Preoperative serum carcinoembryonic antigen level is a prognostic factor in women with early non-small-cell lung cancer. Ann Thorac Surg. 2007 Feb;83(2):419-24.

BACKGROUND: Carcinoembryonic antigen (CEA) is one of the markers evaluated in patients with non-small cell lung cancer (NSCLC). The significance of the preoperative serum CEA level in female patients with NSCLC is seldom discussed. In this study, we conducted a retrospective review to investigate the prognostic significance of the preoperative CEA level in female patients with stage I NSCLC. METHODS: In this study, we looked at 163 female patients with stage I NSCLC. Patient charts were reviewed to collect patient data, including the age of the patient, tumor location, tumor size, visceral pleural invasion, the stage of disease, and the preoperative serum CEA level. The cutoff value of serum CEA level was 6.0 ng/mL. The significance of preoperative CEA level in the prognosis of female patients with stage I NSCLC was evaluated. RESULTS: Among the 163 female patients with stage I NSCLC, 47 patients (28.8%) had abnormal preoperative serum CEA level (>6 ng/mL). Diagnosis of adenocarcinoma and bronchoalveolar carcinoma accounted for 83.4% of these 163 female patients. In-hospital mortality was encountered in 1 patient. Univariate analysis of survival in the other 162 female patients with stage I NSCLC showed that age, stage, tumor size, and preoperative CEA level were prognostic factors. Visceral pleural invasion had no impact on the prognosis of these patients. Multivariate analysis revealed that tumor size and preoperative CEA level were independent prognostic factors in female patients with stage I NSCLC. CONCLUSIONS: Preoperative serum CEA level and tumor size are independent prognostic factors in female patients with stage I NSCLC. In contrast, visceral pleural invasion was not associated with the prognosis. Importantly, these results suggest that female patients with abnormally high preoperative CEA level and tumor size larger than 3 cm may need a thorough preoperative evaluation and careful postoperative follow-up to rule out occult metastasis of early NSCLC.

Clinicopathologic study of resected, peripheral, small-sized, non-small cell lung cancer tumors of 2 cm or less in diameter: pleural invasion and increase of serum carcinoembryonic antigen level as predictors of nodal involvement.J Thorac Cardiovasc Surg. 2006 May;131(5):988-93.

OBJECTIVE: The number of surgical interventions for small-sized lung cancer has increased with the development of computed tomography. We attempted to identify clinicopathologic characteristics of peripheral, small-sized, non-small cell lung cancer to show the limitation of partial resection or segmentectomy. METHODS: A retrospective analysis of 143 patients who underwent a complete resection for a peripheral non-small cell lung cancer of 2 cm or less in diameter was performed. The relationships between nodal involvement and other clinical factors were also assessed in patients who underwent a lobectomy plus node dissection. RESULTS: The overall 5-year survival rate was 88.1%. The 5-year survival rate was 100% for patients with a tumor of 1.5 cm or less. Survival for patients with adenocarcinoma histology was significantly better than for those with nonadenocarcinoma histology (P = .03). The 5-year survival rate for patients without lymph node metastases was 91.6%, whereas it was 62.5% for those with nodal involvement (P < .01). Increase of prethoracotomy serum carcinoembryonic antigen level was an independent predictor of a poor prognosis. Lymph node metastasis was significantly increased in those with pleural invasion by the primary lesion and increased serum carcinoembryonic antigen level. Fourteen (16.9%) of 83 patients with a tumor diameter of larger than 1.5 cm had nodal metastasis. CONCLUSIONS: Nodal involvement should be considered in patients with non-small cell lung cancer of 2 cm or less in diameter who show pleural invasion or an increased carcinoembryonic antigen level. A lobectomy with node dissection is recommended for patients with a tumor larger than 1.5 cm, suspected pleural invasion, or prethoracotomy carcinoembryonic antigen level increase.

Non-small cell lung cancer in the young: a retrospective analysis of diagnosis, management and outcome data. Anticancer Res. 2006 Jul-Aug;26(4B):3175-81.

