Actor Dustin Diamond, best known for his role as Samuel "Screech" Powers in the 1990s teen sitcom "Saved by the Bell," was recently hospitalized in Florida after experiencing "pain all over his body." After exhaustive testing, the 44-year-old was diagnosed with stage IV small-cell lung cancer (SCLC). Diamond underwent one round of chemotherapy and a second round was scheduled. However, it was for naught; .
Following his diagnosis, "Saved by the Bell" castmate Mario Lopez posted on a throw-back and more recent picture of himself and Diamond with the message: "I connected with Dustin earlier this evening and although the news of his diagnosis is heartbreaking, we remain positive that he'll overcome this. Praying for him & his family and for a speedy recovery. God Bless."
Lung Cancer
Lung cancer includes two main types: SCLC and non-small cell lung cancer (NSCLC). The latter is any type of epithelial lung cancer other than SCLC and accounts for approximately 85% of lung cancers. The most common types of NSCLC are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma, with several other types occurring less frequently. Although NSCLCs are associated with cigarette smoking, adenocarcinomas may be found in patients who have never smoked. As a class, NSCLCs are relatively insensitive to chemotherapy and radiation therapy compared with SCLC.
SCLC accounts for approximately 15% of bronchogenic carcinomas. There are two main types: Small-cell carcinoma (sometimes referred to as oat cell cancer) and combined small-cell carcinoma (SCLC combined with neoplastic squamous and/or glandular components).
At the time of diagnosis, approximately 30% of patients with SCLC will have tumors confined to the hemithorax of origin, the mediastinum, or the supraclavicular lymph nodes. These patients are designated as having limited-stage disease (LD). Patients with tumors that have spread beyond the supraclavicular areas are said to have extensive-stage disease (ED).
SCLC is more responsive to chemotherapy and radiation therapy than other cell types of lung cancer; however, a cure is difficult to achieve because SCLC has a greater tendency to be widely disseminated by the time of diagnosis.
Incidence and Mortality
According to , the estimated number of new cases of lung cancer (SCLC and NSCLC combined) in the U.S. in 2020 was 228,820. The number of estimated deaths was 135,720.
Lung cancer is the leading cause of cancer-related mortality in the U.S. Approximately 6.3% of men and women will be diagnosed with lung and bronchus cancer at some point during their lifetime (based on 2015-2017 data).
The overall 5-year survival rate for lung and bronchial cancer is 20.5% but cancer stage at diagnosis is an important factor in survival rates: 5-year survival for patients with lung cancer with local stage is 59%, 31.7% for regional stage, and 5.8% for distant-stage disease. At the time of diagnosis, 17% of patients have localized disease, 22% regional, and 57% distant/metastasized.
Risk Factors
Increasing age is the most important risk factor for most cancers. Other risk factors for lung cancer include the following:
- History of or current tobacco use: cigarettes, pipes, and cigars
- Exposure to cancer-causing substances in secondhand smoke
- Occupational exposure to asbestos, arsenic, chromium, beryllium, nickel, and other agents
- Radiation exposure from any of the following: radiation therapy to the breast or chest; radon exposure in the home or workplace; medical imaging tests, such as computed tomography (CT) scans; atomic bomb radiation
- Living in an area with air pollution
- Family history of lung cancer
Clinical Features
Lung cancer may present with symptoms or be found incidentally on chest imaging. Symptoms and signs may result from the location of the primary local invasion or compression of adjacent thoracic structures, distant metastases, or paraneoplastic phenomena. The most common symptoms at presentation are worsening cough, shortness of breath, and dyspnea. Other presenting symptoms include the following:
- Chest pain
- Hoarseness
- Malaise
- Anorexia
- Weight loss
- Hemoptysis
Symptoms may result from local invasion or compression of adjacent thoracic structures, such as compression involving the esophagus causing dysphagia, compression involving the laryngeal nerves causing hoarseness, or compression involving the superior vena cava causing facial edema and distension of the superficial veins of the head and neck. Symptoms from distant metastases may also be present and include neurological defect or personality change from brain metastases or pain from bone metastases.
Treatment
Chemotherapy and radiation therapy have been shown to improve survival for patients with small cell lung cancer. Chemotherapy and radiation are the primary modalities of treatment for both LD and ED. The combination of platinum and etoposide is the most widely used standard chemotherapeutic regimen.
SCLC is highly radiosensitive and thoracic radiation therapy improves survival of patients with LD and ED tumors. Prophylactic cranial irradiation prevents central nervous system recurrence and may improve the long-term survival of patients with good performance status who have responded to chemoradiation therapy and offers palliation of symptomatic metastatic disease.
The role of surgery in the management of patients with SCLC is unproven. Small case series and population studies have reported favorable outcomes for the minority of LD patients with very limited disease, with small tumors pathologically confined to the lung of origin or the lung and ipsilateral hilar lymph nodes from surgical resection with adjuvant chemotherapy.
In recent years, immune checkpoint inhibitors including programmed cell death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors have been added to the frontline treatment of patients with extensive-stage SCLC. Two PD-L1 inhibitors, atezolizumab (Tecentriq) and durvalumab (Imfinzi), demonstrated prolongation of overall survival when combined with platinum and etoposide, compared with the same combination chemotherapy regimen alone. Pembrolizumab (Keytruda) is also approved as third-line treatment for metastatic SCLC. However, in late 2020, another PD-1 inhibitor, nivolumab (Opdivo), was following negative trial results.
The National Cancer Institute has published a for patients with LD, ED, and recurrent SCLC.
Prognosis and Survival
Regardless of stage, the current prognosis for patients with SCLC is unsatisfactory despite improvements in diagnosis and therapy made during the past 25 years. Without treatment, SCLC has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2 to 4 months. About 10% of the total population of SCLC patients remains free of disease during the 2 years from the start of therapy, which is the time period during which most relapses occur. Even these patients, however, are at risk of dying from lung cancer (both small and non-small cell types). The overall survival at 5 years is 5%-10%.
An important prognostic factor for SCLC is the extent of disease. Patients with LD have a better prognosis than patients with ED. For patients with LD, median survival of 16 to 24 months and 5-year survivals of 14% with current forms of treatment have been reported. Patients diagnosed with LD who smoke should be encouraged to stop smoking before undergoing combined-modality therapy because continued smoking may compromise survival.
Improved long-term survival in patients with LD has been shown with combined-modality therapy. Although long-term survivors have been reported among patients who received either surgery or chemotherapy alone, chemotherapy combined with thoracic radiation therapy (TRT) is considered the standard of care. Adding TRT increases absolute survival by approximately 5% over chemotherapy alone. The optimal timing of TRT relative to chemotherapy has been evaluated in multiple trials and meta-analyses with the weight of evidence suggesting a small benefit to early TRT.
In patients with ED, median survival of 6 to 12 months is reported with currently available therapy, but long-term disease-free survival is rare.
Because the outcome for lung cancer patients is so dependent on the stage at which cancer is detected, researchers have been looking at ways to make the diagnosis earlier. See our story about Peter Fonda to learn about methods being studied to advance early detection.
Current clinical trials for SCLC are .
Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country, including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.