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Next Lesson - Male Urological Conditions
Core
The prostate is a walnut-sized gland found in the pelvis between the bladder and the penis in men. It is involved in secreting part of the spermatic fluid, and for more information on the functions of the prostate gland check out our article on the male reproductive system.
Benign prostatic hyperplasia and prostate cancer are the two main pathologies associated with the prostate and are seen in the majority of men by the time they are 80 years old. These two pathologies along with acute bacterial prostatitis will be discussed in this article.
Benign prostatic hyperplasia (BPH) is an increase in the size of the prostate gland without the presence of malignancy. It is characterised by non-cancerous hyperplasia of glandular epithelial and stromal tissue within the transitional zone of the prostate gland. The majority of elderly men will have some form of BPH by the age of 80 years (source). It is a histological diagnosis as it needs to be differentiated from prostate cancer, but is not routinely investigated for, meaning only symptoms prompt a diagnosis.
Androgens have a role in the development of BPH as, such as dihydrotestosterone and testosterone, which act on the prostate gland to cause hyperplasia. Dihydrotestosterone is produced from testosterone by 5-alpha-reductase and is a more potent androgen, so its production is targeted in the treatment of BPH via 5-alpha-reductase inhibitors, such as finasteride and dutasteride.
- Advancing age
- Family history
- Afro-Caribbean ethnicity
- Obesity
The symptoms that a patient with BPH will typically present with are lower urinary tract symptoms (LUTS), and some of these symptoms can be seen below. The International Prostate Symptom Score can also be used to help determine the severity of the patient’s symptoms.
- Urinary Frequency
- Nocturia – going to the toilet at night
- Urinary Urgency
- Hesitancy – patients will usually also complain of a poor stream and terminal dribbling. They may also complain of needing to push or strain to urinate
- Incomplete Bladder Emptying – patients will complain of still feeling like they need to urinate no matter how often they go
- Prostate Enlargement – the prostate needs to be felt on a digital rectal examination (DRE) to check size, symmetry, smoothness and sulcus. These can help to distinguish between BPH and prostate cancer as BPH will have a smooth and symmetrical texture, while prostate cancer will be hard and irregular
- Palpable Bladder – patients with BPH may have chronic urinary retention due to obstruction of the urethra by the prostate
When investigating benign prostatic hyperplasia, the main aim is to ensure that the cause of the symptoms is BPH and not a more serious pathology like prostatitis or prostate cancer. BPH is investigated using urinalysis, blood tests, urodynamics and imaging. It may also be investigated by a biopsy if there is any uncertainty about the cause.
Urinalysis by urine dipstick and mid-stream urine sample for culture. These tests are used to look for infection (e.g. urinary tract infection, acute bacterial prostatitis) and for haematuria.
Blood Tests – the main blood test that is performed is a prostate-specific antigen (PSA) blood test. This antigen is found in prostate cancer and is checked when investigating BPH as prostate cancer presents very similarly to BPH. Urea and electrolytes may also be checked as BPH can cause renal impairment if the patient develops urinary retention.
Urodynamic Tests – these tests assess how well the bladder and urethra are functioning. There are many different urodynamic tests but some of the urodynamic tests for BPH include:
- Flow Test – this looks at the speed of urine flow over time. A decreased flow test indicates that there is a blockage and can support the diagnosis of BPH
- Urinary Frequency and Volume Chart – these help to show us how frequently the patient is voiding and how much they are voiding each time, and this helps in deciding the management
Ultrasound Scan – a scan of the urinary tract is used to check the size of the prostate and assess other parts of the urinary tract for pathology. An enlarged prostate will be seen on an ultrasound scan.
Transrectal Ultrasound Biopsy of the Prostate – a biopsy of the prostate may be taken if there is suspicion of malignancy, and one method to access the prostate gland is through the rectum. If a patient has surgery for BPH, then the prostate tissue removed is usually sent off to pathology for histological analysis to check for malignancy.
There are three main parts to the treatment of benign prostatic hyperplasia; lifestyle changes, medication and surgery. The early treatment of BPH aims to reduce the symptoms and slow the growth of the prostate, with later stages of treatment aiming to reduce the size of the prostate through surgery.
An incidental finding of BPH with no clinical features or complications can be managed with reassurance and lifestyle changes. Symptomatic BPH is first treated with lifestyle changes and medication, but if there is severe obstruction of no symptom relief with medication and lifestyle changes then surgery may be indicated.