BACKGROUND: Non-small cell lung cancer (NSCLC) in young patients is uncommon and is thought to constitute a distinct oncological entity with characteristic clinicopathological patterns. Since the reported data are scant and discordant, the presentation, management and outcome data of NSCLC patients aged under 45 years of age were analyzed and compared with those of patients over 45 years old. Prognostic factors for risk classification were also evaluated. MATERIALS AND METHODS: The data were abstracted from the Hellenic Cooperative Oncology Group (HeCOG) cancer registry database. The presentation, management and outcome data of patients with histologically confirmed NSCLC, managed from 1989 until 2004 in HeCOG participating centers, were retrospectively analyzed. The clinicopathological characteristics of patients aged < and > than 45 years old were compared and evaluated for prognostic significance regarding outcome. RESULTS: The data for NSCLC patients (1906), of whom 115 were aged <45, were retrieved. In comparative analysis, the young patients were more frequently asymptomatic at diagnosis, while older patients presented significantly higher rates of thoracic pain, cough and fatigue (p<0.01). The young patients were more commonly diagnosed with adenocarcinoma and less frequently with squamous cancer than patients aged over 45. Although the stage distribution was distinct, with older patients presenting higher rates of stage IV disease (21.9% vs. 12.2%), the rates of early lung cancer (stages I-IIIa) were similar. The overall survival (OS) was not significantly different (median OS 12 vs. 11.5 months, p=0.277). Among patients who underwent first-line palliative chemotherapy, young individuals had a significantly shorter time to progression: 4.3 vs. 5.8 months (p=0.0049). Univariate and multivariate regression analyses established the prognostic usefulness of the performance status, disease stage and disease-free interval for the risk of death, both in the total number of patients (1906) and in young patients (115). CONCLUSION: This large retrospective series failed to present strong evidence that NSCLC among young individuals constitutes a distinct clinicopathological entity with differing biological behavior, since the same clinicopathological prognostic factors were valid in both age groups. Molecular phenotypic studies are needed to shed light on this controversial subject.

Impact of large tumor size on survival after resection of pathologically node negative (pN0) non-small cell lung cancer. Ann Thorac Surg. 2005 Apr;79(4):1142-6.

BACKGROUND: The current TNM staging system first adopted the tumor size of 3 cm for subdivision of stage I and II disease. The aim of the present study was to evaluate the impact of tumor size on survival in patients with pathologically node negative (pN0) non-small cell lung cancer after complete resection. METHODS: We retrospectively reviewed the records of 603 patients with pN0 non-small cell lung cancer patients (403 men and 200 women) who underwent a complete resection in five national chest hospitals between 1992 and 1996, with follow-up duration of more than 5 years, and analyzed tumor size and survival. Survival rate was estimated by the Kaplan-Meier method, and differences were compared by log-rank test. For the multivariate analysis, the Cox proportional hazard model was used to identify variables that significantly affected survival. RESULTS: There were 355 adenocarcinomas, 208 squamous cell carcinomas, and 40 large cell carcinomas completely resected. No significant prognostic differences were seen among three groups with smaller-sized tumors (< or =2 cm [n = 171], 2.1 to 3 cm [n = 202], and 3.1 to 5 cm [n = 170]); however, patients with a tumor size greater than 5 cm (n = 60) showed a significantly worse prognosis. The 5-year survival rates were 79.6%, 72.7%, 68.1%, and 46.6%, respectively, in these four groups. Multivariate analysis showed the tumor size to be an independent prognostic predictor in patients with pN0 tumors. CONCLUSIONS: We found that a tumor size of greater than 5 cm was an independent prognostic predictor in pN0 disease; therefore, upgrading the T factor of tumor diameter to greater than 5 cm may be necessary in the next reversion of the TNM staging system.

Prognostic factors in patients with ipsilateral pulmonary metastasis from non-small cell lung cancer.Eur J Cardiothorac Surg. 2005 Oct;28(4):635-9.

