Prostate cancer no longer a death sentence with this superior treatment option
It was first identified in 1853 by Dr John Adams in London Hospital (now The Royal London Hospital) following histological post-mortem examination of the prostate gland.
At that time, prostate cancer was considered a very rare disease but it is currently the sixth most common cancer in Malaysia and fourth most common cancer worldwide.
The first surgical attempt at treating the cancer was carried out by Theodor Billroth in 1867 via partial prostatectomy, a surgical procedure where a portion of the prostate gland is removed.
However, it was only 37 years later in 1904 when Dr Hugh Hampton Young performed the first perineal radical prostatectomy which is still practiced today though with modification and improvement in technique.
Medicine is continuously evolving and when radioactive radium was discovered in 1898, it paved the way for the first brachytherapy procedure in 1909.
The emitted radiation from radium was used to destroy the diseased prostate tissue.
Since the beginning of 20th century, increasingly more men were diagnosed with prostate cancer, with the majority having metastatic disease at presentation.
Fortunately in 1941, future Nobel Laureates, Drs Charles Huggins and Clarence V. Hodges published the landmark paper on the effect of castration, of oestrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate.
Their work accelerated studies on anti-androgen therapies which are still in use today.
The prostate-specific antigen (PSA) test, discovered in 1980, revolutionised the detection and monitoring of prostate cancer.
Over the past two decades, outlook for metastatic prostate cancer has evolved significantly with the introduction of various treatments such as denosumab, zolendronic acid, abiraterone, enzalutamide, olaparib and most recently the radionuclide-based PSMA (prostate-specific membrane antigen) therapy.
Roots of PSMA
PSMA was first identified by Murphy and Horoszewicz's team.
They developed the capromab antibody which targeted the intracellular epitope of PSMA in 1987 and became the foundation of the first United States Food and Drug Administration (FDA)-approved molecular imaging agent for prostate cancer (ProstaScint) in 1996.
Heston and Fair's group managed to clone the PSMA gene in 1993 and that led to a flurry of research up to the development of PSMA-based ligands for PET-CT imaging between 2011 and 2012.
Since then, there has been many studies demonstrating the sensitivity and accuracy of PSMA PET-CT notably the ProPSMA trial.
This multicentre phase 3 clinical trial demonstrated a 27% absolute improvement in diagnostic accuracy of PSMA PET-CT compared to conventional imaging of CT and bone scans.
PSMA PET-CT imaging has been in Malaysia for many years but cost and availability of the services have always been an issue.
It is expensive to set up and maintain the radiotracer generator and unless there is sufficient patient load and acceptable pricing, most hospitals do not offer PSMA services.
Nonetheless, with the FDA-approval of Lutetium-177 PSMA Therapy ( Lu-PSMA) for metastatic castrate-resistant prostate cancer in 2022, there has been growing interest in PSMA PET-CT.
Prostate cancers patients tend to present late as they are usually asymptomatic and most prostate cancers are found incidentally during blood test with elevated PSA levels.
No man with a prostate gland is spared, and even former US President Joe Biden and the creator of Dilbert comic, Scott Adams, publicly revealed in May 2025 that they have metastatic prostate cancer. The 3D Ga68-PET images show the sites of the metastatic prostate cancer before and after treatment. There is significant reduction in the number of lesions and the PSA levels after three cycles of Lu-PSMA therapy. — Dr ALEX KHOO CHEEN HOE
Differing treatment modalities
Treatment for prostate cancer is very dependent on the stage of the disease. It is therefore very crucial for doctors to stage the disease accurately.
The treatment for a patient with stage 1 prostate cancer is very different from a patient with stage 4 disease.
PSMA PET-CT has been shown as aforementioned to accurately stage the cancer.
For early stages and depending on the cancer-risks, treatment options include active surveillance, radical prostatectomy, brachytherapy, radical radiotherapy, long-term anti-androgen therapy (ADT) and various combinations.
Fortunately for patients who develop metastatic disease, there are still treatment options available for those who are hormone naïve (ADT and novel therapies such as apalutamide, darolutamide, enzalutamide) or for those who developed castration-resistant disease (docetaxel, cabazitaxel, PARP inhibitors, Lu-PSMA therapy).
In the past, having metastatic castrate-resistant prostate cancer was like a death sentence with clinician not having much treatment to offer.
However, the 2015 introduction of Lu-PSMA therapy in the prostate cancer treatment armament has provided the much needed reprieve.
Patient suitability
Before doctors embark on treating metastatic castrate-resistant prostate cancer patients with Lu-PSMA therapy, PSMA PET-CT has to be done to determine if the patient is suitable for the treatment.
If the cancerous lesions are not seen to demonstrate PSMA radiotracers on PET, then the patients are not suitable candidates for Lu-PSMA therapy.
If the patient is suitable for treatment, the radioactive used – either gallium-68 (Ga-68) or fluorine-18 (18F) – in PSMA PET-CT of diagnostic value only is exchanged for a different radioactive (Lutetium-177) which has a therapeutic effect.
Some clinicians would advocate doing both 18F-FDG (fludeoxyglucose) and PSMA-base ligand PET-CT upfront as baseline for better treatment selection but cost is usually an issue.
Lu-PSMA therapy is a targeted therapy where intravenously administered radioactive (Lu-177) is is guided by the PSMA ligand to prostate cancer cells, which overexpress PSMA on their surfaces.
The PSMA expression is 100-1,000 times higher in cancerous cells compared to normal tissue.
This differs from conventional treatment (chemotherapy and radiotherapy) where the killing effect affects both normal and cancerous cells.
With the highly selective target and short radiation range (1.5 to 3mm) in the body, the side effects from the radioactive treatment are relatively lower.
This precision approach exemplifies the concept of 'theranostics,' where radioactive treatment can be imaged simultaneously, something unique to nuclear medicine.
Following treatment with Lu-PSMA therapy, doctors are able to determine if the administered radioactive has been distributed to the targeted sites.
Based on the post-therapy imaging, the doctors are also able to determine the next step in treatment.
Prostate cancer continues to be a significant health concern, but early detection and the availability of advanced therapies offer hope.
Men are encouraged to take proactive steps in maintaining prostate health, recognising that not all prostate issues stem from benign prostatic hyperplasia.
With continuous advancements, particularly in PSMA-based theranostics, the outlook for patients with prostate cancer continues to improve.
Lu-PSMA therapy stands at the forefront of this evolution, representing a critical step toward more effective and personalised cancer care.
Dr Alex Khoo Cheen Hoe is a consultant nuclear medicine physician. For more information, email starhealth@thestar.com.my. The information provided is for educational and communication purposes only, and should not be considered as medical advice. The Star does not give any warranty on accuracy, completeness, functionality, usefulness or other assurances as to the content appearing in this article. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.
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