Role of adjuvant radiotherapy in completely resected non-small-cell lung cancer

Most long-term survivors of non-small-cell lung cancer (NSCLC) are patients who have had a completely resected tumour. However, this is only achievable in about 30% of the patients. Even in this highly selected group of patients, there is still a high risk of both local and distant failure. Adjuvant treatments such as chemotherapy (CT) and radiotherapy (RT) have therefore been evaluated in order to improve their outcome. In patients with stage II and III, administration of adjuvant platinum-based chemotherapy is now considered the standard of care, based on level 1 evidence. The role of postoperative radiation therapy (PORT) remains controversial. In the PORT meta-analysis published in 1998, the conclusions were that if PORT was detrimental to patients with stage I and II completely resected NSCLC, the role of PORT in the treatment of tumours with N2 involvement was unclear and further research was warranted. Thus at present, after complete resection, adjuvant radiotherapy should not be administered in patients with early lung cancer. Recent retrospective and non-randomised studies, as well as subgroup analyses of recent randomised trials evaluating adjuvant chemotherapy, provide evidence of the possible benefit of PORT in patients with mediastinal nodal involvement. The role of PORT needs to be evaluated also for patients with proven N2 disease who undergo neoadjuvant chemotherapy followed by surgery. The risk of local recurrence for N2 patients varies between 20% and 60%. Based on currently available data, PORT should be discussed for fit patients with completely resected NSCLC with N2 nodal involvement, preferably after completion of adjuvant chemotherapy or after surgery if patients have had preoperative chemotherapy. There is a need for new randomised evidence to reassess PORT using modern three-dimensional conformal radiation technique, with attention to normal organ sparing, particularly lung and heart, to reduce the possible over-added toxicity. Quality assurance of radiotherapy as well as quality of surgery – and most particularly nodal exploration modality – should both be monitored. A new large multi-institutional randomised trial Lung ART evaluating PORT in this patient population is needed and is now under way.     

Adjuvant therapy of resected non-small-cell lung cancer

Surgical resection of early-stage non-small-cell lung cancer (NSCLC) remains the standard of care in patients fit for surgery. Careful preoperative staging is imperative, as is pathologic documentation of the mediastinal nodal contents. Adjuvant postoperative thoracic radiation therapy (RT) clearly has an impact in reducing locoregional recurrence but has no clear impact on survival. The Postoperative RT (PORT) metaanalysis raised concerns about PORT, particularly in stage I/II NSCLC, suggesting it may negatively impact survival. This was not a concern in stage III NSCLC, in which the risk of locoregional recurrence is higher. However, distant recurrence remains the dominant pattern in resected NSCLC, suggesting that the majority of patients with early-stage resected NSCLC harbor occult micrometastatic disease. Historically, the role of adjuvant chemotherapy has been controversial, and its routine use was not supported by the published data, which consisted of a small number of underpowered trials using inadequately delivered, antiquated chemotherapy. More recently, larger trials have been reported with conflicting results. Like adjuvant PORT, chemotherapy combined with RT has not improved survival over PORT alone. The use of adjuvant cisplatin-based therapy did not show a survival advantage in the Adjuvant Lung Project Italy study but did in the International Adjuvant Lung Trial, creating controversy in the routine implementation of adjuvant therapy in all patients. Recently completed randomized trials by the Cancer and Leukemia Group B and the National Cancer Institute of Canada provide convincing evidence of a substantial benefit from adjuvant therapy in well-staged and completely resected stage I/II NSCLC. Currently, the totality of the data supports a discussion with patients with resected NSCLC regarding the potential benefits of adjuvant therapy.     

ACR Appropriateness Criteria® postoperative adjuvant therapy in non-small cell lung cancer

Therapeutic options for postoperative adjuvant treatment for patients with non-small cell lung cancer (NSCLC) continue to evolve, and may include postoperative radiotherapy (PORT) and chemotherapy, alone or in combination. The use of platinum-based adjuvant chemotherapy has been demonstrated to confer an improvement in overall survival in patients with completely resected, stage N1 or N2 NSCLC, in several randomized trials and 2 meta-analyses. Consideration may also be given to adjuvant chemotherapy in patients with node-negative NSCLC, when the primary tumor is >4 cm, based on subset analyses of recent prospective studies. The precise role of PORT is less well defined. Older randomized studies indicated that the toxicity of PORT outweighed the potential improvement in local control, but studies using more modern radiation techniques show significantly reduced toxicity, inferring that select patients may benefit. Relative indications for PORT include the presence of mediastinal lymph nodes, positive surgical margins, and considerations with regard to the extent and type of resection. This study by the lung cancer expert panel of the American College of Radiology summarizes the recent evidence-based literature that addresses the use of postoperative adjuvant radiotherapy and chemotherapy in patients with NSCLC, illustrated with clinical scenarios. The sequencing of radiotherapy and chemotherapy is discussed, along with issues regarding radiotherapy dose and fractionation, and the appropriate use of intensity modulated radiation therapy and particle therapy.     

