PSMA PET/CT | Clinical Utility in Prostate Imaging
Deficiencies in prostate cancer imaging can affect a physician’s ability to diagnose and treat the disease. Further, current treatment guidelines can impact care of patients with progressive disease. A clear understanding of prostate cancer diagnosis and the extent of disease is necessary to recommend options for surgical and/or radiation therapy planning, as well as for oncologic treatment. Therefore, there is an identified need for physicians to better understand the advanced imaging technology of 68Ga PSMA-11 PET/CT, specifically with respect to its clinical utility in prostate bed imaging.
PSMA-targeted PET/CT is refining the understanding of prostate cancer and increasing confidence in the initial diagnosis by better defining the intraprostatic location(s) of disease. The use of PSMA PET/CT can address key clinical questions such as whether the disease is localized to the prostate gland and whether it is advancing and clinically significant. This can impact surgical planning and outcomes, focus the radiation therapy plans, advance targeted and comprehensive treatment plans, and allow for more informed decisions about what is best for the patient.
In cases of biochemical relapse disease, PSMA PET/CT may provide information to guide therapy and measure treatment response, disease volume, and assess disease biology, particularly in the setting of oligometastatic disease. This may lead to improved treatment planning, including assessing the feasibility of surgical resection, as well as aid in making recommendations for comprehensive, multidisciplinary treatment.
The Urologist’s Perspective
Prostate cancer is difficult to delineate as it does not typically form spherical lesions as do other malignancies. Instead, it infiltrates and replaces prostate tissue and tends to be multifocal and heterogeneous, potentially rendering each lesion a different grade.
“When I see patients in clinic, we struggle to fully characterize both the grade and the location of the primary prostate cancer,” says Clint D. Bahler, MD, MS, assistant professor of urology at the Indiana University School of Medicine. “This creates a huge challenge in terms of accurately planning the treatment.”
Prostate anatomy is also complex, with the bladder and the sphincter at its base and apex, respectively, and nerves running along all sides of the gland.
“MRI really opened our eyes to the opportunity to localize cancer lesions and approach each case differently,” Dr. Bahler adds. However, MRI may miss some lesions.1 In a comparison of MRI with PSMA PET/CT at IU Health, Dr. Bahler and colleagues found that the sensitivity of MRI is closer to 60% whereas PSMA sensitivity is closer to 90%. Therefore, Dr. Bahler says PSMA PET/CT is the ideal modality for guiding surgery.
“We’ve done a suboptimal job on imaging the prostate, and if the only way that we can find the cancer is to shoot it with multiple needles … then it’s probably time to replace the technique that we’re doing, or refine it from the way it’s being done,” says Mark Tann, MD, professor of clinical radiology and imaging sciences at the Indiana University School of Medicine and a diagnostic radiology specialist at IU Health. “Being able to help the urologists manage these patients by adding more accurate imaging is key. But it can only help us as long as we have the appropriate solution for each of the problems concerning location, bulk and grade of disease.” And that is precisely the information that Drs. Tann and Bahler say PSMA PET delivers.
A personalized approach to treatment
Prostate cancer is complex, with varying treatment options – active surveillance, high intensity focal ultrasound, laser ablation, focal radiation, whole gland radiation, or surgery. PSMA imaging delivers the information required to plan and personalize surgery for each case by potentially directing treatment approaches toward less aggressive, tissue-preserving surgery, and improving the patient’s quality of life .
“If you are going to treat, you don’t want to over-treat,” says Dr. Bahler. “PSMA PET showed me that we don't have to (overtreat). We took nerves out before, because if you have to err on the side of leaving cancer or positive margins, or getting (all the cancer), you tend to err on the side of (getting all the) cancer. So for me, it's pushed open this whole idea of very individualized or personalized medicine.”
In one case of a 50-year-old man with a low prostate-specific antigen (PSA) score and a biopsy that indicated a high volume, Gleason 3+4, with the 68Ga-PSMA-11 PET SUVmax of 5, Dr. Bahler wanted to perform nerve sparing surgery to avoid sexual dysfunction. But, with the cancer in the peripheral zone and a margin of contact with the prostate capsule, there was concern for disease spread.
“The PSMA PET gave me the confidence that I couldn’t totally nerve-spare,” Dr. Bahler explains. “It was against the capsule, but based on our experience, I didn't have to take out the whole nerve, either.”
Dr. Bahler was able to tailor the resection to preserve 90% of nerve function on the diseased side of the prostate with negative margins.
“We're gaining confidence to think that each patient should be treated individually,” Dr. Bahler says. “Negative margins are critical but we can optimize the quality of life too.
PSMA PET/CT makes a difference in cases of extraprostatic extension, which is typically microscopic. The risk of positive margin often cannot be reliably predicted with conventional imaging, such as FDG PET and MRI. No imaging modality has the resolution to see extraprostatic extension, which is microscopic, but PSMA-PET/CT does show where the aggressive components within tumors are located with high sensitivity. Therefore, if the aggressive components are noted to be away from the margin of the prostate on PET imaging, surgeons can confidently spare nerves on that side.
Just as important, PSMA PET imaging provides additional opportunity for Drs. Tann and Bahler to collaborate on each patient’s treatment plan, looking at and discussing the PSMA PET images together.
