165
20
Surgery for Bronchoalveolar Lung Cancer
Subrato J. Deb and Claude Deschamps
reported.6,7 Another distinct feature of BAC is the higher proportion of nonsmokers in comparison to the more common NSCLC.6,7 Only 25% to 30%
of patients with BAC have a history of heavy smoking.6 On the basis of histological fi ndings, BACs are divided into three subtypes: mucinous, nonmucinous, and a mixed form. Nonmucinous BAC is composed primarily of Clara cells or type 2 pneumocytes and accounts for 65% to 75% of all BAC. Mucinous BACs are differentiated toward bronchiolar goblet cells, and on gross examina- tion these tumors have a glistening appearance.
Mucin production can lead to bronchorrhea, characterized by the expectoration of water or mucoid material and is a late manifestation of advanced BAC. Three major patterns of BAC are visualized on high-resolution computerized tomography (HRCT).5,6,8 The most common, accounting for almost half of all cases, is a soli- tary nodule or mass. These nodules are often ill defi ned and often lack a solid component, the latter being more typical of invasive adenocarci- noma. Pseudocavitation, heterogeneous attenua- tion, pleural tags, and spiculation may be associated fi ndings.6 The second most common pattern (30%) is consolidation one or more seg- ments or lobes resembling pneumonia or air space disease. These tumors often produce mucin, which accounts for the heterogeneous attenua- tion on CT and has been associated with a worse outcome. Lastly, BAC can manifest radiographi- cally as multifocal disease.6 This multinodular form resembles that of metastatic disease or mili- tary tuberculosis. The nodules are often distrib- uted in a centrilobular fashion and can range in
20.1. Definition of
Bronchoalveolar Carcinoma
Bronchoalveolar carcinoma (BAC) is a distinct subtype of non-small cell lung adenocarcinoma classifi ed by the World Health Organization (WHO) as a peripheral well-differentiated neo- plasm demonstrating lepidic spread along preexisting alveolar structures.1–4 An important histological feature is the preservation of the underlying lung architecture and the absence of invasion into stroma, pleura, or lymphatics of all pure BACs.1–4 Lung adenocarcinomas with a BAC component are now more appropriately classifi ed as adenocarcinomas, mixed subtype.1 Despite the WHO designation as a subtype of adenocarci- noma, BAC has pathological, radiologic, and clinical features that are distinct from those of adenocarcinomas.
Bronchoalveolar carcinomas are rare and account for 3% to 9% of all newly diagnosed lung cancers.1–7 Recent data suggest an increase in the occurrence of pure BAC in conjunction with lung adenocarcinoma.3–7 Solitary peripheral BACs have an excellent prognosis, however, a consen- sus defi nition of a minimally invasive BAC with a favorable prognosis has not been achieved.1
20.1.1. Clinical Features of Bronchoalveolar Carcinoma
The prevalence of BAC is higher in women than other types of non-small cell lung cancer (NSCLC), comprising one third to one half of all cases
size from 1mm to 3cm in diameter.8 Computed tomography appearances are diverse and include well-defi ned or poorly defi ned nodules involving one or both lungs. It is uncertain whether multi- focal BAC is the result of synchronous primary lung cancers or aerogenous metastases.