OBJECTIVE: Pulmonary metastasis of non-small cell lung cancer is classified as an advanced disease stage, with limited indications for surgical treatment. However, the prognosis of patients with pulmonary metastasis of non-small cell lung cancer is better than that of patients with distant metastases. The purpose of the present study was to analyze and detect possible prognostic factors in surgically treated patients with ipsilateral pulmonary metastasis of non-small cell lung cancer. METHODS: Among 1198 patients with non-small cell lung cancer who underwent surgery at Kurashiki Central Hospital (Okayama, Japan) from April 1982 to March 2004, a total of 48 (4.0%) patients with pathologically diagnosed ipsilateral pulmonary metastasis were retrospectively evaluated. The median follow-up time was 20.5 months (range 1-103 months) and 37 patients (77.1%) were completely followed up until their death or more than 5 years after the operation. RESULTS: Among the 48 patients, 31 (64.6%) patients had metastatic nodules in the same lobe as the primary tumor (PM1) and 17 (35.4%) patients had metastatic nodules in different ipsilateral lobes (PM2). There was no significant difference in survival between patients with PM1 and the other patients with pT4-stage IIIB, or between patients with ipsilateral PM2 and the other patients with stage IV. Univariate analysis of postoperative survival stratified according to clinicopathologic factors revealed significant differences for the radicality of resection (complete vs. incomplete), tumor size (0-30 vs. >30mm) and pathological nodal (pN) factor (among pN0, pN1 and pN2-3). Multivariate analysis revealed that tumor size (0-30 vs. >30mm) and pN factor (pN0-1 vs. pN2-3) were independent prognostic factors. CONCLUSIONS: The results of our study suggest that undergoing a complete resection, having a tumor size of 30mm or less and having no mediastinal lymph node metastases were better prognostic factors for surgically treated patients with ipsilateral pulmonary metastasis of non-small cell lung cancer.

Pattern of recurrence after curative resection of local (stage I and II) non-small cell lung cancer: difference according to the histologic type. J Korean Med Sci. 2004 Oct;19(5):674-6.

The aim of the present study was to evaluate the pattern of recurrence after complete resection of pathological stage I, II non-small cell lung cancer, especially according to the cell type. We reviewed the clinical records of 525 patients operated on for pathologic stage I and II lung cancer. The histologic type was found to be squamous in 253 and non-squamous in 229 patients. Median follow-up period was 40 months. Recurrences were identified in 173 (36%) of 482 enrolled patients; distant metastasis in 70%, distant and local recurrence in 11%, and local recurrence in 19%. Distant metastasis was more common in non-squamous than in squamous cell carcinoma (p=0.044). Brain metastasis was more frequently identified in non-squamous than in squamous cell carcinoma (24.2% vs. 7.3%. p=0.005). Multivariate analyses showed that cell type is the significant risk factor for recurrence-free survival in stage I and stage II non-small cell lung cancer. Recurrence-free survival curves showed that non-squamous cell carcinoma had similar risks during early periods of follow-up and more risks after 2 yr from the operation compared to squamous cell carcinoma. Pathological stage and histologic type significantly influence recurrence-free survival.

Long-term results of pathological stage I non-small cell lung cancer: validation of using the number of totally removed lymph nodes as a staging control.Eur J Cardiothorac Surg. 2003 Dec;24(6):994-1001.

OBJECTIVE: The number of totally removed lymph nodes during thoracotomy was used alternatively to represent the quality of lymphadenectomy in patients with pathologic stage I non-small cell lung cancer (NSCLC). We combined this new parameter with other well-established prognostic factors and performed multivariate survival analyses to validate its usage as a stage control. METHODS: Three hundred and twenty-one patients who underwent complete surgical resection for stage I NSCLC were reviewed retrospectively. Aside from the number of lymph nodes removed during thoracotomy, other well-known clinical and histopathological factors were also included as possible prognostic factors for analysis. Two survival analyses, overall death and cancer-related death as study end-point, were performed, using the Kaplan-Meier method and multivariable Cox's proportional hazard regression analysis. Stepwise method of variable selection was employed to choose the 'best' Cox proportional hazard model in each survival analysis. RESULTS: The overall 5- and 10-year survival rates were 48 and 35%, and the cancer-related 5- and 10-year survival rate was 63.3 and 58.3%, respectively. The number of totally removed lymph nodes during thoracotomy, tumor size and smoking history in multivariable analysis significantly affected both overall and cancer-related survival rates. Cell type of adenocarcinoma or large cell carcinoma was associated with a worse cancer-related survival compared with other histological types. CONCLUSIONS: The quality of lymphadenectomy, represented quantitatively by the number of totally removed lymph nodes during thoracotomy, may impact on a more accurate tumor stage, and will affect the survival rate for patients with stage I NSCLC as well as other well known clinical and histopathological factors.

