QuestionSBA
QuestionChoice
This may be useful in investigating voiding dysfunction in patients with lower urinary tract symptoms that point towards chronic bladder outflow obstruction. However, it would not be useful in a patient which has a high clinical likelihood of prostate cancer
32232
e
Urodynamic studies
QuestionChoice
This would be most appropriate in patients with suspected prostate cancer after taking into account relevant risk factors including age, prostate specific antigen level, DRE findings and comorbidities. However, this method is invasive and may risk missing the cancer depending on the area biopsied
32229
b
Transrectal ultrasound biopsy
QuestionChoice
If there is a very high clinical suspicion of localised prostate cancer, clinicians should proceed directly to multiparametric MRI as a first-line investigation. This would reduce the risk of unnecessary prostate biopsies
32228
a
Magnetic resonance imaging (MRI) scan of the prostate
QuestionChoice
This would be useful in investigating causes of obstructive uropathy. However, as prostate cancer is the most likely cause in this scenario given the DRE findings, it is better to proceed with an MRI prostate first
32231
d
Ultrasound of the kidneys, ureters and bladder
QuestionChoice
This would be useful in watchful waiting for asymptomatic patients in whom hormonal therapy is being deferred or as a staging scan for bone metastases. However, it is not the most useful in making a diagnosis of prostate cancer
32230
c
Isotope bone scan
QuestionComment
Great Question!
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# Summary

Prostate cancer is a common malignancy affecting males, particularly in Western societies. It is characterised by abnormal growth of cells in the prostate gland and can be asymptomatic in early stages. Advanced disease may manifest as urinary issues, pelvic discomfort, bone pain, and erectile dysfunction. The primary investigations are digital rectal examination and a urine dip, with PSA (Prostate Specific Antigen) testing, which carries issues of sensitivity and specificity. MRI is a key tool for assessment, alongside a Gleason score for grading biopsy samples. Management ranges from active surveillance for low-grade disease to hormonal therapy and surgery for more advanced cases.

# Definition

Prostate cancer is a malignant tumour that arises from the cells of the prostate, a small walnut-sized gland that produces seminal fluid in men. This condition varies greatly in its presentation, with some cases growing slowly and requiring minimal treatment, while others are aggressive and can spread quickly.

The majority of prostate cancers are adenocarcinomas, and they usually primarily affect the peripheral prostate. They spread lymphatically first via the obturator nodes.


# Epidemiology

Prostate cancer is responsible for approximately 48,000 new diagnoses each year in the UK, accounting for 13% of all cancer cases. It is the second most prevalent cancer among men globally, preceded only by lung cancer.


# Aetiology

### Non-modifiable risk factors

- African ethnicity
- BRCA gene mutations
- Family history of prostate cancer
- Age (risk increases with advancing age)

### Modifiable risk factors

Research into modifiable risk factors is ongoing. Some potential factors are:

- Obesity
- Smoking
- Diet rich in animal fats and dairy products

# Signs and Symptoms

In its early stages, prostate cancer often produces no symptoms as it affects the peripheral prostate. However, as the disease progresses with local advancement (which can cause compression of the urethra), symptoms may include:

- Urinary symptoms, including difficulty initiating or stopping urination
- Poor urine stream
- Haematospermia (blood in semen)
- Pelvic discomfort
- Bone pain, potentially indicating metastatic disease
- Erectile dysfunction

# Differential Diagnosis

Several conditions can mimic the symptoms of prostate cancer and should be considered during evaluation:

- Benign Prostatic Hyperplasia (BPH): Characterised by difficulty in urination, increased frequency of urination, nocturia, and potentially, haematuria.
- Prostatitis: Acute or chronic inflammation of the prostate that can cause pelvic pain, urinary symptoms, and potentially, systemic symptoms such as fever and malaise.
- Urinary Tract Infection (UTI): Can cause dysuria, urinary frequency, urgency, and potentially, systemic signs of infection.
- Bladder cancer: May present with haematuria, dysuria, and urinary frequency.

# Investigations

* Initial examination should include a digital rectal examination and a urine dip.
	* An asymmetrical hard/craggy/nodular prostate with loss median sulcus is suspicious for malignancy.
* A PSA blood test may be considered, despite its lack of sensitivity and specificity. This necessitates patient counselling about the potential for over-investigation and over-treatment. Causes of a falsely raised PSA include:
	* An active urinary infection or within previous 6 weeks.
	* Ejaculation in previous 48 hours.
	* Vigorous exercise, for example cycling, in the previous 48 hours.
	* Urological intervention such as prostate biopsy in previous 6 weeks.

