Metachronous Second Primary Lung Cancer Research Articles

Real-World Survival Comparisons Between Radiotherapy and Surgery for Metachronous Second Primary Lung Cancer and Predictions of Lung Cancer-Specific Outcomes Using Machine Learning: Population-Based Study.

Metachronous second primary lung cancer (MSPLC) is not that rare but is seldom studied. We aim to compare real-world survival outcomes between different surgery strategies and radiotherapy for MSPLC. This retrospective study analyzed data collected from patients with MSPLC between 1988 and 2012 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) analyses and machine learning were performed to compare variables between patients with MSPLC. Survival curves were plotted using the Kaplan-Meier method and were compared using log-rank tests. A total of 2451 MSPLC patients were categorized into the following treatment groups: 864 (35.3%) received radiotherapy, 759 (31%) underwent surgery, 89 (3.6%) had surgery plus radiotherapy, and 739 (30.2%) had neither treatment. After PSM, 470 pairs each for radiotherapy and surgery were generated. The surgery group had significantly better survival than the radiotherapy group (P<.001) and the untreated group (563 pairs; P<.001). Further analysis revealed that both wedge resection (85 pairs; P=.004) and lobectomy (71 pairs; P=.002) outperformed radiotherapy in overall survival for MSPLC patients. Machine learning models (extreme gradient boosting, random forest classifier, adaptive boosting) demonstrated high predictive performance based on area under the curve (AUC) values. Least absolute shrinkage and selection operator (LASSO) regression analysis identified 9 significant variables impacting cancer-specific survival, emphasizing surgery's consistent influence across 1 year to 10 years. These variables encompassed age at diagnosis, sex, year of diagnosis, radiotherapy of initial primary lung cancer (IPLC), primary site, histology, surgery, chemotherapy, and radiotherapy of MPSLC. Competing risk analysis highlighted lower mortality for female MPSLC patients (hazard ratio [HR]=0.79, 95% CI 0.71-0.87) and recent IPLC diagnoses (HR=0.79, 95% CI 0.73-0.85), while radiotherapy for IPLC increased mortality (HR=1.31, 95% CI 1.16-1.50). Surgery alone had the lowest cancer-specific mortality (HR=0.83, 95% CI 0.81-0.85), with sublevel resection having the lowest mortality rate among the surgical approaches (HR=0.26, 95% CI 0.21-0.31). The findings provide valuable insights into the factors that influence cumulative cancer-specific mortality. Surgical resections such as wedge resection and lobectomy confer better survival than radiation therapy for MSPLC, but radiation can be a valid alternative for the treatment of MSPLC.

Enhanced Survival with Lymphadenectomy in Early-Stage Metachronous Second Primary Lung Cancer: A Retrospective Analysis

Introduction: Lymphadenectomy is a cornerstone in the surgical management of resectable primary lung cancer. However, its prognostic significance in early-stage metachronous second primary lung cancer (MSPLC) remains poorly understood. This retrospective study aimed to evaluate the prognostic impact of lymphadenectomy in these patients using data from the Surveillance, Epidemiology, and End Results (SEER) Database. Methods: A retrospective cohort study was conducted using data from the SEER Database for patients surgically treated for stage I MSPLC between 2004 and 2015. Propensity score-matching was employed to create comparable cohorts, and the Cox proportional hazards model was utilized to estimate the hazard ratio (HR) for overall survival after lymphadenectomy compared to non-lymphadenectomy. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. Results: Among 920 identified patients with MSPLC, 574 (62.4%) underwent lymphadenectomy. Propensity score-matching yielded 255 patients in both the lymphadenectomy and non-lymphadenectomy groups. Over a median follow-up of 38 months, the 5-year overall survival probability after a diagnosis of MSPLC was 58.7% in the lymphadenectomy group and 43.9% in the non-lymphadenectomy group (HR: 0.76; 95% confidence interval 0.64–0.90; p = 0.002). Conclusion: In this population-based study, lymphadenectomy is associated with prolonged overall survival in patients with stage I MSPLC. These findings suggest the potential benefit of incorporating lymphadenectomy into the surgical management of MSPLC, providing valuable guidance for thoracic surgeons in clinical decision-making.

Prognostic Nomogram and Therapeutic Option of Cancer-Specific Death in the Patients with Metachronous Second Primary Lung Cancer.

