Small Cell Lung Cancer: Staging, Treatment and Prognosis

Small cell lung cancer: staging, treatment and prognosis

Efficient and correct diagnosis and staging of SCLC are key in improving survival with good quality of life, writes Dr Elaine Wallace

Lung cancer is the leading cause of cancer-related deaths in ative Oncology Group (ECOG) scale and Karnofsky Performance men and women worldwide.1 It is also the leading cause of can- Status (KPS) scale.4,5 cer mortality in Ireland, accounting for almost 20% of all cancer The KPS uses a 100-point scale and 11 measures to describe a deaths.2 patient’s abilities to engage in activities and perform work. The Approximately 95% of all lung cancers are classified as either ECOG uses a five-point scale and has been shown in a compara- small cell lung cancer (SCLC) or non-small cell lung cancer tive study to be a better predictor of prognosis.6 (NSCLC). NSCLC is any type of epithelial lung cancer other than Treatment SCLC. NSCLC is the most common type of lung cancer accounting All patients should be discussed at a multidisciplinary forum for approximately 80% of lung cancers. SCLC accounts for approx- with access to a full lung cancer team so that appropriate treat- imately 15% of bronchogenic carcinomas and is considered ment can be efficiently arranged. Appropriate treatment for SCLC distinct from NSCLC because of its clinical and biologic characteris determined predominantly by the stage of disease, but also by istics. SCLC exhibits aggressive behaviour with rapid growth and assessment of a patient’s performance status, co-morbidities and early spread to distant sites. any associated weight loss. Where performance status is poor or Without treatment, SCLC has the most aggressive clinical course co-morbidities severe, treatment may largely be palliative. of any type of lung cancer, with median survival from diagnosis Limited-stage disease of only two to four months. Compared with other cell types of At the time of diagnosis, approximately 30% of patients with lung cancer, SCLC is more responsive to chemotherapy and radia- SCLC will have limited-stage disease. Standard treatment options tion therapy. However, a cure is difficult to achieve because SCLC with limited-stage SCLC include: has a greater tendency to be widely disseminated by the time of • Chemotherapy and radiation therapy diagnosis. • Combination chemotherapy alone It is the cancer most commonly associated with paraneoplastic • Surgery followed by chemotherapy or radiotherapy syndromes, including Lambert-Eaton myasthenic syndrome, syn- • Prophylactic cranial radiotherapy. drome of inappropriate antidiuretic hormone secretion (SIADH) SCLC is believed to be a systemic disease at diagnosis, thus and paraneoplastic cerebellar degeneration.3 surgery plays no significant role in its management. Patients Evaluation diagnosed with limited-stage disease who smoke should be The main issues to establish in a patient with suspected lung encouraged to stop smoking before undergoing treatment as cancer are: continued smoking may compromise cure rates.7 • The cell type (NSCLC vs SCLC) Chemotherapy improves the survival of patients with limited- • The stage of the disease stage disease or extensive-stage disease, but it is curative in • The functional status of the patient. only a minority of patients.8,9 Although long-term survivors have It is necessary to distinguish whether the disease is SCLC or been reported among patients who received either surgery or NSCLC in order to plan treatment and, because of this, a tissue chemotherapy alone, chemotherapy combined with thoracic diagnosis is vital. radiotherapy is considered the standard of care. Staging Adding thoracic radiotherapy increases absolute survival by In general a two-stage system is used for SCLC: limited-stage approximately 5% over chemotherapy alone.10,11 The optimal disease and extensive-stage disease. Limited-stage is disease timing of thoracic radiotherapy relative to chemotherapy has confined to the hemithorax of origin, the mediastinum or the been evaluated in multiple trials and meta-analyses with the supraclavicular lymph nodes. Extensive-stage is disease present weight of evidence suggesting a small benefit to early thoracic beyond one hemithorax. This distinction is important as patients radiotherapy.12-14 with limited-stage disease may benefit from thoracic radiother- Prophylactic cranial radiation helps prevent central nervous apy in addition to systemic chemotherapy. system (CNS) recurrence and can improve survival in patients Performance status who have had a complete response to chemo-radiation.15,16 A patient’s performance status also dictates the type of treat- Extensive-stage disease ment regime employed. Performance status can be assessed Patients with tumours that have spread beyond the supracla- using a variety of assessment tools including the Eastern Co-oper- vicular areas are said to have extensive-stage disease and have

