We talk a lot here about the strength of the evidence and the standards of care for one treatment over another. But the reality is that our clinical guidelines leave a lot of room for tweaking, with many options listed as “consider X”, “consider Y”. That’s probably how it should be, because people are individuals who often don’t represent a garden variety patient in a classic clinical setting.
Though there is an emphasis in modern conventional medicine on hard evidence to support our clinical management of patients, and this focus on “evidence-based medicine” is probably especially strong in oncology (and with GRACE), every oncologist falls somewhere on a spectrum between being rigidly focused on following exactly what the evidence supports vs. being completely guided by a combination of a good rationale and some intuition. Patients and families also have very different expectations about whether their doctor/medical team is very driven by “current best practices” or more inclined toward “outside the box thinking”. Complementary and alternative medicines are not often accompanied by hard evidence, but their exceptional popularity speaks to the fact that many people don’t feel that they require heaps of evidence to act. Meanwhile, it typically takes years for the cutting edge research concepts of today to become the standard of care later: carefully conducted studies take a lot of time, and in the meantime, we all struggle with which ideas to adopt and which ones to wait on until we learn more.
Neither approach in itself is always the right one. We’ve seen cases where giving an EGFR inhibitor after chemo and radiation for locally advanced NSCLC can be harmful for many patients, despite this being an unexpected finding at the time (and still not something we can explain). We’ve seen that integration of Avastin (bevacizumab), a targeted agent that improves survival in many patients with advanced lung cancer, into chemo/radiation treatment for stage III NSCLC or limited disease SCLC can lead to dangerous or even fatal side effects that weren’t anticipated. But there’s no doubt that some patients today could benefit from what will ultimately prove to be the standard therapies of tomorrow (or at least of 2014). We just aren’t terrific at predicting.
Earlier this week, I presented my general framework for using or not using molecular markers to guide my clinical recommendations, and this represents a setting in which new data are exciting but precede more conclusive results by years. I explained that my personal approach is to not use markers like ERCC1, RRM1, and thymidylate synthase levels to shape my treatment decisions for patients, because they haven’t been proven to be helpful in large prospective trials. Instead, they’ve mostly looked like they could be helpful based on retrospective assessments in which we pick through the data after the study has been completed, which isn’t as helpful as planning to use a variable and then using it to guide treatment prospectively.
Yet, less than 24 hours after I presented this view, I found myself offering a second opinion in which I recommended that we send tumor tissue from a 30 year-old man with NSCLC for molecular marker testing to help us consider what chemo to pursue. Why be such a hypocrite? In his particular case, he was diagnosed in the late fall with a stage IIIA N2 node-positive NSCLC and had received cisplatin-based chemo and concurrent radiation from another oncologist, followed by surgery. Unfortunately, he had a small amount of residual viable cancer in a few mediastinal lymph nodes, a situation that suggests a less favorable prognosis than if the mediastinal nodes were all completely negative for cancer (mediastinal sterilization).
This was a case in which we simply have no good data (and by that I really mean any data), to tell us how we should proceed. The trials that have looked at this situation have generally tried to give a couple of additional post-operative cycles of the same chemo that was given pre-operatively. But there has never been a trial that compared continuing the same treatment vs. trying a to kill the cancer by shooting from a different angle and using different chemotherapy. And in this situation, without any good reference point for guidance, I’d be happy to use imperfect data to help inform my decision. If the molecular marker studies suggest that gemcitabine or more or alimta or more platinum is a very good or poor choice, I’ll take that hint, because it’s not overriding a standard of care here. Similarly, I feel that it’s pretty reasonable to use ERCC1 status to help make a decision about the value of adjuvant chemo for resected NSCLC if a patient is otherwise on the fence about whether it’s worth doing or not, but I’m not comfortable using that data to steer someone away from it if all other indicators suggest that it’s the appropriate thing to do. In other words, I think the threshold to use tentative, imperfect data can be lower for a situation in which there is no right answer than in a situation in which you’d potentially be thumbing your nose at a well-established, evidence-based standard of care.
This is really also the way I feel about alternative medicine approaches. I would hate to see someone dismiss surgery for early stage lung cancer or an EGFR inhibitor if they have an EGFR mutation because they would rather pursue alternative medicines. On the other hand, it’s certainly very appropriate for people to pursue whatever avenue for treatment concepts they’d like to follow if conventional oncology approaches can’t offer much promise.
To sum it up: “In the land of the blind, the one-eyed man is king.” Though it’s ideal to have a solid path you know is right, reality isn’t always that convenient, and it makes sense to just do the best you can under the circumstances in an ambiguous situation. And my own general recommendations are still adapted to the individual person in front of me, as it should probably always be.
As always, I welcome your thoughts.
It is really helpful to my peace of mind to read that you still recommend surgery and standard platinum chemo as first lines in curative attempts – if I read this correctly. I guess that may all change someday, but it is good to remind myself that I have received the best care as is known in this time.
Sure — absolutely yes, for many patients.