With the increase of long-term primary lung cancer survivors, studies focused on metachronous second primary lung cancer (SPLC) have become very urgent. This study aimed to develop a prognostic nomogram and determine therapeutic options of cancer-specific death for patients with metachronous SPLC with and without the competing risk of other-specific death. Study population came from the SEER-18 database between 2006 and 2016. According to the clinical practice guideline of SPLC, the interval time of IPLC and metachronous SPLC was set to 4 years. We constructed nomograms with Lasso + Cox regression model and competing risk model to predict the prognosis and identify therapeutic options of metachronous SPLC patients with the assessment of model performance by the C-index, calibration plot, and decision curve analysis. In addition, two subgroup analyses stratified by histology and tumor size were used to better select therapeutic options for a certain population. 1300 patients with metachronous SPLC were incorporated in this study with 50.1% of the 5-year cumulative incidence in cancer-specific death. Compared with Lasso + Cox regression analysis, competing risk analysis harbored a higher C-index (0.811 vs. 0.76) and better net benefit in predicting cancer-specific death of metachronous SPLC. Two statistical analyses suggested that surgery alone was a preferentially therapeutic option of metachronous SPLC, whereas the effect of surgery + radiation in treating metachronous SPLC was similar to radiation alone. Subgroup analyses indicated that patients with metachronous SPLC were considered receiving different therapeutic options in different histology and tumor size but preferred to receive surgical treatment as the first choice. For primary lung cancer survivors, aggressive surgical treatment was the first-line selection of metachronous SPLC, followed by radiation alone, surgery + radiation, and no surgery + radiation.

Surgical outcomes of ipsilateral metachronous second primary lung cancer.

The optimal surgical approach for metachronous second primary lung cancer (MSPLC), especially ipsilateral MSPLC, remains unclear. This study aimed to review postoperative complications and examine surgical outcomes based on the extent of resection after surgery for ipsilateral MSPLC. Clinical data from 61 consecutive patients who underwent pulmonary resection for ipsilateral MSPLC according to the Martini-Melamed criteria between January 2005 and December 2017 in 3 institutes were retrospectively reviewed. Postoperative complications were identified in 12 patients (19.7%). Regarding the combination of initial and second surgery, intraoperative bleeding was significantly greater in patients with anatomic-anatomic resection than in others (P < 0.001). Operation time was significantly longer in patients with anatomic-anatomic resection than in others (P < 0.001). However, postoperative complications showed no significant differences based on the combination of surgeries. Five-year overall survival rates in patients with anatomic resection and wedge resection after second surgery were 75.8% and 75.8%, respectively (P = 0.738), and 5-year recurrence-free survival rates were 54.2% and 67.6%, respectively (P = 0.368). Cox multivariate analysis identified ever-smoker status (P = 0.029), poor performance status (P = 0.011) and tumour size >20 mm (P = 0.001) as independent predictors of poor overall survival, while ever-smoker status (P = 0.040) and tumour size >20 mm (P = 0.007) were considered independent predictors of poor recurrence-free survival. Regarding postoperative and long-term outcomes for patients with ipsilateral MSPLC, surgical intervention is safe and offers good long-term survival. Wedge resection is an acceptable provided tumours ≤2 cm and ground-glass opacity-predominant as a second surgery for early-stage ipsilateral MSPLC.

Extent of resection and lymph node evaluation in early stage metachronous second primary lung cancer: a population-based study.

BackgroundEvidence of the optimal surgery strategy for early stage metachronous second primary lung cancer (SPLC) has been limited and controversial. This study aims to compare the survival outcomes of different extents of resection and lymph node evaluation in these patients.MethodsEarly stage metachronous SPLC patients, who had received lobectomy for initial primary lung cancer (IPLC) and developed SPLC more than 3 months later, were selected from the Surveillance, Epidemiology, and End Results (SEER) database according to the American College of Chest Physicians (ACCP) guideline. Overall survival (OS) and lung cancer-specific survival (CSS) of different extents of resection and lymph node evaluation were analyzed using Kaplan-Meier method and multivariate Cox regression model.ResultsOverall, 1,784 SPLC patients without nodal or distant metastasis were identified. Lobectomy was associated with significantly longer OS (HR: 0.83, 95% CI: 0.71–0.97, 5-year survival: 59.2% vs. 53.3%, P=0.02) and CSS (HR: 0.72, 95% CI: 0.60–0.88, 5-year survival: 71.5% vs. 63.2%, P=0.001) compared with sublobar resection. In addition, examined lymph node number ≥10 demonstrated longer OS (HR: 0.63, 95% CI: 0.50–0.81, 5-year survival: 66.6% vs. 53.9%, P<0.001) and CSS (HR: 0.54, 95% CI: 0.40–0.74, 5-year survival: 77.4% vs. 64.7%, P<0.001) compared with an examined lymph node number <10. The survival benefits of lobectomy and examined lymph node number ≥10 were further validated in multivariate Cox regression and subgroup analysis stratified by tumor size.ConclusionsLobectomy and thorough lymph node evaluation provided significantly longer survival, and thus should be considered for early stage metachronous SPLC whenever possible.