Lifestyle Changes
- Decrease caffeine, alcohol, carbonated and acidic drink consumption
- Limiting total fluid intake to less than 2.5L per day
- Bladder Retraining – retraining involves having a voiding schedule which they must follow, with the intervals between voiding increasing every week until intervals of 2-3 hours are reached. Over time, this can help reduce the urgency
- Double Voiding – this is where a patient voids more than once every time they go to the toilet. This helps to empty the bladder completely and can be used in patients who have incomplete bladder emptying
Medication
- Alpha Blockers – these cause relaxation of the smooth muscle within the prostate and bladder to allow urine to flow more easily, and relieve the symptoms of BPH
- The main alpha-blocker for BPH is Tamsulosin
- Side effects include dizziness, sexual dysfunction, diarrhoea, headaches, nausea and vomiting
- 5-Alpha Reductase Inhibitors – these help to shrink the prostate by causing androgen deprivation, though it takes time for the effects to be seen. They inhibit 5-alpha reductase to decrease the conversion of testosterone to dihydrotestosterone, which results in a decrease in the number of potent androgens
- Examples include Finasteride and Dutasteride
- Side effects include sexual dysfunction, breast abnormalities and skin reactions
Surgery
There are many surgical procedures that are used to treat benign prostatic hyperplasia and this article will include some of the main procedures used. Indications for surgery include failed lifestyle and medical management, and urinary retention requiring intervention.
- Transurethral Resection of the Prostate (TURP) – involves inserting a cystoscope into the urethra and then using an electrical current to remove prostatic tissue and increase the urethral lumen size to increase urine flow and relieve symptoms
- Holmium Laser Enucleation of the Prostate (HoLEP) – involves inserting a cystoscope into the urethra and then using a laser to remove prostatic tissue to increase the urethral lumen size
- Prostatectomy – this is the removal of prostatic tissue
- Simple prostatectomy involves removal of only part of the prostate. This is the main type of prostatectomy done for benign conditions
- Radical prostatectomy involves removal of the entire prostate along with the vas deferens and the seminal vesicles. This is usually reserved for prostate cancer and is not usually performed for BPH
Prostate cancer is the second most common cancer in men in the world with around 1 in 8 men developing prostate cancer during their life. (source)
Adenocarcinomas are the most common prostate cancer and there are two main forms of adenocarcinomas: acinar and ductal. Acinar adenocarcinomas originate in glandular cells that line the prostate gland and are the most common type. Ductal adenocarcinomas originate in the cells that line the ducts of the prostate gland and less common, but they do tend to grow and metastasise faster than acinar adenocarcinomas.
The growth of prostate cancer is influenced by androgens, and so these are targeted during the treatment of prostate cancer.
Prostate cancer differs from benign prostatic hyperplasia in two main aspects:
- First, prostate cancer is a malignancy while BPH is a non-cancerous growth of tissue
- Second, prostate cancer is more likely to affect the peripheral zone of the prostate and is close to the rectum, so the shape of it can be felt more clearly. BPH affects the transitional zone which is more central within the prostate so the shape can less clearly be felt
- Advancing age
- Family history and genetics – BRAC2 gene mutations are associated with an increased risk of prostate cancer
- Afro-Caribbean men have a 1 in 4 chance of developing prostate cancer in their life (source)
The signs and symptoms of prostate cancer are very similar to those of BPH, but a patient with prostate cancer will have an irregular prostate on DRE while those with BPH will have a smooth prostate. Patients may not present with any symptoms and instead present to primary care asking to have their prostate and PSA checked, which may lead to the diagnosis of prostate cancer.
- Lower Urinary Tract Symptoms – the main symptoms a patient will present with, and include nocturia, urgency, frequency, incomplete emptying, terminal dribble, hesitancy, straining and post-micturition dribble
- Enlarged and Irregular Prostate – found during a DRE for symptoms of prostate cancer or incidentally on DRE. The examination is also used to determine the clinical stage of prostate cancer, as the size of the prostate gives an indication as to how far the prostate cancer has spread locally
- Weight Loss
- Renal Failure – obstruction of the urethra by the enlarged prostate may result in urinary retention which can cause renal failure if left untreated. Although rare, renal failure may be how a patient with prostate cancer first presents
- Bone Pain – patients with metastatic prostate cancer may have bone metastases, so they present with bone pain. Bone metastases in prostate cancer are osteoblastic (sclerotic), which means they cause bone production rather than osteolytic like most other cancers. The main bones that prostate cancer spreads to are the pelvis, ribs, femur and spine, though it can spread to the skull and other bones
Image - Osteoblastic lesions of the vertebrae, most obviously in the L4 vertebral body (the bright white circle)
Creative commons source by Mikael Häggström [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Prostate Specific Antigen (PSA) – the serum PSA is an important blood test when investigating prostate cancer as it is used in the referral of patients to urology and in the staging of prostate cancer. It is a useful tumour marker but is not always specific for prostate cancer as it can be raised in other situations, and this is why it should not be used for routine screening as it can result in over-diagnosis and over-treatment where it is not needed.