Positron emission tomography (PET) has been utilized to evaluate patients with BAC. In a number of F-18 fl uorodeoxyglucose positron tomography (FDG-PET) studies, BAC has been reported to have lower FDG uptake compared with other primary lung cancers.9,10 The reason for the low uptake by BAC is unknown, but may be caused by poor cellularity or slow cell prolif- eration of the tumor. The utility of FDG-PET scan may be to identify mulitfocal BAC.10
20.1.1.1. Ground-Glass Opacification
Ground-glass opacity (GGO) is a fi nding on HRCT images that is described as a hazy, increased attenuation of the lung tissue with preservation of the bronchial and vascular margins. This non- specifi c fi nding may be noted in many types of pulmonary disease, including atypical adenoma- tous hyperplasia (AAH), defi ned by the WHO as a premalignant lesion.11–13 Focal areas of ground- glass attenuation may also be an early sign of localized BAC and is considered a marker for the identifi cation of minimally invasive BAC.11,12 Nakajima studied 20 consecutive resected local- ized GGO for histopathological correlation.11 These authors identifi ed BAC in 50%, AAH in 25%, fi brosis in 15%, and invasive adenocarci- noma in 10%. Whether GGOs should be resected or followed is controversial, as the natural history of these lesions is not clearly defi ned. When radiographic progression of GGO on HRCT is demonstrated, as evidenced by increasing size or the appearance of a solid component or increased density, AAH or BAC is commonly identifi ed and surgical intervention is justifi ed.13
20.2. Surgical Treatment of Bronchoalveolar Carcioma
20.2.1. Available Published Data
A computerized search from the National Center for Biotechnology Information (NCBI) at the U.S.
National Library of Medicine was conducted.
Articles published from 1990 to the present time focusing on the surgical treatment of BAC were selected. Additional key references cited in a recent treatise were also included in the search.14 Manuscripts focusing on radiological, pathologi- cal, or biological aspects of BAC as well as case reports were excluded from analysis. Articles cited in retrieved publications and studying a large number of patients were reviewed.
There is no meta-analysis, randomized, con- trolled trial, or systematic reviews of rand omized, controlled trials in the literature encompassing the above specifi cations. It is not possible to provide the highest level of evidence; as such, our conclusions are based upon limited scientifi c foundation. For the purposes of this writing, we selected well-conducted prospective and retro- spective case control or cohort studies and case series addressing the defi ned criteria. Prior to the WHO classifi cation, publications reviewing BAC applied widely varying histological criteria that has contributed to the lack of randomized data in the literature.
20.2.2. Review of Published Surgical Data for Bronchoalveolar Carcinoma
20.2.2.1. Traditional Resection of Bronchoalveolar Carcinoma
Surgery remains the cornerstone of therapy for BAC as with other forms of early-stage NSCLC.
Patients with resected BAC generally have a better survival and lower recurrence rate than their NSCLC counterparts. The isolation of signifi cant prognostic factors for BAC has been hampered by the relative rarity of pure BAC, the intermingling of BAC with adenocarcinomas in the literature, the evolution in the pathological criteria, and the variability of treatment.3
The Lung Cancer Study Group (LCSG) reviewed their experience with BAC between 1977 and 1988.15 Of 1618 total patients, 235 patients with pure BAC were evaluated, representing the largest reported series of surgically resected BAC to date.
Strict criteria were used to qualify patients for the study, including the demonstration of lepidic growth and the preservation of pulmonary archi- tecture. All patients underwent thoracotomy with surgical resection and lymph node staging. Of
the 235 patients, 158 (67%) were T1 and 85% were N0. This study noted a higher incidence of female involvement and more nonsmokers among its cohort. The authors found that resected BAC patients were earlier stage than patients with non-BAC adenocarcinomas and squamous cell carcinoma (85% were stage I). The long-term mortality rate for stage IA BAC was reported at 7% per year, increasing to 12% per year for IB and 40% per year for stage II and III. Higher stage BAC (2 and 3) has a higher mortality rate than other types of lung cancer. The authors concluded that early resection is particularly important in patients with BAC.
Daly reviewed 134 patients with BAC who underwent surgical resection and analyzed factors that infl uenced survival.16 Most of the lesions (58%) were solitary pulmonary masses, 11% were solitary pulmonary nodules, and 10%
of the patients had multiple lesions. Lung carci- nomas were accepted as BAC if the tumor dem- onstrated growth along lung architecture without evidence of invasion. Anatomical lung resections were performed in 115 patients and 19 underwent wedge excision, with 70% undergoing lobectomy.
