Ann Thorac Surg 2003;75:1740-1744
© 2003 The Society of Thoracic Surgeons
Original article: general thoracic
Poor prognosis after lung resection for patients with adenosquamous carcinoma of the lung
Katsuhiro Nakagawa, MDa*,
Tsutomu Yasumitu, MDa,
Kenjirou Fukuhara, MDa,
Hiroyuki Shiono, MDa,
Masanori Kikui, MDb
a Departments of Surgery, Osaka Prefectural Habikino Hospital, Habikino, Osaka, Japan
b Department of Clinicopathology, Osaka Prefectural Habikino Hospital, Habikino, Osaka, Japan
Accepted for publication December 22, 2002.
* Address reprint requests to Dr Nakagawa, Division of Surgery, Osaka Prefectural Habikino Hospital, 3-7-1, Habikino, Habikino City, Osaka, Japan 583-8588.
e-mail: katuhiro{at}hbk.pref.osaka.jp
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Abstract
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BACKGROUND: We evaluated the prognosis of adenosquamous carcinoma of the lung after lung resection in comparison with other types of carcinoma.
METHODS: We retrospectively reviewed charts of patients who underwent lung resection for lung cancer.
RESULTS: Surgical outcomes for 30 patients with adenosquamous carcinoma of the lung, who were treated between 1976 and 1998, were compared with the surgical results for 1,219 patients similarly treated for adenocarcinoma or squamous cell carcinoma during the same period. Adenosquamous carcinoma comprised only 2.1% of 1,408 lung cancer cases treated by resection. The overall cumulative 5-year survival rate was only 6.2% for the patients with adenosquamous carcinoma, indicating a significantly poorer prognosis than for adenocarcinoma or squamous cell carcinoma.
CONCLUSIONS: The cumulative survival rate for patients with adenosquamous carcinoma in pathologic stages IA to IIB was similar to that of patients with stage IIIA adenocarcinoma or squamous cell carcinoma.
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Introduction
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Adenosquamous carcinoma of the lung is a rare disease. Reports suggest that 0.4% to 4.0% of lung cancer is adenosquamous [1–5]. One reason for this range is the lack of clearly defined criteria: the simple presence of both squamous cell carcinomatous and adenocarcinomatous tissue are defining criteria in the World Health Organization’s histologic classification [6]. As long as physicians are so unsure of what they are dealing with, it is not likely that a useful consensus regarding the prognosis of adenosquamous lung carcinoma will be established. If more rigorous criteria are applied, the sampled population for this relatively rare condition becomes even lower. It is not surprising that findings in studies of adenosquamous lung carcinoma vary so much. Although some investigators have reported that the prognosis is the same as for adenocarcinoma [4, 7], other reports indicate poorer prognosis for adenosquamous carcinoma than for adenocarcinoma or squamous cell carcinoma [8, 9]. To clarify the prognostic value of histologic identification, applying rigorous histologic diagnostic criteria we analyzed the results for 30 patients in our department who underwent lung resection for adenosquamous carcinoma of the lung, and we compared these with results with patients similarly treated for adenocarcinoma or squamous cell carcinoma.
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Patients and methods
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In our department 1,408 patients with lung cancer underwent surgical resection during the period from September 1976 through August 1998. Adenosquamous carcinoma was diagnosed in 30 cases (2.1%). The classification criteria were based on the histologic definition of adenosquamous carcinoma stipulated in the general rule for clinical and pathologic records published by the Japanese Lung Cancer Society [10]. According to these criteria, on routine microscopic examination using hematoxylin and eosin staining, when a sample from a tumor comprises at least 20% each of squamous cell carcinoma and adenocarcinoma the condition is classified as adenosquamous. During the same period, 652 patients were diagnosed with adenocarcinoma and 567 patients with squamous cell carcinoma.
