Dr. Eliezer Van Allen, Assistant Professor of Medicine at Harvard Medical School, a clinician at Dana-Farber/Partners Cancer Care, and an Associate Member at the Broad Institute of MIT and Harvard, focuses on computational cancer genomics, using new technology in precision medicine, and resistance to targeted prostate cancer therapies.
What is the Metastatic Prostate Cancer Project?
Dr. Van Allen: The Metastatic Prostate Cancer Project is a patient-driven research initiative whereby we researchers partner directly with patients to dramatically expand the scope of our understanding prostate cancer genetics. We try to fill in all of the missing gaps that are currently a challenge in our field. Hopefully, we’ll learn what drives advanced prostate cancer, how to treat it more effectively, come up with new drugs, and understand the differences between more indolent cancers and those that progress in the metastatic setting. Essentially, I want to answer the questions I had during my initial clinical observations way back when.
You say you want to partner directly with the patients. How does that disrupt the normal clinical trial process? Normally, patients would access trials through their doctors?
Dr. Van Allen: Exactly. That’s what I’ve done during my postdoctoral training and in my junior faculty stage. That’s what we all do: we devise the research project, write a bunch of protocols and consent forms, and get them approved in our hospitals. Then we rely on the doctors and research teams to approach patients. They consent their patients to the studies that are already defined and set in stone. We use that to research. That’s obviously been a driving force for many modern discoveries. It’s a remarkable thing.
And that’s how we have to lay the first genetic maps of prostate cancer and cancers in general. This project flips genomics on its head. We’ve been working with prostate cancer patients to build a project with, by, and for men with advanced prostate cancer, their families, caregivers, and loved ones in order to resonate with patients. We are creating a mechanism such that patients can consent without leaving their home and participate without necessarily living near an academic medical center. This helps expand the scope of what we were able to learn in new ways.
A couple of years ago, while trying to define the genetic maps of local and advanced prostate cancer, we launched the first of these patient-driven projects at the Broad Institute in metastatic breast cancer. Using social media, patient outreach, advocacy partners, and patients themselves describing what it means to participate in these projects, that study enrolled over 4,000 women and men with metastatic breast cancer. Given that we’re thrilled when the average study to define the genetic maps of prostate cancer enrolls 100 patients over the course of years, if not decades, that number in such short time is remarkable. As we developed that project, I immediately thought of prostate cancer.
Rather than doing a top-down research project whereby we start with an idea in a researcher’s head, we go through the hospital and the doctors, and eventually, the patients, we’re starting with the patients. They’re talking directly to the researchers and building up. That is the ethos of this project.
This is not a traditional, academic project whereby we generate all the data, sit on it in our own little groups while we try to make sense of it, and eventually make it available to the larger community. Rather, as soon as we have a nominal amount of data, we make it immediately available to any researcher around the world who wants to use it. We’re trying to create a resource that anyone could use. The first 100 patients with genetic and clinical data have been made available for researchers pre-competitively. We don’t wait and publish these results in an academic journal or any other medium first.
Publishing in a traditional academic journal can restrict access for patients. If they want to read to read the results, they have to pay $30 to download the article.
Dr. Van Allen: Exactly.
If someone reading this wants to participate, what do they do?
Dr. Van Allen: If you have advanced prostate cancer, simply go to mpcproject.org. There, the homepage describes what’s involved. When you click the “count me in” button, it sends you on what we hope is a very quick journey through a few basic questions. Then, it asks for your permission or consent to participate in this project. There are a few more simple questions after that.
Soon after you register, you’ll receive a box that contains a saliva kit that the patient will spit in and return to get their inherited DNA information. Additionally, there’s a liquid biopsy kit, which is a vial that you bring to your doctor’s appointment to collect a liquid biopsy of your tumor. Then you return the sample to us.
When we receive those materials, we perform genetic profiling and access the medical record data. We de-identify everything to make sure it’s private, so nothing is exposed. We build a cohort and learn as we go.
Each step of the process has been vetted, scrutinized, criticized, and modified based on patient feedback such that we hope it resonates with this group. Part of this is actually iterating as we go. This is a research project. We’re not a clinical lab, so at the moment at least, we do not return results to individuals. But we do regularly engage with patients to share aggregate results of anything we learn in real time.
Patients won’t have access to the results of their tests?
