Role of postoperative radiotherapy in resected non-small cell lung cancer: a reassessment based on new data

In completely resected non-small cell lung cancer (NSCLC) patients with pathologically involved mediastinal lymph nodes (N2), 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) in this group of patients remains controversial. The PORT meta-analysis published in 1998 concluded that adjuvant radiotherapy was detrimental to patients with early-stage completely resected NSCLC, but that the role of PORT in the treatment of tumors with N2 involvement was unclear, and that further research was warranted. Recent retrospective and nonrandomized studies, as well as subgroup analyses of recent randomized trials evaluating adjuvant chemotherapy, provide evidence of the possible benefit of PORT in patients with mediastinal nodal involvement. The role of PORT is also a valid question in patients with proven N2 disease who have undergone only induction chemotherapy followed by surgery, because the local recurrence rate for such patients varies in the range of 20%-60%. Based on the currently available data, PORT should be discussed for fit patients with completely resected NSCLC with N2 nodal involvement, preferably after completion of adjuvant chemotherapy. There is a need for new randomized evidence to evaluate PORT using the modern three-dimensional conformal radiation technique, with attention paid to reducing the risk for, particularly, pulmonary and cardiac toxicity. A new large multi-institutional randomized trial evaluating PORT in this patient population is needed and 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.     

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。     

Consensus development conference on the medical treatment of non-small cell lung cancer: treatment of the early stages

Surgery remains the mainstay of treatment for early non-small cell lung cancer (NSCLC) but more than 80% of recurrences occur within 2 years from radical surgery. The pattern of recurrence may differ by histology with more local recurrences seen for patients with squamous cell carcinoma and more distant metastases seen in patients with adenocarcinoma. A number of studies demonstrate that dissemination of cancer cells at levels much below those detected by any current available imaging techniques, including PET scanning also, affect prognosis of patients with clinical early-stage NSCLC. The current clinical evidence does not recommend adjuvant chemotherapy and/or radiotherapy in completely resected stage I-II-IIIA for N1. There are few randomised trials available for analysis of neo-adjuvant chemotherapy involving patients with resectable stage III disease; overall these trials suggest that induction chemotherapy (with or without radiation) improves survival, particularly in those patients who undergo significant downstaging. Heterogeneous study populations limit the ability to define the optimal patient population who would most benefit from this approach. There is no conclusive evidence that neo-adjuvant chemotherapy in early NSCLC is associated with an increased post surgical morbility and mortality. Additional trials are needed. More recently neo-adjuvant chemotherapy has been tested in resectable stage I-II NSCLC and proved to be feasible and better tolerated than adjuvant chemotherapy. Several randomised trials are currently ongoing. In the next future the role of targeted biological therapies as agents acting on minimal residual disease should be explored.     

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 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.     

Adjuvant chemotherapy for non-small cell lung cancer

Nearly half of all patients who undergo surgical resection of localized non-small cell lung cancer (NSCLC) will develop and ultimately die of recurrent disease. The postoperative radiotherapy (PORT) meta-analysis showed adjuvant thoracic radiotherapy to have a detrimental effect on survival in this patient population. A meta-analysis of early trials of adjuvant chemotherapy by the Non-Small Cell Lung Cancer Collaborative Group showed that while chemotherapy with alkylating agents was also detrimental, chemotherapy with cisplatin-based adjuvant chemotherapy was associated with an improved hazard ratio for death (HR = 0.87), equating to a 5 percent survival benefit at 5 years. However, the result was not statistically significant (p = 0.08). Recently, results have been reported for several large Phase III trials of adjuvant chemotherapy which differed with respect to the stage of resected disease included, the type of chemotherapy used and the use of post-operative radiotherapy. Three trials (IALT, JBR 10, and ANITA) that utilized cisplatin-based doublets showed a significantly positive survival benefit of adjuvant chemotherapy in patients with Stage II-IIIA NSCLC. The magnitude of this benefit, which was suggested to be 4-5 percent at 5 years in the meta-analysis and by the IALT study, may be as large as 8-15 percent as indicated by more recent studies with modern platinum-based doublet chemotherapy. These data indicate that medically fit patients with resected Stage II-IIIA NSCLC should be offered adjuvant chemotherapy with a modern cisplatin-based doublet.     

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...     

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.     

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.     

Use of postoperative radiotherapy for node-positive non-small-cell lung cancer

The appropriate patient selection for adjuvant radiotherapy after primary surgical therapy of non-small-cell lung cancer (NSCLC) is unclear. Four thousand thirteen patients diagnosed from 1988-1995 in 9 registry areas of the Survival, Epidemiology, and End Results program who received primary surgical therapy for pathologic stage T1-3 N1/2 M0 NSCLC were identified. County-level and patient-specific variables associated with the use of postoperative radiotherapy (PORT) were studied by multivariate logistic regression analysis. Prognostic factors for cause-specific survival (CSS) and overall survival (OS) were determined by Cox multivariate analysis. Overall, 58% of node-positive patients received PORT. Use of PORT was independently associated with younger age, more advanced nodal disease, no prior cancer, less extensive surgery than pneumonectomy, and patient residence close to a radiotherapy facility. In multivariate analysis of the entire node-positive population, there were no differences in OS or CSS with the use of PORT. In the patients with N2 disease, PORT was associated with improved OS (5-year OS: 16% without PORT, 22% with PORT; P = 0.001) and CSS (5-year CSS: 25% without PORT, 30% with PORT; P = 0.02). Additionally, patients with = 4 nodes involved also had an improved survival in association with PORT (5-year OS: 11% without PORT, 18% with PORT; P = 0.001; 5-year CSS: 17% without PORT, 25% with PORT; P = 0.009). Therefore, recognizing the inherent limitations of a retrospective, registry-based analysis, patients with more advanced nodal disease appear to have an improved survival with the use of PORT.     

