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Broadening the Concept of the Precocious Metastasis to Define When Local Therapy Makes Sense for Metastatic Cancer
Mon, 05/13/2019 - 11:43
This is an oldie but goodie article from GRACE's archives. Enjoy!
H. Jack West, MD, Founder, President and CEO

From the Grace Archives | Originally Published April 6, 2012 | By Dr West 

A couple of nights ago, I was at a “journal club” discussion with several of my thoracic surgery colleagues and some others in the Seattle area who treat lung cancer, discussing how to decide which patients presenting with a solitary brain metastasis could have a realistic chance of being treated with curative intent in the chest as well as the brain.  The idea behind this concept is that, while metastatic disease is generally recognized as a state that is binary (you have metastatic disease or you don’t) and isn’t curable if cancer has spread from the chest to another part of the body through bloodstream, it’s not always that simple.  

There are exceptions to almost every rule, and we know that a minority of patients (perhaps as high as one in four) with a solitary brain or adrenal metastasis as their only evidence of metastatic spread can be treated aggressively in the chest, have their brain or adrenal metastasis treated locally (resected or possibly radiated), and be alive with no evidence of disease years later.  We also know that having earlier stage lung cancer, discounting the single metastasis, is associated with a much better probability of doing very well.  Specifically, the concept of treating metastatic lung cancer for cure tends to be most feasible for node-negative disease in the chest, but not for people who have nodal involvement, and especially not locally advanced, stage III NSCLC.  In this situation, the metastasis probably isn’t “precocious”: it’s just a metastases coming in when you’d expect to see it.

So that’s the concept of the precocious metastasis.  What I started thinking about was how this question can really be broadened to other situations in lung cancer, or other cancers, that really center on one key question: 

Is it likely that one area of the cancer is so far ahead of the rest of the disease process that it will set the pace for problems, or is it more likely that the pace of the disease will be set by multiple disease areas?

And with this question in mind, we can apply this to many disease settings that essentially hinge on this question.  For instance, this often comes up with technically multifocal bronchioloalveolar carcinoma (BAC), but with one dominant area, and now is the relevant question for the situation of whether to consider a local therapy in the setting of acquired resistance to a targeted therapy, or any other setting of very limited progression.

To illustrate the point about BAC, we know that many patients with BAC have a process that is technically multifocal, or at least suggestive of that, but who might arguably benefit from a local therapy, commonly surgery.  Specifically, a patient often presents with a biopsy-confirmed are of growing BAC or adeno/BAC that is resectable, but we also see several tiny nodules measuring 2-3 mm scattered in the lungs.  Does it make sense to treat with surgery, suspecting that this is actually a multifocal process?

To illustrate another common scenario, a patient with advanced NSCLC with lung and bone metastases has an activating EGFR mutation and demonstrates a terrific response to an EGFR tyrosine kinase inhibitor (TKI) that lasts for 16 months.  A scan then shows a suggestion of one lung lesion growing, and treatment is continued without change, with another CT 8 weeks later showing that this one nodule is growing, now more quickly, against a background of otherwise ongoing great response.  Dr. Weiss just wrote a great post about the concept of pursuing radiation for the area of progression and continuing the EGFR inhibitor.

In both of these cases, I would argue that even if you know that someone has metastatic disease, local therapy makes sense in any situation in which progression in one area is likely to far outpace the rest of the disease process.   On the other hand, if the cancer is progressing visibly in multiple areas between scans a few months apart, that strongly suggests that treating with local therapy isn’t going to be helpful. Even treating all of those spots won’t likely help, because we can anticipate that new spots invisible on the current scan will be present on the next.

I’ll also say that while the concept of the precocious metastasis is framed around the idea that the goal of treatment is cure, I don’t think that the feasibility of cure needs to be the acid test to concluding whether local therapy is appropriate.  Just like giving brain radiation to someone with multifocal brain metastases, the goal can be to address the most survival-limiting (and/or quality of life-limiting) aspect of the disease.  We would readily favor adding a local therapy that can prolong survival by 6 or 12 months or longer, so while cure may be goal in a best-case scenario, falling short of that doesn’t obviate the value of local therapy.

I welcome your thoughts here.  Do people see other cancer care scenarios in which this main question centers on “is the pace set by a local or systemic process?”.



