Evidence Should Inform Guidelines, Not Be Used as a Mandate

Evidence Should Inform Guidelines, Not Be Used as a Mandate

Don S. Dizon, MD, FACP, FASCO

Sep 27, 2016

Evidence-based medicine. It is what we all strive to provide. It means employing the most up-to-date knowledge to the approach of medicine, from preventive care to screening to the diagnostic work-up and treatment. Wherever the data point us, that’s what we should do. Yet putting it into practice can sometimes be the most challenging part of being a doctor.

I was reminded of just how difficult it is when my patient, Jody*, had a recurrence. She had been diagnosed with a rare type of ovarian cancer 2 years earlier. At surgery, it was confined to the pelvis without evidence of abdominal spread. Chemotherapy had followed, and with each cycle, her CA-125 (which was elevated at diagnosis) had decreased until it reached the normal range. Following her sixth cycle, a post-treatment scan showed no evidence of disease.

At her first post-chemotherapy visit, I relayed the results of her CA-125 and CT. “Based on both, you are now in remission.”

“Wow,” she said. “I am so relieved this is over. What comes next, though?”

At that point I discussed her follow-up. “Your risk of recurring will be greatest in the next 3 years,” I said. “As such, I’d like you to be seen here every 3 months for a physical exam that will include a pelvic. I really wouldn’t recommend anything more.”

“Wait—no blood tests? What about imaging?” she asked.

“Well,” I answered, “the data suggest that nothing else will be very helpful. I know we measured your CA-125 during treatment, but it was to help me guide the impact of chemotherapy. After treatment, a large randomized trial done in the United Kingdom showed that routinely measuring CA-125 isn’t helpful.1 In that trial, women entering remission agreed to have their CA-125 levels checked but the results were masked. If their CA-125 rose above twice the upper limit of normal, patients were randomly assigned to one group who were told their CA-125 and asked to start chemotherapy as soon as possible (called the “early” chemotherapy group) or to another group who were not told their CA-125 and only started chemotherapy when clinical or symptomatic relapse was diagnosed (called the “delayed” chemotherapy group). The upshot is that overall survival was no different between either group. The only impact was that women in the early chemotherapy group experienced worsening of their perceived health sooner than those treated in the delayed group.”

“Therefore,” I concluded, “on the basis of pretty good data, it would be very reasonable not to follow your CA-125 if you are feeling well. However, if you develop any symptoms at all, or if you are worried at some point, we could certainly check it. As for imaging, I wouldn’t subject you to CT scans at regular intervals if you feel well. If we do a scan, it should be because there’s a question or a concern.”

She had looked at me then, not quite sure what to make of this. “Okay, but if I want my CA-125 checked every 3 months you’d do it?”

“Yes, I would,” I said. “I just wanted to make sure you had all the information you needed to make that decision.”

“Fine,” she continued. “I would really prefer we checked my CA-125 when I came in for my exams. It just doesn’t make sense to me that it wouldn’t be helpful.”

We initiated follow-up and she remained clinically well. At her last follow-up, she was well and had no symptoms. She had been back to work full-time since the last time I saw her. Overall, she had re-adjusted to her life and achieved her “new normal.” Her exam was normal as well, without anything of worry noted. I ordered her CA-125 and scheduled her to return in another 3 months.

Unfortunately, her CA-125 result came back markedly elevated. I called her and gave her the results, recommending that we get a CT scan. She agreed.

Jody returned to my office the following week. Her CT showed new growth in her abdomen, consistent with peritoneal disease.  I started to review options for treatment, but she stopped me. “I just need you to know that I am angry,” she said. “Thank God I asked to have my CA-125 followed—it’s how we picked up this disease. I can’t even imagine where I’d be had I taken your advice and didn’t do bloodwork and just waited for symptoms. Who on earth would follow such advice? It’s like you had asked me to put my head in the sand and ignore what was going on around me. I’m sorry, but I could never do that—and it turns out, I was right.”

I wasn’t prepared for her anger, especially about a conversation we had had years earlier, but I also knew that rehashing the data would serve no purpose. So, instead of going through the data once more, I did what I thought was best. I apologized:

“Jody, I am sorry that you had felt like I was imposing a recommendation on you. It was not my intent. I had hoped to let you know of your options, so that, together, we could choose a surveillance strategy that made sense to you. To do it,  I wanted to make sure you knew that there was data available. If it came across any other way, then I take responsibility.”

