Treating early-stage prostate cancer in 2023

I. Introduction

This article aims to provide patient-focused information on modern treatments for prostate cancer which is confined within the prostate gland (Localised)

Precision diagnostics, especially the availability of imaging tools including MRI scans and PSMA PET scans and image-guided biopsies are changing the treatment of localised prostate cancer.

We aim to provide men with localised prostate cancer with a solid understanding of the options available to treat prostate cancer based on their diagnosis and the increasing availability of non-invasive prostate cancer treatments in addition to well-established radical prostate cancer treatments.

This article does not cover treatment options for advanced prostate cancer which has spread beyond the prostate gland. 

Quotation

“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 Marc Laniado, Urological Consultant at The Focal Therapy Clinic

Definition of Early Stage Prostate Cancer:

Prostate cancer is a type of malignant tumour that develops in the prostate, a small walnut-sized gland located just below the bladder in men. It is the most common cancer affecting men globally.

Early-stage prostate cancer is defined as prostate cancer with a Gleason score which is no more than 7 and which is still localised within the prostate gland. (T2N0 stage)

Precision Diagnostics and Prostate Cancer

The diagnosis and treatment of prostate cancer continue to be revolutionised by the advent of modern imaging techniques including mpMRI scans and PSMA PET CT scans coupled with precision prostate biopsy strategies. These precision diagnostics have enabled clinicians to identify where prostate cancer is situated within the prostate gland. Targeted therapy aims to destroy cancer cells while sparing adjacent healthy tissue using a range of non-invasive treatments is called Focal Therapy.

Targeted therapy or Focal Therapy has been clinically proven to offer equivalent cancer control to the established radical treatments with minimal impact on the quality of life in terms of rapid recovery, maintained erectile function and urinary and bowel continence.

Statistics of Prostate Cancer Incidence

Prostate cancer is the most common cancer affecting men in the UK. Every year about 50,000 men receive a diagnosis of prostate cancer and 11,000 will die early from the disease

Of the men diagnosed approximately 50% will have early-stage localised prostate cancer, (Clinically described as T stage 1 or 2) which can be managed with little impact on life expectancy.

Men with prostate cancer with a Gleason grade above 7 or stage T3 or T4 face a reduced life expectancy. In these cases established treatments including robotic surgery, combination hormone and radiotherapy treatment and chemotherapy treatment are needed.  

A major UK clinical trial reported in 2016 (the ProtecT trial) provided the following data on the outcomes for 1,643 men with early-stage localised prostate cancer receiving alternative treatments. This trial focused on results from Active Surveillance, Surgery and a combination of Hormone and Radiotherapy treatments. It did not report on Focal Therapy outcomes.         

The results of this clinical trial and others combined with the increased diagnostic precision afforded by modern MRI scans, PSMA Pet scans and precision prostate biopsies is driving a re-appraisal of treatment options for men with localised prostate cancer. Increasingly the focus is to achieve cancer control but also to minimise side effects and damage to men’s quality of life.

Clinical trials carried out in the UK have established that the urinary and erectile function results from Focal Therapy treatment are similar to those from Active Surveillance.

In the NHS to date, the number of men being offered minimally invasive alternatives to well-established therapies is low.

 However, at The Focal Therapy Clinic we provide the very latest in minimally invasive treatments for men who wish to consider this option. We are committed to providing a service which is founded on the highest levels of clinical evidence and patient experience. Our team of world-renowned consultants have decades of experience and offer a number of cutting edge treatment options tailored

II. Understanding Prostate Cancer

What is the Prostate Gland?

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

Prostate Cancer

Prostate cancer is essentially caused by damage to the DNA of a normal prostate cell. These damaged cells form tumours that can be benign but often become malignant and cancerous tumours. Prostate cancer often grows very slowly so there is normally time to explore all of your treatment options before making a decision.

In localised prostate cancer, the lesions are confined within the prostate gland and can be treated, often in a way which preserves the gland and its functionality.

In more advanced cases prostate cancer treatment becomes more intense and radical treatment is needed to destroy the prostate gland and the area around it.

Risk Factors for Developing Prostate Cancer

The exact causes of prostate cancer are unknown, but several risk factors have been identified.

Race, genetics, age and diet are the dominant risk factors for prostate cancer.

