Skip to main content

Advertisement

SpringerLink
Log in

Emerging approaches to advanced bronchioloalveolar carcinoma

  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Bronchioloalveolar carcinoma (BAC) is a subtype of non-small cell lung adenocarcinoma that has distinct epidemiologic, histologic, radiographic, and clinical features. The strict pathologic definition requires an absence of any invasion through the basement membrane into pulmonary parenchyma, but there is a growing consensus based on recent clinical studies that this diagnosis should be considered to be based on the clinical features of diffuse ground-glass opacities with minimal or no extra-thoracic spread and histology demonstrating adenocarcinoma with a lepidic growth pattern characteristic of BAC, even if there is a component of invasive adenocarcinoma. Although unifocal or even potentially oligometastatic disease is appropriately treated with resection, advanced BAC is generally treated with systemic therapy. However, multifocal BAC may be indolent enough to follow asymptomatic patients without any systemic therapy if patients are comfortable with this approach, because the rate of disease progression may be slow enough to warrant no therapy for many months or even years. For patients who have symptoms and/or clear evidence of progression over a short interval, standard chemotherapy is appropriate, but I would consider treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib to be the most appropriate initial therapy. This is based on the well-documented activity of the EGFR TKIs erlotinib and gefitinib, the latter no longer commercially available in advanced BAC. Advanced BAC is now emerging as an area of significant research, and clinical trials are particularly appealing considerations for such patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Liebow A: Bronchiolo-alveolar carcinoma. Adv Intern Med 1960, 10:329–358.

    PubMed  CAS  Google Scholar 

  2. Auerbach O, Garfinkel L: The changing pattern of lung carcinoma. Cancer 1991, 68:1973–1977.

    Article  PubMed  CAS  Google Scholar 

  3. Barsky SH, Grossman DA, Ho J, et al.: The multifocality of bronchioloalveolar lung carcinoma: evidence and implications of a multiclonal origin. Mod Path 1994, 7:633–640.

    CAS  Google Scholar 

  4. Read WL, Page NC, Tierney RM, et al.: The epidemiology of bronchioloalveolar carcinoma. Proc Am Soc Clin Oncol 2002, 21:A#1267.

    Google Scholar 

  5. Ebright MI, Zakowski MF, Martin J, et al.: Clinical pattern and pathologic stage but not histologic features predict outcome for bronchioloalveolar carcinoma. Ann Thorac Surg 2002, 74:1640–1647. Provides key observations about BAC subsets and clinical behavior in a large surgical series from MSKCC.

    Article  PubMed  Google Scholar 

  6. Shraufnagel D, Peloquin A, Pare JAP, et al.: Differentiating bronchioloalveolar carcinoma from adenocarcinoma. Am Rev Respir Dis 1982, 125:74–79.

    Google Scholar 

  7. Barkley JE, Green MR: Bronchioloalveolar carcinoma. J Clin Oncol 1996, 14:2377–2386.

    PubMed  CAS  Google Scholar 

  8. Grover FL, Piantadosi S, Lung Cancer Study Group: Recurrence and survival following resection of bronchioloalveolar carcinoma of the lung--the Lung Cancer Study Group experience. Ann Surg 1989, 209:779–790.

    Article  Google Scholar 

  9. Detterbeck FC, Jones DR, Funkhouser WK Jr: Bronchioloalveolar carcinoma. In Diagnosis and Treatment of Lung Cancer: An Evidence-Based Guide for the Practicing Clinician. Edited by Detterbeck FC. Philadelphia: WB Saunders; 2000:394–407.

    Google Scholar 

  10. National Cancer Institute: Cancer Statistics Review 1973–1981. Washington, DC: US Government Printing Office; 1990: DHHS publication no (NIH) 90-2789.

    Google Scholar 

  11. Falk RT, Pickle LW, Fontham ETH, et al.: Epidemiology of bronchioloalveolar carcinoma. Cancer Epidemiol Biomarkers Prev 1992, 1:329–334.

