GU Cancers 2023 | How real-time molecular imaging can improve the management of prostate cancer
Anthony Victor D’Amico, MD, PhD, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA, discusses how radiotherapy for prostate cancer has evolved over the last 30 years and talks on some of the remaining unmet needs in the field. A key area which needs further research is the use of real-time molecular imaging, which would allow clinicians to understand how the disease is evolving and developing and help them to decide how best to use highly precise local treatment. Prof. D’Amico also highlights the importance of preserving important structures in the prostate, which are at risk of damage when high-dose, short duration radiotherapy is used. Finally, Prof. D’Amico talks on the need to understand how best to combine radiotherapy with appropriate systemic therapies. This interview took place at the ASCO GU Cancers Symposium 2023 in San Francisco, CA.
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Transcript (edited for clarity)
Radiation therapy in the last 30 years, which is the amount of time I’ve been in this field, has come considerably forward, and I’m happy to see that. Just historically, just briefly, when I started in my residency, we did something called 2D radiation where we basically treated people front to back, there was no advanced technology, the imaging that you used to set people up was bone radiology...
Radiation therapy in the last 30 years, which is the amount of time I’ve been in this field, has come considerably forward, and I’m happy to see that. Just historically, just briefly, when I started in my residency, we did something called 2D radiation where we basically treated people front to back, there was no advanced technology, the imaging that you used to set people up was bone radiology. It was prehistoric the way we think about it today. Now we have ways of modulating treatments, image guidance, proton based treatment. There’s even treatment now they can deliver all the treatment at a very high dose rate in seconds. But I think that where we need to go next is something that we’re not at yet, but I would call it a more sophisticated version of advanced imaging that we don’t have that’s in research is molecular imaging, to be able to image in real time on a molecular basis what’s happening in the prostate cancer.
Let me explain why that’s important. There is something called the FLAME trial where they boosted lesions within the prostate that were defined based on MRI to higher dose using the radiation technologies we have. Wonderful. It showed a benefit in delaying progression, PSA failure free survival benefits. Suppose for a minute that we not only can see the anatomic distribution of the disease, but understand its biology and how its biology is evolving. You give them neoadjuvant hormonal therapy of some sort and you watch the biology evolve to something that becomes more radio sensitive or maybe just disappears altogether. Do you then need to treat that area? This is now looking way ahead, maybe 10, 15, 20 years to be able to, in real time, image what’s going on in the tumor at the molecular level so that you can decide how best to use your local treatment.
Radiation at this point is at the level where we can put radiation with high dose with one millimeter precision, you’re not going to get much better than that in terms of precision of treatment localization. What we can do better at, though, is understanding where within the prostate itself and the cancers that exist, because there’s usually multiple cancers, do we need to focus our attention, while not just sterilizing them, but understanding what the biological implications of that disease is. Last point, the urethra, the prosthetic urethra in the bladder neck, two structures that are critical to quality of life. As we go to higher doses of radiation, hypo fractionation with 300 centigrade/fraction, SBRT with 625 centigrade/fraction, we have to ask ourselves, “Are we really mindful of the fact that those structures inside the prostate are seeing full dose?”
This is state of the art now, MRI guided radiation therapy where you can see those structures in real time and where you can adapt the plan in real time so that you can protect the bladder neck and the urethra and then give these very high doses and have the convenience of a very brief treatment, couple of days or even maybe one day, at the same time while keeping those structures safe. But I really do think when you say about an unmet need in oncology, prostate cancer, it’s really being able to molecularly understand what’s going on in the cancer in real time and coupling what we do with local treatment, with appropriate systemic treatments, because the last thing I’ll say on this topic, because that’s really I’m talking about unmet need in oncology more than just radiation oncology, and that is if we know that in the prostate cancer at this point, there’s a targetable lesion that’s not responding well to our local treatment, or even if it is responding well to our local treatment, it’s probably in circulation as well.
Knowing how to target with appropriate systemic agents and choose them wisely or create them in conjunction with pharma, “Hey, we need a drug that targets this particular mutational sequence because we’ve seen it a lot now in prostate cancer,” and this is the path forward.
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