Prostate cancer is the second most common form of cancer affecting men in the United States – 1 in 8 men will be diagnosed with prostate cancer in their lifetimes. The American Cancer Society estimates that in 2022, almost 268,490 new cases of prostate cancer will be detected, and more than 34,500 men will die of the disease. Approximately 3.1 million men in the United States currently identify as prostate cancer survivors. The disease develops more often in both African American men and in Caribbean men of African ancestry than in men of other races. Furthermore, prostate cancer is the second leading cause of cancer death in American men, behind only lung cancer. Estimates predict that about 1 in 41 men will die of prostate cancer. In 2020 and 2021, the FDA has approved novel treatments optimizing theranostics in both the diagnosis and treatment of prostate cancer.
Challenges in Prostate Cancer Imaging
Standard imaging techniques, such as CT scan, have insufficient sensitivity and limited accuracy for assessment of prostate cancer, especially when staging men with intermediate and high-risk localized PCa. A fundamental shortcoming of CT scan in detecting lymph node metastases is its inability to detect architectural changes within normal-sized (< 10 mm) lymph nodes. A large proportion of nodal metastases in prostate cancer, up to 80%, are smaller than 8 mm in size, and thus morphological imaging fails to recognize most of these nodes.
Bone scans offer an advantage of detecting bone metastasis, but they however lack the sensitivity for early lesion detection. PET imaging combined with a tracer is a game changer in imaging for prostate cancer. Prostate specific membrane antigen (PMSA) is a modality that can detect lesions between 4mm and 8mm and is also effective at lower PSA levels unlike conventional imaging modalities, which reduces the risk of undertreatment (leading to disease spread) and overtreatment (leading to unnecessary toxicity or surgery).
Theranostics in the Management of Prostate Cancer
An emerging area with significant ability to combat lesion malignancy is the use of theranostic agents that detect PCa with high sensitivity and can precisely ablate these sites. Theranostics is a novel, two-pronged approach to diagnosing and treating cancers using radiotracers. Radiotracers are compounds made of radiation and chemicals that selectively bind to a specific target in the body and aims to kill cancer cells. Clinicians use a pair of radiotracers that are virtually identical, other than the type of radiation they give off. A radiotracer consists of two pieces: one half is the biologic side that travels through the blood to bind to a unique, designated target – in this case, a type of cancer cell. The other half is the radioactive component. During the diagnostic scan, that radioactive component emits a low amount of radiation that allows us to take pictures of the cancer cells onto which the radiotracer has latched. In this treatment, the biologic side is almost identical, but the radioactive component is a different, more powerful kind of radiation that kills cancer.
In the course of both the diagnostic and treatment procedures, the biologic side must bind itself to that precise target on the tumor cells. Because most other healthy cells lack that target, the radiotracers do not attach to them.
In May of last year, Lantheus received landmark FDA approval for their lead theranostic, Pylarify (piflufolastat F18) in management of prostate cancer (PCa). The approval was supported in large part by findings from the phase 3 CONDOR trial, in which 63.9% of men with biochemically recurrent prostate cancer who had no evidence of disease on standard-of-care imaging had a change in intended management after their 18F-DCFPyL–PET/CT scan. The F18-labeled, prostate-specific membrane antigen (PSMA) targeted positron emission tomography (PET) imaging agent, developed to identify suspected metastasis or recurrence of prostate cancer, is leading as the first commercially available, novel radiotracer for staging PCa patients.
This Women-Led Company Lands FDA Approval for It’s PSMA-Targeted PET Tracer
Lantheus, led by CEO Mary Anne Hein, produces Pylarify and a broad platform of imaging diagnostics, targeted therapeutics and artificial intelligence solutions in both oncologic and non-oncologic conditions. The company merged in 2020 with Progenics Pharmaceuticals where stakeholders anticipated successful performance of the then pipeline candidate, previously known as 18F-DCFPyL.
Earlier this year, Lantheus also announced that both the National Comprehensive Cancer Network (NCCN), who provides clinical guidance on candidacy for initial use of PSMA PET CT/MRI scans, and the Society of Nuclear Medicine and Molecular Imaging (SNMMI), a not-for-profit nuclear medicine professional organization that provides guidance in the advancement and optimization of molecular imaging, have updated their guidelines to include Pylarify for patient selection for PSMA-targeted radioligand therapy (RLT). Evidence shows that 18 [F]PSMA-1007 is in many ways an ideal radiotracer for PCa imaging; it can be produced with purity and in high yield and it can be transported to sites that do not have cyclotron and radiopharmacy facilities. The first FDA approved PSMA PET, [68Ga]Ga-PSMA-11 (approved in 2020) has to be produced on site due the short half-life and low yield. The starting production cost ranges for both of the FDA approved diagnostic radiopharmaceuticals are the same however, [18F]PSMA-1007 is the most compliant of the two. Clinically, [18F]PSMA-1007 outperforms in specificity in detecting recurrences and has a similar behavior to the therapeutical analogue [177Lu]Lu-PSMA-617. This makes the 2021 FDA approved radioligand a better probe for RLT patients eligible.
As Bela Denes, MD, Lantheus Vice President of Medical Affairs stated in their press release, “We believe this will increase the accessibility to PSMA-targeted therapeutics for patients with advanced disease and further validates the benefit and utility that Pylarify provides to the US prostate cancer community.”
The Role of PSMA in Prostate Cancer Detection
PSMA is a transmembrane protein that is present in prostate cells and overrepresented in prostate cancer cells. This protein is the pre-eminent prostate cancer target in clinical practice for diagnostic imaging and aid in the early detection, recurrence monitoring and progression tracking of the disease. Over 100 clinical trials utilize PSMA for imaging or therapy and numerous pathological studies have reported elevated PSMA expression on 85-100% of prostate cancers.
Pylarify (piflufolastat F18) injection is a PSMA-targeted, fluorinated small molecule, which works to identify suspected bone and soft tissue metastasis or recurrence in patients with prostate cancer. By binding to the target, the reader of the PET scan can detect and locate the disease.
The Pylarify PET targets the extracellular PSMA component to visualize prostate cancer cells anywhere in the body. Very few organs exhibit PSMA, however in the setting where a patient has just been diagnosed with cancer and to address concerns specific to metastatic disease, the salivary glands may indicate where PCa cells are. For a patient whose PSA is rising, indicating recurrent disease, Pylarify can aid in identifying where the cancer is localizing. Prostate cancer can range from those with a low malignant potential to those with locally or systemically recurrence after successful local therapy.
Pylarify is specific to prostate cancer but the overall concept is very applicable to other cancers. There are studies being done in theranostic agents that will target other cancers like breast cancer, lung cancer, gastrointestinal cancer.