“Pylarify” is a recently FDA approved tracer for imaging the prostate specific membrane antigen (PSMA) displayed on ~95% of prostate cancer cells. This urea-based radiotracer combines the small molecule DCFPyL, a PSMA targeting agent, with the positron-emitting isotope fluorine F-18 facilitating PET imaging of PSMA expressing prostate cancer cells. In general design it is very similar to the well-researched 68Galium-PSMA PET/CT and has comparable sensitives.
The FDA approval of Pylarify permits PET imaging in biopsy diagnosed unfavorable intermediate-risk and high-risk cancer (D’Amico definition) prior to definitive initial therapy, and also in relapsed cancer.
The approval was based on favorable results of two large clinical trials, OSPREY and CONDOR, both of which compared the safety and performance 18F-DCFPyL to conventional imaging with CT and technetium bone scanning. In both studies the specificity for cancer detection in pretreatment staging and at recurrence was significantly superior.
The forthcoming availability of 18F-DCFPyL will likely have a profound impact on the initial management of men newly diagnosed with advanced prostate cancer. Unlike the 68Ga-PSMA PET/CT, which is only FDA approved at UCLA and UCSF for initial diagnosis, Lantheus Holdings, Inc, will likely make Pylarify nationally available. The manufacture of 68-Ga requires a special generator, but the F-18 agent can be made at local manufacturing sites and be provided to nearby nuclear medicine facilities, similar to the acquisition of the Axumin and F18-FDG tracers.
A pre-treatment Pylarify PET/CT has the potential to change management plans based on conventional imaging.
In the OSPREY trial the Pylarify PET/CT detected metastatic disease in 58% (19 of 33) of men with advanced cancer who were negative for metastases on conventional CT and bone scanning. The men in this study had been scheduled to undergo radical prostatectomy and lymph node dissection. The metastatic disease was confirmed pre-op by extra-pelvic biopsies in 10 of 11 men.
Additionally, 82 men in the study had been considered to have metastatic spread on conventional imaging, but a Pylarify PET/CT downstaged 22% (18 of 82) of men concluding that they were metastases free.
The OSPREY data is similar to the multiple studies reporting that a pre-initial therapy Ga-68 PET/CT in men with advanced disease changes management plans in 50%- 60% of men. Changes might include extending the field of planned surgery or radiation to include the newly found disease, metastases directed therapy (e.g. with CyberKnife) + ADT combined with treatment of the primary, or offering only androgen deprivation therapy.
Considering the 98% specificity of the Pylarify PET/CT compared to conventional imaging, 67%, the use of conventional imaging would likely be avoided.
The Performance of the Pylarify PET/CT at disease recurrence following primary local therapy.
Choyke et al (Journal of Nuclear Medicine, June 2020) addressed this in a prospective study of 18F-DCFPyL PET/CT in 90 men with biochemical recurrence with a median PSA of 2.5 ng/mL (range 0.21-35.5). The men were negative on conventional imaging. “The PSMA PET lesion detection rate correlated with PSA, PSA kinetics, and the original primary tumor grade.” No man had had ADT.
The detection rate was 47.6% at PSA >0.2 to <0.5 ng/mL; 50% at 0.5 to 1.0; 88.9% 1 – <2.0; and 94% at PSA values above 2.0 ng/mL. Tumor recurrence was histologically confirmed in 40% of men.
Their conclusion: the detection rate recurrent disease of nearly 50% in patients with PSA values less than 0.5 ng/ml could “substantially impact clinical management.”
The FDA approval for the Pylarify PET/CT for use prior to initial primary therapy for men with advanced prostate cancer will likely have a significant impact on the management of these men.