“No narrative report is ever going to have the power that you gain by having the urologist and the radiologist looking at the image at the same time, and both interactively providing their input and immediate feedback,” adds Mark A. Green, PhD, professor of radiology and imaging sciences at the Indiana University School of Medicine and director of Radiopharmaceutical Services, Indiana Institute for Biomedical Imaging Sciences. The PSMA PET imaging information has the greatest potential to impact surgery planning in men with intermediate-risk disease. The team at IU is now making use of a short video review of the pertinent imaging findings, which is done by the radiologist and sent to the surgeon for review and re-review on the day of surgery.
It is also possible for PSMA PET/CT to guide biopsy and serve in active surveillance.
“Having PSMA and better cameras with good protocols allows me to have the confidence to commit to findings that will guide my surgeon, hopefully in a positive way,” Dr. Tann says.
In another case, a 63-year-old man had a PSA score of 11.4, mostly pattern 3 with seminal vesicle invasion and a 1-mm positive margin at the bladder neck. This case was early on in the study when the clinicians were only focused on whether nerve sparing would be possible. In hindsight, the PSMA PET/CT helped detect bladder neck involvement, which could have avoided the positive margin. Thus, PSMA PET/CT imaging could help to avoid positive margins in addition to guiding nerve sparing.
Refining the PSMA PET/CT protocol
Prostate cancer imaging generally follows three phases: primary diagnosis, accompanied by surgical biopsy; determining efficacy of surgery and/or evaluating biochemical recurrence; and identifying castrate-resistant disease.
The team at IU Health/Indiana University has optimized their PSMA PET/CT imaging protocols for pre-prostatectomy patients and those with biochemical recurrence. “I think it is important (for) anyone doing PET/CT to try and squeeze the most out of the modality as possible,” says Dr. Tann. “We prefer imaging before the bladder is filled with (radioactive) urine.”
Dr. Tann explains that urine can cause image artifacts, reducing PET/CT image quality and hindering the physician’s ability to differentiate small lesions near the bladder.
Key elements of the biochemical-recurrence protocol include a single IV line for administering both radiopharmaceutical and CT contrast. In this protocol, the patient empties their bladder prior to a “traditional” whole-body PET acquisition performed with contrast-enhanced CT. But, the initial PET image collected from 0-5 minutes post-injection provides complementary detail on 68Ga PSMA-11 localization in the pelvis prior to radioactivity appearing in the urine. Two patients are often imaged back-to-back, with their PET/CT exams staggered to permit early and late imaging with 68Ga PSMA-11.
In most cases, Dr. Tann says, he can see node involvement and recurrent disease in the early images. The CT contrast component also reveals enhancing soft tissue in the prostate bed region. He also utilizes dual-energy CT imaging for a better view of the anatomy and for iodine-based imaging.
Their imaging to better characterize disease prior to prostatectomy has similarly followed a protocol in which PET data are collected from the time of 68Ga-PSMA-11 injection. Images reconstructed from early periods (e.g., 15-25 minutes) consistently reveal the same information as obtained in later imaging (e.g., 40-55 minutes).
The age of enlightenment
Thanks to 68Ga PSMA-11 PET/CT imaging, Dr. Tann can confidently provide urological surgeons and oncologists with the information needed to guide patient care and management.
Although Dr. Tann has long been able to get PSA levels, bone-scan imaging, CT and MR scans of the prostate haven’t provided all the information needed to best manage his patients. “Since we've had PSMA, it's like the age of enlightenment. We can finally understand what is going on and how best to manage it. I feel it has definitely moved us forward in the understanding and management of prostate cancer, more than many other developments I've seen over the years,” he says.
“With PSMA PET, we are all excited about the ability to see where we couldn't before,” says Dr. Bahler. “For me, thus far where it's been most helpful is in guiding the primary treatment because it shows us the most aggressive areas of the cancer. So, then we can preserve tissue where we're confident the cancer is not invading or extending outside the gland. We can preserve nerves (and) muscle at the sphincter. But also, where the PET shows us extension of cancer, we can achieve negative margins.”
Dr. Green has watched the evolution of 68Ga radiopharmaceutical technology for many years. To see the impact it is having on patient care and tumor targeted agents such as 68Ga PSMA-11 is gratifying for him.
“The clinical introduction of PSMA-targeted gallium-68 really is a milestone and an advancement of imaging supporting the clinical care of prostate cancer patients,” Dr. Green says.
A team effort
Clearly, 68Ga PSMA PET is setting the stage for precision medicine in prostate cancer management and requires a collaborative effort of the patient’s entire care team. Communication between all members is important to achieve outcomes that can also improve patients’ quality of life.
Dr. Green emphasizes, “The progress we've made regarding the use of 68Ga PSMA-11 to improve the diagnosis of prostate cancer really comes through a team effort. It is critical to have the urological surgeon, the radiation therapist, and the medical oncologist helping define the clinical problems, which in turn helps develop better radiology tools with improved imaging performance that can address the proximal clinical needs.”
He concludes, “We really couldn't do any of this without functioning as a cohesive care team.”
(1) Mehralivand S, Shih JH, Harmon S, Smith C, Bloom J, Czarniecki M, Gold S, Hale G, Rayn K, Merino MJ, Wood BJ, Pinto PA, Choyke PL, Turkbey B. A grading system for the assessment of risk of extraprostatic extension of prostate cancer at multiparametric MRI. Radiology. 2019 Mar;290(3):709-719. doi: 10.1148/radiol.2018181278.