Prostate Cancer

Treatment of Metastatic Prostate Cancer: Your Guide

Prostate cancer can metastasize to other organs, including the bones, lymph nodes, and the lungs.

To date, there is no cure for metastatic prostate cancer occurring after radical treatment or hormone ablation therapy. There are no effective therapies to prevent prostate cancer progression. 

A range of therapeutic options including hormone ablation, chemotherapy, autologous immunotherapy, and radiation therapies are offered to affected patients and show marginal benefits.

Unfortunately, most of the patients who receive these therapies rapidly develop lethal metastatic castration-resistant prostate cancer.

Thus, it is beneficial to explore some of the identified natural supplements and lifestyle changes that help you fight prostate cancer and potential progression to incurable metastatic disease.

Supplements like pomegranate, lycopene, and Omega-3 fatty acids have shown potent anti-metastatic effects and can help you reduce the risk of lethal metastatic prostate cancer.


For more information on the best prostate supplements, click here.


What is metastatic prostate cancer?

Prostate cancer is metastatic if it has spread to distance tissue and organs. Prostate cancer often spread to the bones, lymph nodes, liver, and lungs and rarely move to other organs.

It is not well understood why prostate cancer metastasis is selective but understanding the mechanisms of this selective spread may hold the key to its prevention. 

Cancer metastasis is a complex process, involving the invasion of the sentinel lymph nodes, which are first cancer draining lymph nodes.

Once in distant lymph nodes and vessels, cancer cells can reach distant organs by following the blood flow or moving in a growth factor-dependent manner.

An important mechanism of this process is tumor-induced angiogenesis, the formation of new vessels from existing blood vessels. Tumor-associated vessels are usually premature and leaky, promoting cancer movement.

Though metastatic prostate cancer has the same cancer cells as the original prostate tumor, they are much difficult to kill. They rarely respond to hormone therapy and has significantly shorter median survival time (Astigueta et al., 2010; Birtle et al., 2003). 

How is metastatic prostate cancer diagnosed?

Generally, pathologists require a prostate biopsy to confirm the presence of cancer and determine the aggressiveness of the cancer cells. This involves the pathologist giving your prostate cancer a Gleason score.

High scores above eight indicate aggressive cancer that is likely to spread to other organs.

Further, recent advancement in cancer detection and monitoring makes it possible to use genetic tests to determine the risk of your prostate cancer spreading quickly more accurately.  

Once prostate cancer stage has been determined, your doctor works to assess the presence of metastasis. If your medical team suspects your cancer has spread to other organs, they will offer you additional tests like;

•    Bone scan 

•    Computerized (CT) or positron emission (PET) tomography scans 

•    Ultrasound 

Getting these scans will depend on individual cases, and your medical provider will help you determine the best scan.

Treatments for metastatic prostate cancer

Localized prostate cancer is treated with radical prostatectomy and radiation therapy. However, many patients eventually develop locally advanced or metastatic cancer, requiring hormone or radiation therapy.

Hormone therapy is used to reduce the levels of androgen and inhibit the growth of prostate cancer cells.

Hormone therapy, coupled with external beam radiation therapy, can also be used for the advanced or metastatic disease after chemical or surgical castration has been exhausted (da Silva et al., 2014).

Unfortunately, many patients do not respond to treatment or relapse, requiring second-line therapy with anti-androgens (enzalutamide), corticosteroids, and CYP17 inhibitors (abiraterone acetate).

These drugs have many side effects that need careful management by your medical team. 

More than 85% of men who receive hormone therapy develop metastatic castration-resistant prostate cancer (CRPC) within 3 years of initiating hormone treatment. This is caused by prostate cancer cells adapting to low androgen levels.

The shift to androgen-independent growth also supports migration of prostate cancer cells into environments with low androgen levels. 

Chemotherapeutic agents like docetaxel and cabazitaxel may be offered to patients with metastatic CRPC. However, both drugs have marginal benefits and stop working after some months.

Efforts to develop less toxic and effective therapies have led to the development of Sipuleucel-T. Sipuleucel-T is a personalized immune therapy for metastatic prostate cancer and has been shown to improve overall survival of men with metastatic prostate cancer (Kantoff et al., 2010).

However, it only improves median survival rate by less than 5 months (Kantoff et al., 2010). 

Radium-223 dichloride is a more recently approved therapy for the treatment of bone metastasis in CRPC, but this is not suitable for patients with visceral metastases.

Similarly, Zoledronic acid, a bisphosphonate is useful for treating bone weakness and pain caused by prostate cancer mediated damage to the bones (Saad et al., 2004).

The limitations of the available therapies and their adverse side effects have strengthened the push to identify novel natural therapies to fight metastatic prostate cancer.

