Editor(s): Eric Vallieres, M.D. Reviewers: Malcolm M. DeCamp, Jr., M.D., David H. Harpole, Jr., M.D., Leslie J. Kohman, M.D., John D. Urschel, M.D.

Overview

Silvestri GA, et al: Specialists Achieve Better Outcomes than Generalists for Lung Cancer Surgery. Chest 1998;114(3):675-680.

The first study in Thoracic Surgery studying the Impact of Additional Training and Specialisation on the results of Lung Cancer Surgery.

Ginsberg RJ, et al (LCSG) : Modern Thirty-Day Operative Mortality for Surgical Resections in Lung Cancer. J Thorac Cardiovasc Surg 1983;86(5):654-658

Multi-institutional prospective data collected by the LCSG over a period of 12 years (2200 resections) reflecting modern day surgical mortality rates in the treatment of lung cancer.

Harpole DH Jr, et al. (The National VA Surgical Risk Study) Prognostic models of 30-day morbidity and mortality after major pulmonary resections, J Thorac Cardiovasc Surg 1999; 117: 969-79.

This is the largest prospective dataset of major pulmonary resections, including a detailed risk-adjustment model form the National VA QI program.

Screening

Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer Action Project: Overall Design and Findings from Baseline Screening. Lancet 1999; 354(9173): 99-105

Initial report from the North American ALCAP which corroborates the Japanese suggestions of a potential role for LD Spiral CT in screening for Lung Cancer in populations at risk

Staging

Mountain CF: Revisions in the international system for staging lung cancer. Chest 1997; 111(6): 1710-1717

Mountain CF, Dresler CM: Regional Lymph Node Classification for Lung Cancer Staging. Chest 1997; 111(6): 1718-23

Revisions of the 1986 Staging System and of the AJCC Nodal Map describing NSCLC staging as it remains

Dales RE, et al: Computed Tomography to Stage Lung Cancer- Approaching a Controversy Using Meta-Analysis. Am Rev Respir Dis 1990; 141(5 Pt1): 1096-1101.

A metaanalytic review of the data addressing the accuracy, sensitivity and specificity of CT as a mediastinal staging tool.

Luke WP et al.: Prospective Evaluation of Mediastinoscopy for Assessment of Carcinoma of the Lung. J Thorac Cardiovasc Surg 1986: 91(1): 53-56

One of the largest series addressing the role of routine mediastinoscopy in te evaluation of lung cancers.

Saunders CAB, et al: Evaluation of FDG Whole Body Positron Emission Tomography Imaging in the Staging of Lung Cancer. Ann Thor Surg 1999; 67: 790-7

One of the many recent reports looking at the value of FDG PET in the work up of patients with potentialy resectable NSCLC ( n = 97)

Ahuja V, et al: The Prognostic Significance of FDG PET Imaging for Patients with NSCLC. Cancer 1998; 83: 918-24

The first series establishing the prognostic value of FDG PET readings in NSCLC.

Surgical treatment of stages 1A-IB-IIA-IIB- IIIA ( T3N1)

Ginsberg RJ, et al. (LCSG 821):Randomized Trial of Lobectomy Versus Limited Resection for T1N0 Non Small Cell Lung Cancer. Lung Cancer Study Group. Ann Thor Surg 1995; 60(3): 615-623.

A Phase III prospective randomized cooperative group trial comparing lobectomy to segmentectomy and wedge resections in the management of T1N0 tumors. (prospective)

Martini N, et al: Management of non-small cell lung cancer with Direct Mediastinal Involvement. Ann Thorac Surg 1994; 58(5): 1447-51

One of the rare series adressing T3 mediastinal disease as a separate group from other T3 tumors. (retrospective data)

Downey RJ, et al: Extent of Chest Wall Invasion and Survival in Patients with Lung Cancer, Ann Thorac Surg 1999; 68(1): 188-93

The largest series on the topic. Survival depends on the completeness of resection and on the nodal status. ( retrospective data)

Surgical treament of stage IIIA ( N2)

Pearson FG, et al: Significance of positive superior mediastinal nodes identified at mediastinoscopy in patients with resectable cancer of the lung. J Thorac Cardiovasc Surg 1982: 83(1):1-11

A classic from The Toronto Thoracic Group demonstrating the value of routine mediastinoscopy in identifying a subset of N2 patients who are unlikely to benefit from resection alone. ( retrospective data, pre-induction chemotherapy era )

Martini N, et al: Results of Resection in Non-Oat Cell Carcinoma of the Lung with Mediastinal Lymph Node Metastases. Ann Surg 1983; 198(3): 386-397

The experience of The Memorial Sloan Kettering Cancer Center when mediastinoscopy was not done routinely. When carefully dissected, this paper actually describes the same subset of N2 patients as in the Toronto paper who may benefit from upfront surgery, however many more patients required "open & close" thoracotomies. ( retrospective data, pre-induction chemotherapy era )

Adjuvant Therapy for resectable NSCLC

The Lung Cancer Study Group. Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. (LCSG 771) N Eng J Med 315: 1377-81, 1986