Stage III lung cancer: two or three modalities? The continued role of thoracic radiotherapy

Lung cancer is the leading cause of cancer mortality in the United States. A significant number of patients present with disease involving mediastinal lymph nodes. As survival after surgery alone for stage III disease is poor, radiation therapy and chemotherapy have been evaluated in the neoadjuvant and adjuvant settings to improve outcomes. The benefit of adjuvant chemotherapy in the subgroup of patients with N2 disease is uncertain. Small randomized trials enrolling patients with stage III disease have shown a benefit of neoadjuvant chemotherapy over surgery alone. Whether neoadjuvant chemotherapy is superior to adjuvant chemotherapy is under investigation. Furthermore, whether neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy is controversial, and few randomized studies comparing these approaches have been reported. Nevertheless, neoadjuvant chemoradiotherapy appears to be associated with higher rates of resection, higher rates of clearance of mediastinal nodal disease, and better local/regional control. The use of postoperative radiation therapy (PORT) has declined since the publication of the 1998 meta-analysis suggested a detriment in survival with this strategy. However, radiation techniques are improving and emerging data support the use of carefully delivered PORT Finally, it remains unclear whether surgical resection offers an advantage over definitive chemoradiotherapy alone for stage III disease. In summary, locally advanced NSCLC remains a formidable challenge with few cures, and optimal treatment requires the careful use of surgery, chemotherapy, and radiation therapy.     

Role of Postoperative Radiotherapy in the Management for Resected NSCLC – Decision Criteria in Clinical Routine Pre- and Post-LungART

BackgroundThe role of postoperative radiation therapy (PORT) in stage III N2 NSCLC is controversial. We analyzed decision-making for PORT among European radiation oncology experts in lung cancer.MethodsTwenty-two experts were asked before and after presentation of the results of the LungART trial to describe their decision criteria for PORT in the management of pN+ NSCLC patients. Treatment strategies were subsequently converted into decision trees and analyzed.ResultsFollowing decision criteria were identified: extracapsular nodal extension, incomplete lymph node resection, multistation lymph nodes, high nodal tumor load, poor response to induction chemotherapy, ineligibility to receive adjuvant chemotherapy, performance status, resection margin, lung function and cardiopulmonary comorbidities. The LungART results had impact on decision-making and reduced the number of recommendations for PORT. The only clear indication for PORT was a R1/2 resection. Six experts out of ten who initially recommended PORT for all R0 resected pN2 patients no longer used PORT routinely for these patients, while four still recommended PORT for all patients with pN2. Fourteen experts used PORT only for patients with risk factors, compared to eleven before the presentation of the LungART trial. Four experts stated that PORT was never recommended in R0 resected pN2 patients regardless of risk factors.ConclusionAfter presentation of the LungART trial results at ESMO 2020, 82% of our experts still used PORT for stage III pN2 NSCLC patients with risk factors. The recommendation for PORT decreased, especially for patients without risk factors. Cardiopulmonary comorbidities became more relevant in the decision-making for PORT.     

Management of Locally Advanced Non Small Cell Lung Cancer from a Surgical Perspective

