68Ga-PSMA-11 PET For Localizing Recurrent Prostate Cancer
The treatment of men with biochemically recurrent prostate cancer has changed significantly in the past few years. Whereas previously few options aside from systemic treatment were available (Androgen Deprivation Treatment or Chemotherapy), today treatment can be guided by more precise localization of local, regional or distant disease. Conventional imaging with computed tomography (CT), magnetic resonance imaging (MRI) and/or standard bone scintigraphy have very limited detection rates in the case of biochemical recurrence at low prostate-specific antigen (PSA) levels. Positron emission tomography (PET) radiotracers, on the other hand, are consistently showing promise to overcome this limitation. For a review of the available radiotracers, see my previous overview article.
Among the available radiotracers are 68 gallium-labeled ligands of the prostate-specific membrane antigen (PSMA). Several large retrospective studies outside of the United States have demonstrated that 68Ga-PSMA-11 improves detection of biochemically recurrent prostate cancer compared with conventional imaging. Prospective studies, however, are needed in order to validate this for FDA approval, and in this article I review two important recent U.S. based prospective studies.
In a study published in March 2019 in the JAMA Oncology, researchers from UCSF and UCLA studied the accuracy of 68Ga-PSMA-11 in 635 patients with biochemically recurrent prostate cancer. 68Ga-PSMA-11 PET was able to localize the site of recurrent prostate cancer in 475 of the 635 (75%) patients. The detection rates where significantly correlated with the level of the increased prostate-specific antigen (PSA): 38% for <0.5 ng/mL, 57% for 0.5 to <1.0 ng/mL, 84% for 1.0 to <2.0 ng/mL, 86% for 2.0 to <5.0 ng/mL, and 97% for ≥5.0 ng/mL. This correlation appears very similar to the published associations with PSA level for the detection rates with other PET imaging agents such as C11-Acetate and Choline.
On a per-patient basis, the true positive detection rate for 68Ga-PSMA-11, as determined by comparison to histopathology, was 84% (in 87 patients). When also compared to follow up imaging the true positive rate was 92% (in 217 patients). Focal therapy that was directed by these PET imaging studies alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients. This study was ended early, as the results are currently being submitted to the FDA for evaluation, which will likely help this agent become FDA approved in the near future.
AXUMIN VS. 68GALLIUM-PSMA-11
A recently published prospective study in the Journal of Clinical Oncology compared Axumin head-to-head with 68Ga-PSMA -11 in a case series of 50 patients with recurrent prostate cancer. Axumin (Fluciclovine or 18F-FACBC), is a recently FDA approved agent which is a fluorine-18 radiolabeled synthetic leucine amino acid. In this study, patients with biochemically recurrent prostate cancer and PSA levels ranging from ≥0.2 to ≤2.0 ng/mL were enrolled. All patients underwent Axumin and PSMA scans within ≤15 days. The results of the study showed a detection rate on a per-patient basis of 69% for PSMA and 34% for Axumin. In 37% of the cases, PSMA scans were positive but the Axumin was entirely negative. The researchers found the detection rates to be consistently lower for Axumin compared to PSMA regardless of the region of recurrence. In the Prostate bed this was 12% vs 20%, pelvic lymph nodes - 14% vs 37%, extra-pelvic lymph nodes - 2% vs 8%, skeleton - 2% vs 8% and in the visceral organs - 2% vs 6%. This analysis showed PSMA detection rates to be more than double compared to the Axumin, and confirmed earlier findings from a separate pilot comparison study (Calais, et al., J Nucl Medicine, May 2018).
In Summary
Accurate re-staging is essential for proper management decisions in recurrent prostate cancer. While Axumin is the only currently FDA approved agent, clinical experience with this agent has consistently demonstrated its generally poor accuracy, with a high false negative rate. This is now further confirmed by a head-to-head comparison with PSMA.
There is still no “perfect” imaging methodology with 100% accuracy, but PSMA-targeted imaging appears to be the most promising path and provides overall high sensitivity and specificity. There are some important and practical limitations with PSMA however, such as lack of PSMA expression in some cancers, false positives in benign vascular lesions, and inability to fully assess the lower pelvis due to high urinary excretion. Despite these limitations, for patients with recurrent prostate cancer signaled by a rising PSA, performance of a sodium fluoride PET bone scan and seeking out one of the current clinical trial studies for PSMA appear to be the best options at this time. The strong data supporting 68Ga-PSMA-11 suggests that this agent will likely be approved by the FDA in the very near future, and subsequently become more widely available.
Fabio Almeida, MD is the Medical Director of the Yuma Regional Cancer Center PET/CT providing his extensive clinical expertise in PET/CT imaging. He is an Integrative Oncologist and Nuclear Medicine Physician. He has authored and participated in several publications in radiology, oncology, information science and nutritional science. Dr. Almeida is also Board Certified in Obesity Medicine and is an expert in Culinary Medicine - he provides extensive nutritional and lifestyle support through his Integrative Medicine Clinic.
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