Prostate Cancer

Prostate Cancer

 

What is prostate cancer?

 

The prostate is a small gland that sits beneath the bladder in men and produces much of the fluid that forms the semen. Prostate cancer develops when abnormal cells in the prostate start to grow in an uncoordinated way. Prostate cancer typically grows very slowly, although this is not always the case.

 

Prostate cancer is the most common cancer diagnosed in Australia, and the third most common cause of cancer death. Around 17,000 new cases of prostate cancer are diagnosed each year in Australia. As many men die from prostate cancer each year as women from breast cancer (about 3000).

 

What are the symptoms of prostate cancer?

 

As men get older the prostate can enlarge, compressing the urethra and making it difficult to pass urine. These men may develop symptoms such as a weak urinary stream, waking up at night to urinate, or being unable to defer urination when the urge arises. This very common condition is called benign prostatic hyperplasia (BPH) and is NOT cancer.

 

Prostate cancer rarely presents with any symptoms. When symptoms are present, it usually indicates locally advanced or metastatic disease. These symptoms can include difficulty urinating, blood in the urine or semen, pain in the lower back or hips, or unexplained weight loss.

 

What are the risk factors for prostate cancer?

 

As men get older, their risk of developing prostate cancer increases. By age seventy-five, 1 in 7 men will be diagnosed with prostate cancer.

 

Men with a family history of prostate cancer have a higher risk of developing the disease themselves. The risk of prostate cancer is twice that of the regular population when a brother or father has been diagnosed. This risk increases further if multiple relatives have been affected, or if these relatives were younger when they were diagnosed. The risk of prostate cancer also increases if a man has a female relative with breast or ovarian cancer.

 

Is there anything I can do to reduce my risk of prostate cancer?

 

A number of dietary supplements and medications have been thoroughly investigated for their potential role in preventing prostate cancer. All of these studies have been negative. In particular, there is no evidence that selenium, Vitamin E, Vitamin C or lycopene reduce the risk of prostate cancer.

Diagnosis

 

How is prostate cancer diagnosed?

 

A prostate biopsy is required to diagnose prostate cancer. This involves using a special needle to take small pieces of tissue from different parts of the prostate. This tissue is then examined by a pathologist to determine whether cancer is present and, if so, how much cancer if present and whether it is an aggressive subtype. Prostate biopsy can either be performed through a transrectal or transperineal approach.

 

The decision to perform a biopsy is based upon the patient’s likelihood of prostate cancer. This takes into account the result of the PSA blood test, any abnormalities noticed on finger examination of the prostate, and whether the patient has a family history of prostate cancer.

 

What is PSA?

 

Prostate specific antigen (PSA) is a chemical produced by prostate cells. Its purpose is to support the sperm by helping keep semen in a liquid state. Whilst normally secreted into the semen, PSA can backflow into the bloodstream and be measured using a blood test.

 

There are many different reasons why the PSA level may be raised. These include:

 

  • Prostate cancer
  • Benign enlargement of the prostate
  • Infection in the urine
  • Infection or inflammation of the prostate
  • Operations on the urinary tract, such as cystoscopy to look into the bladder
  • Recent intercourse and ejaculation
  • External pressure on the prostate, for example from a bicycle seat after a long ride

 

PSA levels can fluctuate over time and vary from person to person. A man with significant prostate cancer may have a normal PSA and, in the same way, a man who does not have prostate cancer may have a raised PSA.

 

PSA density is a measure of the PSA level relative to the volume of the prostate. It is useful in men who may have an elevated PSA due to an enlarged prostate. A PSA density of > 0.15 carries an increased risk of prostate cancer.

 

The free/total PSA ratio is another refinement that can help assess risk. Men with prostate cancer have a greater fraction of PSA that is bound to other proteins in the blood, meaning they have a lower “free” PSA level.  Men with a free/total ratio of < 0.1 have a 56% chance of having prostate cancer. Men with a ratio > 0.25 have only an 8% chance of harbouring the disease.
Other tests

 

Multiparametric MRI of the prostate

 

An MRI (magnetic resonance imaging) scan of the prostate can detect areas that are suspicious for prostate cancer, thereby allowing a more precise prostate biopsy.

 

MRI can also show whether the cancer has spread locally outside the prostate gland. This allows the surgeon to tailor his or her operation to maximise cancer control while still, if possible, preserving the nerves that control erections and continence.

 

PET PSMA 

 

These new scans are very sensitive for picking up recurrent or metastatic prostate cancer. They are often performed in conjunction with CT scan to maximise anatomic information. Many surgeons now use PET PSMA instead of bone scan when staging their high-risk patients.
Grading and Staging

 

The combination of biopsy and imaging tests help determine the grade and stage of cancer.