Opinion statement Stage III, locally advanced NSCLC, represents an incredibly heterogeneous group of patients. Optimal therapy for this group is controversial and the role of surgery is not clearly defined. There have been several randomized trials over the past three decades that have helped to guide our decision-making. In patients with T3N1 tumors, surgery is the primary treatment and there is now evidence for the use of adjuvant chemotherapy. Consensus has shown that the majority of IIIB tumors are not amenable to resection. Exceptions to this are selective T4 tumors by virtue of a satellite nodule or those with isolated invasion of the spine, superior sulcus, carina or vena cava. Such tumors require technically difficult resections and are reserved for patients with excellent performance status and no evidence of N2 disease. Patients with N2 disease represent the largest proportion of patients with stage III disease. There is an increasing understanding of the importance of multi-modality therapy for N2 disease, but the exact role and timing of chemotherapy, radiation and surgery remains unclear. The role of surgery is determined by the bulk of the mediastinal node involvement. Clearly, not all N2 disease is the same. Patients with micometastatic disease and single station nodal involvement have the greatest chance for cure and surgery has a significant role in their treatment. In addition, the ability to sterilize mediastinal lymph nodes with induction therapy correlates strongly with survival. However, the ideal form and timing of induction therapy has yet to be determined. Bulky multi-station disease is frequently not amenable to surgery and is best approached with definitive chemotherapy and radiation.     

Lung cancer

Based on several landmark studies and meta-analyses, the standard of care for stage II - III A NSCLC patients has been adjuvant cisplatin-based doublet chemotherapy performed after appropriate surgical resection. The benefit of this therapy for patients with stage I B NSCLC is less apparent, likely because of the heterogeneity of this population. In Japan, however, many randomized clinical studies have assessed the effectiveness of postoperative adjuvant chemotherapy with tegafur-uracil (UFT)in patients with completely resected NSCLC. Based on these studies and a meta-analysis, UFT is used as the standard postoperative adjuvant chemotherapy for stage I NSCLC patients with a tumor larger than 2 cm. It is necessary to re-evaluate adjuvant chemotherapy strategies according to the new seventh edition of the tumor-nodemetastasis classification system. The role of postoperative radiotherapy(PORT)is also explored there. Recently, several tumor markers such as ERCC1 may have had a predictive value for selecting patients who will benefit from adjuvant platin-based chemotherapy. Targeted agents and vaccine therapy are also being evaluated as adjuvant treatments for use after the resection of NSCLC. Randomized studies are ongoing. If these results are confirmed, we will enter an era of personalized care for resected NSCLC.     

应用倾向评分匹配法评价ⅢA-N2期非小细胞肺癌术后放疗的价值

 目的 分析ⅢA-N2期非小细胞肺癌根治术后辅助放疗（postoperative radiotherapy, PORT）的作用。方法 收集313例非小细胞肺癌根治术后化疗后的ⅢA-N2期患者的临床资料,对PORT（+）组及PORT（-）组资料应用倾向评分匹配方法均衡组间协变量差异,观察两组生存及局控,分析术后放疗的作用及获益人群。结果 匹配后两组患者中,PORT（+）组与PORT（-）组3、5年生存率分别为76.5%、58.3%和52.1%、40.6%（P=0.162）;3、5年局部控制率分别为82.9%、73.7%和56.5%、42.4%（P=0.036）;3、5年无进展生存率分别为74.8%、65.5%和39.5%、29.6%（P=0.021）。分层分析发现术后放疗可降低隆突下淋巴结转移、肿瘤最大径≥3cm、多站转移、非跳跃转移及术前N2亚组的局部复发风险。结论 术后放疗可提高ⅢA-N2期非小细胞肺癌术后化疗后局部控制率及无进展生存率;亚组分析中隆突下淋巴结转移、肿瘤最大径≥3 cm、多站转移、非跳跃转移及术前N2者获益较大。     

Postoperative radiotherapy for elderly patients with stage III lung cancer

BACKGROUND:

The potential role of postoperative radiation therapy (PORT) for patients who have completely resected, stage III nonsmall cell lung cancer (NSCLC) with N2 disease remains controversial. By using population‐based data, the authors of this report compared the survival of a concurrent cohort of elderly patients who had N2 disease treated with and without PORT.

METHODS:

By using the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare records, 1307 patients were identified who had stage III NSCLC with N2 lymph node involvement diagnosed between 1992 and 2005. Propensity scoring methods and instrumental variable analysis were used to compare the survival of patients who did and did not receive PORT after controlling for selection bias.

RESULTS:

Overall, 710 patients (54%) received PORT. Propensity score analysis indicated that PORT was not associated with improved survival in patients with N2 disease (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.97‐1.27). Analyses that were limited to patients who did or did not receive chemotherapy, who received intermediate‐complexity or high‐complexity radiotherapy planning, or adjusted for time trends produced similar results. The instrumental variable estimator for the absolute improvement in 1‐year and 3‐year survival with PORT was ?0.04 (95% CI, ?0.15 to 0.08) and ?0.08 (95% CI, ?0.24 to 0.15), respectively.

