Red Car Syndrome

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Forewarned is Forearmed

Despite prostate cancer being the UK’s number one male cancer, until I was diagnosed with advance metastatic prostate cancer, five years ago, I had never heard of it?

Now that I have my own red car I am reminded of it all the time.

Several friends, work colleagues have since been diagnosed with Prostate Cancer. Some, I found retrospectively, had been diagnosis, previous to my diagnosis, I wasn’t aware …. why would I be?

Many friends, acquaintances, ‘family’ have taken positive action based upon my diagnosis and seeked ‘just in case’ precautionary, medical checks. Some, (at least three so far), have come to me for, direct advice. I had to think long and hard about how to react to those requests.

So far, I have never refused, choosing to share my own experiences, for what they are worth, in the hope that my, shared experiences, might help others, to make the right, difficult choices that will certainly be coming their way.

Have I, did I (always) make the right choices, decisions?

The best way to answer would be ‘knowing where I am now, what I know now, would I change anything’?

Honestly? Yes, I would.   

I (now) consider myself reasonably well informed, (researched) about prostate cancer.

Prostate Cancer is different for everybody.

There are always going to be similarities however, a single, subtle difference – age, additional health conditions, financial situation could make ‘others’ choices, decisions infinitely different to my own? There is no such thing as a one size fits all prostate cancer, case study. You learn as you go. You cannot know enough at the time when you are literally making life changing (extending/ending) choices.

There are barriers.

‘Experts’ will inform you, but they will never tell you what to do (I have discussed this in previous posts). Doctors, consultants, ‘misters’ provide you with options, if there are any, as, in some advanced cases, there might not be, however, it is always up to you to decide.

Good? Or Bad?

Are patients the best placed in this experiment to make important decisions?

Five years ago (myself), no.

Five years on (myself), maybe?

Yes, I know a lot more about prostate cancer now than I did five years ago.

Twenty plus ‘medics’, fifty plus PSA tests, a (painful) biopsy, radical prostatectomy surgery, SABR radio therapy, numerous CT, MRI, PSMA-PET scans, second (and third) opinions, watchful waiting, I am ¾? the way thru my cancer trip?

I have reached a significant milestone, the 30% Club (see previous posts), I continue to seek a cure for the incurable and I have focused my recent efforts researching advancements in the area of Geno/Immune therapies/treatments I thought I would use this post as a ‘catchup’ of my more recent discoveries. 

“For men who have been diagnosed with prostate cancer there is tremendous hope that they’ll be able to live out their disease with fewer problems than their fathers or grandfathers did in the past”  Mr Mark Laniada

One of my priorities was to try do ‘the best I could’ for my son and grandson. BRAC-1 BRAC-2 Genes (see previous posts), predisposition to certain cancers, due to inherited, mutant-genes – No guarantees but, forewarned is forearmed? My son is taking his own precautions, regular, precautionary PSA testing and medical advice.

I did not know what the Prostate Gland was  

The prostate is a gland in the male reproductive system. It makes most of the semen that carries sperm. The walnut-sized gland is located beneath the bladder and surrounds the upper part of the urethra – the tube that carries urine from the bladder.

I did not know what Prostate Cancer is  

Some of us are predisposed to contracting prostate cancer via defective genes. These genes can be detected. The presence of defective genes does not mean you will automatically contract prostate cancer. Prostate cancer is, essentially, caused by changes to the DNA of a normal prostate cell which can have roots in our genes or can be caused by exposure to radiation or by a host of other potential causes.

A Definition of Prostate Cancer

When cancerous cells develop and grow within the prostate gland, they initially appear as defined lesions. A lesion is part of an organ or tissue that has been damaged by cancer. In early-stage prostate cancer the lesions are confined within the prostate gland and can be treated (cured), often in a way which preserves the gland and its functionality.

Like all cancers, the risk to life from prostate cancer is based on the cancer spreading (metastasising) out of the prostate gland and into lymph nodes, bones, and other vital organs. The best way to prevent this spread is to identify, and treat the cancer early.

Symptoms of prostate cancer can easily be confused with other, none life threatening conditions, such as age. Symptoms include; frequent and or difficulty with urination, especially at night, blood in urine and/or semen and increases in PSA levels. While these symptoms may indicate other non-life-threatening conditions such as BHP or Prostatitis (a common, age related swelling of the prostate gland) , it is vital that the possibility of prostate cancer is ruled out.