 

Cancer grade is a measure of aggressiveness. A pathologist classifies cancer grade according to the appearance of the tissue obtained from biopsy or prostatectomy. For the last fifty years the Gleason grading system has classified prostate cancer from a score of 6 (least aggressive) to 10 (most aggressive). From 2016 the new ISUP (International Society of Urologic Pathology) score will gradually be introduced. This system is more intuitive, grading prostate cancer from 1 (least aggressive) to 5 (most aggressive).

 

Cancer stage describes the amount of cancer present and whether it has spread beyond the prostate. When the cancer is confined to the prostate gland it is called “localised” prostate cancer. If the cancer has spread outside the gland to nearby structures such as the seminal vesicles, bladder or rectum, it is called “locally advanced” prostate cancer. “Metastatic” prostate cancer is cancer that has spread to the lymph glands, bones, lungs or liver.

 

This information can be combined to place patients into groups that stratify the risk of the cancer coming back after treatment. Patients are considered Low Risk if they have Gleason grade 6 cancer (ISUP Grade 1), PSA < 10 ng/mL and tumour in no more than one half of one lobe of the prostate on finger examination. If the Gleason score is 7 (ISUP grade 2 or 3), PSA between 10 and 20 ng/mL, or the tumour encompasses more than half of one lobe, but not both lobes, then the patient is at Intermediate Risk of cancer recurrence. High Risk patients have a PSA > 20 ng/mL, Gleason score between 8 and 10 (ISUP grade 4 and 5) or cancer in both lobes of the prostate.
Treatment

 

There are several different options for treating prostate cancer. The choice of treatment must take into account a patient’s age, general health, the grade and stage of their cancer, the likely side effects of treatment and the severity of their symptoms.
The following table outlines the options for treatment depending on whether the cancer is localised, locally advanced or metastatic. This decision should be made through discussion with your treating specialist.

 

STAGE

PARAMETERS

TREATMENT OPTIONS

Localised

Low risk

  • Gleason Grade 3+3=6 (ISUP grade 1)
  • PSA < 10 ng/mL
  • Tumour in no more than one half of one lobe of the prostate on digital examination
  • Active surveillance in younger patients with low volume disease on biopsy
  • Surgery or radiotherapy in patients with high volume disease on biopsy, which suggests more aggressive cancer

Intermediate risk

  • Gleason Grade 3+4=7 or 4+3=7 (ISUP grades 2 and 3)
  • PSA 10 – 20 ng/mL
  • Tumour encompasses more than half of one lobe, but not both lobes, of the prostate on digital examination
  • Surgery
  • Radiotherapy with or without androgen deprivation therapy (ADT)

High risk

  • Gleason Grade 8, 9 or 10 (ISUP grades 4 and 5)
  • PSA > 20 ng/mL
  • Tumour in both lobes of the prostate on digital examination
  • Surgery
  • Radiotherapy +/- ADT
  • Surgery followed by radiotherapy +/- ADT as part of a multimodal approach

Locally-advanced

  • Any PSA
  • Any Gleason score
  • Cancer that has spread beyond the prostate into fat, seminal vesicles or adjacent structures such as the rectum and pelvic muscles
  • Cancer that has spread to the pelvic lymph nodes
  • Surgery
  • Radiotherapy +/- ADT
  • Surgery followed by radiotherapy +/- ADT as part of a multimodal approach

Metastatic

  • Any PSA
  • Any Gleason score
  • Cancer that has spread to bone, liver or lungs
  • ADT
  • Chemotherapy
  • Watchful waiting
Active Surveillance

 

What is active surveillance?

 

Active surveillance is a treatment option for men whose cancer has a low risk of spreading beyond the prostate.

 

In active surveillance, men are carefully watched with regular blood tests, imaging and clinical examination until they develop pre-determined triggers for curative treatment. The goal is to minimize the side effects of treatment, without compromising survival, in men with a long life expectancy who can be cured with surgery or radiotherapy.

 

Active surveillance differs from “watchful waiting,” which is a palliative approach to manage symptoms in patients in whom the risks of treatment outweigh the potential benefits.  The goal of watchful waiting is to minimize treatment-related side effects in older men who are likely to pass away from other medical problems.

 

What is the rationale for active surveillance?

 

  • Many men with a diagnosis of prostate cancer may never develop symptoms that affect their quality of life, or disease that affects their survival
  • Active surveillance avoids the potential long-term side effects of treatment, such at the impotence or incontinence
  • The psychological impact of active surveillance is less than that of unnecessary but curative treatment

 

Am I a candidate for active surveillance?