CONCLUSIONS:

The current data suggested that PORT is not associated with improved survival for elderly patients with N2 disease. These findings have important clinical implications, because SEER data indicate that a large percentage of elderly patients currently receive PORT despite the lack of definitive evidence about its effectiveness. The potential effectiveness of PORT should be evaluated further in randomized controlled trials. Cancer 2012. © 2012 American Cancer Society.     

Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer

PURPOSE: A 1998 meta-analysis of postoperative radiotherapy (PORT) for non-small-cell lung cancer (NSCLC) found that PORT did not improve outcomes. Yet practice guidelines differ in their recommendations with regard to PORT use. We examine temporal trends in PORT use before and after the 1998 meta-analysis. METHODS AND MATERIALS: Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we identified 22,953 patients with Stage I, II, or IIIA NSCLC who had resection between 1992 and 2002 in the United States and characterized each patient according to nodal status (N0, N1, or N2 disease). We measured use of PORT by calendar year. We examined the association between clinical and demographic characteristics and receipt of PORT using logistic regression. RESULTS: For N0, N1, and N2 NSCLC, PORT use has declined. The proportion of patients with N0 disease receiving PORT declined from 8% in 1992 to 4% in 2002. For patients with N1 disease, PORT use declined from 51% in 1992 to 19% in 2002; and for patients with N2 disease, PORT use declined from 65% in 1992 to 37% in 2002. CONCLUSION: In the context of uncertainty about what constitutes optimal adjuvant treatment for resected NSCLC, PORT use has substantially declined.     

Role of Postoperative Radiotherapy After Curative Resection and Adjuvant Chemotherapy for Patients With Pathological Stage N2 Non–Small-Cell Lung Cancer: A Propensity Score Matching Analysis

BackgroundThe objective of this study was to evaluate the role of postoperative radiotherapy (PORT) in the setting of adjuvant chemotherapy for pathological stage N2 (pN2) non–small-cell lung cancer (NSCLC).Materials and MethodsA retrospective review of 219 consecutive pN2 NSCLC patients who underwent curative surgery followed by adjuvant chemotherapy was performed. Forty-one patients additionally received PORT. Propensity scores for PORT receipt were individually calculated and used for matching to compare the outcome between patients who did (+) and did not (-) receive PORT. One hundred eleven patients in the PORT (-) group and 38 patients in PORT (+) group were matched. Clinical and pathologic characteristics were well-balanced.ResultsThe median follow-up duration was 48 months. In the matched patients, PORT resulted in a significantly lower crude locoregional relapse (43.2% vs. 23.7%; P = .032). Also, PORT was associated with improved locoregional control (LRC) rate (5-year LRC 63.7% vs. 48.6%; P = .036), but not distant metastasis-free survival, disease-free survival (DFS), and overall survival. An exploratory subgroup analysis suggested a potential DFS benefit of PORT in patients with multiple station mediastinal lymph node metastases (5-year DFS, 43.2% vs. 16.6%; P = .037) and squamous cell carcinoma histology (5-year DFS, 70.1% vs. 23.3%; P = .011).ConclusionsEven in the setting of adjuvant chemotherapy, PORT significantly increased LRC for patients with curatively resected pN2 NSCLC. Some subgroups appear to benefit from PORT in terms of DFS and LRC. Individualized strategies based on risk factors might be considered.     

Radiotherapy versus chemotherapy plus radiotherapy in surgically treated IIIA N2 non-small-cell lung cancer