Prostate Cancer Diagnosis

Before the development of new precision technologies, surgeons were often compelled to take a one-size-fits-all approach to diagnosis and treatment of prostate cancer.

A non-precision biopsy is unable to pinpoint cancer to a specific region of the prostate, which can result in the unnecessary removal of the entire prostate gland. Radical treatments, such as removing the prostate gland with surgery, or radiating it, potentially causes problems with bladder control and inability to maintain an erection.

The diagnosis of prostate cancer has been revolutionised with the introduction of MRI scans and more precision biopsies which allow for more accurate diagnoses and better, more personalised treatment.

Technology for Prostate Cancer Treatment in the UK

Advances in technology are allowing for a much more precise diagnosis of prostate cancer, which in turn allows for a more personalised treatment plan. This is a major step forwards in offering viable alternatives to potentially unnecessary procedures and ensuring that you have access to much more accurate and appropriate treatment.

For some patients, with early detection of prostate cancer, precision diagnosis will allow them to undergo a form of focal treatment which avoids the need for surgery or radiotherapy. 

Focal Therapy treatment is non-invasive which can preserve the prostate and its function. Focal Therapy, the aim is to get rid of the cancer that is causing concern whilst ensuring that the patient does not become incontinent and has a much lower chance of losing erectile function. Mr Tim Dudderidge 

High Intensity Focused Ultrasound (HIFU), cryotherapy (freezing), laser-based tissue ablation systems, SABR proton Radiotherapy and electroporation (Nanoknife).

What’s New in Prostate Cancer Research?

Research into the causes, prevention, detection, testing, and treatment of prostate cancer is being done in many medical centre’s throughout the world.

Genetics

I have covered this area in greater detail, linked to my own experiences, in previous posts. New research on gene changes linked to prostate cancer is helping scientists better understand how prostate cancer develops. This could make it possible to design medicines to target those changes.

Tests for abnormal prostate cancer genes (BRAC-1 BRAC-2) might also help identify men at high risk who might benefit from screening or from chemoprevention clinical trials, which use drugs to try to keep them from getting cancer.

In men already diagnosed with prostate cancer, tests for certain gene changes can give men and their doctors a better idea of how likely the cancer is to grow and spread, which might influence treatment options.

Prevention

Researchers continue to look for foods (or substances in them) that can help lower prostate cancer risk. Scientists have found some substances in tomatoes (lycopenes) and soybeans (isoflavones) that might help prevent some prostate cancers. Studies are now looking at the possible effects of these compounds more closely.

Scientists are also trying to develop related compounds that are even more potent and might be used as dietary supplements. But so far, most research suggests that a balanced diet including these foods as well as other fruits and vegetables is probably of greater benefit than taking specific substances as dietary supplements.

One vitamin that may be important in prevention is vitamin D. Some studies have found that men with high levels of vitamin D seem to have a lower risk of developing the more lethal forms of prostate cancer. Overall though, studies have not found that vitamin D protects against prostate cancer.

Some research has suggested that men who regularly take certain medicines (such as aspirin or cholesterol-lowering statins) for a long time might have a lower risk of getting or dying from prostate cancer. Still, more research is needed to confirm this, and to confirm that any benefit outweighs potential risks (I have self-medicated 75mg dispersible Aspirin for at least 10 years!).

Scientists have also tested certain hormonal medicines called 5-alpha reductase inhibitors as a way of reducing prostate cancer risk.

Early detection

Doctors agree that the prostate-specific antigen (PSA) blood test is not a perfect test for finding prostate cancer early. It misses some cancers, and it sometimes finds cancers that probably never need to be treated.