Characteristics and prognosis of patients after resection of nonsmall cell lung carcinoma measuring 2 cm or less in greatest dimension. Cancer. 2003 Aug 1;98(3):535-41.

BACKGROUND: There remains ongoing controversy with regard to the optimal management strategy and the prognostic significance of small-sized nonsmall cell lung carcinoma. Therefore, in the current study, the authors analyzed the clinical characteristics of patients who underwent complete resection of these lung tumors, the follow-up data, and the significant prognostic factors. METHODS: Of 1726 consecutive patients surgically treated for proven primary lung carcinoma, 265 patients underwent complete removal of a nonsmall cell lung carcinoma in which the greatest dimension of the resected specimen was < or = 2 cm. RESULTS: The cancer-specific 5-year and 10-year survival rates were 86% and 83%, respectively. Univariate analyses revealed that advanced pathologic stage, a tumor size of 16-20 mm, lymphatic vessel invasion, vascular vessel invasion, a high serum level of carcinoembryonic antigen (CEA), and extended resection were significantly unfavorable prognostic factors. Among these factors, multivariate analyses demonstrated that pathologic stage (P < 0.0001), vascular vessel invasion (P = 0.0040), and CEA level (P = 0.0291) were significant, independent determinants of survival. None of the patients with pathologic Stage I disease, no vascular vessel invasion, and a low serum CEA level died of their disease after undergoing complete resection. CONCLUSIONS: The preoperative level of serum CEA and vascular vessel invasion by tumor cells were found to be independent prognostic factors that were as significant as the well established determinant of pathologic stage for patients with a nonsmall cell lung carcinoma measuring < or = 2 cm in greatest dimension. These data may contribute to the explanation of the lower-than-expected survival of patients after complete surgical resection of such a small-sized tumor.

The prognostic significance of intranodal isolated tumor cells and micrometastases in patients with non-small cell carcinoma of the lung.J Thorac Cardiovasc Surg. 2003 Aug;126(2):551-7.

OBJECTIVE: To study whether isolated tumor cells and micrometastases, as defined by the current American Joint Committee on Cancer criteria for extrapulmonary neoplasms, have prognostic value for patients with resected non-small cell carcinoma of the lung. METHODS: Intrathoracic lymph nodes (n = 1063) from 60 patients with non-small cell carcinoma of the lung were studied for the presence of metastases with serial histologic sections and keratin immunostains. Metastases were classified as isolated tumor cells, pN1mi, pN1, pN2mi, and pN2. Isolated tumor cells were smaller than 0.2 mm, while pN1mi and pN2mi measured 0.2 mm to 2 mm. Survival analysis was performed, stratifying by nodal status and stage. RESULTS: Isolated tumor cells were detected in 11 lymph nodes from 5 of 33 pN0 patients and in 9 pN1 and pN2 patients. The lymph nodes from 3 patients were reclassified as pN1mi. No pN2mi were detected. A survival model based on a stratification of the cohort into stages I to III was significant (chi-square = 7.426, df = 2, P =.024) but demonstrated considerable overlap between the survival curves of stage I and II patients. A model stratifying isolated tumor cells and pN1mi into stage I disease was significant (chi-square = 7.985, df = 2, P =.018) and showed no overlap between the survival curves of stage I and II patients. There were no significant survival function differences between patients with pN0, isolated tumor cells, and pN1mi. CONCLUSIONS: Patients with non-small cell carcinoma of the lung with isolated tumor cells and pN1mi have similar survivals to those with pN0, consistent with the findings reported for breast cancer patients. Future larger studies of patients with non-small cell carcinoma of the lung are needed to confirm whether current American Joint Committee on Cancer staging criteria should be modified to include the pN1mi category.

