UroView: Gallium 68 PSMA–Targeted PET Imaging in Prostate Cancer: Staging and Outcomes

Recent years have ushered in advances in prostate cancer imaging that contribute to better disease localization and more accurate staging, which there-fore affect clinical decision-making. In this UroView™ program, Phillip Kuo, MD, PhD, professor of medical imaging, biomedical engineering, medicine, and cancer biology at the University of Arizona, in Tucson, and Andre Abreu, MD, a urological surgeon at the University of Southern California, in Los Angeles, discuss the role of gallium 68 prostate-specific membrane antigen (PSMA)–targeted PET imaging and its role in staging and disease management of prostate cancer.

Current standard of care and limitations in prostate imaging

According to Abreu, the imaging that is currently available for prostate cancer is mostly conventional, including MRI, CT scans, bone scans, and ultra-sound. Kuo noted that MRI has evolved and improved how clinicians visualize localized disease through high-resolution imaging of the prostate gland and enhanced the ability to assess local invasion of adjacent tissues and seminal vesicles. Abreu added that although MRI is useful for identifying diagnostic lesions and tumor staging of locally advanced disease, it has limited utility for nodal staging and metastases. Kuo added that MRI and CT scans are still primarily structural modalities that require a lymph node to reach a certain size to be detected. A lymph node not reaching the size criteria for detection does not necessarily indicate that cancer is not present.

Alternatives include diffusion-weighted imaging, iodinated contrast on CT, and gadolinium-based contrast agents with MRI. Primarily through bone scans, nuclear medicine has played a significant role in prostate cancer assessment, but limitations also exist with this modality. One of the tracers used in bone scans, technetium 99m-methyl diphosphonate (99m Tc MDP), depends on the reaction of the bone to the tumor. Therefore, the tumor specifically is not being imaged. In addition, Abreu noted that ultra-sound imaging has limited capabilities when used to stage prostate cancer or identify suspicious lesions in the prostate. “There is definitely a need for [a] better imaging modality that would allow us to have a better assessment in evaluation and risk stratification of patients with prostate cancer,” he said.

Regarding PET scans, Kuo noted that initially, the only tracer used was fluorodeoxyglucose (FDG) but added that the FDA approval of Axumin (fluciclovine F18) was a notable break-through in prostate cancer imaging. Axumin is a synthetic amino acid that is taken up to a greater extent in prostate cancer cells compared with surround-ing normal tissue.¹

Kuo anticipates the imminent avail-ability of PSMA PET tracers; however, he noted that FDG PET scans will still play a significant role in certain cases of aggressive forms of prostate cancer (eg, metastatic castrate resistant or neuroendocrine differentiation). With PSMA PET, clinicians will be better able to stratify patients and separate them based on risk and localization of the disease.

“What we expect in the future is that patient populations [will receive] better treatment because we [will] have a better understanding of the disease from the baseline and have better staging. For example, some patients [who we determined to have] just high-risk dis-ease by conventional imaging actually have nodal disease. Now [that] we know that they have nodal disease, they will be classified as [having] oligometastatic disease and will be appropriately treat-ed. [When we use PSMA PET imaging] for [a] patient [who] we thought only [had] oligometastatic disease, we actually realized [that they may] have more disease, and then [we] change the management of [the] patient,” Abreu said.

PSMA PET is bringing something to the space that hadn’t existed before. Abreu added that it is contributing to a change in management of up to 50% of patients with high-risk disease. Kuo noted that this depends on the patient population and agreed that PSMA PET and advanced imaging modalities will have the greatest impact on patients with high-risk, newly diagnosed prostate cancer.

PSMA PET vs conventional imaging

Studies have been conducted that investigate the sensitivity of PSMA PET scans compared with conventional imaging. Investigators subjected patients who had demonstrated bio-chemical recurrence, but no identifiable recurrence by conventional imaging, to PSMA PET.

“Essentially, you’re starting at base-line where the conventional imaging has failed to localize the recurrence. Again, depending on the patient population, sometimes they’re finding sites of recurrence, sometimes [by] a sensitivity of approximately 50%. And there’s a wide range, depending on your PSAs,” Kuo explained.

Kuo stated that by using the new PSMA PET agents, biochemical recurrence can be detected at prostate-specific antigen (PSA) levels, as low as 0.2 to 0.3 ng/mL, which are difficult to identify when using Axumin PET.