Radiotherapy was associated with the lower incidence of metachronous second primary lung cancer

Our study aims to estimate the incidence of metachronous second primary lung cancer(SPLC) in initial primary lung cancer(IPLC) survivors and to determine whether radiotherapy affects the risk of metachronous SPLC in the first five years after the diagnosis of lung cancer. Incidence data of IPLC individuals who survived ≥2 years were obtained from SEER-18 database in 2004–2007. Joinpoint regression analysis and competing risk analysis were used to calculate the incidence of metachronous SPLC. Propensity score matching and decision analysis were available to estimate the effect of radiotherapy on metachronous SPLC. 264 of 11657 IPLC survivors with radiotherapy and 1090 of 24499 IPLC survivors without radiotherapy developed metachronous SPLC during 5-year follow-up, respectively. In joinpoint regression analysis, the 5-year incidence of metachronous SPLC in the radiotherapy group was lower than that in the nonradiotherapy group(2385 per 100,000 vs 4748 per 100,000, HR = 0.43,95% CI:0.39–0.47). Competing risk analysis showed that the survivors with radiotherapy were associated with the lower 5 year incidence of metachronous SPLC compared with those without radiotherapy(2.28% vs 4.47%, HR = 0.49,95% CI:0.43–0.57). Through propensity score matching, 4077 pairs of survivors were available to further study that radiotherapy potentially decreased the risk of developing metachronous SPLC with the adjustment of various factors(2.5% vs 3.3%, HR = 0.72, 95% CI:0.55–0.96). Decision analysis suggested that radiotherapy was a negative independent risk factor of metachronous SPLC with clinical net benefit in a range of risk thresholds (2% to 5%). Survivors of IPLC with radiotherapy likely had a low risk of metachronous SPLC during the first five years follow-up, especially non-small cell lung cancer.

Characteristics of metachronous second primary lung cancers

AIM: In this study, we aimed to investigate the characteristics of metachronous second primary lung cancer (MSPLC) and the differences between primary lung cancer (PLC) and metachronous lung cancer. MATERIALS AND METHODS: Patients diagnosed with lung cancer between January 2014 and December 2016 were retrospectively studied. MSPLC tumor cases and a new diagnosis of PLC were evaluated. Clinical, radiological, and demographic findings of the two groups, previous histopathologic diagnosis of MSPLC, histopathologic diagnosis of lung cancer in both groups, stages of treatment, and treatment history were recorded. All data were analyzed using the Chi-square, t-test, Kaplan–Meier, and Log-rank method. In all tests, P RESULTS: There were 53 (16.1%) cases in MSPLC group and 277 (83.9%) cases in the PLC group. There were no statistically significant differences between clinical, radiological, and demographic findings, cancer histopathologies, tumor stages, oncological, and surgical treatment characteristics of the cases (P > 0.05). The most frequent primary cancers were laryngeal carcinoma (11 cases) in the MSPLC group, with higher age (64 and 61, P = 0.01, respectively). Tumor size was smaller (44 mm and 52 mm, respectively) than the PLC group (P = 0.03). All other characteristics of both groups (P > 0.05) and survival were similar (15 months and 17 months, P = 0.87, respectively). CONCLUSION: Among the lung cancers diagnosed in our clinic, 16% were detected as MSPLC. MSPLC group were older than the PLC group and tumor size is lower than the PLC group. There was no significant difference in treatment options and survival between the two groups.

Incidence trends and risk prediction nomogram of metachronous second primary lung cancer in lung cancer survivors.

