PSMA therapy in metastatic prostate cancer
Dr Lizette Louw informs us how PSMA therapy is a rapidly evolving area for metastatic prostate cancer treatment.
What is nuclear medicine?
Nuclear medicine is a specialised area consisting of two arms: nuclear imaging which uses small amounts of gamma radiation to examine organ function, and nuclear therapy using alpha or beta particles.
In nuclear imaging, a radioactive atom is linked to specific molecules to guide imaging of specific organ systems. Similarly for nuclear therapy, a therapeutic radioactive atom is linked to various specific molecules which is absorbed by the tumour cells and the radiation is deposited within the tumour cells. The specific molecule determines where the compound will go to, whereas the radioactive atom delivers the actual therapeutic radiation. The combination of a targeted molecule with a radioactive atom is called a radioligand and often referred to as targeted radioligand therapy.
Nuclear medicine therapy vs radiation
Radiation oncologists most commonly use external beam therapy or brachytherapy, whilst nuclear physicians don’t. We administer radiation therapy, given either as capsules to swallow or infusions (drips). All these forms of radiation cause damage to cancer cell DNA, which leads to the cancer cells dying.
What is PSMA?
PSMA stands for prostate specific membrane antigen. It’s a protein found in the cellular wall of prostate tissues, including prostate cancer tissues. This molecule can be linked to radioactive atoms for PET/CT imaging, in which case it will detect areas of prostate cancer (PC). The same molecule can be linked to atoms giving off alpha or beta particles to use for therapy.
PSMA PET/CT is a sensitive scan and has evolved rapidly to become a routine scan. It can detect tiny lesions, before they are big enough to appear abnormal on CT. It can even detect small lesions in bone before those lesions show up on a bone scan. Research is ongoing to determine the most suitable patients and the best time points to use PSMA PET/CT scans. The current agreement is:
1. Patients with previous localised PC who were treated but now have rising PSA levels and thus suspected cancer recurrence.
2. Patients with newly diagnosed PC and metastases at diagnosis, to map the full extent of metastases.
3. Patients with newly diagnosed high-risk PC with normal CT and bone scans, to confirm the cancer is truly localised.
PSMA therapy is reserved for patients with metastatic castrate resistant prostate cancer (mCRPC).
This means the cancer doesn’t respond to hormone therapy anymore and has spread outside the prostate gland itself. There are limited therapy options for patients like this.
If such a patient has a positive PSMA PET/CT scan, and other treatment options failed, they would be eligible for possible PSMA therapy. The PSMA PET/CT is a map of all the sites where the PSMA molecule is taken up in the body. If the PSMA PET/CT is negative, or the intensity of PSMA activity in the cancer sites are low, the patient won’t be eligible for PSMA therapy.
PSMA can be linked to either alpha or beta particle atoms for therapy.
The most promising alpha particle atom is Actinium (Ac), but at this stage it’s only used in research centres. The published findings using Ac-PSMA is favourable and hopefully will become commercially available as evidence for its use grows.
The only PSMA therapy available outside of research centres is Lutetium(Lu)-PSMA, which is a beta particle treatment. It’s already in routine use in many countries, but unfortunately the vast majority of medical funders in SA don’t reimburse it yet and patients have to pay out of pocket.
Medical funders in SA have strict criteria to accept reimbursement, such as incorporation of the treatment in international guidelines and sufficient research evidence to prove the treatment benefit to patients and cost-effectiveness compared to other available treatment options. Although Lu-PSMA therapy is promising, it hasn’t been available for long enough and there isn’t enough evidence available just as yet. This situation is dynamic with more research being published every year and funding decisions will most likely change in the upcoming few years.
Patients need be in an acceptable general condition, with good bone marrow and kidney function. The treatment is given in a drip and the patient is hospitalised for one day.
Side effects are minimal. Treatment is repeated every 4-8 weeks up to four treatments, at which point the patient is reassessed with a repeat PSMA PET/CT to determine if there is a response or not. Further treatments can be given in patients who responded well and remain in good general condition.
There are minimal associated short- and long-term toxicities.
How effective is PSMA therapy?
It’s important to understand that mCRPC can’t be cured. The cancer burden can be decreased and minimised with therapy, and then controlled for as long as possible. By achieving this goal, the patient’s life is prolonged, having good life quality during and after treatment. The majority of patients will have a significant drop in PSA levels of >50% with PSMA therapy with a better outcome expected in patients with a bigger drop in PSA levels.
MEET THE EXPERT – Dr Lizette Louw
Dr Lizette Louw is a nuclear physician working at Wits Donald Gordon Medical Centre, Linksfield PET/CT and Rosebank Nuclear Medicine Therapy. She is the 2021 President Elect for The World Federation of Nuclear Medicine and Biology and President of the SA Association of Nuclear Physicians.
This article is sponsored by Ferring Pharmaceuticals. The content and opinions expressed are entirely the medical expert’s own work and not influenced by Ferring in any way.