Ultimately, we moved past this conversation to a more pressing one about how to proceed with treatment. But Jody reminded me once more that evidence has its place­, but it’s not gospel. In the end, the data need to  be interpreted by our patients, in the context of their own preferences and values, and each person will reach a different conclusion. In the end, evidence should inform our guidance, but it should not be used to enforce mandates.

*Name and circumstances changed to protect privacy.



1. Rustin GJ, van der Burg ME, Griffin CL et al. Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet. 2010;376:1155-63.


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Brian E. Lewis, MD

Sep, 30 2016 9:32 PM

Good article, thank you for sharing this story.  How did she do?  If she went into remission again and is alive and well, then I guess the randomized trial was wrong.  If she died shortly after the recurrence, then I guess finding it earlier didn't help at all and just added unnecessarily to her anxiety and worsening perceived health.

Don S. Dizon, MD, FACP

Oct, 01 2016 4:56 PM

Hi Brian, I suppose in the big picture, it isn't relevant is it- the n=1 experience does not negate or affirm the evidence from a randomized trial. However, it is also where the statistics fail to help because no one can see their own journey in hazard ratios and relative risks. In this patient's case, the evidence was entirely irrelevant to her world-view when it came to her cancer and how to approach it. Ultimately, we won't know if I was wrong or right, even were she to die in the near future or much later. It's the art of medicine, isn't it? And, it's also a testament that guidelines can only take us all so far. There is always going to be a human being here that evidence, and reserving the right to make her own conclusions. Thanks for posting! D

Mayer Gorbaty, MD

Oct, 01 2016 5:48 AM

You did the diplomatic thing by apologizing and moving on to what matters- the next step in her treatment.  The reality however is that the response to her question " I can't imagine where I would be ..."  is you would have the same incurable cancer with the same treatment options. Of course you don't want to aggravate her but as physicians we not only need to follow evidence based medicine but like freedom we need to defend it.  You were not wrong to inform her of what the evidence showed;  you were absolutely correct to do so.

My only other comment is to ask whether when she manifested her anger to you- did you suggest she get another opinion elsewhere?  As a community based physician I've observed that anger  at the doctor is an expression of a lack of confidence in the treating physician.  Since the ultimate outcome is poor I usually suggest to an angry patient that they get a second opinion since it helps noone for the patient to second guess everything you do.

Don S. Dizon, MD, FACP

Oct, 01 2016 4:58 PM

Dear Mayer, Thanks for your comments. I do agree we need to understand the evidence, and to do so means to really make an effort to review the data independent of experts, so that we can explain and yes, defend them. My patient and I discussed a second opinion, and ultimately she did just that. I totally agree as well, when confrontation is present, diffusion can come not only by self-awareness of the emotions in the room but also by suggesting a fresh review of the situation and someone else's opinion. Thanks for posting! D

Kenneth Dale Herald, RN, BSN

Oct, 01 2016 4:48 PM

Thank you for your insightful and interesting case presentation and discussion.. I am familiar with the data and completely understand your rationale. I applaud you for educating the patient and allowing her to direct the frequency of the marker assessment.

As you realize, the marker had become more than a protein level to the patient. To her it had likely become a reliable, real and powerful marker of her remission..

To some of us, having some sense of what may lie ahead is what is most important, and that holds true no matter how unreliable the source, nor how ultimately inconsequential the data are to overall survival. Others prefer blissful ignorance.

As a clinician, I like to think I would have chosen to not watch the marker at all. However, when imagining myself in a similar situation, I know that is not the case.

I commend you for allowing this patient to direct her course and for taking her frustration on the chin.

Don S. Dizon, MD, FACP

Oct, 01 2016 5:02 PM

Dear Kenneth,

Thanks for your thoughts. I must state that as an oncologist, we share a role in the power of the tumor marker. In the treatment of ovarian cancer we use it during treatment to gage effectiveness of first-line treatment. We share our relief and joy when the marker goes down, and then again when it normalizes. We share our concern when the CA125 does not normalize, and it helps frame our discussion on treatments going forward. It is no wonder that patients "choose" to follow their CA125 after treatment- often, I think it can be nonsensical to suggest it not be followed. Hence, I agree with you- I too would like to think I could live my life without remeasurement of a tumor marker. But, in reality, I know it would be hard to do just that.

Welcome to Connection! DSD

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