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Prostate Cancer

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Key points ⚡
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Prostate cancer\: most common male malignancy in the UK, with ~48,500 new cases annually, accounting for 25% of new
male cancer cases;
Anatomy\: prostate gland located between bladder neck and external urethral sphincter; four zones (peripheral,

hypogastric and pelvic nerves.
Risk factors\: age >50, Black ethnicity, family history of prostate or other heritable cancers (e.g., breast, colorectal), high
dietary fat intake.
Symptoms\: often asymptomatic; may present with lower urinary tract symptoms (LUTS) such as frequency, urgency,
nocturia, hesitancy, dysuria, post-void dribbling; haematuria, haematospermia, systemic symptoms (weight loss, weakness,
fatigue), bone pain (metastatic disease).
Examination
Investigations\: PSA test (age-speci
transperineal, TRUS-guided), imaging for metastases (DEXA bone scan, CT chest/abdomen/pelvis, PSMA PET scan).
Diagnosis\: based on PSA levels, DRE
system.
Management\:
Low risk\: watchful waiting, active surveillance.
Intermediate risk\: active surveillance, radical prostatectomy, external-beam radiotherapy (EBRT), brachytherapy.
High risk\: active surveillance, radical prostatectomy, EBRT, hormone therapy (GnRH therapy, androgen receptor
antagonists, androgen blockers, bilateral orchiectomy, oestrogen therapy).
Complications\: treatment-related (dysuria, urinary frequency, incontinence, rectal bleeding/proctitis, erectile dysfunction).
Prognosis\: highly curable, with a
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A comprehensive topic overview

Introduction

Prostate cancer causes signi
1
cancer cases diagnosed annually. This represents 25% of all new male cancer cases, making prostate cancer the most
common malignancy among men. 1
Despite its’ prevalence, patients with prostate cancer have a demonstrated
survival rate of 98%.
2

Anatomy

The prostate gland is a walnut-sized gland located between the bladder neck and the external urethral sphincter. The
prostatic urethra runs directly through the prostate, emerging as the membranous and penile urethra. There are four main
zones in the prostate gland- the peripheral zone (posteriorly), the
(centrally) and the transitional zone (surrounding the urethra) (Figure 1). The inferior portion of the prostate gland is termed
the apex. Close relations to the prostate gland include the pubic symphysis (anteriorly), the rectum (posteriorly), the
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external urethral sphincter (inferiorly) and levator ani (laterally)- these are important to consider in the context of cancer
3
metastases. The prostate gland is supplied by the inferior vesical (primary), middle rectal and internal pudendal
arteries. The prostatic plexus directs venous drainage to the internal iliac veins. Lymphatic
iliac and sacral lymph nodes. Finally, the prostate gland is innervated sympathetically by the hypogastric nerve and
parasympathetically via the pelvic nerve.
3
4
Figure 1.Anatomy of the prostate gland, including the central, peripheral,
(adenocarcinoma) is most commonly found in theperipheral zone.

Risk factors

Key risk factors for the development of prostate cancer include\:
5,6
Age >50
Black ethnicity
Family history of prostate cancer
Family history of other heritable cancers e.g. breast or colorectal cancer
High levels of dietary fat

Clinical features

History

Symptoms
The majority of prostate cancer cases are diagnosed when still in the asymptomatic stage, and are often picked up through
an elevated prostate-speci2
The most common presenting symptoms of prostate cancer include\:
Lower urinary tract symptoms (LUTS) including frequency, urgency, nocturia, hesitancy, dysuria and post-void dribbling.
Other symptoms can include\:
Haematuria
Haematospermia
Systemic symptoms\: weight loss, weakness, fatigue
Bone pain (associated with metastatic prostate cancer)
Other important areas to cover in the history include\:
Past medical history\: previous hospitalisations, surgical procedures and history of pelvic radiation.
Medication history
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Family history\: prostate cancer in a 5
and breast cancer (BRCA2 gene is
associated with prostate cancer).
Social history\: alcohol intake, smoking history (a

Clinical examination

In the context of suspected prostate cancer, a digital rectal examination (DRE) is necessary.
*
Typical clinical
Asymmetrical prostate
Nodular prostate
Indurated prostate
*DRE may only detect tumours that are present in the posterior and lateral aspects of the prostate gland as these are often
the only palpable regions; therefore DRE should always be accompanied by a PSA test (more below). 2
Conversely, there
will be patients with prostate cancer who have normal PSA levels and an abnormal DRE. It is, therefore, crucial that both are
performed in suspected cases.