    Google Scholar 

  12. Perk K, Hod I: Sheep lung carcinoma: an endemic analogue of a sporadic human neoplasm. J Natl Cancer Inst 1982, 69:747–749.

    PubMed  CAS  Google Scholar 

  13. Stephens HB, Shipman SJ: Pulmonary alveolar adenomatosis. J Thorac Surg 1950, 19:589–603.

    Google Scholar 

  14. Heimann HL, Samuel E: Pulmonary adenomatosis: case report. S Afr Med J 1953, 27:934–935.

    PubMed  CAS  Google Scholar 

  15. Shipman SJ, Stephens HB, Binkley FM: Pulmonary alveolar adenomatosis. Am Rev Tuberc 1949, 60:788–793.

    PubMed  CAS  Google Scholar 

  16. Mornex JF, Thivolet F, De las Heras, et al.: Pathology of human bronchioloalveolar carcinoma and its relationship to the ovine disease. Curr Top Microbiol Immunol 2003, 275:225–248.

    PubMed  CAS  Google Scholar 

  17. Yousem SA, Finkelstein SD, Swalsky PA, et al.: Absence of jaagsiekte sheep retrovirus DNA and RNA in bronchioloalveolar and conventional human pulmonary adenocarcinoma by PCR and RT-PCR analysis. Hum Pathol 2001, 32:1039–1042.

    Article  PubMed  CAS  Google Scholar 

  18. Daly RC, Trastek VF, Pairolero PC, et al.: Bronchioloalveolar carcinoma: factors affecting survival. Ann Thorac Surg 1991, 51:368–377. Good general discussion of presentation and clinical characteristics of BAC.

    Article  PubMed  CAS  Google Scholar 

  19. Edgerton F, Rao U, Takita H, et al.: Bronchio-alveolar carcinoma: a clinical overview and bibliography. Oncology 1981, 38:269–273.

    Article  PubMed  CAS  Google Scholar 

  20. Levinsky WJ, Kern RA: Fluid, electrolyte, and protein depletion secondary to the bronchorrhea of pulmonary adenomatosis: a complication heretofore unreported. Am J Med Sci 1952, 223:512–521.

    Article  PubMed  CAS  Google Scholar 

  21. Homma H, Kira S, Takahashi Y, et al.: A case of alveolar cell carcinoma accompanied by fluid and electrolyte depletion through production of voluminous amounts of lung liquid. Am Rev Respir Dis 1975, 111:857–862.

    PubMed  CAS  Google Scholar 

  22. Wislez M, Massiani MA, Milleron B, et al.: Clinical characteristics of pulmonic-type adenocarcinoma of the lung. Chest 2003, 123:1868–1877.

    Article  PubMed  Google Scholar 

  23. Heyneman LE, Patz EF: PET imaging in patients with bronchioloalveolar carcinoma. Lung Cancer 2002, 38:261–266.

    Article  PubMed  Google Scholar 

  24. Higashi K, Ueda Y, Seki H, et al.: Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 1998, 39:1016–1020.

    PubMed  CAS  Google Scholar 

  25. Travis WD, Colby TV, Corrin B, et al.: Histologic typing of lung and pleural tumors. In World Health Organization International Histological Classification of Tumors. Berlin: Springer Verlag; 1999:5.

    Google Scholar 

  26. Kris MG, Sandler A, Miller VA, et al.: Cigarette smoking history predicts sensitivity to erlotinib (Tarceva): results of a phase II trial in patients with bronchioloalveolar carcinoma (BAC). Proc Am Soc Clin Oncol 2004, 23:A#7062.

    Google Scholar 

  27. Franklin WA, Chansky K, Gumerlock PH, et al.: Association between activation of ErbB pathway genes and survival following gefitinib treatment in advanced BAC (SWOG 0126). Proc Am Soc Clin Oncol 2004, 23:A#7015.

    Google Scholar 

  28. Okubo K, Mark EJ, Flieder D, et al.: Resection of multifocal non-small cell lung cancer when the bronchioloalveolar subtype is involved. J Thorac Cardiovasc Surg 1999, 118:702–709.

