Carcinoma of the prostate
Carcinoma of the prostate is the commonest malignant tumour in men over the age of 65 years. In England and Wales in 1998 11 000 men were registered and 8000 died from it; the corresponding figures in the USA were 130 000 and 25 000, respectively. If histological section of prostates at autopsy is performed increasingly frequent foci of microscopic prostate cancers are found with increasing age. These foci of prostate cancer have variable potential for progressing clinically to metastatic disease. About 10—15 per cent of younger men who develop prostate cancer have a positive family history of the disease, but the aetiology is unclear. Throughout the world, rates of microscopic foci of prostate cancer are constant, but rates of clinically evident disease are low in men in Japan and China. Carcinoma of the prostate usually originates in the peripheral zone of the prostate (Fig. 66.2), so ‘prostatectomy’ for benign enlargement of the gland confers no protection from subsequent carcinoma.
Types of
prostate cancer
Latent
carcinoma of the prostate
Serial sections of prostates obtained at
routine necropsy demonstrate prostate carcinoma in 15—20 per cent of men
between 50 and 65 years of age. The incidence in men over 80 is in the region of
50 per cent (Franks). Most of these neoplasms are tiny and (if life had
continued) might have remained latent for years.
Types
of prostate cancer
•
Microscopic latent cancer found on autopsy or at cystoprostatectomy
•
Tumours found incidentally during TURP (ha and Tlb); or following
screening by PSA measurement — T1c
•
Early, localised prostate cancer (T2)
• Advanced local prostate cancer
(T3 and T4)
•
Metastatic disease which may arise from a clinically evident tumour (T2,
T3 or T4) or which may arise from an apparently benign gland (T0, T1), i.e.
occult prostate cancer
It
should be noted that only the last two groups cause symptoms and such tumours
are not curable. Only screening or the treatment of incidentally found tumours
can result in cure of the disease. The problem is that many such tumours would
never progress during the patient’s lifetime — herein lies the problem with
prostate cancer.
Histological
appearances
The prostate is a glandular structure
consisting of ducts and acini; therefore the histological pattern is one of an
adenocarcinoma. The prostatic glands are surrounded by a layer of
myoepithelial cells. The first change associated with carcinoma is the loss of
the basement membrane with glands appearing to be in confluence. As the cell
type becomes less differentiated more solid sheets of carcinoma cells are seen.
A classification of the histological pattern based on the degree of glandular de
differentiation and its relation to stroma has been devised by Gleason; this
(and the volume of the cancer) appears to correlate well with the likelihood of
spread and of prognosis.
Local spread
Locally advanced tumours tend to grow upwards
to involve the seminal vesicles, the bladder neck, trigone and, later, the
tumours tend to spread distally to involve the distal sphincter mechanism.
Further upward extension obstructs the lower end of one or both ureters, the
latter terminating in anuria. The rectum may become stenosed by tumour
infiltrating around it, but direct involvement is rare.
Spread by the
bloodstream
Spread by the bloodstream occurs particularly
to bone; indeed the prostate is the most common site of origin for skeletal
metastases, being followed in turn by the breast, the kidney, the bronchus and
the thyroid gland. The bones involved most frequently by carcinoma of the
prostate are the pelvic bones and the lower lumbar vertebrae. The femoral head,
rib cage and skull are other common sites.
Lymphatic
spread
Lymphatic spread may occur (1) via lymphatic
vessels passing to the obturator fossa or along the sides of the rectum to the
lymph nodes beside the internal iliac vein and in the hollow of the sacrum and
(2) via lymphatics which pass over the seminal vesicles and follow the vas
deferens for a short distance to drain into the external iliac lymph nodes. From
retroperitoneal lymph nodes, the mediastinal nodes and occasionally the
supraclavicular nodes may become implicated.
Staging using the tumour, node, metastasis (TNM)
system (Fig.
1.
T1a,
T1b and T1c:
these are incidentally found tumours in a clinically benign gland after
histological examination of a prostatectomy specimen. T1a is a well or
moderately well-differentiated tumour involving less than 5 per cent of the
resected specimen. T1b is a poorly differentiated tumour or a tumour involving
>5 per cent of the resected specimen. T1c tumours are impalpable tumours
found following PSA screening
2.