 

Forty-five per cent of men with PSA-detected prostate cancer will be candidates for some sort of deferred management.

 

Men who are candidates for active surveillance are those with cancer confined to the prostate with features that suggest a low risk of progressing to metastatic disease.

 

Features of low-risk prostate cancer include:

 

  • Prostate biopsy showing only Gleason 3+3=6 disease (ISUP Grade Group 1)
  • Prostate biopsies with only 2 to 3 samples that are positive for Grade Group 1 cancer, and each sample that is positive has <50% cancer involvement
  • Blood PSA levels less than 10 ng/mL
  • PSA density less than 0.15 ng/mL/mL

 

Several different surveillance protocols have been studied and, depending on each patient’s individual circumstances, a doctor may select a patient for active surveillance who does not strictly meet the above criteria. For example, a man older than 70 with low-volume Gleason 3+4=7 (Grade Group 2) prostate cancer may be a candidate for active surveillance.

 

If I am on active surveillance, does that mean I don’t need to worry about my cancer?

 

All men who embark on active surveillance must be willing to comply with regular and ongoing follow-up due to the risk of developing aggressive prostate cancer during surveillance. This is especially important in younger men with a long life expectancy.

 

Why do I need another biopsy?

 

Sometimes the initial biopsy misses an area of high-risk disease. A repeat biopsy, called a confirmatory biopsy, is usually performed within 12 months of the initial biopsy to minimize the risk of missing these more aggressive cancers. An MRI-fusion transperineal biopsy may be considered to maximise coverage of the prostate and target any suspicious areas.

 

What are the triggers for active treatment?

 

Triggers for active treatment should be tailored to the circumstances of each patient and discussed prior to embarking on active surveillance. These triggers may include:

 

  • A rapidly-rising PSA level
  • Repeat biopsy with increase in Grade Group or number of positive cores
  • New abnormalities on digital rectal examination
  • Patient choice
Surgery

 

What does surgery involve?

 

Radical prostatectomy involves removal of the prostate, seminal vesicles and, in many cases, the pelvic lymph nodes. It can be performed through either an open or robotic approach. In localised prostate cancer the goal of this operation is eradicate the disease while preserving continence and, if possible, erectile function. It is suitable for men who have a life expectancy of greater than ten years.

 

Surgery has not been shown to improve survival in men with low volume, Gleason Grade 6 (ISUP Group 1) prostate cancer. These men are better managed with active surveillance, with a plan to undertake surgery or radiotherapy if more aggressive disease develops. Intermediate risk cancers, however, clearly benefit from surgery, with improved overall and cancer-specific survival.

 

In high-risk or advanced disease, radical prostatectomy can be used in combination with radiotherapy and androgen deprivation therapy (ADT) as part of a multimodal approach to maximise cancer control and delay time to disease progression. Patients with high-grade cancers confined to the prostate have a good outcome after prostatectomy, as do locally advanced cancers through multimodality treatment.

 

What is the rationale for removing the lymph nodes?

 

Examination of the pelvic lymph nodes under a microscope is the best way to determine whether they have been involved with cancer. This information can be used to guide management after radical prostatectomy. For example, men with a small number of positive lymph nodes may benefit from postoperative radiotherapy and ADT.

 

Current European guidelines recommend that lymph nodes should be removed in men with intermediate risk prostate cancer if the estimated probability of having positive lymph nodes exceeds 5%. A pelvic lymph node dissection should be performed in all men with high-risk disease.

 

However, it has yet to be proven that removal of the lymph nodes, in and of itself, provides a survival benefit for men with prostate cancer.

 

What are the possible side effects of radical prostatectomy?

 

  • Loss of bladder control (incontinence) – 5-10% at 12 months
  • Erectile dysfunction (impotence) – incidence varies
  • Lack of semen during orgasm (dry orgasm) – all cases
  • Urine leakage during orgasm – incidence varies
  • Bleeding requiring blood transfusion – uncommon with robotic surgery
  • Infection – uncommon
  • Penile shortening – uncommon
  • Lymphatic fluid collection – uncommon
  • Bladder neck contracture – 1%
  • Rectal injury, which may need formation of a temporary stoma to divert bowel contents – rare

 

What is the risk of incontinence after prostatectomy?

 

Most men experience some form of incontinence after surgery. The majority of men regain control of their bladder in the months following their operation. Younger men (<65 years) will recover bladder function earlier and more completely than older men (>75 years).

