With all this recent talk about never-smokers with lung cancer, and the interest in stories of patients with so-called “oligometastatic” cancer (minimal metastatic burden to perhaps a single site), I thought I would describe a recent case in my clinic as an illustration of how I use this information in everyday decision making. Mrs. D, a very fit 36 year-old woman with a young child at home, presented to her family doctor last year with back pain. It didn’t seem to be getting better, so her doctor ordered an x-ray of the back which showed a very nasty-looking spot in the lower spine. An MRI confirmed that there was a large tumor in the lower spine, and a surgeon went in and took a piece of the bone to determine the cause. The result was a metastatic adenocarcinoma, with special tests pointing to a primary site from the lung. She had never smoked, nor had her spouse. A PET scan showed a very small spot in her lung, with no evidence of spread to local lymph nodes, and no evidence of metastatic disease outside of the single metastasis in the spine. An orthopedic surgeon opined that she probably could resect the entire vertebrae involved, but this would be a major undertaking. This type of case, aside from the heartbreaking anguish of having to tell a young mother she has lung cancer, causes all of us in the oncology world fits. How could such a small tumor, less than 1cm in size, be the cause of the spine tumor? Was it worthwhile to discard what we intellectually know about metastatic lung cancer (incurable) and treat her aggressively for cure, and if so would we be putting her through Hell only to make ourselves feel better about not giving up on such a young patient?

I can tell you there was quite a debate in multidisciplinary clinic, as there always is in cases such as this. We know from published series of patients (essentially single institution experiences) that some very unusual patients with metastatic NSCLC can survive 5 years or more with aggressive treatment of the lung tumor and the metastatic site. However, there are some fairly clear indications of who may have a shot and who likely does not. For example, patients with a solitary brain metastasis or adrenal gland metastasis have up to a 10-15% chance of long term survival in some series if the lung cancer and metastatic tumor can be removed. On the other side of things, patients with mediastinal nodal involvement (N2 or N3) or who have metastasis to the bone, to my knowledge, have historically shown little or no chance of cure with aggressive treatment based upon published series on lung cancer (this is not true in other cancers such as breast cancer). So the first step was to confirm this was lung cancer, since pathology from the spine was not 100% certain. She was taken to the operating room and underwent a wedge resection of her small lung nodule, as it was too small to reach by needle, and this confirmed an adenocarcinoma. She also underwent mediastinal nodal sampling, which quite surprisingly showed involvement of several lymph nodes. Clearly this was an aggressive tumor, and she now had at least 2 elements that made it difficult to argue for aggressive treatment of her disease for “cure”. Again there was arguing in case conference, but finally a consensus was reached. As she had never smoked, I sent her tumor for EGFR mutation testing. I had a strong suspicion she harbored an EGFR mutation, but this test takes about a month to come back. I started her on combination chemotherapy with carboplatin, Taxol, and Avastin, which is the most aggressive combination available that has good phase III trial evidence of efficacy (from the ECOG 4599 trial, well documented on this site). As I often do, I left out the Avastin for the first cycle to allow her to heal from her chest surgery. She underwent 4 cycles of chemotherapy, which she tolerated well, and afterward scans showed no evidence of cancer except for her spine lesion. She still had some back pain, and I did not feel at this point that I had evidence on my side to support the huge surgery she would need to remove the spine tumor, so I referred her for palliative radiation to the spine. By this time, we had learned that she did indeed have an EGFR mutation, the exon 19 deletion mutation that is thought to be the most sensitive to drugs like Tarceva (erlotinib). There is now plenty of evidence out there that maintenance therapy (also called early second-line therapy) delays recurrence of lung cancer, so I already knew I wanted to give her more treatment after she finished chemotherapy. In this case, the choice was easy, and I elected to start Tarceva immediately after she finished chemo. Because the ECOG 4599 trial continued Avastin until cancer progression, and because the BeTa trial showed a doubling of progression-free survival in the maintenance setting when Avastin was added to Tarceva, I also elected to continue Avastin even though this is an extrapolation of data from these trials cannot be considered standard. She is now about 6 months into her treatment with Tarceva and has no evidence of cancer outside of her spine. So I am curious to see what others think of this case. I know a point is going to come in the future where she will begin to ask me tough questions, maybe many times as she goes longer and longer without recurrence. Should we take the spine tumor out now? How about after a year? 2 years? I don’t know the right answer, but for now I think I will leave well enough alone. However, if the spine tumor starts to grow again and she can’t get more radiation, it will be tempting to have the surgeon take it out. For “palliation” of course, but secretly I may be hoping for more. After all, I’m only human.