How Can Rapid Autopsies Advance Precision Medicine?

October 20, 2017
Kelly Baldwin, ASCO Staff

“Imagine, for instance, a patient with simultaneous spread of cancer to the lungs, brain, liver, and other vital organs. It would be both impossible and unethical to sample all of these disease sites. A rapid autopsy program makes this feasible - we can understand the diversity of biology in these anatomic sites through securing and analyzing tissue,” said Sumanta Kumar Pal, MD, ASCO Expert.​

In an era of personalized medicine, in depth study of individual patient tumors at the cellular and molecular levels has become an essential tool to inform treatment approaches for patients.

A challenge of precision medicine remains understanding why some cancers do not respond to treatment and others do. Pathologists and oncologists are testing ways in which autopsies can be used to advance our understanding of tumor biology. A recent JCO Precision Oncology article details the feasibility of a rapid autopsy program to examine cancer tissue. ASCO Expert Sumanta Kumar Pal, MD, and lead study author David J. Pisapia, MD, shed light on the value that rapid autopsy provides to cancer science.

ASCO: What should people know about this study?

Dr. Pal: People should be aware that autopsy data is oftentimes difficult to obtain. There are many logistical issues that present challenges, such as patient enrollment or the feasibility of securing and transporting the body of a patient who has recently passed to an academic facility.

Dr. Pisapia: The success of a rapid autopsy program is dependent upon a fundamental altruism of patients and their families; that a deeply personal anatomical gift, a parting shot at a patient’s disease, may build our collective knowledge about cancer so that future patients can potentially benefit. This program primarily depends on patients and their families; nothing could be learned without their support and generosity.

ASCO: Why is this study important?

Dr. Pal: The opportunity to obtain patient samples from multiple, diverse anatomic sites does not otherwise exist. Imagine, for instance, a patient with simultaneous spread of cancer to the lungs, brain, liver, and other vital organs. It would be both impossible and unethical to sample all of these disease sites. A rapid autopsy program makes this feasible - we can understand the diversity of biology in these anatomic sites through securing and analyzing tissue. This is important because a single patient can have several different kinds of tumors based on location site.

Dr. Pisapia: The ability to analyze a patient’s tumor is often limited to the initial biopsy or surgery to remove all or part of the tumor. Rapid autopsy programs enable researchers to discover how a tumor evolves over time, both at the primary and metastatic disease sites, as well as in response to treatment.

ASCO: How can rapid autopsy programs help advance cancer care?

Dr. Pisapia: Understanding how tumors respond, fail to respond, and evolve around treatment is critical to the advancement of cancer care. Moreover, since it is often the metastatic spread of cancers that leads to a patient’s health declining or death, the study of the biology underlying metastasis is critical to patient care. Rapid autopsy programs are fundamental for obtaining the tissues necessary to learn more about these processes.

ASCO: What are the some of the key findings of this study?

Dr. Pisapia: In a case of multiply recurrent metastatic ependymoma, a central nervous system tumor more common in children than adults, we identified genes that were altered in nearly all metastatic sites but absent at the primary site. In a separate case of metastatic melanoma, we identified gene candidates restricted to multiple distinct lung metastases.

The initial phases of this program are a proof of principle that there exists a broad desire to participate, and that there is a collective will between patients, clinicians, and scientists to view death not as a brick wall, but as an opportunity to learn for the greater good.

ASCO: When and why do autopsies need to happen quickly?

Dr. Pisapia: In practical terms, the objective of this autopsy program is to perform the procedure as soon as possible following death; that is, we believe that the availability of the autopsy team itself should not be the limiting factor in securing a short post-mortem interval.

The advantage of performing an autopsy within a short time interval is that the degree of RNA degradation (destruction of individual parts or strands of RNA within a cell) can be reduced and there is a higher probability of obtaining viable tumor cultures for analysis.

ASCO: Is there previous research or case studies of a rapid autopsy program that have yielded actionable information for practicing physicians?

Dr. Pisapia: Autopsy programs have already started to yield important clues regarding acquired resistance to cancer treatment that may help guide clinical trial design for future patients. For example, further examination of data derived from two patients in the current study revealed targetable mutations in chemotherapy-resistant urothelial carcinoma (Faltas et al, 2016).

ASCO: What are the most important ethical considerations of a rapid autopsy program for patients and physicians? What are the practical considerations?

Dr. Pisapia: Cultural and religious factors in addition to the expectations and goals of the patient and next-of-kin need to be recognized, considered, and managed on a case-by-case basis. Every effort must be made to accommodate the wishes of the patient and their family with respect to post-mortem care, timing of the procedure, and extent of tissue sampling.

Dr. Pal: Rapid autopsy protocols require immense considerations, both from a practical and ethical perspective. From an ethical standpoint, one needs to ensure that the rights of a deceased patient are respected. From a practical standpoint, the mechanism for securing tissue (i.e., ensuring that the deceased body is accessible) may present a challenge. 

It is important to bear in mind that the patient's rights are just as important when they are alive as when they have passed away. For this reason it is critical that investigators be mindful of patients' preferences and willingness to participate in autopsy programs. 

ASCO: What are the next steps for this research?

Dr. Pisapia: Given the diversity of cancers, treatment regimens, and outcome parameters, it is essential that cancer autopsy programs endeavor to include all patients with cancer, irrespective of the particular type of cancer or clinical course. With increased numbers of patients and tissues collected from primary and metastatic disease sites we may be able to uncover recurrent mechanisms of:

  • resistance to particular classes of drugs and treatment modalities,
  • metastatic spread,
  • medications particularly effective on specific metastatic sites such as the lungs, liver, or central nervous system.

Research regarding further implementation of autopsy programs should explore and address issues such as logistics so that the program is seamless from the perspective of patients’ families. Another critical component is to expand the program beyond the inpatient setting to those patients in third-party hospice facilities and home hospice settings.

Finally, since patients may frequently transfer their care throughout the course of treatment, inter-institutional collaboration is essential for gathering complete clinical and pathological data on each patient. One model would be to develop a nation-wide, multi-institutional collaborative approach with shared, best-practice autopsy protocols such that specimens can be collectively analyzed across institutions.

ASCO: If such programs became widely available, how would researchers and care teams be able to engage patients in their decision to participate?

Dr. Pal: In order to engage patients in this type of research, it is very important to explain the purpose of the research and the logistics involved. By explaining the great need that a rapid autopsy program serves, patients can fully understand not just the risks but also the benefits that will be associated with their efforts. 

Dr. Pisapia: The rapid autopsy program empowers patients to maximize their own personal contribution to the study of a disease that has so significantly affected their own lives. We have found that most patients and their families are interested in the program when they understand its potential to benefit others. While it may seem very difficult to approach a discussion about rapid autopsy with a patient or patient family, we have found the topic to be a natural fit within a broader discussion about advance directives.