Etsuo Miyaoka

A Japanese Lung Cancer Registry Study: Prognosis of 13,010 Resected Lung Cancers

Purpose: The validation of tumor, node, metastasis staging system in terms of prognosis is an indispensable part of establishing a better staging system in lung cancer. Methods: In 2005, 387 Japanese institutions submitted information regarding the prognosis and clinicopathologic profiles of patients who underwent pulmonary resections for primary lung neoplasms in 1999 to the Japanese Joint Committee of Lung Cancer Registry. The data of 13,010 patients with only lung carcinoma histology (97.6%) were analyzed in terms of prognosis and clinicopathologic characteristics. Results: The 5-year survival rate of the entire group was 61.4%. For the small cell histology (n = 390), the 5-year survival rates according to clinical (c) and pathologic (p) stages were as follows: 58.8% (n = 161) and 58.3% (n = 127) for IA, 58.0% (n = 77) and 60.2% (n = 79) for IB, 47.1% (n = 17) and 40.6% (n = 29) for IIA, 25.3% (n = 38) and 41.1% (n = 29) for IIB, 29.0% (n = 61) and 28.3% (n = 60) for IIIA, 36.3% (n = 19) and 34.6% (n = 40) for IIIB, and 27.8% (n = 12) and 30.8% for IV (n = 13). For the non-small cell histology (n = 12,620), the 5-year survival rates according to c-stage and p-stage were as follows: 77.3% (n = 5642) and 83.9% (n = 4772) for IA, 59.8% (n = 3081) and 66.3% (n = 2629) for IB, 54.1% (n = 205) and 61.0% (n = 361) for IIA, 43.9% (n = 1227) and 47.4% (n = 1330) for IIB, 38.3% (n = 1628) and 32.8% (n = 1862) for IIIA, 32.6% (n = 526) and 29.6% (n = 1108) for IIIB, and 26.5% (n = 198) and 23.1% (n = 375) for IV. Adenocarcinoma, female gender, and age less than 50 years were significant favorable prognostic factors. Conclusion: This large registry study provides benchmark prognostic statistics for lung cancer. The prognostic difference between stages IB and IIA was small despite different stages. Otherwise, the present tumor, node, metastasis staging system well characterizes the stage-specific prognoses.

Japanese lung cancer registry study of 11,663 surgical cases in 2004: demographic and prognosis changes over decade.

Background: The Japan Lung Cancer Society, the Japanese Association for Chest Surgery, and the Japanese Respiratory Society jointly established the Japanese Joint Committee for Lung Cancer Registration, which has regularly conducted lung cancer registries for surgical cases in 5-year periods. We analyzed data obtained in these registries to reveal the most recent surgical outcomes and trends related to lung cancer surgery in Japan. Methods: Using data from the registry in 2010 for cases of surgery performed in 2004, demographics, surgical results, and stage-specific prognoses were analyzed. In addition, trends for those parameters over 10 years were assessed. Results: The 5-year survival rate for all cases (n = 11,663, 7369 males, mean age 66.7 years) was 69.6%. The 5-year survival rates by c-stage and p-stage were as follow: IA, 82.0% (n = 6295) and 86.8% (n = 4978); IB, 66.8% (n = 2339) and 73.9% (n = 2552); IIA, 54.5% (n = 819) and 61.6% (n = 941); IIB, 46.4% (n = 648) and 49.8% (n = 848); IIIA, 42.8% (n = 1216) and 40.9% (n = 1804); IIIB, 40.3% (n = 90) and 27.8% (n = 106); and IV, 31.4% (n = 256) and 27.9% (n = 434), respectively. The percentages of female patients, cases with adenocarcinoma, stage I or II disease, and tumors sized less than 2 cm were increased, while those of operative and hospital deaths were decreased. Furthermore, the prognoses of all cases and cases in each stage improved over the decade. Conclusion: In Japanese cases of lung cancer surgery, demographics, surgical results, and stage-specific prognoses changed over the 10-year study period, while the 5-year survival rate for surgical cases improved to 69.6% in 2004.