Complete mediastinal and pulmonary lymph node sampling was performed in all patients. The authors found only a 7.5% rate of lymph node metastasis, most were N2 nodal disease. Similar to the LCSG study, most patients were early stage I. The operative mortality was 1.5%. At a median follow-up of 8 years, 37.5% developed recurrent disease, primarily within the thorax. Despite early stage at resection, the authors noted 28 recurrences (62%) were among patients with stage IA and IB disease (10 T1 and 18 T2). Overall estimated 5- and 10-year survival for patients undergoing curative resection (122 patients) was 60.8% and 28.1%, respectively; 5-year survival for patients with T1N0 tumors was 90.5% com- pared to 55.4% for patients with T2N0 tumors.
This difference was signifi cant. Five-year sur- vival for multicentric disease was 35.9% for unilateral and 0% for bilateral disease. It can be concluded from this study that the survival is more infl uenced by the extent of lung in - volvement (T stage) than by lymphatic metasta- ses and that unilateral multifocal disease can be considered for resection; however, bilateral disease should not be operated upon. Addition- ally, these authors found that complete resection
offered a signifi cant survival advantage com- pared to incomplete resection and that the extent of pulmonary resection did not infl uence survival.
Dumont reviewed retrospectively reviewed 105 patients who underwent surgical treatment for BAC over a 19-year period.17 Most patients pre- sented with a solitary pulmonary nodule (85%).
Surgical treatment consisted of lobectomy in 87%, bilobectomy in 3%, pneumonectomy in 7%, and 3% underwent wedge excision. All patients underwent complete mediastinal lymph node sampling. Again, the majority of patients (73%) were stage I; however, in contrast to the Daly study, there was a higher incidence of nodal disease with 28 patients (29%) having either N1 or N2 metastasis. Overall survival at 5 and 10 years was 48% and 39%, respectively, with 65%
5-year survival for stage I. Unlike Daly’s study, these authors noted no statistically signifi cant difference in survival between T1 and T2;
however, there was a signifi cant difference between N0 and N1 and between N0 and N2 metastasis. In addition, these authors found no difference between the mucinous and mucinous forms of BAC, unlike previous reports.
Another retrospective review by Regnard eval- uated prognostic factors among 70 patients who underwent surgical treatment for BAC.18 Four patients were unresectable. Of the remaining 66 remaining patients, 51 underwent lobectomy, 4 had bilobectomy, and 11 underwent pneumonec- tomy. There is no mention as to the extent of lymph node sampling or dissection in this paper.
Similarly to previous studies, most patients were stage I (50%). This study had a large percentage of advanced cancers with 25 patients having stage III tumors. There were seven patients with diffuse disease and not staged according to TNM.
The overall 5-year survival was 30%. These authors noted that tumors with nodular mor- phology had a better survival of 39% compared to those with pneumonic or diffuse types. In addition, those patients who were completely resected had a 5-year survival of 34% compared to 0% 5-year survival in those who were in completely resected. Multivariate analysis con- fi rmed the association of early TNM stage and complete resection with a favorable outcome.
Of 61 patients who were completely resected, 59% developed tumor recurrence, primarily
within the thorax, at a mean time period of 21 months, with most recurrence among patients with infi ltrative tumors in comparison to the nodular type. Recurrence based on TNM was not determined.
Ebright reviewed 100 surgically treated patients with adenocarcinomas with various degrees of BAC features. These authors evaluated histologi- cal features that predicted surgical outcome.
