I’ve previously described the concept of the “precocious metastasis”, the situation in which a patient presents with early stage NSCLC, except for a single metastasis, most typically in the brain or adrenal gland. Our conventional teaching is that a patient with any metastatic disease almost certainly has additional micrometastatic disease, cancer cells floating in the bloodstream, that will inevitably lead to development of new areas of visible metastatic disease in the future (so having a small amount of metastatic disease would be like being “a little pregnant”). But as with so much of medicine, there are few absolutes, and about 25% of patients with solitary lesions that are surgically removed (or, presumably, alternatively, radiated with an approach like sterotectic radiosurgery, but this hasn’t really been proven) can have long-term survival. And a recent publication in the Journal of Clinical Oncology by several investigators in the lung cancer group at Moffitt Cancer Center in Tampa, FL (abstract here) provides a much needed characterization of outcomes for patients with solitary adrenal metastases who have undergone an adrenalectomy (removing one of the two adrenal glands, above the kidneys).

The study was a retrospective review of published reports, with at least four patients per publication, who had undergone adrenalectomy along with treatment of their early stage NSCLC. Importantly, the study divided patients into those who had synchronous metastases, meaning that the adrenal met was present when they first found and treated the main tumor in the chest, and metachronous lesions, which are mets that were not present initially but became evident an interval of time after a patient’s initial presentation and treatment (actually, a cutoff of six months is the usual definition of synchronous vs. metachronous).

Oncologists and surgeons have often perceived that patients with synchronous cancers are less likely to do well than those who return with a single metastasis a year or two after their treatment. The metachronous lesion that occurs 18 months later, for instance, has already demonstrated that new lesions aren’t going to be popping up rapidly. With a synchronous metastasis, it’s possible that this is just a snapshot in time, and the cancer is just early on its way to spreading to many areas in the body.

So this review directly compared how patients with a single resected adrenal metastasis and resected, otherwise early stage NSCLC did. After a thorough search of the medical literature, they identified 10 reports that included 114 patients who had sufficient details to include in their summary, of whom 48 (42%) had synchronous metastases and 66 (58%) had metachronous adrenal lesions. Those with synchronous lesions were younger – 54 vs. 68 – reflective of the tendency to be more aggressive and give the “benefit of the doubt” more often to younger patients. None of the patients with an adrenal metastasis had symptoms from it; rather, they were detected by scans during initial workup or follow-up/surveillance. The patients with metachronous metastases presented with them a median of 12 months after their initial presentation with lung cancer.

The highlight was that about 25% of patients remained without any evidence of disease after five years, but the median survival was shorter in the patients with metachronous lesions compared with those who had synchronous mets (12 vs. 31 months).

So those with synchronous mets tended to recur earlier, if they were ever going to, but both groups had a very real chance (1 in 4) of being “cured”, or pretty darn close. Perhaps if someone had an adrenal lesion present 2-3 years after their initial presentation, you’d consider them at risk for another recurrence even beyond five years (the most indolent cancers, such as some bronchioloalveolar carcinomas, can recur many, many years later), but in most NSCLC cases, your likelihood of recurrence is very low that far out.

Importantly, PET scans can be very effective in evaluating a potential candidate for such an approach. First, they can help ensure that a new adrenal lesion is PET avid, which you’d expect for a cancer, but you would expect to see minimal activity in a benign adrenal tumor (and there are many of those, but they generally don’t appear as new or growing lesions over time). PET scans also offer the opportunity to confirm that there are no additional lesions elsewhere. While this approach may be curative for patients with a solitary metastasis, someone with more than one metastasis is far more likely to have a cancer that behaves like regular metastatic NSCLC. The authors also mentioned that a head MRI is valuable before proceeding with surgery, for the same reason. You really want to be sure that you’re resecting all of the disease, just a single focus.

Finally, it’s necessary to point out that there is a difference between having a single metastasis to start with and having a response to chemo (with or without other targeted agents) for more multifocal metastatic disease. While it may be possible to resect the solitary residual active focus of cancer in that setting, I would expect that situation to be less curable than someone who never demonstrates more than a single focus of metastatic spread.

I found this summary to be very encouraging and helpful. It is important to recognize the potential for reporting bias, however, which is a tendency for people to write about the cases that did remarkably well, while the reports about the patients who progressed 4 months after their adrenal surgery either were never written by the disappointed medical team, or were never published by the unimpressed journal editor that received the report. We tend to write and favorably review the results that are positive. Because of that, I think it’s quite possible that the real world numbers may not be as favorable, but there is a clear proof of principle that it is feasible to treat these patients with solitary adrenal lesions aggressively, because some will do remarkably well.