgery. Knowing the stage can help your doctor decide which treatment you need. Types of staging systems There are different systems for staging cancer. Doctors use the number system or the TNM system to stage lung neuroendocrine cancers. They are the same staging systems as for other types of lung cancer. There is also a simplified staging system for small cell lung cancer (SCLC). TNM staging The TNM staging system is the most common way to stage lung neuroendocrine cancers. TNM stands for tumour, node and metastasis: T describes the size of the tumour N describes whether there are cancer cells in the lymph nodes M describes whether the cancer has spread to a different part of the body Number staging Your doctor might tell you the number stage of your lung neuroendocrine cancer. This system divides lung cancers into 4 main groups. The groups depend on the size of the tumour and whether it has spread. Stage 1 is the earliest stage. It means that the cancer is small and hasn't spread to the lymph nodes or other parts of the body. Stage 4 is the most advanced stage. Limited and extensive stage Doctors often use a simple system to stage small cell lung cancer (SCLC). This describes your cancer as limited disease or extensive disease. Limited disease is when the cancer is in a single area that can be treated with radiotherapy. Extensive disease means that the cancer has spread beyond a single area. Or there are cancer cells in the fluid around the lung (a malignant pleural effusion). Treatment for lung neuroendocrine cancers Treatment depends on what type of lung neuroendocrine cancer you have. Treatment also depends on: the stage of the lung neuroendocrine cancer where the cancer is your health and general fitness your choice - your doctor talks to you about how you feel about different treatments and side effects 
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