They classifi ed tumors as pure BAC, BAC with focal invasion, and adenocarcinoma with BAC features.19 This is a pathological review and the extent of surgical resection is not stated. Of the 100 patients, 47 were classifi ed as pure BAC, 21 as BAC with focal invasion, and 32 as adenocarci- noma with BAC features. These authors con- fi rmed the fi ndings of Daly, that nodal metastasis was infrequent, with 2 of 47 patients with pure BAC. At a median follow-up of 86 months, the median disease free interval was 80 months without signifi cant differences among the three groups. However, those patients exhibiting a pneumonic pattern on radiography had the short- est interval to recurrence at 19 months. Survival analysis also identifi ed the pneumonic subtype to have the shortest survival compared to unifocal and mulitfocal patterns. Multivariate analysis only identifi ed stage (I/II vs. III/IV) to have a signifi cant impact on disease-free and overall survival. Of the 47 patients with pure BAC, 9 patients had a new cancer develop and 12 had recurrent disease. Table 20.1 summarizes some of the important fi ndings of the above studies. From the above-mentioned studies, we can conclude that a complete resection is essential to obtaining acceptable long-term results and there appears to be a signifi cant incidence of recurrent disease, with most recurrences occurring within the thorax, unlike other NSCLC. Lymph node sam- pling or dissection should be undertaken to accu-
rately stage the patient, although the incidence of nodal metastasis is unclear. The pattern of radio- graphic appearance may be useful in determina- tion of prognosis, as the infi ltrative pneumonic form is more malignant than a solitary nodule.
20.2.3. Is Pure Bronchoalveolar Carcinoma a Candidate for Limited Resection
Several studies performed retrospective analysis of BAC, specifi cally examining pathological data- bases in a retrospective manner to compare the outcome of pure BAC and invasive adenocarcino- mas of similar stage. The results uniformly reveal that pure BAC has a lower incidence of lymph node spread and better outcome in comparison to same-stage adenocarcinomas. In contrast to the historical experience noted above, it may be possible to perform lesser resection for mini- mally invasive pure BAC.
In the largest such study, Breathnach reviewed stage I BAC and stage I adenocarcinoma other than BAC in 138 patients.20 There were 105 patients with adenocarcinoma and 33 patients with BAC. The pathological diagnoses of speci- mens were consistent with the recent WHO clas- sifi cation. Nineteen patients (58%) with BAC and 69% of patients with adenocarcinoma had under- gone lobectomy. Additional 39% among the BAC group had limited resections and 17% in the adenocarcinoma group had wedge resections.
The median follow-up for the BAC group was 6.2 years and for the adenocarcinoma group was 5.9 years. Recurrence was similar in both groups being 36% of patients with BAC and 37% among the adenocarcinoma patients. There was no sig- nifi cant difference in disease-free survival (DFS) in patients with BAC resected by lobectomy versus limited resection, although there was a trend toward longer DFS in patients who under-
TABLE 20.1. Comparison of published surgical series in the treatment of BAC.
Study Year Patients LN Mets (%) Recurrence rate (%) Survival 5 year 10 years
LCSG15 1989 235 15 7%/year Na na
Daly16 1991 134 8 38 61 28
Dumont17 1998 97 29 na 48 39
Regnards18 1998 42 na 59 30 na
Ebright19 2002 100 4 45 Na na
Abbreviations: LCSG, Lung Cancer Study Group; LN Mets, lymph node metastasis; na, not applicable.
went lobectomy (83% vs. 66%). In contrast, patients with adenocarcinoma who underwent lobectomy had a signifi cantly longer DFS than those patients treated with limited resection (76%
vs. 31%). Patients with BAC lived longer with a 5- year survival of 83% compared to adenocarci- noma with a survival of 63%. There was no signifi cant difference in survival among BAC patients treated with lobectomy or limited resec- tion and interestingly between patients with T1 or T2 lesions.
Two other smaller studies have examined pathological data and retrospectively compared BAC and invasive adenocarcinoma. Rena com- pared 28 patients with stage I peripheral nodular BAC and 80 patients with stage I peripheral adenocarcinoma.21 Both 5-year disease-free and long-term survival were signifi cantly higher in patients with BAC (81 vs. 51% and 86 vs. 71%, respectively). In the other study, Sakurai investi- gated 25 patients with BAC with 83 patients with other adenocarcinoma.22 These authors found lymph node involvement in 36% of adenocarci- noma patients but none for any BAC lesions. At a median duration of follow-up of 5.1 years, the DFS was 100% for BAC compared to 64% for other adenocarcinomas. These studies in addi- tion to the study by Breathnach suggest that the biological behavior of early-stage pure BAC is distinctly different than similar stage adenocar- cinomas and probably NSCLC in general. The traditional approaches to NSCLC may not neces- sarily apply to the minimally invasive tumors.