Symptoms of metastatic prostate cancer

The progression of prostate cancer to advanced metastatic disease can cause many health problems depending on the site and how quickly the cancer is spreading.

Local spread involving the bladder and other pelvic organs can cause urinary problems such as urinary retention and associated infection.

Further, bowel problems often develop when prostate cancer spread to the bowel and rectum. Complications like constipation and diarrhea can reduce your quality of life.   

Beyond local metastases, prostate cancer often spread to the bones, lymph nodes, liver, brain, and lungs.

Men with metastatic castration-resistant prostate cancer have an increased risk of distant metastasis, which is associated with debilitating complications.

In the bone, significant pain and increased risk of fracture are common because cancer cells weaken the bone.

Hypercalcemia, excessive calcium in the blood can also develop following bone metastasis, leading to vomiting, dehydration, and loss of appetite. 

The bone marrow is the production house of blood cells; thus, the spread of prostate cancer cells to the bone marrow can reduce oxygen-carrying red blood cells (Anaemia).

Cancer-associated anemia can cause fatigue, breathing complications, and in severe cases, organ failure due to lack of oxygen. 

Some of these complications can also occur when prostate cancer spread to the liver, while the complications associated with lung metastasis is commonly confounded with other factors.

Finally, the spread of prostate cancer to lymph nodes not only increases the risk of further spread to other organs but can also block the transport of lymph and cause swelling. 

What are some warning signs that you need to have a doctor check you for prostate cancer? 

In many patients, early-stage prostate cancer presents with no symptoms and are only identified through PSA informed tests. For men with symptoms, this will usually include;

•    Frequent urination

•    Blood in either urine or seminal fluid 

•  Erectile dysfunction 

•    Sitting discomfort caused by an enlarged prostate

Though other non-cancerous conditions such as enlarged prostate and prostate inflammation can cause similar symptoms, it is better to get checked by your doctor if you experience the above symptoms.

These conditions are also linked with prostate cancer development, requiring you to treat them to avoid further complications.

Information on some natural ways to help you fight prostate inflammation can be found at  https://www.bensnaturalhealth.com/prostate-health/prostatitis.html.

In rare cases, patients will have advanced prostate cancer which may have symptoms of metastatic prostate cancer including;

•    Swelling in the legs

•    Weight loss and fatigue 

•    Bowel problems

It is important to note that some therapies for managing prostate cancer can cause these symptoms.

For instance, Zoledronic acid used to treat high blood calcium, and bone breakdown can also cause diarrhea and fatigue. You should speak to your doctor about your symptoms.

How important is it to catch metastatic prostate cancer early?

It is important to consult with your doctor if you experience any of these changes mentioned above. This will help your doctor detect prostate cancer early and stop it from developing to advanced lethal disease.

Early cancer detection is central to the management of all cancers, including prostate cancer.

Currently, the treatment goal of advanced and metastatic prostate cancer is to slow cancer growth and spread.

In the absence of a definitive cure, it is critical to detect metastatic prostate cancer early to increase the usefulness of current management approaches.

Supplements and lifestyle changes may help you enhance the effectiveness of those therapies. 

Best supplements to treat metastatic prostate cancer

Prostate cancer is a heterogeneous disease characterized by lethal and indolent phenotypes.

Many men diagnosed with prostate cancer will survive several years after a diagnosis, making it important to identify natural ways to minimize the risk of developing metastatic disease.

Some men present with incurable lethal metastatic prostate cancer, while others progress to castration-resistant prostate cancer following radical treatment.

It is beneficial to use natural methods to maintain a healthy prostate, reduce the risk of developing prostate cancer, and kill metastatic prostate cancer cells.

Several natural supplements, including lycopene, pomegranate, omega-3 fatty acids, and green tea have shown anti-metastatic properties and promising results in clinical trials.

Plant phenolic compounds can help you fight prostate cancer and stop the development of metastasis.

It is noteworthy that the anti-metastatic effect of these natural compounds is influenced by tumor and patient heterogeneity (Dagogo-Jack and Shaw, 2018).

Thus, their use requires careful assessment of your circumstances to ensure the combination and duration of supplementation is appropriate. You should discuss specific needs and concerns with your medical provider.

1.    Lycopene

First, the discussion on the best supplements to treat metastatic prostate cancer must include lycopene, the most studied anti-cancer carotenoid (Giovannucci, 2002).

The anti-cancer activity of lycopene is not surprising since it naturally protects plants from light-induced stress (Coates et al., 2004).

Many studies have shown that lycopene supplementation is useful for reducing the risk of developing different types of cancers including skin, breast, lung, prostate and liver cancers through reducing oxidative stress and inflammation (Khan et al., 2008).