“I’ve been fortunate to read hundreds of these scans, and [using PSMA PET], you start seeing [an indication of cancer in] the tiny Virchow node up in the supraclavicular region, which never would have been seen by CT or MRI or any other modality. You would never have suspected that [it] had prostate cancer. For us, that may be the most significant example of where [the cancer] can just skip all the way up into the supraclavicular region. It’s actually a little bit depressing, honestly, as a nuclear medicine radiologist, when you see the bone scans that look completely negative and then you have a PSMA PET scan [that shows that the] patient is just riddled with bone metastases,” he said. Abreu agreed that by using PSMA PET, they can better identify patients who have only pelvic lymph node metastases versus those in whom the disease has spread to the retroperitoneal lymph nodes.

Because bone scans rely on the reaction of the bone to the tumor, the tumor must grow sufficiently within the bone marrow space to reach a considerable enough size to destroy bone, in order to see the reaction on a bone scan. With PSMA PET, the actual tumor is imaged because the tracer targets and binds to the extracellular portion of the PSMA protein, which is expressed 100-fold higher in aggressive prostate cancers.

Impact on the treatment journey

Abreu expressed that PSMA PET should definitely play a role in every step of the treatment journey for prostate cancer.“[PSMA PET should be used] from diagnosis to staging, to restaging, [and then to] recurrence,” he said. “It should also be used] for evaluation of the treatment afterward, in terms of if there is disease regression or not. When we do the PSMA PET, we can localize the disease.” Abreu added that it is important to know whether the disease is localized to the prostate bed or whether there is nodal disease or metastasis, as this affects dis-ease management.

PSMA PET has played and is currently playing a role in the treatment of prostate cancer, but additional research is needed. Abreu commented that study results will be beneficial for the whole spectrum of prostate cancer.

Gallium 68 PSMA-11 PET for prostate cancer

Kuo indicated that although he does not use gallium 68 tracers often, gallium (Ga) 68-dotatate PET scans are used for imaging of neuroendocrine tumors, and Ga 68 PSMA-11 PET imaging was recently approved by the FDA for prostate cancer.² In comparing Ga 68 with flu-orine-18 (F18), F18 is exclusively produced by a cyclotron and has a half-life of about 2 hours whereas Ga 68 has a 68-minute half-life and can be produced by a cyclotron or a generator. Whether using Ga 68 or F18, it is beneficial to have it produced in as close proximity as possible, so that it can be transported and used within the designated half-life. Kuo stressed that one should check with their imaging site to determine schedule availability and supply chain details.

Abreu indicated that although he has had access to Ga 68 PSMA-11 PET imaging in California, few centers can provide this for patients.

Kuo added that the approval of Ga 68 PSMA-11 PET for imaging in prostate cancer has led investigators to use this type of imaging in additional studies. VISION is a phase 3 clinical trial evaluating patients with metastatic castrate-resistant prostate cancer who are PSMA positive, as determined through Ga 68 PSMA-11 PET imaging, and who are receiving targeted therapy with PSMA-11 bound to lutetium-177.³

“If their tumors express PSMA, they will then take up the radiotracer and show up on our scan; we can actually measure the levels of intensity. If they met certain criteria, then they would receive PSMA-targeted therapy with this lutetium-177,” Kuo said.

Kuo noted recent reports of positive out-comes from the trial, but details have yet to be announced. Although this does not guarantee FDA approval, Kuo added that if outcomes are impressive, approval will be sought. Abreu stated that this would have a positive impact for patients and clinicians would be able to treat with less aggressiveness and invasiveness.

Advancements in prostate cancer imaging will help to personalize therapy and provide more accurate staging. Both Kuo and Abreu are looking forward to encouraging data outcomes from studies on aggressive prostate cancer.

REFERENCES

1. Axumin. Prescribing information. Blue Earth Diagnostics; 2020. Accessed May 7, 2021. https://www.axumin.com/prescribing-information.pdf
2. FDA approves first PSMA-targeted PET imaging drug for men with prostate cancer. Press release. US Food and Drug Administration. December 1, 2020. Accessed May 7, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-psma-targeted-pet-imaging-drug-men-prostate-cancer
3. Study of 177Lu-PSMA-617 in metastatic castrate-resistant prostate cancer (VISION). ClinicalTrials.gov. Updated March 25, 2021. Accessed May 7, 2021. https://clinicaltrials.gov/ct2/show/NCT03511664

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