Prognostic markers in resectable non-small cell lung cancer: a multivariate analysis. Can J Surg. 2001 Jun;44(3):180-8.

OBJECTIVE: To identify the prognostic significance of certain clinical, cellular and immunologic markers in resectable non-small cell lung cancer (NSCLC). DESIGN: A cohort of patients with resectable NSCLC was prospectively followed up for 8 years (100% follow-up). SETTING: A university hospital in a large Canadian city. PATIENTS: One hundred and thirteen consecutive patients who underwent surgical resection of primary NSCLC. MAIN OUTCOME MEASURES: Presence of peritumoral B lymphocytes (identified with antibody to CD20) and T lymphocytes (antibody to CD43), along with tumour markers (carcinoembryonic antigen [CEA], keratin, cytokeratin, S-100 protein, vimentin, chromogranin) and other factors such as age, sex, cell type, American Joint Committee on Cancer (AJCC) stage, histologic grade, DNA ploidy and S-phase fraction were correlated with survival. RESULTS: The mean age of patients in the study was 66.0 years; 60% were male. Histologic types of the tumours were: adenocarcinoma 57 (50.4%), squamous cell 47 (41.6%), adenosquamous 6 (5.3%) and large cell 3 (2.6%). AJCC stages were: I 66 (58.4%), II 20 (17.7%) and III 27 (23.9%). Histologic grades were: I (well differentiated) 31 (27.4%), II 50 (44.2%), III 29 (25.7%) and IV 3 (2.6%). Survival was 85% at 1 year (95% confidence interval [CI] 76%-90%), 44% at 5 years (95% CI 34%-53%) and 34% at 10 years (95% CI 22%-46%). Multivariate analyses using the Cox proportional hazards model for survival confirmed AJCC stage (p < 0.001) in all histologic subtypes to be the strongest factor of independent prognostic significance. It also revealed the presence of CD20-stained B lymphocytes (p = 0.04) in the peritumoral region of all tumours to be a positive prognostic factor. This relation was especially strong for nonsquamous cell carcinomas (p < 0.001). For squamous cell carcinomas, the immunohistochemical presence of CEA was of marginally negative prognostic value (p = 0.04). DNA ploidy and a high S-phase fraction showed no evidence of prognostic value for stage I tumours, but for stages II and III tumours there was strong evidence of prognostic value (p < 0.001 jointly). The evidence for DNA ploidy was especially strong in stages II and III squamous cell tumours (p = 0.008), and for a high S-phase fraction was strongest in stages II and III nonsquamous cell tumours (p = 0.002). CONCLUSIONS: AJCC stage remains the most important prognostic indicator from a variety of clinical variables and tumour markers in postoperative patients with resectable NSCLC. For nonsquamous cell lung carcinomas, the presence of peritumoral B lymphocytes was strongly associated with improved survival, suggesting an important role for humoral mediated immunity.

Predictive survival markers in patients with surgically resected non-small cell lung carcinoma.Clin Cancer Res. 2000 Mar;6(3):1125-34.