BackgroundThis study was designed to estimate the trends in 5-year incidence of metachronous second primary lung cancer(SPLC) and to establish a risk prediction model to identify candidates who were at high risk of developing metachronous SPLC.MethodsIncidence data between 2004 and 2007 were obtained from SEER database, including 42453 participants who survived ≥ 2 years after the initial diagnosis of lung cancer. Joinpoint regression analysis was used to calculate the 5-year incidence rates of metachronous SPLC per 100 000 population. Related risk factors of the survivors who developed MSPLC during five years were identified through logistic regression analysis, followed by establishment of risk prediction nomogram. Discrimination (C-index), calibration and decision analysis were further performed to assess the validation and clinical net benefit of risk prediction nomogram.ResultsA total of 1412 survivors with lung cancer developed MSPLC during five years, with 3546 per 100 000 population of age-adjusted 5-year incidence. Age, histology, tumor stage, and radiation were recognized as risk factors of metachronous SPLC, as indicated by logistic regression analysis. The risk prediction nomogram of metachronous SPLC harbored moderate discrimination(C-index = 0.67) and good calibration, with the risk of 0.01 to 0.11.The decision curve analysis showed that clinical net benefit of this risk prediction nomogram in a range of risk thresholds (0.01 to 0.06) was higher compared to all-screening or no-screening strategies.ConclusionsCollectively, the cumulative risk of metachronous SPLC of the survivors increased over time. The risk prediction nomogram was available to select high-risk survivors who should regularly undergo computed tomography screening.

Lobectomy Versus Sublobectomy in Metachronous Second Primary Lung Cancer: A Propensity Score Study

The optimal surgical approach for metachronous second primary lung cancer (MSPLC) has not been well established yet. In this study, survival outcome of lobectomy was compared with sublobectomy for MSPLC. A retrospective study was conducted based on the Surveillance, Epidemiology, and End Results database. Propensity score matching was used to reduce the potential bias caused by the variance of the clinicopathologic features of the first and second lung cancer. The effect of lobectomy and sublobectomy for MSPLC was assessed and explored in subgroup analyses. We identified 1,392 MSPLC patients, and 454 pairs of patients were matched. Lobectomy was associated with a significantly better survival (p= 0.023). Subgroup analyses showed that lobectomy achieved a significantly better prognosis if previous lung cancer was stage I, whereas sublobectomy had advantages in patients with initial stage III cancer. Moreover, patients with lobectomy had a significantly better prognosis in N0 disease but not in N1 or N2. Stratified by tumor size, the prognosis of sublobectomy was comparable to lobectomy for tumors sized 1 cm or smaller. Lobectomy was associated with a better survival in tumors sized 1 to 2 cm, although without statistical significance. For tumors sized 2 to 3 cm, lobectomy conferred a significantly better survival. This study indicates that lobectomy is still a valid choice for MSPLC. Sublobectomy has value and shows equivalency in tumors sized 2 cm or smaller. For patients with advanced disease or at high risk, additional studies are needed to explore the value of sublobectomy.

Surgical Treatment of Metachronous Second Primary Lung Cancer

Many studies have demonstrated that patients with metachronous second primary lung cancer (MSPLC) benefit from surgery. Owing to the lack of uniform criteria and prospective randomized trials, the extent of resection remains controversial, and prognostic factors are still not fully clear. The present study aimed to assess surgical treatment of MSPLC and identify prognostic factors of outcome. This retrospective analysis included 143 patients who underwent surgical resection of MSPLC in our department from January 2006 to December 2011. Predictors of postoperative complications were analyzed with the binary logistic regression method. Survival was analyzed with Kaplan-Meier and Cox regression methods. Operative mortality was 1.4%, and the complication rate was 34.3%. Age more than 70 years was an independent risk factor for postoperative complications. The overall 5-year survival after resection of MSPLC was 54.5%. TNM stage II or higher (p= 0.025), 20or more pack-years of smoking (p= 0.037), and tumor size greater than 2 cm (p= 0.033) were independent negative prognostic factors for survival. For stage I disease, completion pneumonectomy had a lower 5-year survival rate than others, 44.8% and 65.9, respectively (p= 0.039); lobectomy and sublobar resection have a 5-year survival of 77.1% and 56.7%, respectively (p= 0.203). Surgical treatment of MSPLC is safe and effective. TNM stage I, tumor size 2 cm or less, or less than 20 pack-years smoking are predictors of improved survival. Sublobar resection is acceptable. For stage I disease, lobectomy tends to be associated with better survival than sublobar resection, although the difference is not significant, and completion pneumonectomy is not recommended. Long-term follow-up is necessary even after curative resection of lung cancer.