Pulmonary Resection in Patients Aged 80 Years or Over with Clinical Stage I Non-small Cell Lung Cancer: Prognostic Factors for Overall Survival and Risk Factors for Postoperative Complications

Introduction: This retrospective study was designed to identify the predictors of long-term survival and the risk factors for complications after surgery in patients aged 80 years or older with clinical (c)-stage I non-small cell lung cancer. Methods: The Japanese Joint Committee of Lung Cancer Registry collated the clinicopathological profiles and outcomes of 13,344 patients who underwent pulmonary resection for primary lung cancer in 1999. The data of 367 patients aged 80 years or older with c-stage I non-small cell lung cancer were analyzed for prognostic factors and risk factors for postoperative complications. Results: The median age was 82 years (range, 80-90 years). Of the total patient number, 102 (27.8%) had some form of comorbidity diagnosed preoperatively. Thirty-one (8.4%) patients presented with postoperative complications, and the operative mortality was 1.4%. The 5-year survival rates were 55.7% for c-stage I patients, 62.0% for c-stage IA, and 47.2% for c-stage IB. Advanced pathologic stage and comorbidity were significant independent predictors of shortened survival (p < 0.0001 and p = 0.032, respectively). Comorbidity and mediastinal lymph node dissection were identified as factors that increased the risk of postoperative complications (p < 0.0001 and p = 0.036, respectively). Survival rates were independent of the extent of pulmonary resection (lobectomy or limited resection). Conclusions: Octogenarian patients with c-stage I lung cancer in this study had a satisfactory long-term outcome and low-mortality rate. Comorbidity is a factor associated with both prognosis and operative risks. A selection of the patients who would be curable without mediastinal lymph node dissection after an accurate preoperative staging is beneficial to decrease the postoperative complications because this procedure is a risk factor.

Japanese Lung Cancer Registry Study: First Prospective Enrollment of a Large Number of Surgical and Nonsurgical Cases in 2002

Purpose: To investigate prognoses of lung cancer patients prospectively enrolled in the Japan Lung Cancer Registry Study. Methods: Patients newly diagnosed as having lung cancer exclusively in 2002 were enrolled. Follow-up surveys were performed twice, in 2004 and 2009, and the final follow-up data with prognoses were analyzed for 14,695 patients (79%). Clinical stages were defined according to the sixth edition of the International Union Against Cancer-tumor, node, metastasis classification (2002). Results: The mean age was 67.1 years (range, 18-89 years), and there were 10,194 men (69.3%) and 4315 women (29.7%). The most frequent histology was adenocarcinoma (n = 8325, 56.7%), followed by squamous cell carcinoma (n = 3778, 26%) and small cell carcinoma (n = 1345, 9.2%). The distribution of clinical stages was as follows: IA, 4245 cases (29.3%); IB, 2248 (14.5%); IIA, 208 (1.4%); IIB, 918 (6.3%); IIIA, 1700 (11.8%); IIIB, 2110 (16.3%); and IV, 3037 (21.0%). The 5-year survival rates were 44.3% for all patients, 46.8% for those with non-small cell lung cancer, and 14.7% for those with small cell lung cancer. According to the clinical stage of non-small cell lung cancer and small cell lung cancer, the 5-year survival rates were 79.4 and 52.7% for stage IA, 56.9 and 39.3% for IB, 49.0 and 31.7% for IIA, 42.3 and 29.9% for IIB, 30.9 and 17.2% for IIIA, 16.7 and 12.4% for IIIB, and 5.8 and 3.8% for IV, respectively. Conclusion: Analysis of a large cohort in the Japanese registry study found that stage-specific prognosis was within a range similar to other reports. The data presented should provide an important reference for future clinical trials in Japan.

Visceral Pleura Invasion Impact on Non-small Cell Lung Cancer Patient Survival: Its Implications for the Forthcoming TNM Staging Based on a Large-Scale Nation-Wide Database

Introduction: No analyses have been reported on the impact of visceral pleura invasion (VPI) on staging, in relation with the International Association for the Study of Lung Cancer proposals for the 7th edition of the tumor, node, metastasis (TNM) classification of the International Union Against Cancer staging system. The purpose of this study was to evaluate the impact of VPI on survival and propose a method of incorporating VPI status into the TNM classification. Methods: We reviewed the data on 9758 non-small cell lung cancer patients, who underwent anatomic surgical resection in 1999, accumulated by the Japanese Joint Committee for Lung Cancer Registration, to gain insight into their clinicopathologic characteristics and outcomes. VPI was defined as tumor extension beyond the elastic layer of the visceral pleura. Patients were divided into nine groups according to VPI status and tumor diameter, in accordance with the International Association for the Study of Lung Cancer proposals. Results: On the basis of survival, the nine groups were divided into the following five levels: tumors ≤2 cm without VPI; tumors ≤2 cm with VPI and tumors 2.1 to 3 cm without VPI; tumors 2.1 to 3 cm with VPI and tumors 3.1 to 5 cm without VPI; tumors 3.1 to 5 cm with VPI and tumors 5.1 to 7 cm without VPI; and tumors 5.1 to 7 cm with VPI and tumors >7 cm without VPI or T3 tumors. Conclusions: The T status of tumors, 7 cm or less, with VPI should be upgraded to the next T level in the future edition of the TNM classification of International Union Against Cancer staging system.