Black men are twice as likely as white men to receive a diagnosis of prostate cancer and usually at a younger age. 1 in 8 versus 1 in 4.

Men whose father or brother had a prostate cancer diagnosis have a doubled risk of receiving a diagnosis.

13% of clinically significant prostate cancer is found in men between 50 and 60 and 87% older than 60 with an average age at diagnosis of 66.

Diet and obesity are believed to increase risk with various authors commenting on the consumption of dairy and red meat.

III. Diagnosing Prostate Cancer

Prostate cancer diagnosis usually starts with the use of a blood marker called PSA which provides an early indication of risk. This is normally done by a GP or during a Well Man check-up. In cases where the PSA level is above a level of 3 or 4, the patient is then placed on the Prostate Cancer Diagnostic pathway. 

This starts with a special prostate specific MRI scan which is effective at identifying areas within the prostate gland which may harbour clinically significant prostate cancer.

“The big change has been the advent of MRI and its use in prostate imaging. Using mpMRI we are now about 90% accurate in picking up clinically significant tumours. If you compare that to standard TRUS biopsies, which we know to be about 30%, it’s a completely different league.”

Dr Clare Allen, Uro-Radiologist at The Focal Therapy Clinic

The MRI uses magnets to create an image of the prostate gland and the surrounding tissues. These images allow the radiologist to identify areas of suspicion which will need a biopsy to investigate further.

Prostate biopsy strategies have been significantly improved by the movement from trans-rectal to transperineal biopsies which have a much lower risk of causing infection as well as significantly improved accuracy and diagnostic power.

Transperineal prostate biopsy procedures are carried out under image guidance from an ultrasound probe placed in the rectum with needles inserted into the prostate from the skin just below the scrotum. This allows the urologist to access all areas of the prostate gland accurately and to take biopsy samples from those areas which were suspicious on the MRI scan.

The biopsy samples are processed and reviewed under the microscope. If cancerous cells are found they are given a severity rating, called the Gleason Score.

“A high-quality mpMRI scan combined with a targeted biopsy allows us to know the location and grade of your prostate cancer. We can then treat it with minimal damage to surrounding organs and reduced side effects.”

Mr Raj Nigam, Urological Consultant at The Focal Therapy Clinic

This diagnostic process, powered by the use of MRI scanning, allows prostate cancer to be identified much earlier and more accurately than previously and also gives urologists a previously unobtainable understanding of the precise location and severity of cancerous cells within the prostate gland.

For men with prostate cancer with an intermediate risk prostate cancer, Gleason score 4+3=7 a PSMA PET CT scan may be taken before a decision on any treatment option. The PSMA PET CT scan is an imaging test used to detect prostate cancer cells throughout the body. It gives reassurance that the prostate cancer cells have not spread beyond the prostate gland. 

Benefits of Early Detection of Prostate Cancer

Men with prostate cancer that are detected early with a definitive understanding of the location and extent of the disease have treatment options which were not available before the era of precision diagnostics.

An accurate understanding of disease severity and location has made it possible to offer men non-invasive treatment options which were previously inconceivable. These are Active Surveillance and various Focal Therapy Treatments.

Suitability for treatment options

Suitability for each of the prostate cancer treatment options is determined by a detailed clinical review of MRI scans, biopsy results and overall health but also takes into consideration the values and personal priorities of the man.

This review is done in a multidisciplinary team meeting where a range of clinical specialists including urologists, radiologists and oncologists work together to assess each man’s clinical circumstances and the treatment options available to them.

 The objectives are always to ensure that the primary objective of cancer control can be achieved with the least possible side effects for the man.

The treatment options available for early stage prostate cancer which is confined within the prostate gland (localised) are, in order of severity

• Active Surveillance
• Focal Therapy
• Surgery
• Hormone and Radiotherapy treatment

IV. Treatment options for early-stage prostate cancer

A. Active Surveillance

Prostate cancer treatments can hurt a man’s quality of life. These include side effects such as erectile dysfunction and incontinence where a man is unable to control urinary or bowel functions.  

Many early-stage prostate cancers grow very slowly and cause no symptoms or problems. For this reason, men may choose to delay treatment until there is confirmation that the disease is progressing and that treatment is necessary.

Active surveillance is a management strategy for low-risk prostate cancer that involves monitoring the disease without immediately undergoing treatment. It is a way to avoid the side effects and costs of treatment without having an impact upon lifespan.