    Article  PubMed  CAS  Google Scholar 

  29. Breathnach OS, Ishibe N, Williams J, et al.: Clinical features of patients with stage IIIB or IV bronchioloalveolar carcinoma of the lung. Cancer 1999, 86:1165–1173.

    Article  PubMed  CAS  Google Scholar 

  30. Donovan WD, Yankelevitz DF, Henschke CI, et al.: Endobronchial spread of bronchioloalveolar carcinoma. Chest 1993, 104:951–953.

    PubMed  CAS  Google Scholar 

  31. Feldman ER, Eagan RT, Schaid DJ: Metastatic bronchioloalveolar carcinoma and metastatic adenocarcinoma of the lung: comparison of clinical manifestations, chemotherapeutic responses, and prognosis. Mayo Clin Proc 1992, 67:27–32.

    PubMed  CAS  Google Scholar 

  32. Hidaka N, Hidaka Y, Tajima Y, et al.: Bronchioloalveolar carcinoma presenting aerogenous metastasis to the upper airway. Eur J Cancer 1996, 32A:1261–1262.

    Article  PubMed  CAS  Google Scholar 

  33. Breathnach OS, Kwiatkowski DJ, Finkelstein DM, et al.: Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease. J Thorac Cardiovasc Surg 2001, 121:42–47.

    Article  PubMed  CAS  Google Scholar 

  34. Noguchi M, Morikawa A, Kawasaki M, et al.: Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Cancer 1995, 75:2844–2852. Seminal paper describing the continuum from noninvasive BAC to invasive adenocarcinoma, with corresponding differences in natural history. Several other Japanese papers have suggested classification systems, and this is a good representation of the emerging understanding of the histobiology of BAC.

    Article  PubMed  CAS  Google Scholar 

  35. West HL, Crowley JJ, Vance RB, et al.: Advanced bronchioloalveolar carcinoma: a phase II trial of paclitaxel by 96-hour infusion (SWOG 9714), a Southwest Oncology Group study. Ann Oncol 2005, 16:1076–1080.

    Article  PubMed  CAS  Google Scholar 

  36. West H, Franklin WA, Gumerlock PH, et al.: Gefitinib (ZD1839) therapy for advanced bronchioloalveolar lung cancer (BAC): Southwest Oncology Group (SWOG) Study S0126. Proc Am Soc Clin Oncol 2004, 23:A#7014.

    Google Scholar 

  37. Roberts PF, Straznicka M, Lara PN, et al.: Resection of multifocal non-small cell lung cancer when the bronchioloalveolar subtype is involved. J Thorac Cardiovasc Surg 2003, 126:1597–1602. Good discussion of the feasibility of resecting advanced BAC in the setting of modest lung involvement, with prolonged survival.

    Article  PubMed  Google Scholar 

  38. de Perrot M: Management of lung transplant recipients with bronchogenic carcinoma in the native lung. J Heart Lung Transplant 2003, 22:87–89.

    Article  PubMed  Google Scholar 

  39. Etienne B, Bertocchi M, Gamondes JP, et al.: Successful double-lung transplantation for bronchioloalveolar carcinoma. Chest 1997, 112:1423–1424.

    PubMed  CAS  Google Scholar 

  40. Garver RI: Recurrence of bronchioloalveolar carcinoma in transplanted lungs. N Engl J Med 1999, 340:1071–1074.

    Article  PubMed  Google Scholar 

  41. Geltner C, Jamnig H, Bucher B, et al.: Lung transplantation for bronchiolo-alveolar lung carcinoma. Lung Cancer 2002, 37(Suppl 1):S27.

    Google Scholar 

  42. Paloyan EB, Swinnen LJ, Montoya A, et al.: Lung transplantation for advanced bronchioloalveolar carcinoma confined to the lungs. Transplantation 2000, 69:2446–2448.

    Article  PubMed  CAS  Google Scholar 

  43. Shin MS, HO KJ: Recurrent bronchioloalveolar carcinoma after lung transplantation: radiographic and histologic features of the primary and recurrent tumors. J Thorac Imaging 2004, 19:79–81.