- Situations where the PSA can be raised include infection, exercise, DRE, prostate inflammation and urinary retention
- As the serum PSA can become raised by other causes it may have to be measured after a few days to weeks to prevent a false positive reading. For example, a PSA should not be done within 48 hours of a DRE or within 6-8 weeks of a prostate biopsy
Transrectal Ultrasound Biopsy of the Prostate (TRUSP) – biopsy of the prostate is taken under ultrasound guidance, and is taken through the rectum. Usually, 12 biopsy samples are taken which are then used to determine the Gleason score for the patient.
Transperineal Biopsy – this is a biopsy of the prostate taken through the perineum. It is done under general anaesthetic and allows access to the anterior prostate. As with TRUSP, 12 biopsy samples are taken to determine the Gleason score.
MRI Scan – the first line imaging used to look at the size of the prostate and stage the disease locally. MRI scans can also be used to look for any distant metastases.
CT Abdo-Pelvis and Staging CT Scan – these scans are used to look for distant metastases.
Bone Scan (DEXA scan) – used to look for any bone metastases. A bone scan is indicated if a patient has bone pain or if they have a high serum PSA.
Patients are referred to urology under the two-week wait pathway for suspected cancer. The criteria for referral is either the finding of a malignant prostate on digital rectal examination (i.e. enlarged and irregular prostate) or a PSA level above the age-specific range for that patient’s age group.
The Gleason Score is used to grade prostate cancer. The score is from 6-10, with a high score indicating less differentiation and more abnormal cells. From the biopsies taken, the two largest areas of tumour are given a histological grade from 1-5, which are then added together to give the Gleason Score from 2-10, though for a patient to have prostate cancer they must have a Gleason Score of at least 6.
- For example, a patient may have a Gleason Score of 9 meaning one of the tumour areas is a grade 4 while the other area is a grade 5.
- The Gleason score is often written as a sum of two numbers rather than a single number – this is because a Gleason Score of 6+2 indicates a smaller area of more abnormal cells, whereas a Score of 4+4 indicates a larger area of less abnormal cells.
The management of prostate cancer is discussed in a multidisciplinary team meeting with treatment depending on the risk of prostate cancer, as low-risk prostate cancers may not need treatment of the tumour and may just require symptomatic treatment.
Prostate cancer is risk stratified depending on the PSA, Gleason score and T staging from the TNM score, with the risk indicating how severe the prostate cancer is. Intermediate and high-risk prostate cancers are actively treated while low-risk prostate cancer may just have symptomatic treatment.
Treatment is split into localised, locally advanced and metastatic treatment.
Patients with low-risk prostate cancer do not have treatment for their prostate cancer and instead have symptomatic treatment with either active surveillance or watchful waiting. These surveillance methods are used to check to see if a patient’s prostate cancer progresses and if they require further treatment.
- Active Surveillance – patients are monitored on a schedule to check for progression of prostate cancer. This can be with a PSA test, MRI scan, DRE or biopsy
- Watchful Waiting – patients are given symptomatic and conservative treatment until the patient develops local or systemic symptoms of prostate cancer. This is a symptom-guided approach to treatment with the aim of maintaining the patient’s quality of life
It is important to understand the difference between active surveillance (when the patient is brought back on a schedule for investigation without waiting for a change in symptoms) and watchful waiting (when the patient is investigated only when they have symptoms).
Localised Treatment – the main aim of treatment is to prevent morbidity and mortality from prostate cancer.
- Radical Prostatectomy – the surgical removal of the prostate, seminal vesicles and surrounding tissue. This might include removal of the pelvic lymph nodes if unsure about lymphatic involvement
- Radical prostatectomy can either be laparoscopic, open or robotic surgery
- Side effects of prostatectomy include erectile dysfunction and stress urinary incontinence
- External Beam Radiotherapy – radiotherapy beams targeted at the prostate cancer
- Brachytherapy – radioactive seeds are implanted transperineally into the prostate to destroy the prostate cancer with radiotherapy from within
- Cryotherapy – use of freezing cold gases to destroy cancer cells. Thin needles are put into the prostate and then cold gases are put into the prostate to kill the cancer cells
Locally Advanced Treatment – the main aim of treatment is to prevent or delay morbidity and mortality from prostate cancer.