Among patients with resected non-small cell lung carcinoma, about 50% will present a tumor recurrence. Thus, it would be of major importance to be able to predict and try to prevent these relapses by an active chemotherapy and/or radiotherapy. In an attempt to answer this question, the tumors of 227 patients with a surgically resected non-small cell lung carcinoma were evaluated as follows: tumors were classified as squamous cell carcinoma (n = 132) or adenocarcinoma (n = 95), and tumor differentiation was evaluated for each type. Then, all tumors were classified in respect to their pathological TNM staging (WHO) and screened by immunohistochemistry for the detection of the expression of the following antigens: Bcl-2, A+B+H blood group antigens, c-erb-b2, p53, and Pan-Ras antigens. Furthermore, adenocarcinomas were screened for the presence of point mutations in Ki-Ras codons 1-31. Finally, the patient blood group was defined, and patient survival was analyzed using nonparametric tests and proportional hazard Cox models. Using Kaplan-Meier survival curves, disease pathological TNM staging was shown to be a strong predictive factor of survival for both squamous cell carcinoma and adenocarcinoma. Patients with squamous cell carcinoma experienced fewer relapses than those with adenocarcinoma (42% versus 63%; P = 0.0002) and had a significantly better survival. All evaluated antigens were more often present in squamous cell carcinoma than in adenocarcinoma except for Pan-Ras (three times more frequent in adenocarcinoma). In patients with squamous cell carcinoma, only tumor staging had a significant prognosis value (P = 0.01). In patients with lung adenocarcinoma, a well-differentiated tumor (P = 0.009) as well as a positive Bcl-2 staining (P = 0.009) and an A+B+H antigen tumor staining (P = 0.024) were associated with a better survival. In contrast, patients with a stage I or II disease and a p53-positive tumor staining and patients with the O blood group (P = 0.01) had a shorter survival. Interestingly, no relation with patient survival was related to c-erb-b2 and Pan-Ras staining. Finally, 12 point mutations were found out of 81 tumors (15%) evaluated for Ki-Ras codons 1-31; they involved codon 12 but also 8, 14, and 15 without any relationship to survival. In respect to lung adenocarcinoma, using Cox proportional hazard models stratified on tumor staging, the following markers were shown to be related to survival: (a) Independent markers of longer survival (ie., high histological degree of tumor differentiation and positive Bcl-2 and A+B+H blood group antigen expression by tumor cells); and (b) Independent markers of shorter survival (i.e., O blood group for all patients and p53 tumor staining in patients with stage I and II diseases). This study suggests that, in patients who undergo surgery for lung adenocarcinoma, the presence or absence of these criteria could be used to define a subset of patients who may benefit from a more specific follow-up.

Conventional clinicopathologic prognostic factors in surgically resected nonsmall cell lung carcinoma. A comparison of prognostic factors for each pathologic TNM stage based on multivariate analyses.Cancer. 1999 Nov 15;86(10):1976-84.

BACKGROUND: A number of prognostic factors have been reported for resected nonsmall cell lung carcinoma. None of them, however, has been reported to have greater prognostic impact than the pathologic TNM staging system. The authors evaluated 18 conventional clinicopathologic prognostic factors in each pathologic stage. METHODS: A retrospective study was conducted on surgically resected 836 lung carcinoma patients, and the following conventional prognostic factors were evaluated in multivariate analyses: age, gender, pack-year smoking, serum carcinoembryonic antigen and squamous cell carcinoma antigen levels, laterality of tumor, clinical N status, histologic type of tumor, greatest tumor dimension, grade of differentiation, pleural involvement, lymphatic invasion, vascular invasion, degree of fibrosing scarring, nuclear atypia, mitotic activity, and curativity of resection. RESULTS: The overall 5-year survival rate was 63.8%. In 430 cases of pathologic Stage I disease, multivariate analyses revealed 3 significant prognostic factors: clinical N status (P < 0.001), vascular invasion (P = 0.001), and curativity of resection (P < 0.001). In 406 cases of more advanced disease, i.e., pathologic Stage II, IIIA, IIIB, or IV, multivariate analyses revealed 4 factors as significant: histology (P = 0.001), pathologic N status (P < 0.001), tumor size (P < 0.001), and curativity of resection (P = 0.002). CONCLUSIONS: Conventional clinicopathologic prognostic factors had a different impact on prognosis in each pathologic TNM stage among patients who underwent surgical resection of nonsmall cell lung carcinoma. These factors should be analyzed separately in each pathologic TNM stage.

Pathological and radiological correlation of endobronchial neoplasms: part II, malignant tumors. Ann Diagn Pathol 1998;2:31–34.