One approach is to try to improve on the test that measures the total PSA level, another approach is to develop new tests based on other forms of PSA, or other tumour markers. Several newer tests seem to be more accurate than the PSA test, including:

• The Prostate Health Index (PHI), which combines the results of total PSA, free PSA, and proPSA to help determine how likely it is that a man has prostate cancer that might need treatment
• The 4Kscore test, which combines the results of total PSA, free PSA, intact PSA, and human kallikrein 2 (hK2), along with some other factors, to help determine how likely a man is to have prostate cancer that might need treatment
• Tests (such as Progensa) that look at the level of prostate cancer antigen 3 (PCA3) in the urine after a digital rectal exam (DRE). The DRE pushes some of the prostate cells into the urine. The higher the level, the more likely that prostate cancer is present.
• Tests that look for an abnormal gene change called TMPRSS2:ERG in prostate cells in urine collected after a DRE. This gene change is found in some prostate cancers, but it is rarely found in the cells of men without prostate cancer.
• ExoDx Prostate(IntelliScore), or EPI, a test that looks at levels of 3 biomarkers in a urine sample to help determine a man’s risk of having aggressive (high-grade) prostate cancer.
• ConfirmMDx, which is a test that looks at certain genes in the cells from a prostate biopsy sample.

These tests aren’t likely to replace the PSA test any time soon, but they might be helpful in certain situations. For example, some of these tests might be useful in men with a slightly elevated PSA, to help determine whether they should have a prostate biopsy. Some of these tests might be more helpful in determining if men who have already had a prostate biopsy that didn’t find cancer should have another biopsy.

Doctors and researchers are trying to determine the best way to use each of these tests.

Diagnosis

Doctors doing prostate biopsies often rely on transrectal ultrasound (TRUS), which creates black and white images of the prostate using sound waves, to know where to take samples from. But standard ultrasound may miss some areas containing cancer. There are several newer approaches to diagnosing prostate cancer.

• One approach measures blood flow within the gland using a technique called colour Doppler ultrasound. (Tumours often have more blood vessels around them than normal tissue.) It may make prostate biopsies more accurate by helping to ensure the right part of the gland is sampled.
• An even newer technique may enhance colour Doppler further. The patient is first injected with a contrast agent containing microbubbles, which helps improve the ultrasound images. Promising early results have been reported, and further research on this technique is under way.
• Another approach combines MRI and TRUS images to help guide prostate biopsies, especially in men who previously had negative TRUS-guided biopsies but the doctor still suspects have cancer. This test, known as MRI/TRUS fusion-guided biopsy, is discussed in Tests to Diagnose and Stage Prostate Cancer.

Staging

Determining the stage (extent) of prostate cancer plays a key role in determining a man’s treatment options. But imaging tests for prostate cancer such as CT and MRI scans can’t detect all areas of cancer, especially small areas of cancer in lymph nodes, so doctors are now looking at newer types of imaging tests.

Multiparametric MRI can be used to help determine the extent of the cancer and how aggressive it might be, which might affect a man’s treatment options. For this test, a standard MRI is done to look at the anatomy of the prostate, and then at least one other type of MRI (such as diffusion weighted imaging [DWI], dynamic contrast enhanced [DCE] MRI, or MR spectroscopy) is done to look at other parameters of the prostate tissue. The results of the different scans are then compared to help find abnormal areas.

Enhanced MRI may help find lymph nodes that contain cancer cells. Patients first have a standard MRI. They are then injected with tiny magnetic particles and have another scan the next day. Differences between the 2 scans point to possible cancer cells in the lymph nodes. Early results of this technique are promising, but it needs more research before it becomes widely used.

For standard positron-emission tomography (PET) scans, a type of radioactive tracer known as FDG is injected into the body and then detected with a special camera. Unfortunately, these scans aren’t very helpful in staging prostate cancer.

Newer types of PET scans may be more helpful in detecting prostate cancer in different parts of the body. These newer tests use tracers other than FDG, such as radioactive sodium fluoride, fluciclovine, choline, or carbon acetate. Some tests (known as PSMA PET scans) use radioactive tracers that attach to prostate-specific membrane antigen (PSMA), a substance that is often found in large amounts on prostate cancer cells.

Some of these tests are now being used in certain centre’s, I was promised such a test once my PSA reached a certain (‘detectable’) threshold, a level where such a scan would be useful. Once I had reached that agreed level, the, required boundary level was suddenly, without explanation, increased and my promised scans were cancelled. This had a massive, physiologically, damaging effect.

At the same time, availability, in Liverpool, for PSMA-PET scans was suspended, I was eventually offered a PSMA-PET scan in Manchester, but by that time I had arranged for the scans in Australia (see previous posts).

