Prostate-Specific Membrane Antigen, or PSMA, is a protein found on the surface of prostate cells. While present in healthy prostate tissue, PSMA is found in significantly higher amounts on cancerous prostate cells. This elevated expression makes PSMA a distinct target, leading to important advancements in prostate cancer diagnosis and treatment.
PSMA in Imaging and Diagnosis
PSMA positron emission tomography, known as PSMA PET, is an imaging technique that helps locate prostate cancer throughout the body. A radioactive tracer is injected into a patient’s vein, engineered to attach to PSMA proteins on prostate cancer cells. Once bound to PSMA-expressing cells, a PET scanner detects the emitted radiation, creating detailed images that highlight cancer’s location. This imaging is often combined with a computed tomography (CT) or magnetic resonance imaging (MRI) scan to offer more precise anatomical detail.
PSMA PET scans are used in several clinical situations. They are particularly valuable for initial staging in patients with newly diagnosed high-risk prostate cancer, helping to determine if the cancer has spread beyond the prostate. This imaging modality also plays a role in detecting biochemical recurrence, which is when prostate cancer returns after initial treatment, indicated by a rising prostate-specific antigen (PSA) level.
PSMA PET scans can detect very small tumors, often missed by conventional imaging like standard CT or bone scans. For instance, PSMA PET-CT has demonstrated superior accuracy in detecting metastases, even identifying bone metastases where bone scintigraphy yielded negative results. Its ability to pinpoint disease earlier and more accurately can significantly influence treatment planning.
PSMA Targeted Therapy
PSMA targeted therapy, also known as radioligand therapy (RLT), offers a precise method to treat prostate cancer by delivering radiation directly to cancer cells. This approach utilizes a molecule designed to seek out and bind specifically to the PSMA protein on prostate cancer cells. This cancer-seeking molecule is linked to a radioactive particle, creating a radioligand.
Once injected into the bloodstream, this radioligand travels throughout the body. When it encounters a prostate cancer cell expressing PSMA, it binds to it, and the radioactive particle delivers a localized dose of radiation. This radiation induces DNA damage within the cancer cell, ultimately leading to its destruction, while minimizing exposure to surrounding healthy tissues.
The primary treatment of this type currently used is Lutetium-177 vipivotide tetraxetan (Pluvicto), which combines the therapeutic radionuclide lutetium-177 with a PSMA-targeting ligand. This radioactive substance emits particles that travel a short distance, effectively damaging targeted cancer cells and nearby cells. This localized delivery helps spare healthy organs from widespread radiation effects.
Patient Candidacy for PSMA Procedures
Patient eligibility for PSMA procedures depends on the specific application, whether for imaging or targeted therapy.
PSMA PET Imaging Candidacy
PSMA PET imaging is typically recommended for men newly diagnosed with prostate cancer who are at high risk for metastatic disease. It helps determine the extent of the cancer’s spread before treatment decisions are made.
Patients who have undergone prior prostate cancer treatment, such as radiation therapy or prostatectomy, and are experiencing a rising PSA level, indicating biochemical recurrence, are also candidates for PSMA PET scans. These scans help locate the site of recurrence, even at low PSA levels, which is crucial for guiding salvage therapies.
PSMA Targeted Therapy Candidacy
For PSMA targeted therapy, such as Lutetium-177 vipivotide tetraxetan, patients are generally those with metastatic castration-resistant prostate cancer (mCRPC). This means their cancer has spread beyond the prostate and is no longer responding to hormone therapy.
Patients typically considered for this therapy have already received other treatments, including androgen receptor pathway inhibitors and often taxane-based chemotherapy. Prior to receiving PSMA targeted therapy, a PSMA PET scan is required to confirm that the patient’s tumors express sufficient levels of PSMA, ensuring the treatment will be effective.
The Theranostic Approach
The theranostic approach integrates diagnostic imaging and therapeutic treatment using the same molecular target. This term combines “therapy” and “diagnostics,” highlighting a personalized medicine approach. In prostate cancer, PSMA serves as this unifying molecular target.
This strategy operates on the principle of “see what you treat, treat what you see.” A diagnostic PSMA PET scan first identifies all PSMA-expressing cancer lesions throughout the body. This diagnostic step helps confirm that the patient’s tumors are indeed PSMA-positive, making them suitable for PSMA-targeted therapy.
Following this confirmation, a therapeutic radioligand, also targeting PSMA, is administered. This ensures precise radiation delivery to the identified cancer cells. This synergy optimizes treatment delivery while minimizing damage to healthy tissues.