The Active Surveillance monitoring protocol involves regular prostate-specific antigen (PSA) tests, MRI scans and transperineal targeted prostate biopsies to monitor any potential progression. Treatment will begin if clinically significant progression is detected.

The benefit of Active Surveillance is to reduce the risk of side effects from over-treatment and allow a man to delay treatment until it becomes necessary.

The drawback is that Active Surveillance requires a significant commitment on behalf of men and clinicians to maintain this monitoring protocol over time to minimise the risk of progression towards dangerous life-threatening metastatic prostate cancer. Some men find that the Active Surveillance protocol can become a source of significant anxiety over time.

35% of men diagnosed in the UK annually are placed on the Active Surveillance Protocol for a period.

 Approximately 50% of men on the Active Surveillance protocol proceed to radical treatment within 3 years of starting the protocol.

B. Focal Therapies

Focal Therapy is a term for treatments which involve a partial ablation of the prostate gland focusing on killing prostate cancer cells and minimising the impact on healthy prostate tissue.   

Focal Therapy is enabled by precision imaging using MRI and sometimes PSMA PET scans to confirm where the prostate cancer cells are located and that they are confined within the prostate gland. These are followed up by transperineal image-guided biopsies of the prostate which can both determine the presence of cancer in the areas identified by imaging and the absence of cancer cells in the rest of the prostate gland. 

Focal Therapy is a treatment for men with early stage and intermediate stage prostate cancers which are confined within the prostate gland (Gleason 3+4=7 or 4+3=7.

UK Clinical Trials have established that Focal Therapy provides cancer control equivalent to surgery at 8 years but with a minimal recovery period and almost no impact on erectile function or urinary or bowel continence.

Focal Therapy in the NHS is only offered to a small percentage of eligible patients.

Criteria for Focal Therapy Suitability

• Large volume Gleason 6
• Gleason 3+4=7 and 4+3=7
• MRI identified lesions which are concordant with biopsy results  
• Patient has a preference for Focal Therapy
• Patient accepts the need for ongoing monitoring

Once it has been established that a man meets the suitability criteria for Focal Therapy then a decision is needed about what type of Focal Therapy treatment to offer.

There is constant innovation in the field of Focal Therapy treatments however the major treatments in regular clinical use at this time are

– High Intensity Focal Ultrasound (HIFU)

– Cryotherpay

– NanoKnife (IRE)

– High Intensity Focused Ultrasound (HIFU)

HIFU has been in use for the treatment of prostate cancer since the late 1990s. It is approved for clinical use in the USA and Europe and there have been over 50,000 procedures carried out and many clinical trials have been carried out.

HIFU Focal Therapy is carried out under a general anaesthetic when an ultrasound probe is inserted into the rectum and high-intensity ultrasound waves are directed at the prostate cancer under image guidance. The Ultrasound waves are targeted toward cancer cells which are heated to 80*C to 100*C resulting in cell death.

The whole process is carried out using sophisticated 3D imaging technology which integrates the results of MRI scans and Biopsies to ensure that targeted cancer cells are killed and that healthy tissue is spared.

HIFU is performed in a day case setting with men going home with minimal discomfort a few hours after treatment although they do need to have a catheter in place for approximately 5 days.

Once the catheter has been removed almost all men have full control of their urinary function and 95% of men who had erections sufficient for intercourse before the procedure report no problems at 6 weeks after treatment.

Cancer control at 8 years is comparable to surgery or radiotherapy treatments with 10 % of men needing treatment for recurrence.

HIFU is the preferred treatment option for men whose cancers are located in the parts of the prostate gland which are close to the rectum. 70% to 75% of intermediate prostate cancer cases occur in this area.

– Cryotherapy

Cryotherapy which involves freezing areas of tissue to cause selected cell death has been used clinically for many years for the treatment of skin, breast and cervical cancers.   

Cryotherapy in the prostate gland is carried out under a general anaesthetic and involves the placement of cryotherapy needles around the prostate cancer cells to be killed under guidance from the ultrasound imaging probe placed in the rectum.

Freezing is achieved by injecting cooling argon gas through the needles to form ice balls and risks to critical structures from the cold temperature are minimised by use of warming fluids in the urethra.

Cryotherapy is a complementary treatment to HIFU in that it is effective at treating 25 – 30% of prostate cancers which are more distant from the rectum.