Di

LUTS are common in older men, therefore it can be challenging to di
of the urinary tract. For the purposes of this article, we present di
distinguishing features (Table 1). 6,2
Table 1. Di
Di
Benign prostatic hyperplasia (BPH)
DRE reveals b e n i g n-f e e l i n g , e n l a r g e d
prostate, with no obvious nodules*
Biopsy would di
BPH and malignancy
Symptoms develop over 3 months to
Chronic prostatitis
1 year
Microscopy of prostate secretions
reveal leukocytes and in
PSA is normally only mildly elevated
Treatment with antibiotics can be
trialled if there is a high degree of
clinical suspicion
History of recent intervention can
*A trick for distinguishing between benign and malignant-feeling conditions\: soft,
on the lips, the tip of the nose, and the forehead, respectively.

Investigations

Patients with suspected prostate cancer should undergo a series of laboratory and imaging tests to investigate further.
6,2

Laboratory

Serum prostate-speci
Normal PSA levels are age-speci
years old with a PSA ≥3ng/ml and for men aged 70+ with a PSA >5ng/ml. 7
Note\: PSA can be raised by prostatitis, BPH or
UTI, leading to a higher baseline. Therefore, it may be important to repeat the PSA to con
U&Es
Cancer may be obstructing ureters, leading to hydronephrosis and kidney dysfunction.
FBC
Anaemia
Other laboratory tests
The following are lab tests to be performed speci
treatment option (more below)\:
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Testosterone levels
LFTs\: due to the risk of hepatitis with treatment

Imaging

Depending on PSA and lab results, multiparametric MRI may be warranted. MRI results are reported on a 5-
point Likert scale. Biopsy is recommended for patients with a score of 3+
.
* There are a variety of di
biopsies, including\:
8
Template transperineal biopsy, under general anaesthetic
Transperineal biopsy, under local anaesthetic
Transrectal ultrasound (TRUS)-guided needle biopsy
MRI-TRUS fusion-guided needle biopsy
TRUS cognitive-targeted
Prostate-speci
9
To investigate potential metastases, the following imaging may be indicated\:
DEXA bone scan- for bone metastases
CT chest, abdomen, pelvis for visceral metastases
PSMA PET scan is good for detecting metastases, in patients with low PSA levels
*Biopsy is important to ascertain the grade of prostate cancer. The Gleason grading system is a widely-adopted tool used
to classify the histological di10
The Gleason score is calculated
by adding the two most prevalent di
common). The International Society of Urologic Pathologists (ISUP) has translated the Gleason score into
graded correlates (Table 2). Table 2. ISUP grading system for prostate cancer, incorporating the Gleason score
10
Gleason score Tumour grade Clinical signi
≤6 1
Low-grade tumour,
sometimes “clinically
insigni
7 (3+4) 2
Intermediate-grade
tumour. More favourable
outcome than 4+3
7 (4+3) 3
Intermediate-grade
tumour. Less favourable
outcome than 3+4
8 4 High-grade tumour
In addition to tumour grade, it is valuable to stage prostate cancer using the TNM staging system.

Prostate cancer screening

Prostate cancer screening is controversial for several reasons. Those in favour of PSA
screening often cite research that denotes modest reductions in mortality; while critics argue that the relative indolent
nature of disease coupled with overdiagnosis and unnecessary investigations create harm for patients. 11
At present, there is
no formal screening program for prostate cancer in the UK. However, men >50 years old are eligible to request a PSA test,
following discussions with their GP about the pros and cons.
12

Management

The approach to managing prostate cancer is heavily dependent on the patient’s risk group, projected survival and
personal wishes. Patient’s may be strati
predicted based on G8 and Mini-COG instruments. 6
Depending on the risk group, a variety of management strategies may
be followed\: 13 Low risk
Low risk = PSA \<10ng/ml + Gleason score ≤6 + clinical stage T1-2a
Watchful waiting (non-intentional for curative treatment)
In a joint discussion between patient and provider, men may opt to undergo watchful waiting. This means that they will
undergo no treatment; however, will generally have regular DRE examinations and PSA tests. Should there be a signi
change in symptoms or PSA levels, palliative care may be initiated, depending on the patient’s wishes. Used if Gleason
score 2-4 at any age OR score 5-6 in the elderly/un
Active surveillance (intent for curative treatment, but delayed)
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In men who undergo active surveillance, regular DRE, PSA tests and often prostate biopsies (no more than annually), are
performed. Should there be a signi
surgery) may be initiated, depending on the patient’s wishes. OR Gleason score 7 OR T2b stage