Surgical treatment of metachronous second primary lung cancer after complete resection of non–small cell lung cancer

To clarify the perioperative and oncologic outcome of pulmonary resection for a metachronous second primary lung cancer (MSPLC) following resection of an initial non-small cell lung cancer (NSCLC). Retrospective chart review identified 161 patients (88 men and 73 women) with a median age of 70 years (range, 34-88 years) who underwent pulmonary resection for MSPLC between January 2000 and December 2009. Operative morbidity, mortality, and relevant factors were analyzed with χ(2) test or Fisher exact test and Mann-Whitney U test. Survival was analyzed with Kaplan-Meier and Cox proportional hazard method. The median interval between the initial and subsequent resection for MSPLC was 42.7 months (range, 7-205 months). There was no operative mortality and postoperative complication rate was 29%. In multivariate analysis, ipsilateral operation (P = .0002) and a lower predicted preoperative percent forced expiratory volume in the first second (P = .0035) were significant risk factors for postoperative complications. Five-year overall survival rates after resection of the initial and second metachronous NSCLC were 87.4% and 60.8%, respectively. Significant negative long-term prognostic factors for survival following resection of a MSPLC in multivariate analysis were tumor size >2 cm (P = .003) and number of pack years of smoking (P = .005). Metastatic nodal disease (P = .19) or a sublobar resection (P = .17) were not associated with worse survival. Surgical treatment of a MSPLC can be undertaken with 5-year survival rate of 60%. Expected operative morbidity and mortality are comparable to primary surgery. Tumors 2 cm or smaller are associated with improved survival and freedom from recurrence. Close long-term follow-up of patients who have undergone resection of NSCLC is recommended.

Characteristics and outcome of patients with second primary lung cancer

Patients with lung cancer are at risk of developing a second primary lung cancer (SPLC). However, the characteristics of patients at risk remain largely speculative. We reviewed 2816 lung cancer patients from our institution for the occurrence of SPLC. Any SPLC was categorised as synchronous when diagnosed within 2 years of the first primary lung cancer (FPLC) and after direct histological comparison of both tumours. All other SPLCs were considered as metachronous. 139 patients developed a second malignancy including 69 nonsmall cell lung cancer (NSCLC) and 9 small cell lung cancer. The median interval for diagnosis of metachronous SPLC (n=59) after FPLC occurrence was 72 months. SPLC detected within 5 years of FPLC diagnosis had a more favourable stage distribution (p=0.02). After diagnosis of SPLC, patients had a superior median overall survival compared to controls (57.7 versus 18.1 months; p<0.0001). Interestingly, comparing only stage IV NSCLC patients, a history of FPLC was also associated with a favourable survival (median 27.4 versus 8.97 months; p=0.007). In summary, previous lung cancer treatment does not lead to impaired prognosis after diagnosis of SPLC. Improved surveillance programmes beyond 5 years after FPLC treatment may result in more favourable disease stages for detected SPLC.

Second primary lung malignancy in head and neck cancer patients

Second primary lung cancer (SPLC) is generally of poor prognosis in patients presenting with head and neck cancer. Between January 2000 and June 2008, 39 patients with head and neck squamous-cell carcinoma (HNSCC) patients diagnosed with SPLC were included. Fourteen SPLC were classified as synchronous and 25 as metachronous. SPLC and HNSCC staging correlated (P=0.0496). Patients with metachronous tumor showed longer median overall survival than those with synchronous tumor (92.9 months versus 15.7 months; Hazard ratio (HR), 0.323; 95% CI, 0.042-0.559; P=0.0045). In the subgroup of 11 patients with SPLC diagnosed more than 5 years after HNSCC, prognosis was better (128.1 versus 29.7 months; HR, 0.288; 95% CI, 0.053-0.353; P<0.0001). In the present study, in contrast to the literature, improved prognosis and survival were found in the subgroup in which SPLC developed more than 12 months after initial HNSCC diagnosis, and even more specifically in that in which SPLC developed more than 5 years after initial HNSCC diagnosis. SPLC in HNSCC is generally described as unequivocally aggressive and of poor prognosis. Metachronous SPLC, however, especially when diagnosed more than 5 years after HNSCC, was clearly associated with better prognosis.

Primary lung cancer after treatment of head and neck cancer without lymph node metastasis: Is there a role for autofluorescence bronchoscopy?