Interpretation of PSA results:

| Age (years) | Prostate-specific antigen threshold (micrograms/L) |
|-------------|--------------------------------------------------|
| Below 40    | Use clinical judgement                            |
| 40–49       | More than 2.5                                    |
| 50–59       | More than 3.5                                    |
| 60–69       | More than 4.5                                    |
| 70–79       | More than 6.5                                    |
| Above 79    | Use clinical judgement                            |


* **Multi-parametric MRI** is the gold standard radiological investigation, and can show specific areas which can be targetted for biopsy. If metastatic disease is suspected, additional imaging such as CT scans (can show e.g. sclerotic bony lesions) and bone isotope scans may be required.
* The Gleason grading system is used to assess prostate cancer severity on initial biopsy. It involves analysing the morphological features of prostatic tissue and assigning a score from 1 (normal tissue) to 5 (very poorly differentiated cells). The sum of the two most common scores represents the Gleason score, which has prognostic value.

### 2 week wait referral criteria

- Refer if their prostate feels malignant on DRE.
- Consider referring a person with possible symptoms of prostate cancer using a suspected cancer pathway referral (for an appointment within 2 weeks) if their PSA level is above the threshold for their age (see above)

# Classification

The TNM staging system for prostate cancer provides a standardised way to describe the extent of the disease based on three key parameters: tumour size and extent (T), involvement of regional lymph nodes (N), and the presence of distant metastasis (M).

- **T (Tumour):**
  - **T1:** The tumour is not palpable or visible by imaging.
    - T1a: Tumour found incidentally in less than 5% of tissue removed.
    - T1b: Tumour found incidentally in more than 5% of tissue removed.
    - T1c: Identified by needle biopsy due to elevated PSA (prostate-specific antigen) levels.
  - **T2:** The tumour is confined to the prostate.
    - T2a: Tumour involves half or less of one side of the prostate.
    - T2b: Tumour involves more than half of one side but not both sides.
    - T2c: Tumour involves both sides.
  - **T3:** The tumour extends beyond the prostate.
    - T3a: Tumour extends through the prostate capsule.
    - T3b: Tumor invades seminal vesicle(s).
  - **T4:** The tumour invades adjacent structures other than seminal vesicles (e.g., bladder, rectum).

- **N (Lymph Nodes):**
  - **N0:** No regional lymph node involvement.
  - **N1:** Regional lymph node involvement.

- **M (Metastasis):**
  - **M0:** No distant metastasis.
  - **M1:** Distant metastasis present.
    - M1a: Non-regional lymph nodes.
    - M1b: Bones.
    - M1c: Other sites or multiple sites.


# Management

Here is a summary table demonstrating management approaches according to TNM staging:

| TNM Stage                | Management Options                                     |
|--------------------------|--------------------------------------------------------|
| T1 (T1a, T1b, T1c)       |  Active surveillance (for low-risk cases)              |
|                          |  Watchful waiting                                      |
|                          |  Radical prostatectomy (for selected cases)           |
| T2 (T2a, T2b, T2c)       |  Radical prostatectomy (standard treatment)            |
|                          |  External beam radiation therapy                      |
|                          |  Brachytherapy (seed implantation)                    |
|                          |  Active surveillance (for low-risk cases)              |
| T3 (T3a, T3b)            |  Hormonal therapy (to delay progression)               |
|                          |  Radical prostatectomy (selected cases)               |
|                          |  External beam radiation therapy                      |
| T4                       |  Hormonal therapy (palliative, delays progression)    |
|                          |  Radiation therapy (palliative)                       |
|                          |  Symptomatic management                               |
| Not Fit for Radical Prostatectomy |  Hormonal therapy (palliative)                  |
| Metastatic (M1)          |  Hormonal therapy (androgen deprivation)              |
|                          |  Chemotherapy (docetaxel, cabazitaxel)                 |
|                          |  Targeted therapy (abiraterone, enzalutamide)         |
|                          |  Immunotherapy (sipuleucel-T)                         |


## Active Surveillance

This approach is suitable for patients with low-grade prostate cancer and involves repeating investigations periodically to monitor disease progression.

## Radiotherapy

Radiotherapy can be used either as a curative measure or for palliation to reduce tumour bulk and associated pain.

## Surgical Management

Surgical removal of the prostate and any affected organs is an option for patients without metastatic disease. Minimally invasive techniques such as robotically assisted laparoscopic prostatectomy (RALP) are becoming more common.

## Hormonal Management

Hormonal therapies aim to reduce testosterone levels, slowing the progression of metastatic prostate cancer. This can be achieved with GnRH analogues, androgen antagonists, or GnRH antagonists. 

Hormonal therapies may cause sexual side effects, including decreased libido, impotence, infertility, and gynecomastia. Metabolic side effects include weight gain, osteoporosis, diabetes, and ischemic heart disease. Haematological side effects include anaemia.

# NICE Guidelines

[Click here for the NICE Guidelines](https://www.nice.org.uk/guidance/ng131)
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Urology
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In cases of suspected prostate cancer, multiparametric MRI is the preferred initial investigation to minimise unnecessary biopsies.
A 85 year old male is admitted with acute urinary retention. Over the past year, he has been having urinary hesitancy and poor stream with nocturia up to 5-6 times a night. He had an objective 3kg loss of weight in the last year.

Digital rectal examination (DRE) reveals a hard, asymmetrically enlarged prostate. Prostate specific antigen is elevated at 15ng/mL.

Which of the following is the next most appropriate investigation?
a