By Dr. H. Jack West
One ongoing controversy in the world of managing cancer, especially one in which cures are elusive, is how high the bar should be to guide treatment recommendations. The “gold standard” to change treatment is a significant improvement in the primary endpoint, ideally overall survival, in a prospective, randomized phase III trial with several hundred or even several thousand people. In some settings, treatment recommendations may not even change until a few randomized phase III trials show the same significant improvement with a new treatment approach.
But the reality is that sometimes we want or need to apply promising ideas that don’t have an overwhelming amount of evidence yet. That may be because a very promising result in phase II will typically take 3-5 years before the results of a subsequent larger phase III trial is completed and reported, with another 6-12 months before that new agent or combination is FDA approved and commercially available. That may also be because some of these clinical questions are too rare to test in a large phase III trial setting. For people with a ROS-1 rearrangement, who represent 1% of NSCLC, or those with leptomeningeal carcinomatosis, we can’t realistically expect to complete a randomized phase III trial with hundreds of patients assigned to one treatment or another.
- So the first question is whether the medical community should be guided by a specific level of evidence to shape cancer treatment, and can the standard be lowered for clinical subgroups or settings in which the numbers are too small to ever run a large trial? And should the standard be higher in a curable setting like early lung cancer (is stereotactic body radiation therapy an appropriate alternative to surgery?) vs. metastatic disease because there is “more to lose”?
- Second, should patients be able to dictate a lower level of evidence being required if they provide “informed consent” that one approach is conceptually attractive but not well tested?
And related to both of these points, is there a lower standard required when the cost of the treatment is low and/or the patient is paying and not insurance/broader society? If proton beam radiation therapy is three times as expensive as conventional radiation and has no actual evidence it’s superior, is it appropriate for institutions to market it (at a handsome profit) and/or
patients to expect it? Is it more appropriate if patients pay for some or all of the cost difference vs. passing on the costs to the others?
These are timely, important questions, so please join us on Thursday, October 10th, at 8 PM Eastern, 5 PM Pacific. Just get on twitter, filter your messages and add the hashtag #lcsm to your tweets, and join the conversation!
By Dr. H. Jack West
The concept of “over-treatment” of lung cancer may sound heretical to some here, as it is unquestionably a fearsome cancer. Nevertheless, it’s important to recognize that cancers can range from quite indolent to virulently aggressive and that some forms may be so minimally threatening that treatment may be worse than the disease. We’ve certainly recognized this about several other cancers, like prostate cancer and chronic lymphocytic leukemia (CLL), which medical students are taught are diseases that most people “die with but not of” because they typically follow a natural history that extends out decades. More recently, much of the debate about mammography screening in breast cancer has centered around the concern that too many of the detected cancers are extremely indolent “ductal carcinoma in situ” (DCIS), a pre-malignant version of a more threatening cancer, and that the escalation of larger numbers of breast cancer and some others, such as many PSA-detected prostate cancers, may represent a misguided and potentially even financially driven overzealous effort to treat people who don’t need it, raising costs and posing unacceptable risks to patients that aren’t balanced by a real risk from the disease.
Dr. Otis Brawley, the Chief Medical Officer of the American Cancer Society, has even written a highly regarded but invariably contentious book about rampant over-treatment of cancer and the inherent profit motive that feeds this strategy. And there is a lot of discussion about re-naming some diseases currently defined as a form as a cancer into IDLE (indolent lesions of epithelial origin) lesions in order to discourage them from being over-treated just because they have a name that includes the term “cancer” or “carcinoma”.
Lung cancer is arguably different, since it’s the undisputed leading cause of cancer death in the US (28%) — no other cancer even comes close. Is overtreatment of such a terrifying threat really a realistic concern? We’ll discuss this in our next lung cancer social media (#lcsm) community tweet chat Thursday, September 5th, at 8 PM Eastern, 5 PM Pacific.
Specifically, we’ll start with the question of whether health care practitioners, patients, and caregivers really accept that there can be such a thing as overtreatment of a cancer that accounts for 150,000 or more deaths in the US each year. Do doctors treating lung cancer see patterns that lead them to be concerned that we’re detecting too many indolent cancers that are resected even when they pose little or no threat? Are patients getting chemo or radiation or other treatments for even potentially advanced lung cancer that may progress so slowly that we could do as well or better by treating less? Are patients comfortable considering the idea of just watching nodules that might be cancer, or leaving in a biopsy proven cancer that has grown only 1 mm over 2 years, even if a surgeon suggests it’s not clearly necessary to treat it? What are the forms in which we may see over-treatment of cancer, if we can agree that there is some merit to the concept? Or are we not good enough yet at differentiating indolent from aggressive cancer that the only safe way to treat a lung cancer is to mount the most aggressive attack possible?
We’ll then turn to some of the incentives that might lead to a trend toward overtreatment. We have a fee for service system in the US. Are doctors incentivized to do surgery when it might not be indicated, or to give chemo for an indolent or extensively treated advanced lung cancer, in part or largely because it pays to do so? Are marketing messages and perhaps even mass media feeding a frenzy that more is almost always better, even if unproven? Is it largely stemming from anxiety among patients, so that doctors might feel (as is rather often expressed) “they expect (or demand) this treatment, and if they don’t get it from me, they’re just going to go to the next doctor to get it.”
Should we be concerned that an evidence-based broader use of lung cancer screening will lead to far more non-threatening lung nodules being detected, or that we’ll see expensive new cancer treatments used in settings for which there is little or no evidence to support them?
We hope you’ll join us for the discussion on Thursday, 9/5, or at least share your opinions on these timely and important issues in comments here.