- Radical Prostatectomy – with locally advanced treatment, radical prostatectomy is followed by adjuvant radiotherapy and adjuvant androgen deprivation therapy
- External Beam Radiotherapy – with locally advanced disease, radiotherapy is often given with neoadjuvant and adjuvant androgen deprivation therapy
Metastatic Treatment – the main aim of treatment is symptomatic relief and prolong survival as metastatic disease is incurable. The prostate is typically not removed or treated in metastatic prostate cancer unless it is causing severe symptoms.
- Castration – this helps to decrease the level of testosterone in the body and slow the growth of prostate cancer. Castration is either surgical or by hormones
- Hormonal castration uses either a LHRH agonist or a LHRH antagonist (anti-androgen)
- LHRH agonists work by causing continuous release of LHRH which initially increases testosterone before then inhibiting testosterone release due to constant stimulation. LHRH agonists are typically used in combination with an anti-androgen at first to inhibit the effects of the initial rise in testosterone caused by the LHRH agonist
- LHRH antagonists work by blocking the stimulation of testosterone production, leading to a decrease in testosterone production
- Chemotherapy – increases survival of patients with metastatic prostate cancer. It is also used if the prostate cancer has relapsed or is testosterone-resistant
- Radiotherapy – patients may undergo radiotherapy directed at the prostate to relieve urinary symptoms. It can also be targeted at metastases to relieve pain
- Bone Metastases Treatment – if a patient has bone metastases then radiotherapy can be given to help slow the growth of the metastases. Bisphosphonates (drugs used to strengthen bone) can also be given to prevent fractures
Prostatitis is inflammation of the prostate gland. There are different types of prostatitis which include acute bacterial prostatitis, chronic bacterial prostatitis, non-bacterial prostatitis and prostatodynia (a condition with symptoms of prostatitis with no visible inflammation). The main cause of prostatitis is acute bacterial prostatitis and so this is what this article will cover.
Acute bacterial prostatitis is an uncommon condition that occurs mainly in younger (18-35yrs) and older men (>65yrs). The main cause is Escherichia coli but other causes include Proteus, Klebsiella, Enterobacter, Serratia and Pseudomonas. Some sexually transmitted infections (STIs) can cause prostatitis, though this is less common than the other causes. Acute bacterial prostatitis can become chronic if the infection is not treated.
- Phimosis – difficulty retracting the foreskin
- Intraprostatic ductal reflux – the flow of semen the wrong way through the ducts in the prostate
- Unprotected sex
- Urinary tract infection
- Indwelling catheter
- Transurethral biopsy or surgery – transurethral procedures involve using the urethra to access the bladder, prostate or kidneys
- Prostate biopsy
- Immune deficiency
- Lower urinary tract symptoms – dysuria, urgency, frequency, incomplete emptying, terminal dribble, hesitancy, straining and post-micturition dribble.
- Fever
- Malaise
- Perineal or suprapubic pain
- Urethral discharge
- Tender and enlarged prostate
- Inguinal lymphadenopathy
The first investigations that should be undertaken are a midstream urinalysis and a urine culture. The urinalysis is used to look for white blood cells in the urine while the urine culture is used to determine the bacteria and its antibiotic sensitivities. These are the two main investigations and are used together with the history to confirm the diagnosis.
Other investigations may be used in the diagnosis of acute bacterial prostatitis and to look for complications. Blood tests can be used to look for infection and check kidney function, while an STI screen may be helpful in finding the causative organism. A transrectal prostatic ultrasound scan or a CT scan may be used to assess for a prostatic abscess, and these are especially indicated in immunocompromised patients.
The main treatment for patients with acute bacterial prostatitis is a prolonged course of antibiotics, usually 14 days. Quinolones are the main antibiotics used, e.g. ciprofloxacin and levofloxacin. The patient should also be advised to increase fluid intake and take analgesia as necessary.
If acute bacterial prostatitis persists and becomes chronic then the patient needs to be referred to urology for further investigations and treatment. Patients can also be referred to urology if there is suspicion of an underlying urological condition or if they have a pre-existing urological condition.
Chronic bacterial prostatitis can be treated with a longer course of antibiotics and may be given an alpha blocker to treat LUTS if they are severe.
Edited by: Dr. Maddie Swannack
Uploaded by: Dr. Thomas Burnell
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