The majority of lung neoplasms are malignant. Many of these are central and have an associated endobronchial component. Most such neoplasms are of surface epithelial origin; however, neoplasms of submucosal gland, mesenchymal, and lymphoreticular origin may also demonstrate an endobronchial component. Because of their endobronchial location and associated symptoms, these patients often present at an earlier stage than purely parenchymal lung malignancies. The radiographic features in such cases may be similar to those associated with benign endobronchial tumors; however, there are certain radiological signs that are more suggestive of a malignant process. Despite these circumstances, conservative management such as endoscopic excision are inappropriate in most instances. The clinicopathologic and radiological features of these lesions are detailed.

Tumour regression in non-small-cell lung cancer following neoadjuvant therapy. Histological assessment. J Cancer Res Clin Oncol. 1997;123(9):469-77.

In the scope of a prospective multi-centre study after neoadjuvant combined chemotherapy (carboplatin, ifosfamide, etoposide, vindesine) and radiotherapy (45 Gy) 40 resection specimens of locally advanced non-small-cell lung cancer were analysed in order to establish reproducible pathological/anatomical results of tumour regression. Resection specimens of 28 squamous cell carcinomas and 12 adenocarcinomas were investigated using serial sections of the primary lesion. The mean age of the patients was 57 years. The results were compared to spontaneous regressive changes in a control group of 50 untreated non-small-cell lung cancers. Marked scarry fibrosis in the region of the former primary tumour, concentric foci of fresh tumour necroses and surrounding foam cell clusters with transition into vascular granulation tissue could be established as characteristic features of therapy-induced tumour regression, whereas untreated carcinomas revealed necroses with adjoining vital tumour tissue. Using a three-step regression system, 3 tumours could be classified as grade I (no or only slight tumour regression), 10 tumours as grade IIA (marked but incomplete tumour regression, more than 10% vital tumour tissue), 20 tumours as grade IIB (less than 10% vital tumour tissue) and 7 tumours as grade III (complete tumour regression without vital tumour tissue). After a median follow-up period of 32.3 months in patients with grade IIB or III tumour regression ("responders") the median survival time of 27.9 months was found to be significantly longer than in patients with grade I or IIA tumour regression ("non-responders") with a median survival period of 13.7 months (log-rank test, P = 0.020). The resection specimens analysed, which were obtained 7 weeks (on average) after the end of radiochemotherapy, did not show specific changes due to preoperative therapy, but quite characteristic histological alterations in the former tumour area were registered, which had been induced by combined neoadjuvant radiation and chemotherapy. The grade of therapy-induced tumour regression could be shown to be a significant prognostic factor in non-small-cell lung cancer.

How reliable is the diagnosis of lung cancer using small biopsy specimens? Report of a UKCCCR Lung Cancer Working Party.Thorax. 1993 Nov;48(11):1135-9.

BACKGROUND--A study was undertaken to investigate the accuracy of typing of a series of bronchial carcinomas by experienced pathologists with an interest in lung cancer from the examination of bronchoscopic biopsy specimens. METHODS--Eighty bronchial biopsy specimens showing positive results for bronchial carcinoma were circulated to five pathologists, who recorded diagnostic criteria and diagnosis for each. Diagnoses were then compared with the diagnosis agreed from the resection specimen corresponding to each biopsy specimen. A "non-small cell carcinoma, not further specified" classification group was introduced for small biopsy specimens. RESULTS--A diagnostic accuracy of 75% was achieved for squamous cell carcinomas, 66% for small cell carcinomas, and 50% for adenocarcinomas. There was diagnostic confusion between small cell and non-small cell carcinoma in less than 10% of cases. The introduction of a non-specific non-small cell classification improved diagnostic accuracy by 10-15% for each non-small cell tumour group. CONCLUSIONS--There are appreciable inaccuracies in applying the World Health Organisation's 1981 classification of lung cancer to the diagnosis of bronchial carcinoma from small biopsy specimens and these inaccuracies have been measured. They can be diminished by introducing a less specific "non-small cell" category for use with this sort of biopsy material. Care should be taken not to overinterpret small biopsy specimens in lung cancer.