Survival Differences by Gender for Resected Non-small Cell Lung Cancer: A Retrospective Analysis of 12,509 Cases in a Japanese Lung Cancer Registry Study

Introduction: Women with non-small cell lung cancer (NSCLC) are more likely to have better survival than men. This study intended to assess gender differences in the survival of these patients in a large registry population. Methods: In 2005, the Japanese Joint Committee for Lung Cancer Registration performed a nationwide retrospective registry study regarding the prognosis and clinicopathologic profiles of patients who underwent resection for primary lung neoplasms in 1999. The registry data of 12,509 patients with NSCLC were analyzed in terms of gender differences in prognosis and clinicopathologic features. Results: There were 8353 (66.8%) men and 4156 (33.2%) women with a mean age at operation of 66.4 and 65.0 years, respectively (p < 0.001). Women had a higher incidence of adenocarcinoma (p < 0.001) and stage IA disease (p < 0.001) than men. The overall survival was significantly better in women than men. The 5-year survival rates (5-YSRs) for women and men were 75.6 and 57.9%, respectively (p = 0.0000). According to histology, the overall survival of women was significantly better than that of men for both adenocarcinoma (5-YSR, 77.7 versus 61.9%, p = 0.0000) and nonadenocarcinoma (5-YSR, 59.3 versus 53.1%, p = 0.035). In adenocarcinoma, women had a significantly better prognosis than men for pathologic stage I/II disease. However, in nonadenocarcinoma, there was no significant prognostic difference between the two genders in pathologic stage I/II disease. Conclusions: Women with NSCLC, especially with an adenocarcinoma histology, had better survival than men. Women were more likely to have adenocarcinoma and stage IA disease, which might account for the better prognosis in women.

Prognostic Factors in 3315 Completely Resected Cases of Clinical Stage I Non-small Cell Lung Cancer in Japan

Background: The objective of this retrospective study was to identify prognostic factors in completely resected clinical (c-) stage I non-small cell lung cancer cases. Methods: In 2001, the Japanese Joint Committee of Lung Cancer Registry collected data on the outcome and clinicopathological profiles of 7408 patients who had undergone resection for primary lung cancer in 1994. They included 3315 c-stage I patients who underwent complete resection, and in this study attempted to identify prognostic factors in the c-stage IA and c-stage IB cases. Results: The overall 5-year survival rate was 66.5%: 74.7% in the 2085 c-stage IA cases and 52.5% in the 1230 c-stage IB cases. The survival curve of the c-stage IA cases was higher than that of the c-stage IB cases. Multivariate analysis of the c-stage IA cases revealed six factors that predicted a significantly better outcome: age, gender, pathological (p-) T status, p-N status, nodal dissection, and tumor diameter (≤2 cm), and the same analysis of the c-stage IB cases revealed six factors: age, gender, p-T status, p-N status, operative procedure, and tumor diameter (<5 cm). The c-stage IA patients whose tumor diameter was 2 cm or less had a higher survival rate than the patients whose tumor diameter was more than 2 cm, and the c-stage IB patients whose tumor diameter was less than 5 cm had a higher survival rate than the patients whose tumor diameter was 5 cm or more. Conclusion: Tumor size is an independent prognostic factor for postoperative survival in c-stage I patients.

Visceral Pleural Invasion Classification in Non-Small- Cell Lung Cancer in the 7th Edition of the Tumor , Node, Metastasis Classification for Lung Cancer: Validation Analysis Based on a Large-Scale Nationwide Database

