Imaging Prostate Cancer
Posted: Nov 01, 2018
POSTED: April 22, 2019
Dr. Timothy J. Daskivich is a urologic oncologist in the Cedars-Sinai Urology Academic Program and the director of Health Services Research for the Cedars-Sinai Department of Surgery.
Prostatepedia spoke with him about his clinical trial on using high-resolution PET/MRI in planning high-intensity focused ultrasound (HIFU) for prostate cancer.
Dr. Daskivich: I always knew that I loved science, but I wanted to do something where I could impact individual lives. I’m also a people person, and I love to get to know people and hear their stories. Being a doctor is a kind of mash-up of those two interests: my love of science and discovery with the human aspect of being a doctor.
Now I’m a physician-scientist: I do the science part of my work half of my time, and for the other half, I see patients and operate. They’re related but very different, and I love the dichotomy.
Dr. Daskivich: Absolutely. I actually have a good example of how my research connects these two parts of my job. I have a Mentored Clinical Scientist Research Career Development K08 Award from National Cancer Institute that aims to improve communication between doctors and patients about life expectancy after a new diagnosis of prostate, kidney, or bladder cancer. This study involves recording treatment consultation consultations between doctors and patients to better understand what is being said about life expectancy in these discussions. We follow this with a structured interview with the patient to ask about what worked well or what could have been improved. Based on what we observe, we’re planning to create a patient-centered approach to discussing life expectancy. This study allows me to talk to the patients, hear their stories, and then bring their perspective back to physicians to try to improve communication. It’s a lot of fun, and one aspect informs the other.
Dr. Daskivich: Our clinical trial involves testing whether fluciclovine PET-MRI can improve localization of tumors within the prostate (compared to standard multiparametric MRI) prior to focal treatment with high-intensity focused ultrasound (HIFU).
To help you understand why this trial is important, let me first give you some background. For many years, we used surgery or radiation to treat the entire prostate for patients with prostate cancer. We either removed or radiated the entire gland. That was the standard of care for a long time. But the problem with whole-gland treatment is that it incurs a lot of side effects—erectile dysfunction, urinary incontinence, or irritative urinary symptoms—by damaging structures near the prostate like the nerves that supply the erectile function of the penis and the bladder neck.
In order to minimize those side effects, there’s been a movement to consider focally treating the prostate cancer lesions and leaving the rest of the prostate intact. That had been a pipe dream for a long time, until recently when the technology has become available to identify and focally treat prostate cancer lesions in a minimally invasive and highly precise way. It’s actually a confluence of three technologies that have made focal therapy possible.
The first of these technologies is high-intensity focused ultrasound (HIFU). HIFU directs high-intensity ultrasound waves to a point in space, and that point is destroyed. It’s a little bit like using a magnifying glass to harness the rays of the sun to burn a leaf. When you pass your hand between the magnifying glass and the leaf, you don’t get burned. With HIFU, you can place a probe into the rectum, direct the ultrasound waves to destroy an area in the prostate and destroy it while leaving all the intervening tissue unharmed.
The second technology is MRI, which we use to localize cancers within the prostate. MRI has about 80% sensitivity for detection of high-grade cancers within the prostate. And not only can it detect them, but it can define exactly where they are.
The third technology is MRI-ultrasound fusion. This technology allows us to overlay MRI images—including the location of tumors—onto ultrasound images in real time. This is important since we use ultrasound as our primary imaging modality to direct HIFU to the areas of the prostate that are affected by cancer. Now with MR/US-fusion technology, we can superimpose the location of tumors as identified by MRI directly onto the ultrasound when we’re targeting our HIFU beam.
All of these technologies—MRI of the prostate to identify location of tumors, ultrasound fusion to target the tumors in real time, and HIFU to precisely transmit energy to these areas—have made focal therapy of the prostate possible.
Our study acknowledges the fact that focal treatment of prostate cancer is entirely dependent on imaging. If I’m going to take out the entire prostate gland, there is a huge safety net for error. If we thought that the cancer was on the right side, but lo and behold, there were a few lesions on the left, it’s no problem–we’ve taken the whole thing out, so we’ve removed the unseen cancer. However, now that we’re doing focal therapy, that safety net is gone. If you fail to detect a prostate cancer prior to doing a focal treatment and therefore don’t treat that area, then you haven’t fully treated the cancer.
In this study, we’re using high-resolution PET/MRI to precisely identify prostate cancers during HIFU planning. Before HIFU, all the patients on the trial get a high-resolution MRI (six-fold improved resolution compared with standard MRI) and fluciclovine PET-MRI to map out where prostate cancers may be located. We then biopsy all lesions that are positive on the PET or on the high-resolution MRI using ultrasound fusion technology. Then based on that map, we do focal HIFU on all areas that are positive for cancer.
With improved cancer mapping using high-resolution PET/MRI, we hope to be better at treating the cancer completely. By maximizing our imaging, we hope to maximize the cure rate.
Dr. Daskivich: At six months after focal therapy with HIFU, patients get another prostate MRI and targeted biopsy in both the treated and untreated zones. We also follow with serial PSA levels.
Dr. Daskivich: Patients come to us already having been diagnosed with prostate cancer on biopsy. We then do the high-resolution PET MRI and repeat targeted biopsy based on the advanced imaging at Cedars Sinai. Patients who remain eligible and interested in HIFU go on to get this treatment at Cedars Sinai.
Dr. Daskivich: Yes, patients do need to do follow up MRI and targeted prostate biopsy at 6 months at Cedars Sinai. PSA testing can be done at a remote location if necessary.
Dr. Daskivich: All procedures that are not standard-of-care are funded by the trial. This includes the high-resolution and PET components of the MRI. Importantly, though, the HIFU is an out-of-pocket cost for participants, since it is a standard of care procedure and we’re studying the imaging and not the HIFU procedure itself.
Dr. Daskivich: Most often, insurers cover follow up imaging for prostate cancer treated with HIFU as standard of care.
Dr. Daskivich: Participants on this trial must either have clinically localized, unilateral high-grade (Gleason 7 or higher) or high-volume Gleason 6 (>50% of cores involved) disease. Those with unilateral high-grade disease can also have contra-lateral low-grade (Gleason 6) disease, but they cannot have bilateral high-grade disease. PSA must also be less than 20.
We specifically designed the study to exclude patients with low-volume Gleason 6 disease (<50% percent of the cores involved). This is because active surveillance is a better treatment option for most patients with low-volume, low-risk prostate cancer.
Dr. Daskivich: I was initially a skeptic about focal therapy, and that’s why I wrote this trial. I wanted to document all of the outcomes in a very systematic way and convince myself that it was effective. Having used focal therapy with HIFU for some time now, I’ve been pleasantly surprised at how effective and minimally morbid it is, at least in the short term. Cancer control has been excellent in the short term and the side effect profile is much better than traditional therapies like surgery or radiation. HIFU is done as outpatient treatment as well, so it is also convenient. It’s honestly quite refreshing to have a prostate cancer therapy that doesn’t come along with the traditional baggage of urinary incontinence and erectile dysfunction.
Dr. Daskivich: Which can be very debilitating, even if it is experienced for only a short period of time. If the long-term cancer control of focal therapies for prostate cancer like HIFU turn out to be durable, then it could change the standard-of-care for unilateral high-grade disease. Time will tell.