20.2.4. Limited Resections for Bronchoalveolar Carcinoma
The LCSG published a randomized, prospective trial comparing limited resection (segmentec- tomy or wedge resection) with lobectomy for
T1N0 NSCLC. This study clearly demonstrated the inferior results of limited resection when compared to lobectomy in survival and loco- regional recurrence.23 More recently, Miller pub- lished the results of surgical resection for NSCLC 1cm or less in diameter.24 These authors identi- fi ed a 7% incidence of lymph nodal spread and at 43 months median follow-up, 18% of patients developed recurrent disease. These authors note that patients who underwent lobectomy had a signifi cantly better survival and less recurrence than patients who underwent lesser resections.
Despite these results, based on the favorable behavior of pure BAC, several authors have recently published the surgical results of lesser resections for localized BAC. These results of four surgical series described below are tabulated in Table 20.2.
In a prospective review of limited resection for small peripheral BAC, the authors studied 42 patients with tumors 2cm or less. Of these patients, 34 underwent wedge resection.25 The authors converted to lobectomy if invasive features were identifi ed at surgery. At 30-month follow-up, all patients who underwent lesser resection are alive and without recurrence. In another study by Watanabe, 17 patients with pure ground-glass attenuation on HRCT underwent limited pulmonary resection.26 Fourteen under- went wedge excision and 3 underwent segmentec- tomy. No nodal dissection was performed. At 32-month-follow up, no death or cancer recur- rence is noted. These authors recommend wedge resection with video-assisted thoracoscopic surgery (VATS) as a minimally invasive curative surgery of this type of cancer. In another pro- spective analysis, Nakata examined 33 patients with pure GGO lesion that were 1cm or less.27 Thoracoscopic wedge resection was completed in these 33 patients with the fi ndings of BAC in 23,
TABLE 20.2. Results of limited resection.
Study Year Patients Criteria for resection Follow-up (months) Recurrence (%) Death (%)
Yamato25 2001 42 BAC <20mm 30 0 0
Watanabe26 2002 17 Pure GGA 32 0 0
Nakata27 2003 33 Pure GGO <1cm 18 0 0 Yamada28 2004 28 Pure GGO <2cm 29 0 0 Abbreviations: BAC, bronchoalveolar carcinoma; GGA, ground-glass attenuation; GGO, ground glass opacity.
AAH in 9, and adenocarcinoma in 1. At median follow-up of 18 months, there has been no evi- dence of tumor recurrence or postoperative death. These authors recommend lobectomy and mediastinal dissection for mixed GGO (those revealing heterogeneous attenuation with a solid component) and pure GGO larger than 1cm because of the higher incidence of invasive ade- nocarcinoma among these lesions. Yamada eval- uated 39 patients who demonstrated pure GGO less than or equal to 2cm on HRCT.28 Twenty- eight patients underwent wedge excision and 11 underwent segmentectomy or lobectomy, 9 patients had multiple lesions. The authors divided the fi nal pathology based on the extend of fi bro- blastic proliferation and utilized Naguchi’s clas- sifi cation for small adenocarcinomas to stratify their results. Of the 39 patients, 29 patients had localized BAC without active proliferation (Noguchi A or B). At a mean follow-up of 29 months, no death or recurrence was noted among the localized BAC patients. The above studies support the notion that limited resections can be performed pure BAC, however, direct compari- son with formal anatomical resection has not been made in a prospective manner.
20.2.5. Limited Resection Versus Traditional Resection
Three retrospective studies have compared limited resection by wedge excision to anatomi- cal resection by lobectomy or segmentectomy.
The major limitation of all three studies are the small number of patients undergoing limited resections and the last study described below failed to reach a statistical difference.
