Transcription:
Considerations in Radiation in the Treatment of Prostate Cancer

Melanie:  Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, I invite you to listen as we examine considerations in radiation in the treatment of prostate cancer. Joining me is Dr. Sean Sachdev. He's a radiation oncologist at Northwestern Medicine.

Dr. Sachdev, it's a pleasure to have you join us today. I really love this topic. It's so interesting to me. So you have a unique focus on stereotactic radiotherapy of prostate cancers, tell us a little bit more about this focus and what's the main areas of your work.

Dr Sean Sachdev: Sure thing, Melanie. It's a pleasure to be on here and it's a pleasure to have the opportunity to talk a little bit about what I'm passionate about and my clinical work. So stereotactic radiotherapy is a very modern, sophisticated way to deliver radiation therapy using state-of-the-art imaging guidance, as well as precisely targeted radiation beam-led technology. And in doing so, it allows us to deliver a laser-like focus of energy, exactly where it needs to go in the body, exactly where the cancer is.

And while historically, as it was developed, it was used for other areas of the body. Now with more experience in technological advancement and experience in how to use it, it also represents a very potentially powerful tool for treating prostate cancers in as little as five sessions of treatment.

I started the stereotactic prostate treatment program at Northwestern and I believe, you know, over time, we've developed a very capable and sophisticated workflow and program, and now we have many successful outcomes under our belt. But of course, this is not a treatment, like everything else in medicine, that is right for every patient or, in this case, every man who has prostate cancer.

For example, for the men who have more advanced forms of disease and for whom we may need to deliver cancer-killing dose to the pelvic lymph nodes, this is not the ideal treatment.

Melanie: Then a recent Journal of Clinical Oncology paper you authored discusses the significance of the right imaging for prostate cancer at diagnosis. Why is this important, doctor? Tell us about the best imaging solutions for prostate cancer.

Dr Sean Sachdev: Well, as cancer-treating physicians, one of our desires and challenges has always been to utilize a form of imaging that can show us exactly the amount of disease in the body and where it's located. That's particularly true for myself as a radiation oncologist, because then I have the capability to use modern forms of technology to deliver cancer-killing dose exactly where the cancer is situated.

Now, when we're trying to look for cancer in the body for most cancers, this is most commonly accomplished using more generic anatomic forms of imaging, such as CT scans to basically look at all the major organs in the body and see if there are abnormalities where they shouldn't be. But sometimes it's unclear with these older scanning technologies if there is disease present or not, or if we're potentially dealing with an abnormality that isn't related to cancer.

So ideally, you know, this is on our wishlist. We prefer a tool that can light up, if you will, where the cancer is in the body. And fortunately for prostate cancer, there has been a lot of advancement in PET-based imaging, that can light up exactly where the cancer may be located. And PET stands for positron emission tomography. And that is generally a kind of technology that has been around for quite some time, but it has never been able to be utilized in a sophisticated manner as it is becoming currently for prostate cancer.

So there is already an FDA approved imaging modality using PET and a molecule called fluciclovine, which goes by the brand name Axumin that is available at Northwestern. However, we're really excited about another molecule-based imaging tool also utilizing PET that we really, expect and hope should be approved nationally by the FDA sometime this year. This is called, and it's a long term, but prostate-specific membrane antigen or PSMA for short. And it has been in wide use in other parts of the world, including in Europe and Australia. And we're hoping that by the end of this year, we'll have access to this agent nationally in the United States as well.

So while new technology is exciting, as a message of caution, we recently authored this scientific paper warning against over utilizing imaging information for certain scans when we're still developing a better understanding of exactly what we're looking at. By which I simply mean, in other words, we don't want to take a man who would have been cured using an existing validated approach that has been proven over decades for multiple clinical trials and simply, because of an isolated imaging finding, which may or may not have an impact on his cancer outcomes, not offer him curative treatment.

PET-based imaging is obviously a wonderful tool that will help many men, but we need to use, like everything else, science to help us figure out how to best use it. And in Northwestern, we are soon to participate in a National Cancer Institute-sponsored cooperative group clinical trial that will help us gather data, that will shape how we optimally use such imaging in clinical care of men to help them beat prostate cancer.

Basically, while we're all really excited about these new forms of imaging that can light up cancer where it exists, we authored this multi-disciplinary, author-based scientific paper just warning the general cancer community to use such information appropriately and not to overreact on it. Basically, if you can cure someone based on what we know now, don't look in an isolated imaging finding for this powerfully new potential tool that we're still learning how to use fully and take them off the curative path.

Melanie: That's great advice. What good points, doctor. And the same paper mentions androgen deprivation therapy in combination with radiation as an effective therapy. So share the benefits a little bit of this approach and tell us about your outcomes.

Dr Sean Sachdev: Sure. Androgen deprivation therapy or ADT for short is used in the treatment of multiple forms of prostate cancer, including localized disease, by which I simply mean all the cancer is still within the prostate gland, as well as when it becomes more advanced and metastatic or it spreads throughout the body.

And essentially, what androgen deprivation therapy is, is basically depriving as the name implies the prostate cancer cells from having a supply of testosterone, which is an androgen, which allows them to grow and to flourish. There are certain cancers in the body that are very influenced by hormones. There are many forms of breast cancer, for example, that are encouraged to grow and to flourish in the setting of estrogen. And one of the most effective treatments that we have for those kinds of cancers is to deprive the body or to block the estrogen.

The same is true when it comes to prostate cancer. When you take this powerful treatment and when you combine it with radiation therapy, it can allow a combinatorial synergy that lets the radiation treatment work even better, like a boost, if you will. And just like everything else, this is something that is a tool that needs to be applied to the right prostate cancer stage and for the right patient. For example, there are certain forms of prostate cancer for which radiation therapy alone works very effectively, and we don't need to use androgen deprivation therapy.