T2a disease presents as a
suspicious nodule (Fig. 66.17) on rectal examination of <2 cm
T2b disease
is a nodule involving greater than 2 cm
T2c is
tumour in both lobes but still clinically confined
3.
T3 is a tumour involving the seminal vesicles or bladder neck
4.
T4 is a tumour involving the
rectum or pelvic side wall
Clinical
features
Only advanced cases give rise to symptoms, but
even advanced cases may be asymptomatic. Symptoms of advanced disease include:
•
BOO;
• pelvic pain and haematuria;
• bone pain, malaise, ‘arthritis’, anaemia or pancytopaenia;
• renal failure;
• locally advanced disease or even asymptomatic metastases may be
found incidentally on investigation of other symptoms.
Early prostate cancer is asymptomatic and it
may be found:
• incidentally following TURP for clinically benign disease (T1);
• as a nodule (T2) on rectal examination.
Rectal
examination
Examination under anaesthesia together with
cystoscopy and needle biopsy (Fig. 66.18) or TRUS may be used to assess the
local stage. Irregular induration, characteristically stony hard in part or in
the whole of the gland — with obliteration of the median sulcus — suggests
carcinoma. Extension beyond the capsule up into the bladder base and vesicles (Fig.
66.19) is diagnostic, as is deformity and projection outwards of the
capsule (Fig. 66.20).
General blood
tests
These are normal in early disease, but in
metastatic disease there may be leucoerythroblastic anaemia secondary to
extensive marrow invasion or anaemia may be secondary to renal failure. There
may be thrombocytopenia and evidence of
disseminated intravascular coagulopathy with increased fibrinogen degradation
products (FDPs).
Liver function
tests
These will be abnormal if there is extensive
metastatic invasion of the liver. The alkaline phosphatase may be raised from
either hepatic involvement or secondaries in the bone. These can be
distinguished by measurement of isoenzymes or gamma-glutamyl transferase.
Prostate-specific
antigen
This is discussed earlier in this chapter. It
is good at following the course of advanced disease. It is lacking in
sensitivity and specificity in the diagnosis of early localised prostate cancer.
Nevertheless, the finding of a PSA >10 nmol/ml is suggestive of cancer and
>35 ng/mI is diagnostic of advanced prostate cancer. A decrease of PSA to the
normal range following hormonal ablation is a good prognostic sign.
Acid
phosphatase
Acid phosphatase has been superseded by
measurement of PSA.
Radiological
examination
X-ray of the chest may reveal metastases
either in the lung fields or the ribs. An abdominal X-ray may show the
characteristic sclerotic metastases in lumbar vertebrae and pelvic bones (Fig.
66.21). The bone appears dense and coarse and sometimes difficulty is found
distinguishing the change from that in Pager’s disease of bone. Osteolytic
metastases nevertheless are very common in prostate cancer and may coexist
with sclerotic ones. Information about the upper urinary tracts can be obtained
by excretion urography or ultrasound.
Ultrasonography
TRUS remains the most accurate method of
staging the local disease. It can be used in the early detection of tumours in
screening programmes. Local (T2) disease can be diagnosed with increased
sensitivity by TRUS (Fig. 66.17) compared with rectal examination, but
nevertheless many tumours will be missed. This problem remains a real one in
screening for early prostate cancer; in comparison with breast cancer where
mammography will detect 70—8 0 per cent of tumours, TRUS plus rectal
examination and measurement of PSA will detect only 30—50 per cent of cancers
that are known to be present on autopsy studies (although it may detect the
larger, more significant cancers).
Bone scan
Once the diagnosis has been established, it
would be normal to perform a bone scan as part of the staging procedure if the
PSA is >20 nmol/ml. If the PSA is <20 nmol/ml then a bone scan would only
be performed on clinical indications. The bone scan is performed by the
injection of technetium-99m, which is then monitored using a gamma camera. It is
more sensitive in the diagnosis of metastases (Fig.
66.22) than a skeletal
survey, but false positives occur in areas of arthritis, osteomyelitis or a
healing fracture.
Lymphangiography
This is no longer carried out. If accurate
information is required then pelvic lymphadenectomy can be performed by means of
laparoscopic surgery.
Bone marrow
aspiration
Sometimes examination of the bone marrow will
reveal the presence of metastatic carcinoma cells.