The 5-year survival rate for the all stages was 42.1% in patients with adenocarcinoma and 42.8% in patients with squamous cell carcinoma, and the prognosis for adenocarcinoma or squamous cell carcinoma was closely similar at each pathologic stage. Consequently, we evaluated the patients with these two histologic types as a single group and carried out comparison with the adenosquamous group. T and N were evaluated according to the International Union Against Cancer (UICC) TNM staging system [11] and intrapulmonary metastasis was evaluated according to the criteria of the Japan Lung Cancer Society [10]. Table 1
lists characteristics of the patients. Between the two groups, there are significant differences in pathologic primary tumor and pathologic pleural invasion characteristics. No significant differences between the two groups were apparent for age, sex, postoperative pathologic lymph node metastases, pathologic distant metastasis, and pathologic stage. In all, 13 patients with adenosquamous carcinoma and 561 patients with adenocarcinoma or squamous cell carcinoma received radiotherapy or perioperative chemotherapy with platinum drugs. Perioperative treatment was similar for both groups.
All statistical analyses were conducted using the SAS program package (SAS Institute Inc, Cary, NC). The survival rates were calculated using the Kaplan-Meier method [12]. Statistical significance was evaluated with the log rank test, with significance set at p less than 0.05. The Cox proportional hazards model [13] was used to identify factors that had a significant influence on survival after lung resection.
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Results
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The cumulative postoperative survival rate at 5 years was 6.2% for the 30 patients with adenosquamous carcinoma was and 41.5% for the 1,219 patients with adenocarcinoma or squamous cell carcinoma. A significant difference (p < 0.0001) between these two groups (Fig 1)
was apparent.
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Fig 1. Comparative overall cumulative 5-year survival rate of study patients. The prognosis for patients with adenosquamous carcinoma (ADSQ) was significantly worse than for those with adenocarcinoma (AD) or squamous cell carcinoma (SQ). At 6.2% for the 30 patients with adenosquamous carcinoma, the 5-year survival rate was significantly lower (p < 0.0001, log rank test) than the 41.5% survival of 1,219 patients with adenocarcinoma or squamous cell carcinoma.
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At pathologic stages IA, IB, IIA, and IIB, the cumulative survival rates at 5 years were 9.7% for 18 patients with adenosquamous cell carcinoma and 55.4% for 771 patients with adenocarcinoma or squamous cell carcinoma. At each of these stages, there were significant differences (p < 0.0001) between the groups (Fig 2). At pathologic stage IIIA, the cumulative survival rate at 5 years was not reached by 5 patients (20%) with adenosquamous carcinoma and 284 patients (26.0%) with adenocarcinoma or squamous cell carcinoma. No significant differences were detected between these two groups (Fig 3).
At pathologic stages IIIB and IV, no significant differences were recognized between the groups. Cross-comparison of different pathologic stages indicates strong correlation cumulative survival rates at 5 years between the early stages of adenosquamous cell carcinoma and the later stages in the adenocarcinoma or squamous cell carcinoma. In particular, the prospects of survival for 18 adenosquamous cell carcinoma patients at stages IA to IIB were not significantly different from the prospects of 284 adenocarcinoma or squamous cell carcinoma patients at stage IIIA. The survival rate of 20.7% for the 448 adenocarcinoma and squamous cell carcinoma patients in stages IIIA, IIIB, and IV was not significantly different from the survival rate for the 18 patients with adenosquamous cell carcinoma. The results show that the survival rates for patients at stage IA to IIB with adenosquamous cell carcinoma are very poor, the same as the rates for patients with stage IIIA adenocarcinoma or squamous cell carcinoma. In other words the prognosis for early-stage adenosquamous cell carcinoma group was very poor, the same as for stage IIIA in the adenocarcinoma or squamous cell carcinoma group.
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Fig 2. Comparative cumulative 5-year survival rate at stages IA and IIB. At stages IA to IIB, there were significant differences (p < 0.0001) between the two groups. The 5-year survival rate was 9.7% for 18 patients with adenosquamous carcinoma (ADSQ) and 55.4% for 771 patients with adenocarcinoma (AD) or squamous cell carcinoma (SQ).
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Fig 3. Comparative overall cumulative 5-year survival rate at stage IIIA. At stage IIIA there were no significant differences between the two groups. The 5-year survival rate for 284 patients with adenocarcinoma (AD) or squamous cell carcinoma (SQ) was 26.0%, whereas 5 patients with adenosquamous carcinoma (ADSQ) failed to survive to year 5.
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Cause of death data were similar for both groups (Table 2).