However, for other more advanced forms of prostate cancer, the combination of the two has been shown from multiple excellent clinical trials that have been run over the past 10, 15, 20 years to improve essentially every important cancer-related outcome that we worry about for cancers, including the chance of the prostate cancer coming back where it existed and the chance that it could spread elsewhere in the body.

And most importantly, it's been shown to help a person live longer who has been diagnosed with prostate cancer. So androgen deprivation therapy remains one of the most effective weapons that we have against cancer and, in the right scenario, when you combine it with radiation therapy, can really improve all outcomes.

Melanie: What an exciting time to be in your field, doctor. So you've also published work showing the benefits of post-operative radiotherapy for prostate cancer in JAMA Oncology. How is this found to be effective? Speak about that one.

Dr Sean Sachdev: The two most common well-validated and accepted ways of treating localized prostate cancer, which is again when the cancer has not spread more distantly elsewhere in the body to become metastatic, are, one, removal of the prostate gland by surgery or prostatectomy or, two, radiation therapy that is delivered to the gland where it sits.

Sometimes when the first attempt is surgery, we discover at the time of surgery that the prostate gland was more affected by disease than we had previously imagined or predicted or, after surgery, we can detect rising levels of PSA, which can be used as a disease marker and that would show us basically that there may have been more disease left behind than we had anticipated and that disease is now growing again. We can see rising levels of PSA.

Just as a quick recap, PSA or prostate-specific antigen is a protein or chemical that's released by prostate cells and prostate cancer cells. So ideally, the goal of surgery is that if you can take the gland out with all the cancer within it, well, if you've taken out the prostate cells and the prostate cancer cells, the PSA should be zero because there's nothing left to secrete PSA anymore.

But if we see that the PSA's still detectable after surgery and we're especially worrisome if we can see that that level is rising, which indicates that there is a collection of cancer cells that is growing. On that scenario, radiation therapy can be utilized to get rid of the residual disease and render the patient back to curative state.

The problem is there's quite a lot of variation in how this is done nationally as well as globally. And so for this paper and for this scientific review in order to better solve that problem, we assembled a multidisciplinary panel of nationally recognized prostate cancer experts from radiation oncology, importantly, as well as medical oncology and urologic oncology to review all of the existing data and the newly arriving data from more recently completed clinical trials, looking specifically at this kind of treatment.

At Northwestern in this multidisciplinary panel of experts, we had Ted Schaeffer, Dr. Schaefferr, who's the Chair of Urology, as well as Dr. Hussain, who's a worldwide recognized leader in prostate medical oncology. And what we did is we assembled other colleagues throughout the country from very good cancer centers and with a lot of experience and we analyzed the data with a goal to provide a consensus opinion on how we should apply such data for daily clinical use when it comes to delivering radiation therapy after prostate surgery. Particularly, we focused on some very timely, large clinical trials that have been recently reported, which have been very successful in attempting to define the right population of men for whom this treatment can be very successful.

So historically, instead of, reactively prescribing postoperative radiation therapy for men who may have some advanced features at the time of surgery, this would advocate for more careful monitoring of PSA values after surgery and reserving the treatment for those patients and those men who may benefit best from the cancer therapy. In other words, these data allow us to spare men from unnecessary treatment while delivering it to those that are most likely to benefit and get them back to a curative state after surgery.

Melanie: What an important topic we're discussing today. So, Dr. Sachdev, before we wrap up, as a summary, is there anything else you're working on to advance diagnosis and treatment of prostate cancer that you want to share? What research excites you most and where do you see this going? Give us a little blueprint for future research. And while you're telling us that, what do you wish more urologists knew about radiation oncology?

Dr Sean Sachdev: Sure, Melanie. We have a lot of exciting research that is currently underway. So the FDA recently approved a newer oral form of androgen deprivation therapy that potentially has some benefits in terms of cardiovascular side effects, as well as ease of administration. And we are currently working on some clinical trials that study the best way to combine radiation therapy with this newer agent,

We are also now activating and working on clinical trials that allow us to better use genomic information to help guide treatment, which is basically, in other words, while prostate cancer management for decades has largely been based on how cancer cells look under the microscope after biopsy, this will allow us to better utilize information at the genomic or DNA level, meaning how is this cancer likely to behave based on its genomic component.

And several tests are out there in the market that are commercially available that exists currently for this purpose, but they require more rigorous, scientific validation, and we have to best figure out how to act on such genetic information and ideally define populations for whom we would either deliver more intense treatment or, for the right people, less intense treatment based on their risk and trials asking such questions are being activated at Northwestern as we speak.

For my colleagues in urology, I'm fortunate to work with a wonderful group of colleagues here at Northwestern Urologic Oncology. And there are a lot of options for personalization of treatment in prostate cancer and not every treatment is right for every person. So in order to benefit our patients the most, which is our ultimate goal, we have to work as a team to figure out which option is right for which patient.

Radiation oncology has undergone and amazing technological metamorphosis over the past 15 to 20 years, even while treatment before that point was very successful and with limited side effects. Now, we are better suited than ever to deliver curative treatment either for intact cancer within the prostate gland or for treatment after surgery for postoperative treatment. And we can do this now in a more abbreviated format that requires fewer sessions and delivers treatment accurately and in a sophisticated manner with minimal side effects. And I believe our colleagues and partners in urology are starting to see that.

Melanie: What a great episode and such informative information. Thank you so much, doctor, for joining us today. To refer your patient or for more information, please visit our website at nm.org to get connected with one of our providers. And that concludes today's episode of Better Edge, a Northwestern Medicine podcast for physicians. Please remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.