Preoperative chemotherapy in patients with stage III non-small-cell lung cancer (NSCLC) remains controversial. Phase II trials utilizing preoperative chemotherapy in selected patients have achieved complete resection rates of 50%-70% with 3-5 year failure-free survival rates of 15%-33%. Between October 1992 and November 1994, 57 adults (50 of whom were evaluable) with surgically staged IIIA NSCLC and pathologically documented ipsilateral mediastinal nodal involvement (N2) were enrolled in a Cancer and Leukemia Group B randomized trial. Preoperative therapy was thought to be critical to facilitating surgical resectability. For patients randomized to the radiotherapy/surgery/radiotherapy (RSR) arm (n = 24), treatment consisted of preoperative radiation therapy (RT) at 40 Gy, surgery, and then additional RT at 14-20 Gy. For patients randomized to the chemotherapy/surgery/chemotherapy/radiotherapy (CSCR) arm (n = 26), treatment consisted of 2 cycles of cisplatin/etoposide with filgrastim support (PE) followed by surgery, 2 more cycles of PE, then RT 54-60 Gy. The total dose of RT on either arm was 54 Gy if completely resected or 60 Gy if incompletely resected or unresected. Clinical characteristics were well balanced between the two arms. Thoracotomy was performed in 42 patients (84%), 28 (67%) of whom had complete resection. The median failure-free and overall survival rates were 12 months (95% confidence interval [CI], 9-23 months) and 23 months (95% CI, 19 months-infinity) for the RSR arm and 11 months (95% CI, 5-20 months) and 18 months (95% CI, 12-32 months) for the CSCR arm. The rates of overall and complete surgical resection, downstaging of nodal involvement, and failure-free (P = 0.92) and overall survival (P = 0.41) did not differ between the two treatment arms. Moreover, in this trial, the chemotherapy regimen was sufficiently toxic to have had a lower completion rate of prescribed therapy in the CSCR arm than in the RSR arm.     

Postoperative adjuvant chemotherapy for non-small cell lung cancer

Patients with completely resected non-small-cell lung cancer (NSCLC) are subjects for postoperative adjuvant treatment. Recently, several randomized trials with a large number of enrolled patients have shown that platinum-based chemotherapy has potential for improving survival among patients with completely resected NSCLC in Western countries. In Japan, uracil-tegafur was also shown to improve survival among patients with completely resected stage I adenocarcinoma. This review evaluated the role of adjuvant chemotherapy, based on the results of randomized trials and meta-analyses.     

A phase III study of surgical resection and paclitaxel/carboplatin chemotherapy with or without adjuvant radiation therapy for resected stage III non-small-cell lung cancer: Cancer and Leukemia Group B 9734

PURPOSE: Patients with completely resected stage IIIA (N2) non-small-cell lung cancer (NSCLC) are at substantial risk for locoregional and systemic recurrence. Adjuvant chemotherapy has recently improved overall control for these patients. We added adjuvant chemotherapy to control presumed micrometastatic disease and then randomized patients to receive radiation therapy (RT) or observation to determine the benefit of local radiation consolidation. PATIENTS AND METHODS: Patient eligibility required histologically documented stage IIIA (radiographically occult N2) NSCLC that was completely resected, with no known residual disease, surgical staging per protocol requirements, Cancer and Leukemia Group B performance status of 0/1, no previous chemotherapy or RT, and minimal laboratory values. All eligible patients received 4 cycles of paclitaxel 200 mg/m2 over 3 hours with carboplatin at an area under the curve of 6 on days 1, 22, 43, and 64 beginning 4-8 weeks after surgery. Two to 4 weeks after chemotherapy, patients were randomized to receive RT as 5000 cGy in 25 fractions over 5 weeks or observation. RESULTS: The study closed after 2 years because of slow accrual. Forty-four patients entered the study; 2 were ineligible, and 5 were not randomized because of progression, adverse reaction, or patient withdrawal. Thirty-seven patients were the basis of this analysis. Median failure-free survival was 16.8 months on the observation arm and 33.7 months on the RT arm, with a 1-year survival rate of 72% on the observation arm and 74% on the RT arm. There were no statistical differences between the observation and RT arms for failure-free survival or overall survival. CONCLUSION: In this small study, consolidation RT after complete resection and adjuvant chemotherapy in stage IIIA NSCLC did not significantly improve outcome for this high-risk population.     

Efficacy of postoperative adjuvant therapy for resected non-small cell lung cancer--an evidence-based review

Efficacy of postoperative adjuvant therapy for non-small cell lung cancer (NSCLC) was examined based on recent evidence. In 2003, when a clinical guideline for lung cancer had been published, the efficacy of postoperative adjuvant therapy had not been established. However, results of randomized controlled studies and metaanalysis on the efficacy of postoperative chemotherapy, platinum-based chemotherapy or UFT, were presented at the annual meetings of the American Society of Clinical Oncology (ASCO) held in 2003-2005. Thus, postoperative adjuvant chemotherapy for completely resected NSCLC cases is now a standard care of therapy.     