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Table 1 and modern multidisciplinary management of SCLC have led to Prognostic factors of survival in SCLC20 improved short-term and long-term survival with good quality of life. A recent trial of early versus standard referral to specialist palliative care has shown that early palliative care intervention • Limited disease results in improved quality of life and survival.26 Thus the early integration of palliative care into the disease-specific therapies • Good performance status for patients with advanced lung cancer should be considered. Dr Elaine Wallace is a clinical fellow at Princess Margaret Hospital in Toronto, • Female gender Canada References 1. WHO. Cancer Fact Sheet No 297. October 2011. Available at http://www.who.int/ • No significant weight loss mediacentre/factsheets/fs297/en/ 2. Irish Thoracic Society – Lung cancer sub-committee. Guidelines for the diagnosis and treatment of lung cancer. Third edition. 2009. Available at http://www.irishthoracicsociety. • White cell count com/images/uploads/file/ITSLungCancerGuidelinesFebruary2010.pdf 3. Govindan R et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. • Platelet count J Clin Oncol 24. 2006; (28): 4539-44 4. Eastern Co-operative Oncology Group (ECOG). Available at http://www.ecog.org/general/perf_stat.html • Lactate dehydrogenase (LDH) 5. Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM (Ed), Evaluation of chemotherapeutic agents. Columbia Univ Press.1949: 196 6. Buccheri G, Ferrigno D, Tamburin M. Karnofsky and ECOG performance status scoring in lung cancer: a prospective, longitudinal study of 536 patients from a single institution. Eur J Cancer. 1996; Jun; 32A(7): 1135-41 a worse prognosis than patients with limited-stage disease. 7. Videtic GM et al. Continued cigarette smoking by patients receiving concurrent chemora- Chemotherapy for extensive-stage SCLC is commonly given as a diotherapy for limited-stage small-cell lung cancer is associated with decreased survival. J Clin Oncol. 2003; 21 (8): 1544-9 two-drug combination with platinum-based compounds in doses 8. Comis RL, Friedland DM, Good BC. Small-cell lung cancer: a perspective on the past and a associated with at least moderate toxic effects.17 preview of the future. Oncology (Huntingt). 1998; 12 (1 Suppl 2): 44-50 Commonly used chemotherapeutic regimes include carbo- 9. Agra Y et al. Chemotherapy versus best supportive care for extensive small cell lung cancer. Cochrane Database Syst Rev. 2003; (4): CD001990 platin/etoposide, cisplatin/etoposide, cisplatin/irinotecan and 10. Pignon JP, Arriagada R, Ihde DC, et al. A meta-analysis of thoracic radiotherapy for cyclophosphamide/doxorubicin/vincristine. Cisplatin is associated small-cell lung cancer. N Engl J Med 327. 1992; (23): 1618-24 with significant toxic effects and requires fluid hydration, which 11. Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol. 1992; 10(6): can be problematic in patients with cardiovascular disease. 890-5 Carboplatin is active in SCLC, is dosed according to renal func- 12. Murray N et al. Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada tion and is associated with less non-haematological toxic effects. Clinical Trials Group. J Clin Oncol. 1993; 11(2): 336-44 Doses and schedules used in current regimes yield response rates 13. Perry MC et al. Chemotherapy with or without radiation therapy in limited small-cell of 50-80% and complete response rates of 0-30% in patients with carcinoma of the lung. N Engl J Med. 1987; 316(15): 912-8 14. Takada M et al. Phase III study of concurrent versus sequential thoracic radiotherapy in 18,19 extensive-stage disease. combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results Palliative whole-brain radiotherapy should be used for radio- of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002; 20(14): 3054-60 15. Aupérin A et al. Prophylactic cranial irradiation for patients with small-cell lung cancer logically-proven cranial metastases. Radiotherapy should also be in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N considered for the palliation of other metastatic lesions requiring Engl J Med. 1999; 341(7): 476-84 symptom control. 16. Slotman B et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007; 357(7): 664-72 Prognosis 17. Okamoto H et al. Randomised phase III trial of carboplatin plus etoposide vs split doses The most important prognostic factor is the stage of disease at of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007; 97(2): 162-9 presentation. Patients with involvement of the CNS or liver at the 18. Roth BJ et al. Randomized study of cyclophosphamide, doxorubicin, and vincristine ver- time of diagnosis have a significantly worse outcome. A number sus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell of biochemical factors including white cell count, platelet count lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992; 10(2): 282-91 and lactate dehydrogenase (LDH) have also been found to inde- 19. Pujol JL, Carestia L, Daurès JP. Is there a case for cisplatin in the treatment of small-cell pendently correlate with outcome20 (see Table 1). lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus Factors of survival a regimen without this alkylating agent. Br J Cancer. 2000; 83(1): 8-15 20. Bremnes RM et al. The value of prognostic factors in small cell lung cancer: results from Regardless of stage, the current prognosis for patients with a randomised multicenter study with minimum five year follow-up. Lung Cancer. 2003; SCLC is poor despite improvements in diagnosis and therapy Mar; 39(3): 303-13 21. Johnson BE et al. Ten-year survival of patients with small-cell lung cancer treated with during the past 25 years. The overall survival at five years is combination chemotherapy with or without irradiation. J Clin Oncol. 1990; 8(3): 396-401 approximately 5-10%.12,21-23 22. Fry WA, Menck HR, Winchester DP. The National Cancer Data Base report on lung cancer. For patients with limited-stage disease, median survival of Cancer 77. 1996; (9): 1947-55 23. Lassen U et al. Long-term survival in small-cell lung cancer: posttreatment characteris- 16-24 months and five-year survivals of 14% with current forms of tics in patients surviving five to 18+ years – an analysis of 1,714 consecutive patients. J Clin treatment have been reported.12,22,24,25 For patients with extensive- Oncol. 1996; 13(5): 1215-20 24. Turrisi AT 3rd et al. Twice-daily compared with once-daily thoracic radiotherapy in lim- stage disease, median survival of six to 12 months is reported with ited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. currently available therapy, but long-term disease-free survival is 1999; 340(4): 265-71 rare. Most of the two-year disease-free survivors come from the 25. Jänne PA et al. Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America. Cancer 95. 2002; (7): 1528-38 limited-stage disease group. 26. Temel J et al. Early palliative care for patients with metastatic non–small-cell lung can- Earlier diagnosis, efficient and correct diagnosis and staging, cer. N Engl J Med. 2010; 363: 733-42

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