Clinical significance of the lymph node micro-metastasis in pateints with early stage non-small-cell lung cancer

The postoperative 5-year survival rate is about 50-85% in the patient with the stage I non-small-cell lung cancer (NSCLC). It is remains unclear how we should give these patients adjuvant radiotherapy and chemotherapy after operation. We performed a postspective study to assess the prognostic and treatment guiding significance of lymph nodes micrometastasis (LMM) in patients with completely resected NSCLC at stage I.MATERIALS AND METHODS We collected paraffin-embedded lymph nodes…     

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.     

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.     

Postoperative adjuvant therapy for completely resected early-stage non-small cell lung cancer

Consensus on adjuvant therapy for completely resected non-small cell lung cancer until 2002 was as follows. (1) There was no significant impact of postoperative adjuvant chemotherapy based on meta-analysis and previous clinical trials. (2) Confirmatory studies are necessary in large-scale prospective clinical trials. However, recent mega trials have introduced epoch-making changes for postoperative adjuvant chemotherapy in clinical practice since ASCO 2003. The effectiveness of UFT in N0 patients was confirmed. Patients with completely resected stage I non-small cell lung cancer, especially T2N0 adenocarcinoma, will benefit from adjuvant chemotherapy with UFT. The results of the International Adjuvant Lung Trial (IALT) have confirmed the meta-analysis in 1995. Also, both the JBR10 and Cancer and Leukemia Group B (CALGB) 9633 studies have also confirmed positive IALT results of the benefit for postoperative platinum-based chemotherapy in completely resected non-small cell lung cancer. Adjuvant chemotherapy for pathological stage IB to II, completely resected non-small cell lung cancer is standard care based on clinical trials. UFT showed the strongest evidence for IB in Japan. Platinum doublet chemotherapy with third-generation anticancer agents is also recommended. Adjuvant chemotherapy should be offered as standard care to patients after completely resected early stage non-small cell lung cancer. However, there is no evidence of the feasibility and efficacy for adjuvant chemotherapy with the platinum-based regimen in Japan. Careful management should be necessary in such treatment.The ASCO-JSCO Joint Symposium was held in Kyoto, Japan, on October 29, 2004.     

Toxicities and Deaths From Intercurrent Disease Following Contemporary Postoperative Radiotherapy in Resected Non-Small-Cell Lung Cancer

IntroductionThe role of postoperative radiotherapy (PORT) in patients with resected locally advanced non-small-cell lung cancer (NSCLC) remains controversial due to the radiation techniques used in randomized trials. We conducted a retrospective cohort study evaluating contemporary PORT techniques to evaluate the safety of PORT and risk of death from intercurrent disease .Materials and MethodsWe analyzed consecutive patients with NSCLC treated in a single center that underwent PORT for pN2 disease and/or positive margin, with 3-dimensional conformal radiotherapy (3DRT), intensity modulated radiotherapy , or proton RT (PRT), between 2008 and 2019. Clinical details were collected including intercurrent deaths, defined as death without cancer recurrence. Kaplan-Meier and Cox-Proportional Hazards Models were used.ResultsOf 119 patients, 21 (17.6%) received 3DRT, 47 (39.5%) intensity modulated radiotherapy, and 51 (42.9%) PRT. Median follow-up was 40 months (range 8-136) and median RT dose was 5040cGy. Most patients (65.5%) received sequential adjuvant chemoRT; 18.5% received concurrent chemoRT. The rate of grade 3 toxicities was 9.2%. There were 13 (10.9%) deaths from intercurrent diseases, including 6 from second primary cancers and 2 from cardiopulmonary diseases. There were 2 additional deaths from cardiopulmonary disease in patients with cancer progression at time of death. Mean, V5Gy, V30Gy heart doses and mean lung doses were significantly lower with PRT. Three-year OS and disease-free-survival were 70.1% and 49.9%.ConclusionPORT using contemporary techniques was well tolerated with acceptable toxicity and low rates of intercurrent deaths. Proton therapy significantly reduced heart and lung doses, but radiotherapy modality was not associated with differences in intercurrent disease.     

Neoadjuvant chemotherapy in non small cell lung cancer

Standards of care for non small cell lung cancer (NSCLC) are not, yet, totally established. The role of induction chemotherapy is still debated while it has been established that adjuvant cisplatin based chemotherapy improve overall survival in completely resected patients. We will review the feasibility and efficacy of induction chemotherapy for patients with early-stage and locally advanced NSCLC, particularly with N2 disease. In the neoadjuvant setting, a 32 to 60% response rate is awaited considering the high treatment compliance. Near to 10% pathologic complete response rate is reported. Nevertheless, no large randomised phase III trial has demonstrated that induction chemotherapy could prolong patients overall survival. Suboptimal cytotoxic combinations and an increased surgical mortality might explain this result. Studies suggested that patient's subgroups (as downstaged N2 disease) could benefit from induction treatment. This still need to be confirmed in randomised trial and meta-analysis based on individual data.     

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.