Tests to assess prostate cancer risks

For men with prostate cancer that is localised (not thought to have spread beyond/outside the prostate gland), a major issue is that it’s often hard to tell how quickly the cancer is likely to grow and spread. This can affect whether the cancer needs to be treated right away, as well as which types of treatment might be good options. 

Some types of newer lab tests (known as genomic or proteomic tests) can be used along with other information (such as the PSA level and grade of the cancer) to help better predict how quickly a prostate cancer might grow or spread. These tests look at which genes (or proteins) are active inside the prostate cancer cells. Examples of such tests include:

• Oncotype DX Prostate: This test measures the activity of certain genes in prostate cancer cells and reports it as a score on a scale from 0 to 100 (higher scores indicate a cancer that is more likely to grow and spread quickly, as well as a higher risk of dying from prostate cancer). 
• Prolaris: This test measures the activity of a different set of genes in prostate cancer cells and reports it as a score on a scale from 0 to 10 (higher scores indicate a cancer that is more likely to grow and spread quickly, as well as a higher risk of dying from prostate cancer).
• ProMark: This test measures the activity of a set of proteins in prostate cancer cells and reports it as a score that helps predict how likely a cancer is to grow and spread quickly.
• Decipher: For men who choose surgery to treat their cancer, this test can help determine the risk that the cancer will come back in other parts of the body after surgery (and therefore if these men should consider further treatment). This test measures the activity of certain genes in prostate cancer cells from the surgery specimen.

Treatment

Newer treatments are being developed, and improvements are being made among many standard prostate cancer treatment methods.

Surgery

Doctors are constantly improving the surgical techniques used to treat prostate cancer. The goal is to remove all of the cancer while lowering the risk of complications and side effects from surgery.

Radiation therapy

Advances in technology are making it possible to aim radiation more precisely than in the past. Current methods such as conformal radiation therapy (CRT), intensity modulated radiation therapy (IMRT), and proton beam radiation (SABR) help doctors avoid giving radiation to normal tissues as much as possible. These methods are expected to increase the effectiveness of radiation therapy while reducing the side effects. I had, successful, focused proton beam, radiation therapy to remove a 2cm tumour in a lymph node, around my abdominal area.

Computer programs allow doctors to better plan the radiation doses and approaches for both external radiation therapy and brachytherapy. Planning for brachytherapy can now even be done during the procedure (intraoperatively).

Newer treatments for early-stage cancers

One treatment, known as high-intensity focused ultrasound (HIFU), destroys cancer cells by heating them with highly focused ultrasonic beams. This treatment has been used in some countries for a while, (the United States). Its safety and effectiveness are now being studied, although most doctors in the US don’t consider it to be a proven first-line treatment for prostate cancer at this time.

Nutrition and lifestyle changes

Many studies have looked at the possible benefits of specific nutrients (often as supplements) in helping to treat prostate cancer, although so far none have shown a clear benefit. Some compounds being studied include extracts from pomegranate, green tea, broccoli, turmeric, flaxseed, Alma powder (Indian Gooseberry extract) and soy.

One study has found that men who choose not to have treatment for their localised prostate cancer may be able to slow its growth with intensive lifestyle changes. The men in the study ate a vegan diet (no meat, fish, eggs, or dairy products) and exercised frequently. They also took part in support groups and yoga.

After one year the men saw, on average, a slight drop in their PSA level. It isn’t known if this effect will last since the report only followed the men for 1 year. The regimen may also be hard for some men to follow. Quality of life?

Hormone therapy

Several newer forms of hormone therapy have been developed in recent years. Some of these may be helpful when standard forms of hormone therapy are no longer working.

Some examples include abiraterone (Zytiga), enzalutamide (Xtandi), and apalutamide (Erleada), others are now being studied as well, not all are available via the NHS. Some are expensive

5-alpha reductase inhibitors, such as finasteride (Proscar) and dutasteride (Avodart), are drugs that block the conversion of testosterone to the more active dihydrotestosterone (DHT). These drugs are being studied to treat prostate cancer, either to help with active surveillance, or if the PSA level rises after prostatectomy.

