PSMA PET/CT Imaging in Prostate Cancer – Real World Experience

GU Oncology Now Staff

Over the past five years, molecular targeting of prostate specific membrane antigen (PSMA) has become viewed as an increasingly important approach not only in the staging but also in the treatment of prostate cancer (theranostics). PSMA scans can detect metastatic lesions that are undetectable by  conventional imaging modalities. PSMA ligand therapy is also an upcoming treatment modality that has been shown to be beneficial with reasonable toxicity in patients with advanced prostate cancer who have progressed on prior therapy.

GU Oncology Now spoke with Catherine H. Marshall, MD, MPH, Assistant Professor of Oncology at The Johns Hopkins School of Medicine, Baltimore, about how PSMA targeted agents are being incorporated into clinical practice for the management of prostate cancer, its advantages and disadvantages, and how its use may expand in the future.

GU Oncology Now:  How are you using PSMA PET/CT in your clinical practice?

 Dr Marshall:  In May 2021, the PSMA PET/CT imaging agent piflufolastat F 18 (Pylarify, Lantheus) was approved by the Food and Drug Administration (FDA) for PET imaging of PSMA-positive lesions in men with prostate cancer.1 It is indicated for use in men with suspected metastases who are candidates  for initial definitive therapy and for men with suspected recurrence based on elevated PSA level after initial treatment. Since this approval, I have been able to use it more often in my clinical practice. Prior to this,  PSMA PET/CT imaging was available only in the setting of a clinical trial. As a medical oncologist, I have started to use PSMA PET/CT scans mostly in the setting of biochemical recurrent prostate cancer, i.e., men who have a rising PSA after initial surgery or radiation.

GU Oncology Now:  How does PSMA PET/CT help you to tailor treatment? 

Dr Marshall: The standard treatment option for men with biochemical recurrence after radical prostatectomy is salvage radiation. If PSMA PET/CT scans do not show any evidence of PSMA-positive lesions outside the treatment area, typically radiation therapy will be given. If  evidence of oligometastatic disease is detected by PSMA PET/CT outside the pelvis, stereotactic radiation will sometimes be applied to the extra pelvic sites.  

GU Oncology Now: What challenges have you encountered using PSMA PET , given that it is such a new agent? 

Dr Marshall: The major challenges of incorporating these scans into clinical practice to date have been insurance coverage, cost, and availability. These are the major barriers. Because of this, it  takes a few weeks before patients can get the scans done.  Currently, PSMA scans are covered by some insurance companies as well as Medicare, but each plan differs and so they have different requirements for approval and different processes for approval. It’s not easy to calculate the cost-effectiveness of this procedure for different patients.

I haven’t started to use PSMA/PET scanning in patients with very low PSA levels, where there is little clinical utility,  or in those with very high PSA levels, where disease will likely be detected on conventional scans.

 GU Oncology Now: Turning to the topic of PSMA-targeted radioligand therapy, we were all very excited by the results of the Phase 3 VISION trial, reported in 2021.2 

Dr Marshall: The VISION Trial tested the efficacy of lutetium-177 (177Lu}-PSMA-617  treatment in 831 patients with metastatic castration resistant prostate cancer that had progressive disease after treatment with at least one novel androgen-receptor targeting treatment and one or two taxane therapies. All patients had PSMA PET/CT scans that showed PSMA-positive lesions and no PSMA-negative lesions. Patients were randomized 2:1 to either 177Lu-PSMA-617 or standard of care. The study showed that treatment with 177Lu-PSMA-617 was associated with a 60% decreased risk of progression-free survival and an approximately 40% decreased risk of death. Radiographic progression free survival was extended by a median of 5.3 months and overall survival by 4 months. On the basis of these results, the FDA granted Breakthrough Therapy Designation for 177Lu-PSMA-617,3 and we look forward to the regulatory review early in 2022.

GU Oncology Now: Do you have any reservations about the results of the VISION trial? 

Dr Marshall:  While the trial was positive, there are a few important take away points. I would first note that over 1000 patients were screened for the trial and of those, 87% met the imaging criteria of having at least one PSMA-positive lesion and no PSMA-negative lesions. So while this represents the vast majority of patients with metastatic castration resistant prostate cancer, it is not everyone. We also have to remember the side effects of therapy.  Common adverse events were fatigue, nausea, dry mouth, and myelosuppression and about 15% of patients had to interrupt or discontinue treatment due to adverse events.

In our practice, radioligand therapy is administered by the nuclear medicine physicians, so it is essential that we work closely with them to refer patients and continue to follow these patients.

Also, since 177Lu-PSMA-617 is not yet FDA approved or commercially available, we have not yet had to figure out insurance or cost issues that can come up, so it remains to be seen if these will be an impediment to treatment.

GU Oncology Now: What questions do you think remain to be answered about PSMA in imaging and in treatment? 

Dr Marshall: I think learning how imaging changes in response to treatment will be important to know. Should PSMA PET/CT be repeated? If so, when should it be repeated and how often should they be repeated?

With regard to treatment, how to sequence 177Lu-PSMA-617 treatment with other FDA-approved therapies will be key. Should it be combined with other therapies?

We are also waiting for the results of ongoing clinical trials looking at whether 177Lu-PSMA-617 is efficacious earlier in the disease course, like PSMAfore (NCT04689828) and PSMAddition (NCT04720157).

References

  1. Food and Drug Administration (FDA). FDA approves second PSMA-targeted PET imaging drug for men with prostate cancer. May 27, 2021. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-second-psma-targeted-pet-imaging-drug-men-prostate-cancer Accessed December 30, 2021.
  2. Sartor O, de Bono J, Chi KN, et al; VISION Investigators. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. DOI: 1056/NEJMoa2107322
  3. FDA grants Priority Review for investigational targeted radioligand therapy 177Lu-PSMA-617 for patients with metastatic castration-resistant prostate cancer (mCRPC). Press release, Novartis. September 28, 2021. https://www.novartis.com/news/fda-grants-priority-review-investigational-targeted-radioligand-therapy-177lu-psma-617-patients-metastatic-castration-resistant-prostate-cancer-mcrpc Accessed January 2, 2022.