In the evaluation by Okubo, the authors studied 119 patients with BAC. Among this group, 58 patients had lesions larger than 3cm and 14 patients had multiple lesions.29 The median follow-up was 7 years; these authors noted an overall survival of 69% at 5 years and 57% at 10 years among the 107 patients who underwent resection. The authors identifi ed wedge resection and nodal involvement as having a negative impact on survival. Although this is a large study of patients, it should be noted that the study group included only 17 patients with pure BAC, with the remainder of patients having adenocar-
cinoma and various percentages of BAC. In another retrospective analysis, Liu reviewed 153 patients with BAC, of which 93 underwent surgi- cal resection.30 Most patients presented with a solitary pulmonary nodule (85%). Eighty patients underwent either lobectomy or bilobectomy and 7 were treated with pneumonectomy. Only 7 patients underwent wedge excision, for reasons not clearly defi ned. Most patients (66%) were stage I. Patients who underwent lobectomy or bilobectomy noted a higher survival although the wedge group was very small. Nodal involvement was noted to have a signifi cant negative impact on survival. Lastly, Furak analyzed 67 patients with BAC in a retrospective analysis.31 Among the 55 patients without multifocal disease, surgical procedures included anatomical resection in 49 patients and only 6 patients underwent wedge excision. Histological analysis conformed to current WHO guidelines. Almost 30% of patients had lymph node metastasis and the overall 5-year survival was 62%. When comparison between wedge resection was made against lobectomy and pneumonectomy, the 5-year survival favored anatomical resection (60% vs. 37%) but did not reach statistical signifi cance.
20.2.6. Defining Criteria for Limited Resection
As evident in the previous reviewed studies, the criteria applied to select patients for limited resection are unclear, with some parameters infl uenced by subjective bias. To better defi ne objective criteria, several authors have focused on HRCT fi ndings that may better predict those patients who should undergo limited resection.32–37 The specifi c criteria found in these studies are summarized in Table 20.3.
20.2.7. Multifocal and Advanced Bronchoalveolar Carcinoma
Mulitfocal disease has been shown to have favorable outcomes in several published series evaluating BAC.16,17,19 In addition, investigators have reported the effi cacy of resecting multiple synchronous or metachronous NSCLC.38–40 Daly found a survival around 36% at 5-year survival for unilateral multicentric disease but no survi-
vors with bilateral multicentric disease.16 Donker evaluated the impact of surgery and chemother- apy in patients with advanced BAC.41 These authors’ evaluated 126 patients, and 51 patients (41%) had advanced disease (stages IIIb and IV).
Surgery was associated with prolonged survival in patients with mulitfocal disease in comparison to supportive care. The median survival reported was better among patients with multifocal lesions confi ned to a single lobe than multiple lobes.
Interestingly, those patients who underwent surgery plus chemotherapy did not demonstrate a survival advantage to those who underwent surgery alone. One signifi cant limitation to this retrospective analysis is that the pathology specimens were not re-reviewed to confi rm the diagnosis of BAC. In another analysis, Roberts evaluated 73 patients with BAC, of whom 14 patients had multifocal disease without evidence of lymph node metastasis.42 These authors note an overall 5-year survival after resection of mul- tifocal BAC at 64%; in contrast to the previous study, these authors found no difference is sur- vival between unilateral and bilateral distribution.
With more diffuse and bilateral disease, the survival is dismal and often less than 1 year. The tendency of BAC to metastasize locally within the thorax has prompted evaluation of radical local therapy. Patients with the mucinous variety of BAC can experience severe disabling bronchor- rhea or refractory hypoxia, decreasing the quality of life. Zorn and others have reported successful single- and double-lung transplant for patients with advanced BAC.43,44 Although symptom relief
was impressive, the recurrence rate of the origi- nal tumor is high. The indication for lung trans- plantation in this situation remains controversial.
Others have reported successful palliative pneu- monectomy in select patients with unequal distribution of disease.45 The effi cacy of this pro- cedure remains to be proven.
20.2.8. Molecular Targeting Therapy for Advanced Bronchoalveolar Carcinoma
The epidermal growth factor receptor (EGRF) has recently emerged as a leading target for the treatment of NSCLC. The EGRF tyrosine kinase inhibitors, gefi tinib and erlotinib, have been found to be effective in some patients with in advanced BAC.46–48 Interestingly, the greatest response rates have been reported in women and never smokers.