Consistently, studies investigating lycopene for treating advanced prostate cancer have reported the modulation of markers of disease progression and recurrence. 

Pre-clinical studies on mice injected with human androgen-independent metastatic prostate cancer cells demonstrated lycopene’s ability to decrease tumor growth at 4 – 16 mg/kg body per day (Tang et al., 2011; Yang et al., 2011, 2012).

Androgen-independent prostate cancer cells are usually used to study the mechanisms of metastatic castration-resistant prostate cancer. Thus, these results show the usefulness of lycopene in the treatment of metastatic prostate cancer.

Lycopene metabolites released after its break down can increase adhesion molecules, increasing cell to cell attachment and communication.

Metastatic prostate cancer cells express low levels of adhesion molecules, facilitating their detachment from the local prostate environment and invasion of distance organs (Mein et al., 2008).

Thus, lycopene’s activity on cell adhesion can stop prostate cancer cells from invading other organs.

Combined with its antioxidant effects, this anti-migratory effect may help you fight metastatic prostate cancer using lycopene supplements. Indeed, men with localized prostate cancer have better outcome compared to those with advanced disease.

Lycopene intervention studies in human metastatic or advanced prostate cancer.

Several human clinical studies have investigated the therapeutic benefits of lycopene in metastatic prostate cancer, albeit with some heterogeneous results.

Yang and Wang demonstrated in phase II clinical trial that lycopene supplementation reduced the levels of prostate-specific antigen (PSA) in men with prostate cancer (Zhang et al., 2014).

Interestingly, the results of previous clinical trials investigating the effect of lycopene on PSA levels collaborated this result by Zhang (Barber et al., 2006; Kucuk et al., 2002).

These results suggest that lycopene may be useful for fighting metastatic prostate cancer.

Though PSA is not a unique indicator of localized/metastatic prostate cancer, it is highly elevated in the circulation of patients with metastatic prostate cancer. Modulation of PSA by natural supplements indicate they can reduce progression to advanced prostate cancer.

Further, it may be beneficial to combine lycopene supplementation with the radical treatment offered to some patients.

Here, a clinical trial involving patients with metastatic prostate cancer showed that 4 mg/day of lycopene after orchiectomy (the surgical removal of the testicles to inhibit androgen activity) reduced PSA levels and caused significant reduction of both primary and secondary tumors (Ansari and Gupta, 2003). 

In contrast, Schwenke and colleagues did not observe significant clinical benefits after administering 15 mg/day of lycopene (Schwenke et al., 2009).

Further, high dose lycopene (25 mg to 30 mg per day) failed to modify PSA or improve clinical outcome in androgen-independent prostate cancer that usually present with increased risk of prostate cancer progression and metastasis (Bunker et al., 2007; Gann et al., 2015).

These results highlight the importance of accounting for patient heterogeneity and the dosage of lycopene.

The available evidence, including pre-clinical and clinical trials, shows that lycopene supplementation can modulate markers of metastatic prostate cancer.

Though more trials are needed to help resolve the discrepancies in dosage, lycopene can help you reduce the risk of metastatic prostate cancer. 


For more information on prostate supplements, click here.


2.    Pomegranate

Pomegranate juice/extract is another studied natural supplement to fight prostate cancer progression.

Pomegranate fruit contains several bioactive polyphenolic ellagitannins, which have anti-oxidant and anti-cancer activities. Like lycopene, treating prostate cancer cells with pomegranate derived phenolic compounds inhibit their growth (Gasmi and Sanderson, 2010).

Further, pomegranate extract kills testosterone stimulated prostate cancer cells and initiate cell-cycle arrest in a range of prostate cancer cells (Koyama et al., 2010; Turrini et al., 2015). 

As stated earlier, two key aspects of cancer metastasis are the loss of tissue commitment and adhesion molecules, both of which can be modulated by pomegranate extract.

Pomegranate can also stop prostate cancer metastasis through the inhibition of important mediators of epithelial to mesenchymal transition and induction of cell adhesion (Rocha et al., 2012).

Tumor inflammation is often associated with an increased risk of prostate cancer progression, reducing patient survival.

Globally, pomegranate extracts can reduce pro-inflammatory mediators, thereby having the additional potential to fight cancer development by inhibiting the establishment of a new metastatic niche. 

One study using cell invasion techniques showed that pomegranate juice significantly reduced the migratory and invasiveness of prostate cancer cells (Lansky et al., 2005).

Lansky and colleagues demonstrated this is through the reduction of an enzyme responsible for prostaglandin production.

