Prostate Cancer

Prostate cancer is the most common cancer in men. It varies in how aggressive it is, and many prostate cancers are very slow-growing and do not cause death. Advanced prostate cancer most commonly spreads to the lymph nodes and bones. Prostate cancer is almost always androgen-dependent, meaning they rely on androgen hormones (e.g., testosterone) to grow. The majority are adenocarcinomas and grow in the peripheral zone of the prostate.

There is a challenge with prostate cancer, as the ideal situation is to:

  • Find and treat clinically significant prostate cancers early
  • Avoid picking up cancers that would not turn out to be clinically significant (avoiding unnecessary stress, investigations and treatment)

 

The key risk factors for prostate cancer are:

  • Increasing age
  • Family history
  • Black African or Caribbean origin
  • Tall stature
  • Anabolic steroids 

 

Presentation 

Prostate cancer may be asymptomatic. It may also present with lower urinary tract symptoms (LUTS), similar to benign prostate hyperplasia. These symptoms include hesitancy, frequency, weak flow, terminal dribbling and nocturia.

Other symptoms include:

  • Haematuria
  • Erectile dysfunction 
  • Symptoms of advanced disease or metastasis (e.g., weight loss, bone pain or cauda equina syndrome)

 

Prostate-Specific Antigen

The epithelial cells of the prostate produce prostate-specific antigen (PSA). PSA is a glycoprotein that is secreted in the semen, with a small amount entering the blood. Its enzymatic activity helps thin the thick semen into a liquid consistency after ejaculation. It is specific to the prostate, meaning it is not produced anywhere else in the body. A raised level can be an indicator of prostate cancer.

Prostate-specific antigen testing may lead to the early detection of prostate cancer, potentially leading to effective treatment and preventing significant problems. However, research has failed to show that the benefits of using PSA for screening outweigh the risks. In the UK, men over 50 can request a PSA test if they would like one.

PSA testing is unreliable, with a high rate of false positives (75%) and false negatives (15%). 

Common causes of a raised PSA are:

  • Prostate cancer
  • Benign prostatic hyperplasia
  • Prostatitis
  • Urinary tract infections
  • Vigorous exercise (notably cycling)
  • Recent ejaculation or prostate stimulation

 

False positives may lead to further investigations, including invasive prostate biopsies, which have complications and may be unnecessary. Additionally, it may lead to the unnecessary diagnosis and treatment of prostate cancer that would never have caused problems (the patient would have died of other causes before experiencing any adverse effects of the prostate cancer).

False negatives may lead to false reassurance.

TOM TIP: Counselling a patient about whether to have a PSA test is a common OSCE scenario. They are trying to test whether you understand the concept and implications of false positives and false negatives, and whether you can explain this to a patient to allow them to make an informed decision for themselves. 

 

Prostate Examination

A prostate examination is performed during a digital rectal examination.

A benign prostate feels smooth, symmetrical and slightly soft, with a maintained central sulcus (the dip in the middle between the right and left lobe). There may be generalised enlargement in prostatic hyperplasia. 

An infected or inflamed prostate (prostatitis) may be enlarged, tender and warm.

A cancerous prostate may feel firm or hard, asymmetrical, craggy or irregular, with loss of the central sulcus. There may be a hard nodule. Any of these features can indicate prostate cancer and warrant further investigation. In primary care, these findings require a two week wait urgent cancer referral to urology.

 

Multiparametric MRI

Multiparametric MRI of the prostate is now the usual first-line investigation for suspected localised prostate cancer. The results are reported on a Likert scale, scored as:

  • 1 – very low suspicion
  • 2 – low suspicion
  • 3 – equivocal
  • 4 – probable cancer
  • 5 – definite cancer

 

Prostate Biopsy

Prostate biopsy is the next step in establishing a diagnosis. The decision to perform a biopsy depends on the MRI findings (e.g., Likert 3 or above) and the clinical suspicion (i.e. examination and PSA level). 

Prostate biopsy carries a risk of false-negative results if the biopsy misses the cancerous area. Multiple needles are used to take samples from different areas of the prostate. The MRI scan results can guide the biopsy to decide the best target for the needles.