20.3. Summary of Surgical Data
Prior to 1999, the WHO classifi cation of BAC sur- gical series included pure BAC as well as adeno- carcinoma with various degrees of BAC. This conglomeration may have contributed to the dis- crepancies in outcome and the overall poor outcome of resected BAC. There is no random- ized level 1 data to draw defi nite conclusions. The following is a synopsis of the major fi ndings and conclusions.
1. Bronchoalveolar carcinoma is curable with appropriate surgical therapy; incomplete resec- tion results in dismal prognosis.
2. The incidence and value of lymph node dissection is not clearly defi ned.
3. The prognosis of BAC is dependent on its presenting CT appearance.
4. Stage I pure BAC biologically behaves in a more favorable manner than similar stage inva- sive adenocarcinomas and may be a candidate for lesser resections. Level of evidence is 2+ and rec- ommendation grade is B.
5. Patients with pure BAC, presenting as GGO less than 1cm, may be candidates for limited resection with excellent early results. These patients will have to be identifi ed prior to surgery based on specifi c HRCT characteristics. Level of evidence is 2++ and recommendation grade is B.
TABLE 20.3. Preoperative predictors of favorable outcome to limited resection.
Total patients Predictor for Study Year analyzed favorable outcome Nakamura 2004 100 Pure GGO <2cm Nakata37 2005 146 GGO opacity ration >90%
Higashiyama36 1999 206 BAC component of peropheral Ad Ca >50%
Suzuki35 2002 1540 Pure GGO component Namori34 2003 100 Single peak at low CT
number on histogram Kodama33 2001 104 BAC with GGO area >50%
Matsuguma32 2004 90 GGO area >50%
Abbreviations: Ad Ca, adenocarcinoma; BAC, bronchoalveolar carcinoma;
CT, computed tomography; GGO, ground glass opacity.
6. All other patients with BAC should undergo standard anatomical lung resection based on pulmonary function capacity. This is supported by randomized data. Level of evidence is 1+ and recommendation grade is A.
7. Patients with ipsilateral or bilateral multifo- cal disease may be candidates for aggressive surgical resection if complete resection can be accomplished.
8. There may be a role for palliative surgical intervention with pneumonectomy or lung trans- plantation in select patients for symptom control.
This is controversial.
9. Patients with unresectable advanced disease should be enrolled into appropriate clinical trials.
EGFR tyrosine kinase inhibitors hold future promise.
20.4. Opinion of the Authors
It is our opinion that until longer follow-up and randomized, prospective data is available, the standard therapy for patients presenting with early-stage BAC should be complete anatomical resection and complete mediastinal lymph node dissection. Patients with GGO that are observed to change after a period of 3 to 6 months should undergo resection. If adenocarcinoma is identi- fi ed on intraoperative frozen section analysis, complete surgical resection should be performed.
As we have shown previously,24 even cancers less than 1cm can result in recurrence and systemic metastasis. We reserve limited resection only for
those patients with compromised lung function who would not tolerate a formal lung resection.
Thorascopic techniques can be applied success- fully in the management of early-stage lung cancer without compromising the oncologic principles and should be tailored to each indi- vidual surgeon’s comfort level.
Patients with multifocal disease, either unilat- eral or bilateral, are candidates for parenchymal- sparing lung resection. The benefi t of lobectomy in these patients is not supported and in our practice, multiple wedge resections and medias- tinal lymph node dissection is performed. Pallia- tive pneumonectomy should be performed for patients with severe incapacitating bronchorrhea or refractory hypoxia.
Future studies will need to evaluate in a ran- domized prospective analysis, if patients with pure BAC presenting as GGO should undergo limited resection or traditional surgery. With the survival benefi t demonstrated for early-stage lung cancer treated with postoperative adjuvant therapy, further studies need to be done using EGFR inhibitors in this application specifi cally in patients with BAC.
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