A cooperative group phase III randomized trial showing that adjuvant radiotherapy, despite reducing the incidence of loco-regional recurrences after complete resection of squamous cell cancers, has no effect whatsoever on the survival of the patients. (prospective)

Medical Research Council Lung Cancer Working Party: The role of postoperative radiotherapy in non small cell lung cancer: A multi center randomized trial in patients with pathologically staged T1-2, N1-2, M-0 disease. British Journal of Cancer 74: 632-639, 1996

Twenty years after the LCSG 771 study, the question is revisited: open to all NSCLC histologies, still no survival benefit (prospective)

PORT Meta-analysis Trialists' Group: Postoperative radiotherapy in NSCLC: Systematic review and metaanalysis of individual patient data from nine randomized controlled trials. Lancet 352: 257-63, 1998

A meta-analytic review of the question which suggests a detrimental effect of adjuvant radiotherapy after the complete resection of stage II NSCLC. No detriment nor survival advantage in stage III. (meta-analysis)

Feld R, et al. (LCSG) : Adjuvant chemotherapy with cyclophosphamide, doxorubicin, and cisplatin in patients with completely resected stage I NSCLC. A Lung Cancer Study Group Trial. J Natl Cancer Inst 1993; 85(4):299.

One of the many negative phase III randomized LCSG studies evaluating adjuvant CAP chemotherapy. (prospective)

Niiranen A, et al: Adjuvant chemotherapy after radical surgery for NSCLC: A randomized study. J Clin Oncol 1992; 10: 1927-1932

The only positive phase III randomized adjuvant CAP chemotherapy trial. Restricted to N0 patients, 50 patients each arm ( prospective)

Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials. Brit Med Jour 1995; 311:899

A meta-analytic analysis of the potential role of adjuvant chemotherapy in NSCLC suggesting a non statistically significant 13% reduction of the risk of death and a possible 5% absolute benefit in survival at 5 years with the use of a adjuvant platinum based chemotherapy. ( p 0.08) (meta-analysis)

Wada H, et al. Adjuvant chemotherapy after complete resection in non-small cell lung cancer. J Clin Oncol 1996; 14(4):1048-1054

A positive 3 arm randomized study showing a significant improvement in 5 year survival for patients receiving adjuvant oral UFT chemotherapy for 1 year after surgery ( prospective)

Induction Therapy for resectable NSCLC

Richardson GE, et al: Smoking Cessation after Successful Treatment of Small- Cell Lung Cancer is Associated with Fewer Smoking-related Second Primary Cancers. Ann Intern Med 1993; 119(5): 383-390

Small Cell related but clearly demonstrating the benefits of smoking discontinuance after the successful treatment of a first lung cancer.

Rosell R, et al: A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with NSCLC. N Eng J Med 1994; 330: 153-8

Roth JA, et al: A randomized trial comparing perioperative chemotherapy and surgery and surgery alone in resectable stage IIIA NSCLC. J Natl Cancer Inst 1994; 86(9): 673-680.

Rosell R et al. Preresectional Chemotherapy in Stage IIIA NSCLC: a 7 year assessment of a Randomized Controlled Trial. Lung Cancer 1999; 26(1):7-14

Roth JA et al. Long-Term Follow-up of Patients Enrolled in a Randomized Trial Comparing Perioperative Chemotherapy and Surgery with Surgery Alone in Resectable Stage IIIA NSCLC Lung Cancer 1998; 21(1): 1-6

Both the Rosell and the Roth series are the first randomized phase III trials to have shown a significant advantage of induction chemotherapy over that of surgery alone in the management of "higher" stage, potentially resectable NSCLC. Small numbers but statistically significant. Addendum: Both have updated their early follow-up since (1997, 1998).

Pisters KM, et al.: Induction Chemotherapy before Surgery for Early-Stage Lung Cancer: a Novel Approach. Bimodality Lung Oncology Team. J Thorac Cardiovasc Surg 2000; 119(3): 429-39.

The BLOT study, a phase II prospective multicentered study showing the feasability and safety of induction carboplatin and paclitaxel chemotherapy followed by resection for early clinical stages NSCLC. This study has lead to the ongoing phase III SWOG 9900 study. ( see below)

Treatment of stage IIIA and IIIB

Dillman RO, et al: A Randomized Trial of Induction Chemotherapy plus High-Dose Radiation versus Radiation Alone in Stage III NSCLC. N Engl J Med 1990; 323(14): 940-5.

Dillman RO, et al. Improved Survival in Stage III NSCLC: Seven Year Follow-up of Cancer and Leukemia Group B 8433 Trial. J Natl Cancer Inst 1996; 88(17): 1210-5

The first randomized trial showing an advantage of combining chemo and radiotherapy in treating stage III disease.Updated follow-up in 1996

Albain KS, et al: Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non small cell lung cancer: Mature results of Southwest Oncology Group Phase II study 8805. J Clin Oncol 13(8): 1880-1892, 1995.