Objective: In the 7th tumor, node, metastasis (TNM) classification, visceral pleural invasion (VPI) is defined as invasion beyond the elastic layer, including invasion to the visceral pleural surface, and T1 tumors with VPI are upgraded to T2a. To validate this, we analyzed the survival of non–small-cell lung cancer patients from a nationwide database and evaluated the prognostic impact of VPI. Methods: The clinicopathological characteristics and prognosis of 4995 patients who were included in the registry study of the Japanese Joint Committee of Lung Cancer Registry were retrospectively analyzed with a special interest in the prognostic impact of VPI. These patients underwent surgery in 2004 and were pathologically staged as T1a-3N0. VPI was defined as including PL1 and PL2 according to the 7th TNM Classification, but the Japanese Joint Committee of Lung Cancer Registry did not collect data regarding staining or how extensively VPI was evaluated in each participating institution. Results: The survival differences were statistically significant between PL0 and PL1, PL1 and PL2, as well as PL2 and T3. There were no significant survival differences between T1a with VPI and T1b without VPI, or between T1a with VPI and T2a without VPI. There were no significant survival differences between T1b with VPI and T2a without VPI, or between T1b with VPI and T2b without VPI. There were no significant survival differences between T2a with VPI and T2b without VPI, or between T2b with VPI and T2b without VPI. T3 showed significantly worse prognosis than T2a with VPI and T2b with VPI. Conclusions: In addition to the current TNM classification recommendations, in which T1 tumors with VPI are upgraded to T2a, T2a tumors with VPI should be classified as T2b.

Surgical Outcome of Stage IIIA- cN2/pN2 Non–Small-Cell Lung Cancer Patients in Japanese Lung Cancer Registry Study in 2004

Background: The role of surgery in the treatment of non–small-cell lung cancer (NSCLC) with clinically manifested mediastinal node metastasis is controversial even in resectable cases because it is often accompanied by systemic micrometastasis. However, surgery is occasionally indicated for cases with single-station N2 disease or within multimodal treatment regimens, and in clinical trials. The aim of this study is to evaluate surgical outcomes in a modern cohort of patients with clinical (c-) stage IIIA-N2 NSCLC whose nodal metastasis was confirmed by pathology (cN2/pN2). Methods: From the central database of lung cancer patients undergoing surgery in 2004, which was founded by the Japanese Joint Committee for Lung Cancer Registration, data of patients having all conditions of NSCLC, c-stage IIIA, cN2, and pN2 were extracted, and the clinicopathologic profile of patients and surgical outcomes were evaluated. Results: Among 11,663 registered NSCLC cases, 436 patients (3.8%) (332 men and 104 women) had been extracted. Their mean age was 65 years, and histologic types included adenocarcinoma (n = 246), squamous cell carcinoma (n = 132), and others (n = 58). The proportion of R0 resection was 82.5% and the proportion of the hospital deaths among the cause of death was 2.3%. The 5-year survival rate was 30.1% for the selected group of patients. The postoperative prognosis was significantly better than those of corresponding populations extracted from the 1994 (p = 0.0001) and 1999 databases (p = 0.0411). Men and women experienced a significantly different survival outcome (p = 0.025) with 5-year survivals of 27.5% and 37.8%, respectively. Single-station N2 cases occupied 60.9 % of the cohort and showed a significantly better prognosis than multistation N2 (p = 0.0053, 35.8 % versus 22.0 % survival rate at 5 years). Conclusions: The surgical outcomes of c-stage IIIA-cN2/pN2 NSCLC patients in 2004 were favorable in comparison with those ever reported.

Improvements in surgical results for lung cancer from 1989 to 1999 in Japan.

Background: In 1986, Japanese Association for Thoracic Surgery started a nationwide survey of the number of primary lung cancer undergoing resection and this survey was continued annually. Thereafter, investigations of lung cancer surgical results have been conducted three times. The postoperative overall 5-year survival rate was 47.8% in resected cases in 1989, 52.3% in 1994, and 62.0% in 1999, showing improvement over the decade (p < 0.01). Objective: To clarify the factors influencing survival improvements retrospectively. Patients and Methods: The subjects of the investigation are the patients who underwent resection for primary lung cancers in 1989, 1994, and 1999. Postoperatively, after 5 years, surveys of surgical results were sent to institutes where lung cancer resection had been performed. The subjects undergoing resection who provided 10 items (age, sex, pathologic T factor, pathologic N factor, pathologic M factor, date of resection, histology, curability, prognosis, and survival time) numbered 3004 in 1989, 6895 in 1994, and 12,235 in 1999. They were classified according to the Union International Contre le Cancer 1997 revised tumor, node, and metastasis classification. Differences in age, gender, histology, pathologic stage, curability, and operative death rates were analyzed for each survey year. Results: According to the changes in proportions, the cases over 70 years of age, women, and pathologic stage I increased significantly (p < 0.001), whereas in cases with small cell lung cancer, incomplete resection and operative death decreased significantly over time (p < 0.001). Conclusion: The postoperative 5-year survival rate in Japan improved between 1989 and 1999. The main cause of this improvement was the increase in early stage lung cancer, especially cases with tumors 2 cm or less in size.