Who this is for
Metastatic prostate cancer does not behave the same way in every man.
This article is for men who have recently been diagnosed with metastatic prostate cancer and are trying to understand why their doctor is recommending different treatments, scans, or genetic tests.
It may also be helpful for patients seeking a prostate cancer second opinion in Melbourne, Australia, Sri Lanka, Maldives, Indonesia or the Philippines.
Clinical observation
Ten years ago, many men with newly diagnosed metastatic prostate cancer were treated in a very similar way.
Today, that is no longer the case.
I recently saw a 65-year-old gentleman with a PSA of approximately 22.
His scans showed metastatic prostate cancer.
At first glance, his situation appeared similar to many other men I see in the clinic.
However, when we look more closely, we now know that not all metastatic prostate cancers behave the same way.
Two men may have similar PSA levels.
Both may have cancer visible on scans.
However, their outcomes can still be very different.
One man may respond well to treatment for many years.
Another may develop resistance much earlier.
The reason is that metastatic prostate cancer is not one single disease.
The biology of the cancer matters.
The question is no longer simply:
“Has the cancer spread?”
The better question is:
“What type of metastatic prostate cancer is this?”
- The first clue: how much cancer is visible on conventional scans?
Several major studies demonstrated that men with high-volume metastatic disease generally have poorer outcomes than men with low-volume disease. This observation emerged from analyses of studies including CHAARTED and STAMPEDE and remains clinically relevant today.
In practical terms, high-volume disease usually means:
- Multiple bone metastases
- Metastases outside the skeleton
- Larger burden of visible cancer
Low-volume disease generally refers to a smaller number of metastatic sites and no visceral involvement.
Why does this matter?
Because the biology is often different.
A man with three small bone metastases frequently behaves very differently from a man with extensive disease involving dozens of lesions throughout the skeleton.
This is one of the reasons treatment intensification has become increasingly important in higher-volume disease.
The second clue: what do the genes tell us?
One of the biggest changes in prostate cancer management has been the routine use of genomic testing.
We are increasingly recognising that some prostate cancers may have more aggressive biological features from the beginning.
The scan may be showing the visible result of that underlying biology.
PTEN loss
PTEN is one of the most important tumour suppressor genes in prostate cancer.
When PTEN is lost, cancer cells gain the ability to activate the PI3K/AKT pathway, promoting growth and resistance to treatment.
Multiple studies have demonstrated that PTEN loss is associated with:
- Shorter progression-free survival
- Earlier treatment resistance
- Poorer overall outcomes
Importantly, PTEN loss is increasingly being recognised as both a prognostic marker and a potential therapeutic target.
For patients, the practical message is simple:
Not all metastatic prostate cancers are equally aggressive.
PTEN loss is generally considered an adverse biological feature and may influence prognosis and future treatment discussions.
BRCA2 mutations
Another major prognostic marker is BRCA2.
Many patients associate BRCA mutations with breast or ovarian cancer.
However, BRCA2 is also one of the most important genes in advanced prostate cancer.
Men with BRCA2-mutated prostate cancer often present with:
- More aggressive disease
- Earlier metastatic spread
- Shorter survival compared with men without BRCA2 mutations
Historically this was bad news.
Today, however, identifying a BRCA2 mutation can also create treatment opportunities.
PARP inhibitors have changed the treatment landscape for many men with BRCA-associated advanced prostate cancer. Increasingly, clinical trials are also exploring whether these treatments should be used earlier in selected patients.
The third clue: was the cancer found only on PSMA PET?
Perhaps the most fascinating development has been the widespread adoption of PSMA PET imaging.
Many men now undergo PSMA PET scans at diagnosis.
These scans are dramatically more sensitive than conventional CT and bone scans.
As a result, we increasingly see patients whose:
- CT scan is negative
- Bone scan is negative
- PSMA PET identifies a very small amount of metastatic disease
This creates an entirely new category of patient.
Interestingly, emerging evidence suggests that some men whose disease is detected only by PSMA PET may have a lower disease burden and potentially better outcomes than men whose metastases are already visible on conventional imaging.
However, this remains an evolving area, and treatment decisions still need careful specialist interpretation.
This makes intuitive sense.
If cancer can only be seen using the most sensitive imaging available, the overall tumour burden is often lower.
However, there is an important practical point.
Most of the level-1 evidence that guides modern prostate cancer treatment was developed using conventional CT and bone scans rather than PSMA PET.