Dr. Van Allen: Right. Unfortunately, we can’t provide individualized results, at the moment at least, because it’s beyond the scope of this project. It’s something we’re very interested in trying to explore. It creates many additional complexities. There is a holy patient/doctor relationship that we want to respect. That being said, often men will ask what’s in it for them and ask why would I want to do this?
We try to share aggregate results as regularly as possible. Patients can take those aggregate results, or any sort of interesting findings, to their doctor to consider if it’s relevant to them. Also, it’s a beautiful thing to see how patients themselves get when it comes to helping others: This is for the brothers, the sons, the patients that come after me, and I want to contribute. I want to help solve this puzzle, even if I may not see it in my lifetime. That altruistic aspect is genuinely great.
They do get to participate.
Dr. Van Allen: Yes. They’re just surprised that folks like myself, or anyone in the research world, is even talking to them. But patients are the most powerful people in this world. They have the power to really make these kinds of change
I think most people would want to participate if it’s easy to do. Are you providing detailed information about the kinds of tests you’re running so that if patients wanted to repeat them with their own doctor they could?
Dr. Van Allen: We’re doing whole exome sequencing, which looks at all the coding region of the genome on the tumor and the inherited DNA.
We are also piloting sending in liquid biopsies. One emerging technology that’s arrived over the last couple of years is the ability to detect circulating DNA that has shed from the tumor into the blood. That is an important advance for this project because most men with metastatic prostate cancer will not have had a biopsy of their tumor at the time of metastatic disease. They may have had a prostate biopsy years, if not decades, before but that tumor from way back when isn’t an accurate snapshot of what the tumor is like in the metastatic setting. Detecting a tumor in relative real time using blood is something we’re pretty excited to explore as part of this project.
For the men we sequence, we do our best effort to track down their tumor block. We go through every precaution to ensure that we don’t exhaust the tumor biopsy and that clinical care comes first. If there’s ever a need for it down the road, that’s the number one priority. We’re exploring how to use these liquid biopsies to help us in this project.
Do you handle the liquid biopsies?
Dr. Van Allen: Yes, it’s the Broad Institute.
Can anyone participate? Can non-Americans participate?
Dr. Van Allen: At the moment, we are approved so that anyone from the United States and Canada can participate. Anyone in other parts of the world can complete the survey and provide some of the patient-reported data, but we don’t currently have permission to do the subsequent genomic profiling for them. In our soft launch, we’ve scanned through self-reported information from almost 200 patients. That has already initiated some ideas for research projects we never would have imagined.
This patient-reported data is quite valuable. Anyone who, at the moment, may not be eligible by virtue of not qualifying from a regulatory perspective for our institutional review board can still contribute to this project in a meaningful way.
A fair number of people travel for medical procedures. If someone travels to the United States for radiation, for example, could they have the samples collected at a United States institution and therefore participate in that way?
Dr. Van Allen: For now, the study can only collect samples and medical records from residents of the United States and Canada. We are actively investigating methods for including international patients.
Is there a fee to participate, or is this free for men?
Dr. Van Allen: Free.
Is there anything else you think men should know about the project?
Dr. Van Allen: We’ve been concerned about patient interest and openness. In our first project for breast cancer, the social media footprint was quite high. The social media chatter is noticeable and folks feel pretty comfortable expressing their thoughts, feelings, and opinions about their disease. Even though incidents of disease is roughly the same in the United States for breast and prostate cancer, the social media footprint for prostate cancer is the complete opposite.
As we geared up for our soft launch, we were curious to see if we’d end up with the same number of participants, even if we weren’t seeing any social media chatter. People don’t talk about this disease. Indeed, on the first version of the saliva kit that we mail out to the patients, metastatic prostate cancer project was printed on the box. Men asked us to take that off the box. We didn’t understand why. One guy explained: “I don’t want the mailman to know I have prostate cancer.”
It’s that kind of challenge we’d like to help overcome. We want to make men feel more comfortable talking about this disease amongst friends, families, and coworkers. We hope this project can be the mechanism to help men open up about it. It’s encouraging that in the first ten days we’ve accrued an almost identical number of patients as we did with the breast cancer soft launch a couple of years ago. Nobody talks about prostate cancer on Twitter and Facebook, at least in open settings. We’re very curious to learn how patients become comfortable talking about this disease and about this project.