Prostaglandin is important for the production of matrix proteins, which are implicated in tumor metastasis (Kessenbrock et al., 2010). 

Consistent with the multiple mechanisms of pomegranate’s anti-metastatic activity, a phase II clinical trial involving patients with rising PSA showed that 8 oz of oral pomegranate juice significantly increased the doubling time of PSA and inhibited progression to metastatic disease (Pantuck et al., 2005).

More recent randomized trial of multicomponent food supplements that included a significant proportion of pomegranate extract also showed slowing of PSA increase in men experiencing prostate cancer recurrence (Paller et al., 2017). 

Paller and colleagues conducted a randomized, multi-center and dose-exploring trial involving men with rising PSA and no metastases.

They reported a 6 months increase in the length of PSA doubling time, indicating clinical benefits without inducing any adverse effects (Paller et al., 2013).

In the absence of any associated adverse effects, its extract/juice can help you fight metastatic prostate cancer.

3.  Multicomponent dietary supplements

Several studies have investigated the usefulness of multi-component supplements, including many plant-based materials that can reduce prostate cancer progression to lethal disease.

For instance, a placebo-controlled and randomized trial assigned 199 men with localized prostate cancer to either a food supplement containing pomegranate, green tea, broccoli, and turmeric or placebo control for 6 months (Thomas et al., 2014).

The study reported a significant reduction in PSA in the food supplement group compared to the placebo.

These ingredients were derived from raw and dried plant materials and cause no adverse events.

Similarly, a mixed daily supplementation with 35 mg lycopene, 55 ug selenium, and 600 mg green tea catechins showed some clinical benefits, albeit to a lesser extent (Gontero et al., 2015).

What are some supplements that can help you prevent prostate cancer? 

Though genetic/epigenetic changes can influence the development and progression of prostate cancer, diet and nutrition are very important in the development of many cancers.

Inadequate levels of important anti-oxidants and dysfunctions in the bodies detoxification systems can increase your risk of developing prostate cancer. 

In addition to lycopene and pomegranate, other supplements like Vitamin D and Omega-3 fatty acids can reduce your risk of developing prostate cancer.

Vitamin D has been shown to reduce the risk of prostate cancer development and progression by reducing oxidative stress and inflammation (Posadzki et al., 2013).

Similarly, polyunsaturated Omega-3 fatty acids can reduce oxidative stress and inflammation (Berquin et al., 2007), reducing the risk of prostate cancer development.

These supplements not only protect you from prostate cancer but also cancers occurring in other organs.

Conclusion

The causes of prostate cancer remain largely unknown, making it difficult to prevent its development. However, diet, supplements, and physical activity are natural ways to reduce your risk.

Note that a high intake of red meat and dairy products increase your prostate cancer risk, whilst the intake of tomato products and fatty fish reduces your risk. The accumulating evidence suggests that you can use lifestyle changes to modify the risk of prostate cancer. 

Specifically, high body mass index (BMI) is strongly associated with cancer development and progression. Prostate cancer patients with high BMI are more likely to progress to lethal/metastatic prostate cancer independent of clinical factors.

Consistently, a low-fat diet rich in fruit and vegetables can lower your risk of prostate cancer. Consider reducing your consumption of meat, oils, and dairy products.


For more information on the best prostate diet, click here.


Reducing your BMI can reduce your prostate cancer-specific mortality and recurrence by more than 20% (Cao and Ma, 2011). The importance of healthy BMI is highlighted in the observation that weight gain after a prostate cancer diagnosis is associated with poor patient outcome (Bonn et al., 2014).

An active lifestyle can positively modify key components of prostate cancer development, including oxidative stress, inflammation, and immune function.

Indeed, studies have consistently shown that an active lifestyle can reduce your risk of developing prostate cancer. Preventing prostate cancer development is perhaps the best way to prevent metastatic prostate cancer.

You should aim to maintain a healthy weekly activity level to reduce your risk of developing lethal prostate cancer.

Activities that increase your heart and respiratory rates such as cycling, jogging, and swimming can reduce your prostate cancer risk by up 65% compared to men with lower weekly activity (Kenfield et al., 2011). 

You can find information on natural products that can help you maintain a healthy prostate by reducing your risk of prostate inflammation at https://www.bensnaturalhealth.com/prostate-health/bph-inflammation.html.

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About Our Author Dr. Chinedu Anthony Anene

Alternative Text
Dr. Chinedu Anene is a biomedical researcher, interested in the epi-genetic links between angiogenesis, cardiovascular disease, and cancer. He is interested in using bioinformatics and machine learning approaches to translate knowledge of molecular biology to disease biomarkers and novel therapeutic targets. He has expertise in preparing readily accessible reference materials.

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