The largest phase II multicentered trial evaluating the safety and feasability of induction chemoradiotherapy and surgery in pathologically proven stages IIIA and IIIB diseases. This study has led to the ongoing Intergroup 0139 phase III trial. ( see below)

Treatment of stage IV

Rapp E, et al.: Chemotherapy can Prolong Survival in Patients with Advanced NSCLC- Report of a Canadian Multicenter randomized Trial. J Clin Oncol 1988; 6(4): 633-41

A phase III randomized study showing the survival and quality of life assessment superiorities of chemotherapy over that of supportive care alone in treating good performance status patients with stage IV disease.

Martini N: Rationale for Surgical Treatment of Brain Metastasis in NSCLC, Editorial. Ann Thorac Surg 1986; 42(4): 357-58

An editorial discussing the merits of combined thoracic and cranial surgeries in selected patients with solitary brain metastases from primary NSCLC.

Thymoma

Venuta F, et al. "Multi-modality Treatment of Thymoma: A Prospective Study," Ann Thorac Surg 64(6): 1585-92, 1997.

Interesting early experience with the combined modality therapy of thymomas.

Mesothelioma

Sugarbaker DJ, et al, "Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: Results in 183 patients. J Thorac Cardiovasc Surg 1999; 117(1): 54-65.

The largest reported series of extrapleural pneumonectomies and adjuvant chemo and radiotherapy for mesothelioma

Recent Abstracts

Depierre A, et al. (FTCG) Phase III trial of neo-adjuvant chemotherapy in resectable stage Ib, II, IIIa NSCLC: the French Experience. Proc Am Soc Clin Oncol 1999; 18: 465a. Abstract 1792

The first randomized phase III trial addressing induction chemotherapy in early clinical NSCLC

Keller SM, et al.: Complete Mediastinal Lymph Node Dissection Improves Survival in Patients with Resected Stages II and IIIA NSCLC. Society of Thoracic Surgeons, The 2000 J. Maxwell Chamberlain Memorial Paper .

Suggests a possible therapeutic role for radical lymphadenectomy in the resection of NSCLC. Non randomized data, reenforces the need to complete the ACOSOG Z0030 trial. ( See below)

Ohmatsu H, et al. Lung Cancer Screening with Low Dose Spiral CT. Proc Am Soc Clin Oncol 1999; Abstract 1787

Data from the Japanese Anti-Lung Cancer Association that has triggerred all the excitement about the possible screening role of Low dose Spiral CT in populations at risk.

Kraut MJ, Rusch VW, et al. Induction Chemoradiotherapy plus Surgical Resection is a Feasible and Highly Effective Treatment for Pancoast Tumors: Results of SWOG 9416 (Int 0160) Trial. Proc Am Soc Clin Oncol 2000; 19: 487a. Abstract 1906

The largest prospective series evaluating the safety and feasability of combined modality therapy for Pancoast Tumors. Early results, but considered by many the new standard of care for resectable Pancoast Tumors.

Gandara DR, et al. Prolonged Survival in Pathological Stage IIIB NSCLC with Concurrent Chemoradiationtherapy followed by Consolidation Docetaxel: A Phase II Study ( SWOG 9504) Proc Am Soc Clin Oncol 2000; 19: 490a. Abstract 1916

Historically, the best results for IIIB disease. Consolidation Docetaxel appears encouraging.

Sauvaget J, et al. Study of Neo-Adjuvant MVP versus MVP plus chemo-radiotherapy in Stage III NSCLC. Proc Am Soc Clin Oncol 2000; 19: 495a. Abstract 1935

Single institution phase III study comparing the strategy of induction chemotherapy alone versus that of induction chemotherapy and radiotherapy given sequentially.( n= 92) Despite higher response rates and resectability rates were in the latter group, the patterns of failure were equivalent as were the the 3 year survival rates and median survival for both IIIa and IIIb diseases.

Ongoing Phase III Surgical Trials

SWOG 9900 : Surgery with or without induction cbdca/ paclitaxel chemotherapy for clinical Stage IB, IIA, IIB and T3N1 diseases. ( Paul A Bunn, Chair )

RTOG 9309 (INT 0139) : Induction concurrent chemoradiation therapy (cddp/etoposide) with or without resection for IIIA N2 disease. (David S. Ettinger, Chair)

CALGB 9633: Adjuvant carboplatin/ paclitaxel or not after complete resection of IB disease. (Gary M. Strauss, Chair)

CALGB 9734: Adjuvant carboplatin/ paclitaxel with or without radiotherapy after resection of IIIA NSCLC. ( Leslie Kohman, Chair) (CLOSED)

NCIC BR 10: Adjuvant cddp/ vinorelbine or not after complete resection of Stages IB, IIA and IIB diseases. (Timothy Winton, Chair)

ACOSOG Z0030: Mediastinal lymph node sampling versus complete lymphadenectomy in patients with N0 and N1 (less than hilar ) NSCLC. (Mark S Allen, Chair )

ACOSOG Z0040: Prognostic significance of occult metastases with resectable NSCLC. (RG Cohen, Chair)

EORTC 08941: Surgery versus radiotherapy for IIIA N2 disease after induction cddp or cbdca containing chemotherapy. ( TAW Splinter, Chair )