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. 66.16)

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.