There are two options for prostate biopsy:

  • Transrectal ultrasound-guided biopsy (TRUS)
  • Transperineal biopsy

 

Transrectal ultrasound-guided biopsy involves an ultrasound probe inserted into the rectum, providing a good indicate of the size and shape of the prostate. Guided biopsies are taken through the wall of the rectum, into the prostate. 

Transperineal biopsy involves needles inserted through the perineum. It is usually under local anaesthetic.

The main risks of a prostate biopsy are:

  • Pain (particularly lower abdominal, rectal or perineal pain)
  • Bleeding (blood in the stools, urine or semen)
  • Infection
  • Urinary retention due to short term swelling of the prostate
  • Erectile dysfunction (rare)

 

Isotope Bone Scan

An isotope bone scan (also called a radionuclide scan or bone scintigraphy) can be used to look for bony metastasis. 

A radioactive isotope is given by intravenous injection, followed by a short wait (2-3 hours) to allow the bones to take up the isotope. A gamma camera is used to take pictures of the entire skeleton. Metastatic bone lesions take up more of the isotope, making them stand out on the scan.

 

Gleason Grading System

The Gleason grading system is based on the histology from the prostate biopsies. It is specific to prostate cancer and helps to determine what treatment is most appropriate. The greater the Gleason score, the more poorly differentiated the tumour is (the cells have mutated further from normal prostate tissue) and the worse the prognosis is. The tissue samples are graded 1 (closest to normal) to 5 (most abnormal). 

The Gleason score will be made up of two numbers added together for the total score (for example, 3 + 4 = 7):

  • The first number is the grade of the most prevalent pattern in the biopsy
  • The second number is the grade of the second most prevalent pattern in the biopsy

 

A Gleason score of:

  • 6 is considered low risk
  • 7 is intermediate risk (3 + 4 is lower risk than 4 + 3)
  • 8 or above is deemed to be high risk

 

TNM Staging for Prostate Cancer

The TNM staging system can be used for prostate cancer, rating the T (tumour), N (lymph nodes) and M (metastasis).

T for Tumour:

  • TX – unable to assess size
  • T1 – too small to be felt on examination or seen on scans
  • T2 – contained within the prostate
  • T3 – extends out of the prostate
  • T4 – spread to nearby organs

 

N for Nodes:

  • NX – unable to assess nodes
  • N0 – no nodal spread
  • N1 – spread to lymph nodes

 

M for Metastasis:

  • M0 – no metastasis
  • M1 – metastasis

 

Management

Management of any cancer is guided by a multidisciplinary team (MDT) meeting to decide the best course of action for the individual patient.

Depending on the grade and stage of prostate cancer, treatment can involve:

  • Surveillance or watchful waiting in early prostate cancer
  • External beam radiotherapy directed at the prostate
  • Brachytherapy
  • Hormone therapy
  • Surgery

 

A key complication of external beam radiotherapy is proctitis (inflammation in the rectum) caused by radiation affecting the rectum. Proctitis can cause pain, altered bowel habit, rectal bleeding and discharge. Prednisolone suppositories can help reduce inflammation.

Brachytherapy involves implanting radioactive metal “seeds” into the prostate. This delivers continuous, targeted radiotherapy to the prostate. The radiation can cause inflammation in nearby organs, such as the bladder (cystitis) or rectum (proctitis). Other side effects include erectile dysfunction, incontinence and increased risk of bladder or rectal cancer.

Hormone therapy aims to reduce the level of androgens (e.g., testosterone) that stimulate the cancer to grow. They are usually either used in combination with radiotherapy, or alone in advanced disease where cure is not possible. The options are:

  • Androgen-receptor blockers such as bicalutamide
  • GnRH agonists such as goserelin (Zoladex) or leuprorelin (Prostap)
  • Bilateral orchidectomy to remove the testicles (rarely used)

 

Side effects of hormone therapy include:

  • Hot flushes
  • Sexual dysfunction
  • Gynaecomastia
  • Fatigue 
  • Osteoporosis

 

Radical prostatectomy involves a surgical operation to remove the entire prostate. The aim is to cure prostate cancer confined to the prostate. Key complications are erectile dysfunction and urinary incontinence.

 

Last updated May 2021
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