Chemotherapy

Studies in recent years have shown that many chemotherapy drugs can affect prostate cancer. Some, such as docetaxel (Taxotere) and cabazitaxel (Jevtana) have been shown to help men live longer.

Results of large studies have shown that giving men with metastatic prostate cancer chemotherapy (docetaxel) earlier in the course of the disease might help them live longer.

Immunotherapy

The goal of immunotherapy is to boost the body’s immune system to help fight off or destroy cancer cells.

Vaccines

Unlike vaccines against infections like measles or mumps, prostate cancer vaccines are designed to help treat, not prevent, prostate cancer. One possible advantage of these types of treatments is that they seem to have very limited side effects. An example of this type of vaccine is sipuleucel-T (Provenge), currently no longer available in the UK (cost was £67,000 per injection, with an average of five injections required).

Other types of vaccines to treat prostate cancer are being tested in clinical trials (UK trials are currently difficult to gain access to if your disease has not advanced to a certain stage).

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking other normal cells in the body. To do this, it uses “checkpoints” – proteins on immune cells that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. But newer drugs that target these checkpoints hold a lot of promise as cancer treatments.

For example, newer drugs such as pembrolizumab (Keytruda) and nivolumab (Opdivo) target the immune checkpoint protein PD-1, while atezolizumab (Tecentriq) targets the related PD-L1 protein. These types of drugs have been shown to be useful in treating many types of cancer, including some prostate cancers with DNA mismatch repair (MMR) gene changes (although these are rare in prostate cancer).

One promising approach for the future might be to combine a checkpoint inhibitor with another drug. For example, combining it with a prostate cancer vaccine might strengthen the immune response and help the vaccine work better. Other types of drugs might help the immune system better recognize the cancer cells, which might help the checkpoint inhibitor itself work better.

Chimeric antigen receptor (CAR) T-cell therapy

In this treatment, immune cells called T cells are removed from the patient’s blood and altered in the lab so they have receptors called chimeric antigen receptors (CARs) on their surface. These receptors can be made to attach to proteins on the surface of prostate cells. The altered T cells are then multiplied in the lab and put back into the patient’s blood. The hope is that they can then find the prostate cancer cells in the body and launch a precise immune attack against them.

This technique has shown some encouraging results against prostate cancer in early clinical trials, but more research is needed to see how useful it can be. CAR T-cell therapy for prostate cancer is a complex treatment with potentially serious side effects, and it is only available in clinical trials (in the US only) at this time.

Targeted therapy drugs

Newer drugs are being developed that target specific parts of cancer cells or their surrounding environments. Each type of targeted therapy works differently, but all alter the way a cancer cell grows, divides, repairs itself, or interacts with other cells.

PARP inhibitors

Some men with prostate cancer have mutations in DNA repair genes (such as BRCA2) that make it hard for cancer cells to fix damaged DNA. Drugs called poly-adenosine diphosphate ribose polymerase (PARP) inhibitors work by blocking a different DNA repair pathway. Cancer cells are more likely to be affected by these drugs than normal cells.

PARP inhibitors such as olaparib, rucaparib, and niraparib have shown promising results in early studies of men with one of these gene mutations, and these drugs are now being studied in larger clinical trials.

Monoclonal antibodies

These are manmade versions of immune proteins that can be designed to attach to very specific targets on cancer cells (such as the PSMA protein on prostate cancer cells). For prostate cancer, most of the monoclonal antibodies being studied are linked to chemo drugs or to small radioactive molecules. The hope is that once injected into the body, the antibody will act like a homing device, bringing the drug or radioactive molecule directly to the cancer cells, which might help them work better. Several monoclonal antibodies are now being studied in clinical trials.

Treating prostate cancer that has spread to the bones

Doctors are studying the use of radiofrequency ablation (RFA) to help control pain in men whose prostate cancer has spread to one or more areas in the bones. During RFA, the doctor uses a CT scan or ultrasound to guide a small metal probe into the area of the tumour. A high-frequency current is passed through the probe to heat and destroy the tumour. RFA has been used for many years to treat tumours in other organs such as the liver, but its use in treating bone pain is still fairly new. Still, early results are promising.

Advice?

Do your own research …. As quickly as possible?

Thanks for reading

Peace