I’m completing a chapter in a key lung cancer textbook on managing multi-focal bronchioloalveolar carcinoma, a clinical entity that is in the process of being re-labeled lepidic predominant adenocarcinoma (LPA) (lepidic meaning scale-like, which is the classic way that the cells are defined as spreading when looked at under a microscope). I suspect that it will continue to be called multifocal or advanced BAC for a long time (after all, the formal staging of small cell lung cancer goes from stages 1 to 4, but nobody ever uses that, classifying it as just limited or extensive stage).
When asked to write this chapter, I faced the challenge of there being very little actual hard data on managing multifocal BAC. Though many experts have a very similar approach, this is actually based on expertise, good judgment, and clinical experience more than data we can point to, and I don’t think this approach has ever been articulated in a scientific paper or book chapter, so I’m hoping this will be a valuable addition to the literature.
As I reviewed the papers out there, what struck me most are two things:
1) There is incredible variability in the appearance and clinical behavior of what is called advanced BAC in the clinical world — some of it is aggressive and imminently threatening, and much of it is very slow growing and among the least threatening cases ever labeled as lung cancer.
2) People with a very slow growth rate are likely to do very, very well no matter what treatments they get, as much despite as because of those treatments. In many cases, interventions are pursued on patients who are destined to do very well, and then when their short term survival is good, the people who did that intervention write a paper saying how their approach is feasible and attractive because the patients did well — not recognizing, or at least glossing over the idea, that they were going to do very well anyway.
I would say that in no other area of lung cancer care is it more important to distinguish between what can be done and what should be done. And the real experts know when to not intervene.
So here is the algorithm I developed, which isn’t beautiful, but you can see that it focuses on seeing what is actually changing rather than treating reflexively based on a label on a pathology report or single a scan finding. Essentially, it says to try to avoid intervening at all unless or until you see clinically significant change (which I would consider as something that is readily apparent as progression on scans done 6 months apart or less), and then if you see progression, clarify whether it’s limited to one lesion or progressing more diffusely in multiple areas.
It’s not uncommon for a question here to be about the a pathologist’s terminology on a report that equivocates about whether a lesion is bronchioloalveolar carcinoma (BAC) or another form of adenocarcinoma, perhaps “well-differentiated adenocarcinoma”, especially if it has a radiographic appearance of a hazy infiltrate or many small ground glass opacities. Meanwhile, there’s a new classification of lung cancer subtypes that obliterates the term BAC, instead favoring a definition of adenocarcinoma in situ, classifying small non-invasive lesions previously called BAC as a pre-malignant condition. How have the changes over the past few years changed how we should approach BAC?
I would have to say that the new reassignment of BAC as adenocarcinoma in situ hasn’t taken the lung cancer world by storm and that I still think of the clinical entity as BAC. For the preceding decade, the definition the pathologist’s used technically excluded a lesion with even 1% or 5% of the lesion being invasive as being called BAC, even if it acted for all the world like BAC. Clinicians learned not to be too hung up on a pathologist’s technical definitions and tended to define BAC more functionally/operationally. General oncologists and expert lung cancer specialists alike managed BAC based on the overall picture of how it behaved if it looked like a BAC pattern.
Bronchioloalveolar carcinoma, or BAC, is a unique subtype of non-small cell lung cancer (NSCLC) that has unique features in terms of the demographics of who gets it, how it appears on scans, how it often behaves, and potentially in how it responds to treatment. It is a subset of lung cancer for which most of what we know emerged in the last 10 years, with our understanding of this entity, and even the definition of BAC, still evolving.
What is BAC?
BAC was first identified and defined as a separate subtype of lung cancer by Dr. Averill Liebow in 1960. At that time, he highlighted it as a form of well differentiated adenocarcinoma of the lung that appeared to not be able to invade the surrounding lung scaffolding and spread within the lung(s), presumably aerogenously and/or through lymphatic channels.
This is the first part of a case presentation I did with two great colleagues: Dr. Anne Tsao, who is a medical oncologist and lung cancer expert at MD Anderson Cancer Center in Houston, and Dr. Alex Farivar, who is a terrific thoracic surgeon at my own institution, Swedish Cancer Institute in Seattle.
This case is an elderly gentleman who has a very indolent but growing lung lesion. His story brings up questions of how concerned to be in following a nodule in a patient of advanced age and with competing medical issues, whether surgery that is less than a lobectomy might be considered, as well as the systemic therapy options for bronchioloalveolar carcinoma.
Here are the audio and video versions of the podcast, along with the transcript and figures.
This is a continuation of my discussion with Dr. Matthew Horton, a pathologist with a special training and a great expertise in lung pathology who works here in Seattle at a company called CellNetix.
This portion of our discussion covers the spectrum of neuroendocrine lung tumors, ranging from carcinoids to small cell lung cancer and large cell neuroendocrine carcinomas; we then turn to a discussion of bronchioloalveolar carcinoma (BAC), including everything from a little history to a look forward at a new interpretation of BAC. Below you’ll find the audio and video versions of our discussion (the video with a few images of what we’re talking about), and the associated transcript and figures.
The most expert lung cancer pathologists in the world are planning a revision of the classification of lung adenocarcinomas that is expected to be approved and implemented next year, and it’s going to make some big changes. Specifically, it’s planning to eliminate the diagnosis of bronchioloalveolar carcinoma (BAC), reflecting our evolving understanding of this disease.
BAC with lesions less than 2 cm is now being designated as a pre-cancerous adenocarcinoma in situ (AIS), which essentially means it’s a pre-invasive condition with a favorable prognosis. In fact, the available literature, largely from Japan but also including evidence from other parts of the world, shows a 100% 5-year survival for a <2 cm AIS, which is far more commonly the non-mucinous BAC sybtype. The size limit is significant, however, because larger lesions are felt far more likely to have at least some area of invasive disease.
The invasive portion of what is now in the spectrum of BAC with focal invasion to adenocarcinoma with BAC features has a major impact on prognosis. In fact, the size of that invasive component is what drives prognosis, not the invasive part:
So a largely pre-invasive (adenocarcinoma in situ) lesion with a small area of invasiveness will now be designated as minimally invasive adenocarcinoma, and it also has a 100% cancer-specific survival at 5 years.
I’ve been involved in a wide range of discussions, both here and in my own clinical, about the fairly common situation of how to approach a situation in which the story on paper and what you see actually happening are incompatible. For instance, last week I and several of my colleagues participated in a journal club (a group discussion of a new and/or controversial journal article or two), in which the topic was the potential utility of doing surgery for unusually early small cell lung cancer tumors. We’ve also had several recent questions about patients in whom the diagnosis of bronchioloalveolar carcinoma (BAC) is being considered, and it’s not clear whether to treat this sometimes very indolent cancer as a full-fledged NSCLC, a non-entity that might sometimes be ignored, or as a separate category worthy of being managed differently from the standard approaches for other NSCLC subtypes.
It’s important to highlight that the discrepancy between the expected outcome based on a pathology report and the clinical picture in front of you can cut both ways. In some cases, you may have a biopsy of a lung nodule that shows no cancer, but if it’s growing and continues to grow, that’s not very reassuring, and you’d suspect that the biopsy missed the diagnostic part of the tumor that would confirm viable cancer. In other settings, a biopsy of a lung nodule might diagnose cancer, leading down a path toward the typical management with surgery, etc., but if you happened to have old films that showed that the nodule was actually minimally changed over 3 years or more, it might be reason to take a step back and wonder whether you haven’t already been furnished with some valuable information that might lead you to individualize and change your treatment plan.