 

We expect 90% of men to recover bladder function by 12 months after surgery, which is defined as using either zero pads or one small security pad for strenuous activities (golf, picking up the grandkids, etc). Depending on the degree of incontinence, men who fail to recover bladder function after 12 months may require further treatment.

 

What is the likelihood of recovering erectile function after surgery?

 

Men are more likely to recover erectile function after surgery if they have good erectile function to begin with, are younger than 60 years old, and have undergone nerve-sparing surgery. This recovery is gradual and can take several months. Some men notice their erections continue to improve for up to three years after treatment for prostate cancer. Nerve-sparing surgery is not appropriate if there is a risk of leaving cancer behind.

 

What is penile rehabilitation therapy?

 

Penile rehabilitation therapy involves taking medications to increase blood flow to the penis, thereby reducing the scarring of erectile tissue that occurs from prolonged lack of oxygen from not having erections. It is usually started within two months of surgery. Although the optimal treatment strategy is still unknown, a typical regimen may involve taking a small dose of Viagra or Cialis every night.

 

Is robotic surgery better than open surgery?

 

At the end of the day, the most important factor that will determine the outcome of prostate cancer surgery is the surgeon. Having said that, robotic prostatectomy has been shown to be a faster operation with a shorter length of hospital stay, lower blood loss, and lower transfusion rates when compared to open surgery.  Recent systematic reviews of major research studies have shown improved 12-month urinary continence, improved 12-month potency and equivalent early cancer outcomes with robotic prostatectomy compared with open and pure laparoscopic surgery. We currently await the longer-term results of a recent randomised-controlled Australian study, which found fewer perioperative complications with robotic surgery but no difference in functional (continence and potency) outcomes at 12 weeks.

 

Radiotherapy
As this is a surgical website, the discussion of radiotherapy shall remain brief. We recommend that interested patients seek the opinion of an experienced radiation oncologist.

 

Radiotherapy is generally offered as an alternative to surgery, particularly in men in whom surgery may not be appropriate. Radiotherapy has a role in multimodality treatment after surgery, and also for situations where not of all the cancer has been removed after prostatectomy. Surgery is still an option in situations where prior radiotherapy has failed to cure cancer, although in this setting the functional outcomes are worse.

 

How does radiotherapy work?

 

Radiotherapy uses high-energy radiation to cause fatal damage to cancer cells. This radiation is either produced in machine called a linear accelerator and directed towards the prostate in a beam, called external beam radiotherapy (EBRT), or emitted from radioactive seeds injected directly into the prostate, called brachytherapy.

 

What are the possible side effects of EBRT?

 

  • Inflammation of the bladder, causing burning pain, urgency and bleeding – 20%
  • Blood in the urine – 18%
  • Inflammation of the rectum, causing bleeding, diarrhoea or faecal urgenchy – 30% (long term 3%)
  • Urethral stricture – 4-8%
  • Incontinence – 1%
  • Erectile dysfunction – 25-60%
  • Pain on ejaculation
  • Dry orgasms
  • Infertility
  • Skin irritation
  • Tiredness
  • Secondary cancer in up to 1 in 70 patients, which may take several years to develop

 

What are the possible side effects of brachytherapy?

 

  • Worsening bladder symptoms – 20%
  • Inability to pass urine – 1.5-22%
  • Need for a TURP after seed implantation – up to 8.7%
  • Incontinence – 0-19%
  • Inflammation of the rectum – 5-21%
  • ED in 40% of patients after 3-5 years
  • Blood in the semen, painful ejaculation
  • Radioactive seeds migrating to other parts of the body- 10%
  • Urethral stricture – 10-25%
  • Abnormal connection between urethra and rectum, causing faeces in the urine or vice versa 2%

 

Androgen deprivation therapy (ADT)

 

What is ADT?

 

Prostate cancer cells require the male hormone testosterone to grow. Androgen deprivation therapy (ADT) involves reducing the level of testosterone in the blood through medications or surgery, thereby slowing prostate cancer growth. ADT is administered as a series of injections, usually every three months.

 

ADT is often used concurrently with radiotherapy in a curative setting for localised disease. When used to manage metastatic disease the goal is no longer to cure the cancer but to keep it under control for months or years.

 

What are some of the side effects of ADT?

 

  • Hot flashes
  • Painful enlargement of breast tissue
  • Osteoporosis
  • High cholesterol
  • Insulin resistance and diabetes
  • Heart disease
  • Decreased libido
  • Erectile dysfunction
  • Problems with memory and clear-thinking
  • Depression
  • Weight gain
  • Loss of muscle mass
  • Low red blood cell count
  • Fatigue
  • Infertility