Secondary bone cancer prognosis

Study objective: Bronehioloalveolar carcinoma (BAC) is an uncommon pulmonary neoplasm with various radiologic and clinical presentations. In this article, we analyze the initial radiologic findings, TNM stagings, surgical types, and radiologic features of recurrence, and correlate them with patient survival.

Design: A retrospective review of 93 patients who underwent resection for BAC from February 1989 to May 1999.

Patients: There were a total of 153 patients with BAC diagnosed during this period. Among them, 60 patients (39.2%) had diffuse disease and received medical therapy only, and the remaining 93 patients (60.8%), who had localized disease, underwent surgical resection. Patients who received surgical resection were enrolled in this study.

Measurements: Data regarding demographics, presentation symptoms, initial radiologic features, surgical type, tumor staging, recurrence status, radiologic patterns of recurrence, and survival were obtained from all patients.

Results: Female patients were significantly younger than male patients. Patients who were female, nonsmoking, undergoing curative surgery, lobectomy, or bilobectomy, and with early tumor staging and no nodal involvement had a better prognosis. Patients with a right lung tumor had a longer survival than those with a left lung tumor, with borderline significance. Among those who suffered from recurrent diseases, a second resection yielded a better survival. Multivariate analysis showed curative surgery, initial surgical type, recurrence status, radiologic patterns of recurrence, and duration from surgical resection to recurrence all had a significant impact on survival.

Conclusions: Those patients with localized, early-stage BAC who underwent curative surgery had a better survival. Patients with localized recurrence after the initial surgery warranted a second resection. Those with a diffuse radiologic pattern of recurrence and/or early recurrence had a worse prognosis. (CHEST 2000; 118:940--947)

Key words: bronchioloalveolar carcinoma; recurrence; survival; thoracic surgery

Abbreviation: BAC = bronchioloalveolar carcinoma

Bronchioloalveolar carcinoma (BAC) is an uncommon primary malignant pulmonary neoplasm, and it accounts for 2 to 14% of all pulmonary malignancies.[1,2] It was first described by Malassez[3] in 1876, as a bilateral, multinodular form of malignant lung tumor. In 1903, Musser[4] discovered another form: a diffuse, infiltrative type of BAC involving a single lobe or the entire lung simulating pneumonia. In 1953, Storey et al[5] recognized that the most frequent form was a solitary peripheral pulmonary nodule, and BAC was then disclosed as having three different major radiologic patterns.

According to World Health Organization categorization, BAC is a subtype of adenocarcinoma. The current definition of BAC is similar to the entity described by Liebow[6] in 1960 and includes the following: malignant neoplasms of the lung that have no evidence of extrathoracic primary adenocarcinoma, an absence of a central bronchogenic source, a peripheral parenchymal location, no distortion of the pulmonary interstitium, and neoplastic cells growing along the alveolar septa. The origin of the malignant cells is still controversial, and both unicentric and the multicentric hypotheses have been postulated. However, one article[7] favored a monoclonal origin for multifocal disease. It is generally accepted that BAC represents two distinct clinical entities of identical histologic appearance.[8,9] The solitary or focal form has a better prognosis following curative resection and less progress toward diffuse disease; the diffuse form (multinodules, diffuse, or infiltrating) tends to be relentlessly progressive with a worse prognosis regardless of intervention.[8-12] However, the previous literature mentions little about whether or not recurrent characteristics, such as early or late recurrence, recurrent radiologic patterns, and salvage surgery, could affect the patient's survival.

In this study, we reviewed Chinese BAC patients who had received surgical resection, to investigate the natural course of BAC following surgery and to analyze the prognostic factors of the disease. The importance of salvage surgery is also discussed.

MATERIALS AND METHODS

We retrospectively reviewed and analyzed the chart records and computer files of patients with a pathologic diagnosis of BAC following surgery at Veterans General Hospital-Taipei from February 1989 to May 1999. Veterans General Hospital-Taipei is a general teaching hospital with [is greater than] 2,500 beds. During the study period, BAC was diagnosed in 153 patients and 93 patients received surgical resection as the initial treatment modality. The preoperative workup included chest radiograph, fiberoptic bronchoscopy, pulmonary function test, chest CT scan, bone scan, and brain CT scan. All patients met the histopathologic criteria for a diagnosis of BAC, ie, an absence of an identifiable primary malignancy elsewhere, an absence of endobronchial carcinoma, a pattern of malignant cells growing along the alveolar walls, and preservation of the general interstitial framework of the lung.[13] Papillary tumors with well-developed fibrovascular cores were classified as papillary adenocarcinoma and excluded from the present study.

Each patient's clinical characteristics, including age, gender, smoking history, initial presenting symptoms, and the duration of symptoms before surgery, were recorded. All preoperative chest radiographs were reviewed to determine the presenting radiologic features of BAC. The radiologic features of BAC were classified as either nodular or infiltrating forms. The lesion was classified as an infiltrating form if it was a poorly delineated opacity without defined borders. A well-circumscribed lesion completely surrounded by pulmonary parenchyma was classified as a solitary pulmonary nodule. The type of surgery, surgical staging, recurrence status, location and radiologic pattern of recurrence, and the length of time from initial surgery to recurrence were all recorded. Each patient's disease was staged according to the TNM staging system.[14] Curative surgery was defined as a total removal of visible and/or palpable lesion(s) based on the surgeon's judgment, and the cut-end was free from tumor according to the pathologic report. Patients were followed until their death or last follow-up. Survival was defined as the time between date of surgery and date of death.

For the statistical study, the Kaplan-Meier method with a log-rank test was used for survival analysis, the Cox-regression method was used for multivariate survival analysis, and the Mann-Whitney test was used as a nonparametric test. SPSS statistical software (SPSS; Chicago, IL) was used for these analyses.

RESULTS

One hundred fifty-three cases of BAC were diagnosed in our hospital from February 1989 to May 1999. Among them, 60 patients (39.2%) had diffuse disease and received medical treatment only. The remaining 93 patients (60.8%), who had localized disease, underwent surgical resection initially. Of these 93 patients studied, 54 were men (58%) and 39 were women (42%), with a mean age of 66.9 years (range, 42 to 89 years). Female patients (63.2 [+ or -] 9.6 years) were significantly younger than male patients (69.6 [+ or -] 7.7 years; p = 0.002). Forty-one patients (44%) had a history of cigarette smoking. Forty patients (43%) were asymptomatic at the time of diagnosis. Cough was the most common presenting symptom (28 patients; 30.1%), followed by hemoptysis (12 patients; 12.9%), chest pain (6 patients; 6.5%), body weight loss (2 patients; 2.2%), and dyspnea (2 patients; 2.2%). Another three patients (3.2%) presented with delayed resolution of pneumonia. The mean duration of symptoms was 11.8 weeks (range, 0 to 107 weeks).

The pattern and frequency of the initial chest radiologic presentations of these 93 surgically resected BAC patients are listed in Table 1. A solitary peripheral nodule was the most frequent finding, occurring in 79 cases (84.9%), followed by an infiltrating or pneumonic mass in 11 cases (11.8%), multinodular lesions of the same side of the lung in 2 cases, and a mass with cavity in 1 case. The most frequent location of the tumor was the right upper lobe (37.6%), followed by the left upper lobe (22.6%), the right lower lobe and the left lower lobe (both 15.1%), and the right middle lobe (7.5%).

Table 1--Initial Chest Radiologic Patterns and Locations of 93 Surgically Resected [BACs](*)