    Article  PubMed  Google Scholar 

  44. Zorn GL, McGiffin DC, Young KR, et al.: Pulmonary transplantation for advanced bronchioloalveolar carcinoma. J Thorac Cardiovasc Surg 2003, 125:45–48.

    Article  PubMed  Google Scholar 

  45. Miller VA, Hirsch FR, Johnson DH: Systemic therapy of advanced bronchioloalveolar cell carcinoma: advances and opportunities. J Clin Oncol 2005, 23:3288–3293. Important contemporary discussion of the current understanding of systemic therapy options and emerging clinical research in advanced BAC.

    Article  PubMed  CAS  Google Scholar 

  46. Lau DH, Quock J, Lara P, et al.: Computer-assisted image analysis of response of bronchioloalveolar carcinoma to weekly paclitaxel. Proc Am Assoc Cancer Res 1999, 40:A#1231.

    Google Scholar 

  47. Travis WD, Garg K, Franklin WA, et al.: Evolving concepts in the pathology and computed tomography imaging of lung adenocarcinoma and bronchioloalveolar carcinoma. J Clin Oncol 2005, 23:3279–3287. Very good broad review of the ongoing controversies surrounding pathology classification and optimal imaging for BAC.

    Article  PubMed  Google Scholar 

  48. Scagliotti GV, Smit E, Bsoque L, et al.: A phase II study of paclitaxel in advanced bronchioloalveolar carcinoma (EORTC trial 08956). Lung Cancer 2005, 50:91–96.

    Article  PubMed  Google Scholar 

  49. Hirsch FR, Scagliotti GV, Langer CJ, et al.: Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies. Lung Cancer 2003, 41(Suppl 1):S29-S42. Thorough discussion of the improving understanding of molecularly targeted therapies based on ongoing translational research in lung cancer.

    Article  PubMed  Google Scholar 

  50. Kris MG, Natale RB, Herbst RS, et al.: Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003, 290:2149–2158.

    Article  PubMed  CAS  Google Scholar 

  51. Fukuoka M, Yano S, Giaccone G, et al.: Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 2003, 21:2237–2246.

    Article  PubMed  CAS  Google Scholar 

  52. Miller VA, Kris MG, Shah N, et al.: Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol 2004, 22:1103–1109.

    Article  PubMed  CAS  Google Scholar 

  53. Aghajanian C, Soignet S, Dizon D, et al.: A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies. Clin Cancer Res 2002, 8:2505–2511.

    PubMed  CAS  Google Scholar 

  54. Stevenson J, Nho CW, Schick J, et al.: Phase II clinical/pharmacodynamic trial of the proteasome inhibitor PS-341 in advanced non-small cell lung cancer. Proc Am Soc Clin Oncol 2003, 22:A#810.

    Google Scholar 

  55. Schenkein D: Bortezomib in bronchioloalveolar carcinoma. Paper presented at the 5th International Lung Cancer Congress. Kauai, HI, June 30–July 4, 2004.

  56. Nemunaitis J, Sterman D, Jablons D, et al.: Granulocytemacrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small cell lung cancer. J Natl Cancer Inst 2004, 96:326–331.

    Article  PubMed  CAS  Google Scholar 

  57. Tracy S, JÄnne PA, Johnson BE: Sensitivity of bronchioloalveolar carcinoma and adenocarcinoma of the lung to pemetrexed. Proc Am Assoc Cancer Res 2005, 46:A#5–6.

    Google Scholar 

  58. Sandler AB, Gray R, Brahmer J, et al.: Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab (NSC#704865): An Eastern Cooperative Oncology Group (ECOG) Trial--E4599. Proc Am Soc Clin Oncol 2005, 23:A#LBA4.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Swedish Cancer Institute, 1221 Madison Street, Second Floor, 98104, Seattle, WA, USA

    Howard West MD

Authors
  1. Howard West MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

West, H. Emerging approaches to advanced bronchioloalveolar carcinoma. Curr. Treat. Options in Oncol. 7, 69–76 (2006). https://doi.org/10.1007/s11864-006-0033-6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-006-0033-6

Keywords

Search

Navigation