ORLANDO, FL, USA (UroToday.com) - Enhanced detection of early-stage metastatic disease using novel imaging modalities may offer the potential for more effective early treatment and possibly better patient outcomes in prostate cancer. And, it seems that advances in this area are sorely needed.
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“We need help in this field,” Pete A. Pinto, MD, said at the outset of his presentation, “The Evolving Role of Multimodality Treatment in Low-Volume Hormone-Sensitive Metastatic Disease,” at the 2015 GU Cancers Symposium in Orlando, FL. Dr. Pinto is head of the prostate cancer section at the National Cancer Institute (NCI), at the National Institutes of Health, in Bethesda, MD, where he and his team have a history of conducting pioneering work into new imaging modalities for prostate cancer.
The implications for patient care in this area are profound, “especially for the high-risk patient,” Dr. Pinto said. “If we had the ability to detect early metastatic disease, we could better select which pot to put patients in for the best outcomes.” There is also the additional opportunity to improve how treatment is monitored and assessed for response vs failure earlier in the treatment cycle—also an unmet need and a promising goal.
What is available today is not good enough, Dr. Pinto said. CT, MRI, bone scans, and traditional FGT-PET perform poorly at identifying patients with early metastatic disease.
Alongside his team of medical researchers at the NCI, Dr. Pinto is directing the development and assessment of the several new imaging modalities he highlighted in his lecture.
Sodium fluoride, which is used to detect osseous metastasis, is acquiring clinical utility at some centers. As a result, Dr. Pinto said, the traditional bone scan may slowly being phased out. There is a good reason for this. Even though evidence in the literature is not sufficient to say that this is clearly a better modality over bone scan, “…there is evidence for an improvement in specificity with this tracer when compared with an FGT-PET,” which, he added, “…has performed poorly for patients with early metastatic disease.”
Sodium fluoride scans are often part of the imaging workup in a clinic the group shares with oncology colleagues at the NCI. Especially for (detection of) occult metastasis following biochemical failure after treatment, Dr. Pinto stated, “there seems to be an improved role for this. “
One patient case illustrates this point. A 64-year old healthy male with a high PSA and high clinical tumor volume on MRI underwent a biopsy that revealed high-grade cancer. For this patient type, Dr. Pinto said, the bone scan fails the challenge of ruling out distant disease, and along with it, the possibility of long-term durable response with either surgical resection or radiation. But, “at three separate levels,” he said, “a sodium fluoride PET scan was able to find confirmation of osseous metastasis. This is a good example of having the opportunity early on in the treatment algorithm to provide the best care possible.”
Choline is a lipid metabolism (C-11 or F-18) transport tracer that is supported by some data suggesting that it can reflect tumor grade, PSA, Gleason score, and possibly provide prognostic indication of the tumor.
But, there are problems with this tracer, said Dr. Pinto. Because the half-life of C-11 is short, the administering facility has to have an onsite cyclotron to produce the tracer. Although it is not available in the U.S., (but approved in Europe), an alternative, F-18, has 5 times the half-life of C-11 choline.
There are other issues with choline, however. Evidence in the published literature suggests that high PSAs reflect better imaging with this modality, so if early the early detection of metastases is the issue, this modality may fall short (for men with lower PSAs).
C-11 acetate offers similar utility as choline. It is lipid-membrane incorporated with excretion in the pancreas. Acetate may provide good-quality imaging of the lymph nodes around the kidney, ureter, or bladder. For this tracer, however, at this time there is a scant body of literature to support its use.
18F-FACBC is an amino acid synthetic analog whose transport mechanism is still not clearly understood. In a small series of published literature, this tracer shows some improvement over choline, “but not much,” Dr. Pinto qualified. Nevertheless, there is some implication that 18F-FACBC may have potential to monitor response to therapy, and this may have clear value. It may allow for patients to move off therapy quickly when the response fails. “With a high affinity to the androgen receptor—in essence an ability in essence to monitor the androgen receptor—this tracer offers hope that we can monitor response to treatment, and down the road, act more quickly on therapy.”
PSMA (prostate-specific membrane antigen) has been the target of perhaps the “most interesting“ recent work. PSMA is a well-known trans-membrane tracer—not just for prostate but also for other tissues. “Although the GI gut can express this,” Dr. Pinto said, “there is “clear expression in prostate cancer.” Although its precise role in prostate cancer is somewhat clear, it is still being elucidated.
The radiotracer 18F- DCFBC is a PET probe with significant promise. It is currently under investigation at the NIH. Its advantage concerns the potential to offer more opportunities for diagnosis vs choline acetate scans. In particular, it may offer the opportunity for monitoring of the peritoneum, explore and reveal approaches for targeting treatments, and further inform tumor biology.
Iron-based MR scans may have the potential for use in imaging for micrometastases in the lymph nodes. Sadly, Dr. Pinto added that the initial work did not carry through from an imaging standpoint to let investigators use it in the U.S.
However, another iron oxide agent, ferumoxytal, that was initially approved by the FDA as an iron replacement therapy for patients with anemia due to chronic renal failure has shown promise and is under study for detection of malignancy in lymph nodes. Trials with iron oxide agents are currently in planning or underway in the United States.
Although not robust with long-term data, these imaging agents are novel and promising. Data are coming in the form of small patient series that give clinicians hope that there will be a better opportunity to characterize early metastasis going forward. “This work is robust,” Dr. Pinto said. “The research is active; and with time, more information is bound to build upon what is a currently solidly rich research base.”
Clinical context: Using New Imaging Modalities to Identify Early Metastatic Disease. In: General Session 2: Evolving role of Multimodality Treatment in Low-Volume Hormone-Sensitive Metastatic Disease.
Presented by Peter A. Pinto, MD at the 2015 Genitourinary Cancers Symposium - "Integrating Biology Into Patient-Centric Care" - February 26 - 28, 2015 - Rosen Shingle Creek - Orlando, Florida USA
Staff Clinician, Urologic Oncology Branch, Head, Prostate Cancer Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD USA