  • Dr. Weiss says:

    April 6, 2012 at 11:10 am

    All of us, patients, doctors, caregivers want cure when possible but are too often faced with incurable cancer. I really like the point here that sometimes local therapy can be helpful even when cure is not the goal. In certain situations, there is high level evidence that local therapy can improve quality of life even when it may not improve duration of life; good examples include painful bone mets or cancer pushing on an airway. There are other situations where local therapy does not have the potential to improve either quality or duration of life; an example would be a patient with many spots of metastasis that are all behaving the same. But is there a middle ground where local therapy can indeed improve duration and quality of life, even when it can’t cure? Here, we need high quality trials to really prove what helps and what doesn’t help. Good ideas need to be tested to really find out if they help, harm, or neither.

  • ssflxl says:

    April 6, 2012 at 9:31 pm

    Drs. West, Weiss

    I think this makes a lot of sense. If there is only one area of growth, then local therapy would make a lot of sense and also because that would decrease the significant side effects from systemic chemo. Even if local treatment doesn’t decrease overall survival,( which is a very high bar to pass), it may help with the symptom created by a limited growth of the cancer. thanks for posting your thoughts.


  • slimer says:

    April 12, 2012 at 11:43 am

    Question provoked by Dr. West’s “Precocious Metastasis” article.

    If local therapy can be used in a Stage 4 situation in which one tumor grows (Precocious Metastasis) while others retreat, why can’t local therapy be used in cases where only the chest is involved, ie multiple lymph nodes, multiple nodules in both lungs resolved through chemotherapy, but the primary tumor remains, markedly reduced but still there, and presumably still shedding cells? Why not surgery or ablation to eliminate it? At my big HMO, there are Depts of Intervention Radiology, but in their protocol on Stages, Stage 4 patients are only allowed chemotherapy. What is the difference between your precocious metastasis example and the above example? I’m sure many Stage 4, or Stage IIIB folks would be interested in your comments.

    In my case, my onc does not believe I have CTC (circulating tumor cells) in my blood. Not sure if that can be true. After all, the poison is infused in my circulatory system to get to lymph nodes, but if true, why can’t the remaining primary tumor be surgically removed or ablated?

    And as follow up question, are both the right and left lungs considered separate organs for the purpose of declaring a Stage 4 if no other outside organs or bony structures are involved? Or is it the involvement of the chest lymph nodes that makes it Stage 4? My onc says the former milinary effect in both my lungs came from the lymph nodes. He also says nobody would recommend surgery or ablation in my case. Your article makes me question that pronouncement.

  • Dr West says:

    April 12, 2012 at 12:22 pm

    If there’s a long interval and there’s just one single area that still appears viable, that’s a reasonable thought. However, I don’t want to suggest that this is the current standard of care. It’s still pushing the envelope, and the current clear evidence-based standard is systemic therapy.

    It is true that spread to the other lung is metastatic, stage IV. Unless every spot is an independent cancer (which is very unlikely), the spread is through the bloodstream, and the very clear general rule is that in such cases, cancer isn’t likely at all to be limited to what you can see.

    I wouldn’t want to imply that many or most people with advanced NSCLC should undergo local therapy. It is overwhelmingly likely that most won’t be helped by that — but a minority could be.

    -Dr. West

  • MelanieLynn says:

    April 27, 2012 at 5:52 pm

    I had a brain met removed in Aug. followed by cyber knife radiation, max dose. A PET showed a 5mm spot on perichardial lymph and a small hot spot in apex of right lung where scar tissue has been present for years. No primary has been found. I had 4 rounds cisplatin, alimta and avastin, {was in remission after 3rd round} then 4 more rounds avastin and alimta. I am now set to have 7 weeks radiation to apex of lung and lymph nodes. All futher PETs and MRI have shown no activity. My oncologist has presented my case twice to the thoracic tumor board and has told me, “I know I shouldn’t say this with a stage VI cancer, but I hope to cure you.” I hope so too.
    What say you?

  • Dr West says:

    April 28, 2012 at 4:51 pm

    I think it’s a reasonable approach to pursue, and reasonable to hope for the possibility of cure, given the very limited extent of disease.

    -Dr. West

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