Intermediate risk

Intermediate risk = PSA 10-20ng/ml
Active surveillance
For men with intermediate risk, or those who refuse active treatment.
Surgery
Radical prostatectomy\: total removal of the prostate through open, laparoscopic or robotic-assisted approaches. Used for
T1-T3 tumours in patients with a life expectancy of greater than 10 years.
Radiotherapy
External-beam radiotherapy (EBRT)\: beams of radiation are targeted to cancer cells in the prostate. Therapy is typically
given for 7-8 weeks. Used for T1-3 tumours. Brachytherapy\: an innovative form of radiotherapy for prostate cancer,
brachytherapy involves the permanent implantation of small balls of radioactive material into the prostate gland. Radiation
is constantly provided in order to shrink tumour cells. Used for localised T1-2 tumours with a Gleason score of 7, PSA
\<20ng/ml and life expectancy greater than 5 years. High risk
High risk = PSA >20ng/ml OR Gleason score 8-10 OR ≥ T2c
stage
Active surveillance
For men who refuse active treatment.
Surgery
Radical prostatectomy\: total removal of the prostate through open, laparoscopic or robotic-assisted approaches. Used for
T1-T3 tumours and in patients with a life expectancy of greater than 10 years.
Radiotherapy
External-beam radiotherapy (EBRT)\: beams of radiation are targeted to cancer cells in the prostate. Used for T1-3 tumours.
Parallel hormone therapy may be considered as an adjuvant to radiotherapy, or on its’ own for metastatic disease
Strategies include\:
Gonadotropin-releasing hormone (GnRH) therapy\: GnRH antagonists competitively bind GnRH receptors in the anterior
pituitary, resulting in a decrease in testosterone. GnRH agonists active GnRH receptors over a prolonged period of time,
leading to desensitization and decreased androgen secretion. Starving the prostate of androgens will result in shrinkage
of the gland and the associated malignancy.
Androgen receptor antagonists (e.g. bicalutamide,
receptors, leading to decreased androgen-driven malignant growth.
Androgen blockers targeting the adrenal glands\: androgens are also formed in the adrenal glands and can be blocked
from release using medications such as abiraterone and ketoconazole.
Bilateral orchiectomy\: removal of the testicles starves the prostate gland of testosterone.
Oestrogen therapy\: not frequently used anymore. Oestrogen therapy inhibits GnRH via negative feedback, decreasing
testosterone levels. Side e
Side e
altered lipids and more. These are important to discuss with patients, in consideration of androgen deprivation therapy for
prostate cancer.

Complications

Treatment complications of radical treatment for prostate cancer include\:
6
Dysuria
Urinary frequency
Urinary incontinence
Rectal bleeding/proctitis (mainly associated with radiotherapy)
Erectile dysfunction (may be caused by surgery or androgen deprivation therapy)

Prognosis

Prostate cancer is a highly curable cancer, with a 2
However, patients may incur signi
morbidity due to treatment regimens, including persistent dysuria, urinary frequency, erectile dysfunction, rectal bleeding
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and incontinence.

References

Cancer Research UK. Prostate c a n c e r s t a t i s t i c s . Published in 2017. [LINK]
Taplin, Mary-Ellen; Philip W Kanto[LINK]
Singh, Omesh; Bolla Rao S. A n a t o m y , A b d o m e n a n d P e l v i s , P r o s t a t e . Published in 2020. [LINK]
Haggstrom M. P r o s t a t e Z o n e s . Published in 2019. [LINK]
Sartor AO. R i s k f a c t o r s f o r p r o s t a t e c a n c e r . Published in 2020. [LINK]
Wallace, Timothy; Anscher M. P r o s t a t e c a n c e r . Published in 2020. [LINK]
P r o s t a t e c a n c e r r i s k m a n a g e m e n t p r o gr a m m e ( P C R M P ) \: b e n e [LINK]
Frydenberg M, Stricker PD, Kaye KW. P r o s t a t e c a n c e r d i a g n o s i s a n d m a n a ge m e n t . Published in 2019. [LINK]
Ho
C a n c e r . Published in 2018. [LINK]
Yang X. I n t e r p r e t a t i o n o f p r o s t a t e b i o p s y . Tikkinen KAO, Dahm P, Lytvyn L, e t a l . Published in 2019. [LINK]
P r o s t a t e c a n c e r s c r e e n i n g w i t h p r o s t a t e-s p e c i
g u i d e l i n e . Published in 2018. [LINK]
NHS. PSA t e s t i n g . [LINK]
Bhatt, Nikita; Manecksha, Rustom; Flynn R. U r o l o g y H a n d b o o k f o r M e d i c a l S t u d e n t s . Published in 2017. [LINK]

Reviewer

Nikita Bhatt
Urology SpR

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Contents

Introduction
Anatomy
Risk factors
Clinical features
Di
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Investigations
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