Even after censoring cases involving patients who succumbed to another cause of death, we could not find any differences between the prognosis for the patients with adenosquamous carcinoma and for patients with adenocarcinoma or squamous cell carcinoma. Furthermore, even after calculating the prognosis for three separate groups (patients with adenosquamous carcinoma, adenocarcinoma, or squamous cell carcinoma), the prognosis remained the same for all three groups.
The Cox proportional hazards model was used to examine independent prognostic factors for resected patients with adenosquamous carcinoma and adenocarcinoma or squamous cell carcinoma (Table 3). Analysis revealed that in addition to histologic type, N factor, M factor, resection radicality, age, and sex were significant independent prognostic factors. The prognosis for patients with adenosquamous carcinoma was significantly (p < 0.0001) worse than for patients with adenocarcinoma or squamous cell carcinoma. The mortality rate for patients with adenocarcinoma and patients with squamous cell carcinoma was almost the same (relative risk 1.033). However, patients with adenosquamous carcinoma were 2.618 times more likely to die within 5 years than were patients with adenocarcinoma or squamous cell carcinoma. For all patients who died, the recurrence pattern was clearly evaluated by roentgenography, computed tomography, and other techniques. Table 4
shows the pattern of recurrent disease. No significant differences were apparent.
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Comment
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Partly because of low incidence, the clinicopathologic characteristics of adenosquamous carcinoma of the lung have not been clearly defined [1–5]. In this study we adhered to the diagnostic criteria of general rule for clinical and pathologic records of the Japan Lung Cancer Society [10]. The lack of generally agreed criteria also makes prognosis controversial. Some reports suggest poorer prognosis for adenosquamous carcinoma than for other non–small cell lung carcinomas [5, 7–9]. Data from Takamori and colleagues [9] indicate that, at all stages, the prognosis for adenosquamous carcinoma is poorer than for adenocarcinoma or squamous cell carcinoma. Similarly, Shimizu and associates [5] reported that the prognosis for adenosquamous cell carcinoma is statistically worse than for squamous cell carcinoma or adenocarcinoma because of the advanced pathologic stage of adenosquamous cell carcinoma. However, Hsia and colleagues [4] have reported that the survival rates of patients with adenosquamous carcinoma do not differ significantly from those with other histologic types.
Because our study is based on a small sample of 30 patients with adenosquamous carcinoma, it is unwise to overgeneralize from our results. Nevertheless, in stages IA to IIB, the prognosis for these patients was significantly worse than for those with adenocarcinoma or squamous cell carcinoma. At stage IIIA and beyond, there were no significant differences in survival rates between the histologic types. Steele and Netteshelm [14] and Ichinose and colleagues [15] have suggested that bipotential-undifferentiated cells may be present in adenosquamous tissue. Electron microscopy study of squamous carcinomas and adenocarcinomas revealed signs of dual differentiation along glandular and squamous lines [15]. Univariate analysis of our data indicated significantly greater progression of pathologic primary tumor and pathologic pleural invasion in adenosquamous carcinoma than in adenocarcinoma or squamous cell carcinoma. Shimizu and associates [5] also reported that the percentage of advanced T factor cases (T3 or T4) occurring among patients with adenosquamous carcinoma (43%) is larger than those with adenocarcinoma (24%). Although we found no pathologic lymph node metastasis factor differences between our two groups, both Hsia and colleagues [4] and Shimizu and associates [5] have reported finding more advanced N factors in adenosquamous carcinoma than in adenocarcinoma or squamous carcinoma and suggest that this progression is linked with poorer prognosis for adenosquamous carcinoma. Using the Cox proportional hazards model to identify the independent prognostic factors, we found that N factor, M factor, radicality of resection, age, sex, and histologic type were significant independent prognostic factors. Comparative findings that are more useful in the evaluation of prognosis for adenosquamous carcinoma will be forthcoming only if immunohistochemical or molecular techniques are applied to identify some unique characteristic that clearly separates adenosquamous carcinoma from more common non–small cell lung cancers. Subsequently it would be possible to establish internationally accepted diagnostic criteria for adenosquamous carcinoma.
Our findings indicate that, from our rigorously defined sample of adenosquamous carcinoma 30 patients, those in pathologic stages IA to IIB had a cumulative survival rate similar to that of stage IIIA adenocarcinoma or squamous cell carcinoma patients. In this study, the histologic type of carcinoma was a significant independent prognostic factor.
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References
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Abstract
Introduction