Cryotherapy is especially useful in treating men with recurrent cancer after failed Brachytherapy radiotherapy procedures as its effectiveness is not impacted by residual radioactive seeds.

A drawback of Cryotherapy is that temperature control is more complex and larger treatment areas are needed to ensure full cancer control leading to a small increase in the risk of side effects such as urinary incontinence and erectile function compared to HIFU. Surgical time is typically 2 to 3 hours.

– NanoKnife

NanoKnife has been used clinically since 2010 to kill solid tumours. It has achieved clinical acceptance and rapid adoption in the areas of pancreatic and liver cancer. In the last 5 years, it has been used clinically for treating prostate cancer tumours.

NanoKnife is a non-thermal treatment which is effective at killing cancer cells by using strong electrical fields to create permanent nano-sized pores in the membranes of cancer cells. This results in cell death within seconds and leaves a well-demarcated region of ablation with a sharp boundary between treated and untreated areas and minimal inflammation or damage to nearby nerves or blood vessels. 

NanoKnife is carried out under a general anaesthetic and the electrical current is directed by needle electrodes which are placed using sophisticated 3D imaging under ultrasound guidance following the recommended treatment plan developed by the uro-radiologist and the urologist.

An advantage of NanoKnife is that it is relatively simple to administer with a normal treatment time of less than 1 hour and very rapid recovery.

Early clinical data indicate high effectiveness at killing cancer cells with rapid recovery and minimal side effects but more time is needed for longer-term clinical trials to be completed.

NanoKnife is increasingly seen as an ideal complement to HIFU treatment in the treatment of Focal Prostate Cancers and it is likely to replace Cryotherapy in the primary treatment of focal prostate cancer tumours which are not located close to the rectum.

 C. Surgery – Robotic Prostatectomy

Surgery to remove the entire prostate gland and surrounding tissues, “Radical Prostatectomy” is one of the most established treatments for prostate cancer.

According to the National Prostate Cancer Audit for England and Wales 5,000 men had a radical prostatectomy in 2021 compared to 14,00 who had hormone and radiotherapy treatment.

Surgery is effective at cancer control and is the established standard of treatment for men whose prostate cancer has not spread beyond the region of the prostate gland. It is effective at curing prostate cancer confined within the prostate gland or where there is a risk of extra-capsular extension.

Surgery is routinely offered to men who are healthy enough to undertake the procedure and who have an estimated life expectancy of 10 years or more.

Over the last decade, there have been continuous innovations in surgical techniques that improve continence and erection outcomes for men. These include the

• Da Vinci robot has given the surgeon greatly improved precision and led to a reduction in the length of hospital stays to 3 versus 6 days and a reduction in blood loss.
• Retzius-Sparing techniques can reduce the impact on the bladder and reduce incontinence problems leading to a faster recovery of urinary continence
• Neurosafe techniques help to reduce the impact on the nerves controlling erections reducing the risk of the loss of erectile function.

Clinical data shows that surgery is highly effective at controlling prostate cancer with 98% still alive at 10 years after treatment and 75% showing no rise in PSA readings.

The side effects of Radical prostatectomy are significant.

Men take on average 6 to 10 weeks to recover from the surgery and while all are impotent and incontinent immediately after surgery there is improvement for the majority of men within the first year.

The ProtecT clinical trial mentioned above showed that 10 years after surgery urinary problems impact 71% of men and erectile problems 66% of men.

These rates are significantly higher than would be anticipated through the normal ageing process. The Active Surveillance cohort of the ProtecT trial showed that after 10 years urinary problems impact 39% of men and erectile problems 45% of men.

D. Combination Hormone /Radiation Therapy

In the UK the dominant treatment for prostate cancer is a combination of hormone and radiotherapy treatment. ( to suppress testosterone levels and External Beam Radiation Treatment (EBRT))

This is the standard of care for men who

– have localised disease but are not fit enough to undergo surgery

– have high Gleason score cancer

– have cancer that has spread beyond the prostate gland (T3 or T4) 

According to the National Prostate Cancer Audit for England and Wales 5,000 men had a radical prostatectomy in 2021 compared to 14,00 who had combination hormone and radiotherapy treatment.

Combination hormone and radiotherapy treatment offers an improved prostate specific survival rate at 10 years cure rate compared to radiotherapy alone but these treatments do carry side effects.