That is why I frequently recommend obtaining conventional imaging even when a PSMA PET has already been performed.
The two scans provide different information.
The PSMA PET tells us where disease is.
The conventional scans help us understand how that disease relates to the clinical trials that established modern standards of care.
Metastatic prostate cancer: Why treatment is becoming more personalised
Ten years ago, two men with metastatic prostate cancer often received very similar treatment.
Today, treatment is increasingly tailored according to:
- Disease volume
- Genomic findings
- PSMA PET characteristics
- Patient fitness and goals
For example, a man with a small amount of metastatic disease may need a different treatment plan from a man with more widespread disease.
If the cancer has a BRCA2 mutation, PARP inhibitor treatment may become an option in some situations.
If the cancer has PTEN loss, newer targeted treatments may become relevant in the future.
One example is CAPItello-281, a phase III study evaluating capivasertib with abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer.
Early results suggest this approach may improve radiographic progression-free survival.
However, this is still an evolving area, and mature overall survival data and local access pathways need to be considered carefully.
Overall, metastatic prostate cancer treatment is becoming more personalised because doctors are increasingly looking at disease volume, cancer genetics and PSMA PET findings together.
Key takeaways
- Metastatic prostate cancer does not behave the same way in every man
Two men may have similar scan findings, but the biology of their cancer can be very different. - Disease volume and cancer genetics matter
Features such as disease burden, PTEN loss, BRCA2 mutations and visceral metastases can help doctors understand risk and guide treatment discussions. - PSMA PET has changed how prostate cancer is staged
Some cancers are now detected earlier or more accurately than they were with older scans, but doctors still need to interpret these findings carefully. - Treatment is becoming more personalised
Modern prostate cancer care is moving toward understanding what is driving the cancer, not just where the cancer is seen on scans.
Key evidence
- Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737-746. doi:10.1056/NEJMoa1503747
- Clarke NW, Ali A, Ingleby FC, et al. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019;30(12):1992-2003.
- Ferraldeschi R, Nava Rodrigues D, Riisnaes R, et al. PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate. Eur Urol. 2015;67(4):795-802. doi:10.1016/j.eururo.2014.10.027
- Castro E, Goh C, Leongamornlert D, et al. Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. Eur Urol. 2015;68(2):186-193. doi:10.1016/j.eururo.2014.10.022
- Abida W, Patnaik A, Campbell D, et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration. J Clin Oncol. 2020;38(32):3763-3772. doi:10.1200/JCO.20.01035
- Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid. 2022;1(9). doi:10.1056/EVIDoa2200043
- Hofman MS, Lawrentschuk N, Francis RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395(10231):1208-1216. doi:10.1016/S0140-6736(20)30314-7
- Leow BYJ, Eade T, Hruby G, et al. Prognostic impact of prostate-specific membrane antigen positron emission tomography staging for clinically node-positive prostate cancer. J Med Imaging Radiat Oncol. 2024;68(6):721-728. doi:10.1111/1754-9485.13655
- Fizazi K, De Santis M, James N, et al. Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study. Ann Oncol. 2026;37(1):53-68. doi:10.1016/j.annonc.2025.10.007
Frequently asked questions (FAQ)
- Do I still need a CT scan and bone scan if I already had a PSMA PET scan?
Often, yes.
PSMA PET is the most sensitive scan we currently have.
However, most of the landmark clinical trials that guide treatment decisions were based on conventional CT and bone scans.
Having both can help accurately determine disease volume and place your situation into the context of the strongest available evidence.
- What are the most important bad prognostic signs?
Some of the most consistently recognised adverse prognostic features include:
- High-volume metastatic disease
- PTEN loss
- BRCA2 mutation
- Visceral metastases
- Early treatment resistance
These features do not determine your outcome, but they help doctors estimate risk and choose treatment intensity.
- Are there any good prognostic signs?
Generally speaking:
- Low-volume metastatic disease
- Metastases detectable only on PSMA PET
- Absence of visceral metastases
- Favourable genomic findings
are associated with better outcomes.
- Are genomic tests now influencing treatment from the beginning?
Increasingly, yes.
Modern prostate cancer care is moving toward biology-driven treatment rather than relying solely on scan findings.
The goal is not simply to identify risk.
The goal is to identify opportunities.
Dr Dilanka De Silva
MBBS, MRCP(UK), MRCP(UK SCE Oncology), FRACP, PhD
Medical Oncologist & Cancer Genetics Physician
Memorial Sloan Kettering Cancer Center Fellow (New York, USA)