Head and neck cancer (HNC) is the 5th most common cancer worldwide. As good locoregional tumor control can be achieved with current treatment strategies, patients who develop second primary tumors from field cancerization have poorer prognosis. To determine if autofluorescence bronchoscopy (AF) played a role in the detection of second primary lung cancer (SPLC), and impact of SPLC on survival of patients with HNC and no cervical lymph node metastasis (N0). Patients with HNC(N0) referred for symptoms and/or radiology suspicious for lung cancer were assessed with AF. Data on patient demographics, smoking, cancer characteristics, and outcome were prospectively collected. Fifty-one patients (44 males) with curatively treated HNC(N0) were evaluated. Median age was 70 years, all were current or former smokers of 35 pack years, and 25 had chronic obstructive lung disease. Over a median follow up of 60 months, 8 patients were diagnosed with synchronous and 26 with metachronous SPLC. Forty-two SPLC were found; 12 (29%) affected the tracheobronchial tree and 30 (71%) involved the lung parenchyma. Median time to metachronous SPLC was 22 months. Most of SPLC were surgically resectable. Five radiographically occult lung cancers detected by AF were successfully treated with endobronchial therapy. Lung cancer mortality was 24%. HNC patients who developed synchronous and metachronous SPLCs had significantly shorter survival (51 and 144 months) compared to those without (240 months) (p=0.0005). SPLC impacted negatively on the survival of patients with HNC. Close surveillance with AF and CT for SPLC combined with aggressive treatment of early stage lung cancer might be a strategy to improve outcome.

The management of second primary lung cancers. A single centre experience in 15 years.

In patients treated for an initial lung cancer, the cumulative risk of developing a second primary lung cancer is a recognised occurrence. This study reviews our experience in the clinical assessment and surgical management of second primary lung cancer (SPLC). Between 1985-1999 a series of 892 patients with primary carcinoma of lung underwent surgical resection with curative intent in our institution. Using criteria set out by Martini and Melamed (J Thorac Cardiovasc Surg 70 (1975) 606) we were able to identify 51 patients who had developed a SPLC identified as the first site of re-occurrence. Forty-one patients developed a metachronous SPLC within a mean of 46+/-14 months of the first operation while ten patients had synchronous double lung cancer (six unilateral, four bilateral). The cumulative probability of cancer free interval for metachronous cancers was 39% at 3 years, 15% at 5 years and 2% at 10 years. There were three postoperative deaths among the metachronous cancers (7.5%) and there were no operative deaths among patients with synchronous cancers. The overall actuarial 5-year survival for all patients with SPLC was 38% with a median survival of 40 months (range 1-142 months). The actuarial 5-year survival for metachronous SPLC was 44%, median survival of 49 months (range 1-142 months), while the actuarial 5-years survival for synchronous SLPC was 10% with a median survival of 31 months (range 4-78 months). Aggressive assessment and surgical intervention is safe, effective and warranted in patients with a second lung primary cancer if they satisfy the usual criteria of operability after full assessment. This is true for patients with metachronous cancers, while patients with synchronous cancers tend to have worse prognosis. A long term follow-up policy after the initial resection of the primary lung cancer is recommended at intervals of 6 months for at least 3-5 years and then annually to enable the early detection of the second cancer.

Second primary lung cancer

We reviewed our experience with second primary lung cancer (SPLC) at the Little Rock Veterans Affairs Medical Center from 1966 to 1993. Fifty-four patients were found to have 65 such lesions after 1,572 "curative" resections for lung cancer (4.1%). Eleven patients had at least a third primary tumor (3 having more). Metachronous SPLCs comprised 60% (39/65) and synchronous 40% (26/65). The mean interval between first and second tumors was 54.63 +/- 8 (standard error) months (range, 5 to 218 months), and that between second and third was 26.1 +/- 7.4 (standard error) (range, 5.5 to 51 months). Squamous cell carcinoma comprised 58.4% (38/65), adenocarcinoma 30.8% (20/65), and small cell carcinoma 10.8% (7/65). Histology of the SPLC was the same as that of the first tumor in 50.7% (33/65). Stage I primary tumors comprised 76% (41/54) of index tumors, 61.1% (33/54) of SPLCs, and 72.2% (8/11) of third primary tumors. Second primary lung cancer followed minimal resection in 44% (24/54), lobectomy in 37% (20/54), and pneumonectomy in 13% (7/54) of cases. There was no evidence that minimal resection for the first primary tumor predisposed to SPLC. After 1983 the majority of SPLCs were diagnosed with computed tomographic scanning. After resection of SPLCs, survival rates at 3 and 5 years were 26% and 18%, metachronous 39% and 23.4%, and synchronous 12.25% and 12.25%.