术后放疗在Ⅲ(pN2)期EGFR基因野生型肺腺癌辅助化疗患者中价值

目的:探讨Ⅲ(pN 2)期表皮生长因子受体(EGFR)基因野生型肺腺癌完全切除并辅助化疗患者术后放疗(PORT)的价值及预后影响因素。 方法:回顾性分析2009—2016年间郑州大学附属肿瘤医院完全切除的Ⅲ(pN 2)期EGFR基因野生型肺腺癌患者172例,均接受>4个周期含铂两药联合...     

Current development of adjuvant treatment of non-small-cell lung cancer

Although radical surgery remains the mainstay therapeutic modality for early-stage non-small-cell lung cancer (NSCLC), long-term survival of patients with completely resected NSCLC tumors remains suboptimal. Globally, the 5-year survival rate of patients who undergo complete surgical resection is in the range of 40%-50%. The majority of postsurgical relapses are represented by distant metastases, with the risk of a local recurrence being < 10%. Postoperative treatments, including chemotherapy, radiation therapy, or both, have been widely evaluated during recent decades. After almost 2 decades of disappointing results, the positive outcomes of 3 randomized studies have recently generated new hopes for a significant impact on survival by adjuvant chemotherapy. The 2 largest randomized studies of adjuvant chemotherapy in all stages (I-IIIA) of completely resected NSCLC that were adequately powered to detect small differences in survival yielded partially conflicting results but indicated that, if any benefit from adjuvant chemotherapy exists, it is approximately 5% at 5 years, as previously anticipated by a metaanalysis. More recently, 2 other randomized studies in selected subgroups of patients (one selectively performed in stage IB disease, the other in stage IB/II disease) indicate an unexpected significant benefit of approximately 15% at 5 years. Potential confounding factors may have contributed to such a significant benefit. A feature common to all these trials is the suboptimal therapeutic compliance to adjuvant chemotherapy, suggesting the need for careful selection of patients to be considered for adjuvant treatment. Genomic- and proteomic-driven chemotherapy as well as molecularly targeted therapies may represent additional areas of near-future clinical investigations.     

An Updated Review on Radiation Treatment Management in Thymus Cancers

This narrative review aims to summarize the currently available evidence for the role of radiation in the treatment of thymus cancers. Thymus cancers are rare, heterogeneous tumors with limited evidence to guide their clinical management. There remains some controversy over the role of radiation in the adjuvant and induction/definitive setting. We performed a systematic search of the MEDLINE/PubMed database, focusing on studies published within the last 30 years. Our search queried “thymoma [OR] thymic carcinoma [AND] radiation” and was limited only to prospective and retrospective studies and metanalyses, omitting books, documents, and reviews. Our search resulted in 174 total references, of which only 31 references were within the scope of interest ranging from 1988 to 2021. For resectable disease, there is prospective evidence to support the avoidance of postoperative radiation (PORT) in completely resected Masaoka stage I thymoma, but there is a lack of prospective evidence guiding the use of PORT in other situations. Several retrospective studies and metanalyses have suggested a benefit with PORT for positive margins and advanced stage disease, although it remains controversial whether PORT is beneficial for all completely resected Masaoka stage II thymoma. For unresectable disease, induction chemotherapy followed by reassessment of resectability is the preferred management. Prospective evidence exists to support the use of induction chemoradiation for patients unable to tolerate anthracycline-based chemotherapy and the use of definitive chemoradiation for those unable to undergo surgery. An effective multidisciplinary approach is the optimal strategy for achieving the best outcomes in patients with thymus cancers.     

A randomized trial comparing adjuvant chemotherapy versus surgery alone for completely resected pN2 non-small cell lung cancer (JCOG9304)

The purpose of this study was to evaluate the efficacy of adjuvant chemotherapy with three courses of cisplatin and vindesine, in comparison to observation only, for N2 non-small cell lung cancer that had been completely resected. Patients with pathologically demonstrated mediastinal lymph node metastasis (N2), who had undergone complete resection, were randomized to observation or adjuvant chemotherapy (cisplatin 80 mg/m2 on day 1; vindesine 3 mg/m2 on days 1 and 8: x3 courses). Cycles started within 6 weeks after complete resection and were repeated every 4 weeks. This trial was terminated before accumulation of the planned numbers for registration because of a slow accrual rate. A total of 119 patients were randomized (59 patients in the adjuvant arm and 60 with surgery alone). The median survival was 36 months for both groups. Postoperative cisplatin with vindesine chemotherapy was not shown to be efficacious in cases of completely resected N2 non-small cell lung cancer in this setting of timing, dose and agents studied.