For early stage prostate cancer Hormone Therapy (androgen deprivation therapy) is normally given for 3 – 6 months before radiation treatment but is not continued afterwards. This suppresses testosterone levels in the body which reduces the size of the prostate gland and makes prostate cancer cells more vulnerable to radiation treatment.

Men on Hormone Therapy can expect a reduction in libido and erectile function and a risk of hot flushes, sweating, weight gain, depression and brain fog. Once the hormone therapy is stopped these symptoms reduce .within a few months.

Radiotherapy itself is normally given for 4 to 8 weeks. Radiotherapy’s short terms side effects include tiredness and discomfort around the bottom which may include diarrhoea and rectal bleeding. Longer term there is a risk of erectile issues and a small risk of bowel continence issues.

There have been major improvements in the provision of radiotherapy treatments in the UK. Currently IMRT (Image guided radiotherapy) is dominant but further improvements are being introduced including the use of Gels to minimise the risk to damage to the rectum and Stereotactic Radiotherapy which reduces the length of treatment.

Cancer control rates for prostate cancer have been the subject of many clinical trials and men with early-stage localised prostate cancer can expect a 10 year survival rate equivalent to that of surgery or focal therapy of over 99%.

The ProtecT clinical trial mentioned above showed that 10 years after combination hormone and radiotherapy treatment urinary problems impact 38%% of men, erectile problems 48%% of men and bowel problems 5% of men.

The rates for erectile function and bowel problems are higher than would be anticipated through the normal ageing process.

 Active Surveillance cohort of the ProtecT trial showed that after 10 years urinary problems impact 39% of men, erectile problems 29% of men and bowel problems 2% of men.

V. Choosing the Best Treatment

A. Understanding Your Risk Group

The first step in choosing the best treatment for prostate cancer is understanding your risk group. This is typically determined by a combination of factors, including the stage of the cancer, the PSA level, the biopsy results, and other relevant health conditions. Understanding your risk group is important because it helps determine the most appropriate treatment option.

B. Quality of Life Considerations

Another important factor to consider when choosing a treatment for prostate cancer is quality of life. Different treatments have different side effects and impacts on a person’s daily life. For example, active surveillance may not involve any immediate treatments, but it does require regular monitoring and biopsies. Focal Therapy is easily tolerated with minimal side effects for men who are detected early. Radical prostatectomy, on the other hand, can lead to urinary incontinence and erectile dysfunction.

The Europa Uomo study which was reported in 2022 provided useful information about the quality of life implications of radical prostate cancer treatments 5 years after treatment for almost 3000 men. It showed that the damage to sexual health was felt most severely.

Another question asked the men 5 years after radical prostate treatment at an average age of 71 years to comment on their perception of sexual problems 5 years after treatment. 

C. Consultation with a Specialist

The final step in choosing the best treatment for prostate cancer is consultation with a specialist. This can be a urologist, radiation oncologist, or medical oncologist, depending on your specific needs and treatment plan. A specialist can help you understand your risk group, the available treatment options, and the pros and cons of each option. They can also help you understand the expected outcomes and side effects of each treatment.

VI. Conclusion

A. Summary of the article

The article discussed the various treatments available for prostate cancer, starting with early-stage prostate cancer and progressing to intermediate stages.

The article also emphasized the importance of understanding one’s risk group, the potential side effects of each treatment, and the need to consider quality of life when making treatment decisions.

B. Importance of early detection and treatment

Early detection and treatment of prostate cancer is crucial in ensuring the best outcome. Regular screening tests, such as the prostate-specific antigen (PSA) test and biopsy, help to identify prostate cancer in its early stages, which increases the chances of successful treatment. By detecting the cancer early, individuals can choose from a range of treatment options and avoid more aggressive treatments that may have a greater impact on their quality of life.

C. Impact of Precision Diagnostics

Advanced diagnostics, MRI and PSMA scans combined with precision biopsies, have made it possible to understand the location of prostate cancer and to enable improved decisions about treatment options for men.

They have also facilitated the development of minimally invasive Focal Therapy treatments which offer many men with organ confined disease a minimally invasive and low side effect treatment option.

They have also supported increased sophistication for surgery and combination hormone and radiotherapy options which are improving cure rates and significantly reducing side effects