Should rapid autopsy be requested for every participant in a clinical trial?
Rapid autopsy should be requested for all patients on a clinical trial. I would go one step further to say rapid autopsy should be requested for all patients who die of cancer. Part of our limitation in learning about cancer is that we have very little understanding of the evolution of the disease. Most patients have a biopsy at the time of their initial diagnosis, which is used to inform all subsequent treatment. We have realized there can be some degree of tumor heterogeneity. In breast cancer, for example, up to a quarter of patients will have changed their receptor status at the time of metastases.
Some elegant rapid autopsy studies that have been done show there is certainly a revolutionary pathway in cancer — the initial tumor is much different than the tumors at the time of death. Tumor heterogeneity and evolution are some of the reasons why we don’t have a cure for cancer.
Our only way to truly understand and make a long-term impact with metastatic cancer is to trace metastases over time. It is difficult to do serial biopsies due to the discomfort and risk for complications. At the time of death, we learn how those tumors have tracked and changed over time, how they look alike and different, and what might predict specific pathways. What you can learn from rapid autopsy is limitless.
In our metastatic breast cancer program at University of Pittsburgh School of Medicine, we wanted to establish a more robust rapid autopsy program, so we looked at different factors that may impact patient interest and recruitment. We evaluated patient attitudes toward rapid autopsy. Although we initially thought patients wouldn’t be interested, we found the exact opposite. Rather, the medical team expressed discomfort in asking patients to do an autopsy. We also found a reluctance of asking and knowing when to ask, although patients said they preferred to be asked earlier rather than later. We now have an education program for patients newly diagnosed with metastatic disease and rapid autopsy is discussed at that time. It is not an end-of-life discussion, but something that the patients and families can plan for.
It will take more than a couple institutions to make these programs effective. If rapid autopsy is more universally accepted and linked to a clinical trial, it would be more efficient, because that is a patient population motivated to improve learning about cancer. It will ultimately take an organization like American Cancer Society to reach out to the community to make patients feel it is a natural part of their disease.
Shannon L. Puhalla, MD, is assistant professor of medicine at University of Pittsburgh School of Medicine, and a medical oncologist and hematologist at UPMC Hillman Cancer Center. She can be reached at firstname.lastname@example.org. Disclosure: Puhalla reports no relevant financial disclosures.
A rapid autopsy should not be ordered on every patient enrolled in a clinical trial. Autopsy is a very invasive procedure to do on the body of a patient who is somebody’s loved one. If you are doing an autopsy, like any medical test, it should have a purpose. So, what is the question? If you use the tissue from the body because it will help in a clinical trial, improve treatment strategies or enable us to see the effect a drug has on the tissue, then it is justified. You have particular scientific questions that need to be answered.
However, rapid autopsy — also called warm autopsy — is different from a normal autopsy and requires a quick turnaround and additional infrastructure and resources. A patient can die at any time of the night so you would need people on-call for this type of program. Rapid autopsy is costly and logistics in organizing it are very difficult. A rapid autopsy needs to be performed shortly after death. If it’s delayed, then it won’t be a rapid autopsy.
Rapid autopsy should be directly pointed toward answering a particular question for a particular trial. Otherwise, I don’t see the point of doing it. It is costly, invasive and organizing it is difficult. Why would a family or patient consent to that if you don’t have a compelling reason to answer a question for scientists to gain more information in order to help and treat someone else?
It also depends on what tissue they want from the patient. If I am treating a patient with drug A or B and want to see what each one does to the tumor, then it would make sense to take the tissue postmortem so we can study the material and genetics. That is a compelling and reasonable question. But, if you are doing it on all trials without a particular aim, what is the purpose and why are we using all of our resources? We also need to be mindful about emotional impact on a patient’s family because the short time interval needed to perform the rapid autopsy may deprive them from the needed time to say goodbye to their loved one.
If a clinical trial requires rapid autopsy, all the patients on that particular trial could be eligible as long as the patient consents. For any particular clinical trial that has a question, then rapid autopsy is reasonable. But, if all clinical trials require rapid autopsy for patients with all types of cancer, no matter what, I would say no.
Gissou Azabdaftari, MD, is chief of the division of cytopathology and associate professor of oncology in the department of pathology and laboratory medicine at Roswell Park Comprehensive Cancer Center. She can be reached at email@example.com. Disclosure: Azabdaftari reports no relevant financial disclosures.