Prostate cancer

Prostate cancer

Prostate cancer
Most prostate cancers are adenocarcinomas arising in the peripheral zone of the prostate gland. The majority of prostate cancers are slow growing, but some prostate cancers are aggressive. When prostate cancer occurs in younger men it is often more aggressive. In the UK, cancer of the prostate is currently the second most common cause of cancer death in men (lung cancer is the most common).

Pathophysiology
The aetiology of prostate cancer is unknown, genetic and environmental factors are thought to play a role; the cancer is not thought to be related to benign prostatic hyperplasia. BRCA 1 and BRCA 2 genes are important risk factors for breast and ovarian cancers, and have been implicated in prostate cancer risk. They are linked to the aggressive form of prostate cancer; knowing this will have implications for treatment.
The risk of prostate cancer increases with age. Male hormones affect the growth of the prostate and prostate cancer seems to be related to life?long levels of testosterone; they are testosterone dependent until late in the course of the disease.

Signs and symptoms
The symptoms of growths in the prostate are similar, be they benign or malignant. Early stage prostate cancers can be asymptomatic. Lower urinary symptoms, for example urinary frequency, A hesitancy, nocturia and slow stream do not increase the risk of prostate cancer.

Local disease
Raised prostate specific antigen; weak stream; hesitancy; sensation of incomplete emptying; urinary frequency; urgency; urge incontinence; urinary tract infection.

Locally invasive disease
Haematuria; dysuria; incontinence; haematospermia; perineal and suprapubic pain; obstruction of ureters; loin pain; anuria; symptoms of renal failure; erectile dysfunction; rectal symptoms such as tenesmus

Metastatic disease
Bone pain or sciatica; paraplegia secondary to spinal cord compression; lymphadenopathy; loin pain or anuria due to ureteric obstruction by lymph nodes; lethargy (anaemia, uraemia); weight loss; cachexia.
Advanced disease: malaise; bone pain; anorexia; weight loss; obstructive nephropathy; paralysis due to cord compression; abdominal palpation may demonstrate a palpable bladder due to outflow obstruction.

Signs
Digital rectal examination (DRE) may reveal a hard, irregular gland. Indications of possible prostate cancer are: asymmetry of the gland, nodule within one lobe, induration of part or all of the prostate. lack of mobility – adhesion to surrounding tissue, palpable seminal vesicles.
Physical examination only cannot reliably differentiate benign prostatic disease from cancer. A biopsy is needed to establish a diagnosis; multiple biopsies may be needed before prostate cancer is detected. If cancer is suspected, determining whether the disease is localized or extends outside the capsule is essential for planning treatment. Locally advanced disease is often indicated by obliteration of the lateral sulcus or involvement of the seminal vesical. Findings in men with advanced disease can include: cancer cachexia, bony tenderness, lower?extremity lymphoedema or deep venous thrombosis, adenopathy, overdistended bladder. Neurological examination, including determination of external anal sphincter tone, helps detect possible spinal cord compression.

Investigations
Screening for prostate cancer is a contentious topic. DRE and PSA evaluation are the two components used in prostate cancer screening. Transrectal ultrasonography (TRUS) has been linked with a high false?positive rate, which makes it unsuitable as a screening tool. However, it has an established role in directing prostatic biopsies.
•a•? PSA assessment
•a•? Digital rectal examination
•a•? Rectal ultrasound
•a•? Needle biopsy
•a•? Template biopsy
•a•? Intravenous urogram
Other tests:
•a•? Bone scan
•a•? X?rays
•a•? MRI CT scans
•a•? Abdominal ultra sound

Management
Staging of the cancer determines how far the cancer has spread. The various investigations provide information about the stage and this helps decide on treatment options.

Low?risk localized prostate cancer
If the tumour is small and well differentiated, active monitoring or active surveillance monitors the cancer to see whether it begins to develop.

High?risk localized prostate cancer
This refers to cancer that has broken through to the prostatic capsule.
A number of approaches can be offered to the man but these depend on the stage of the disease (the TNM staging system is used), this includes the presence (or not) of metatastic spread as well as the man’s own choice. It is essential all options are offered to the man and an informed decision is reached. Treatment options may be used in isolation or a combined approach may be used.
Options will include:
•a•? Surgery: radical prostatectomy (robot assisted, retropubic,
A?perineal, laparoscopic)
•a•? Radiotherapy: external beam radiation therapy
•a•? Brachytherapy
•a•? Hormone therapy (androgen depravation therapy)
•a•? Cryotherapy
•a•? High frequency ultrasound therapy
•a•? Orchidectomy (androgen depravation therapy)
•a•? Chemotherapy
•a•? Palliative care
Testicular cancer
Approximately 50% of all cases occur in men under 35; testicular cancer rarely occurs before puberty. It is the most common cancer in men aged 15–44 years. The incidence of this cancer has increased over the years and the reasons for this are unknown.

Pathophysiology
The cause of testicular cancer is unknown. The majority of testicular tumours arise from the germ cells. Testicular germ cell tumours can be subdivided into seminoma and non?seminomatous germ cell tumours. Half of all germ cell tumours are non?seminomas and about 45% seminomas. The non?germ cell tumours include Leydig cell tumours, Sertoli cell tumours and sarcomas.
There are a number of risk factors associated with testicular cancer: cryptorchidism, Klinefelter’s syndrome, family history, infertility, low birth weight, young maternal and paternal age, multi?parity, breach delivery, infantile hernia, taller men and testicular microlithiasis on ultrasound. A genetic factor is that most testicular tumours display an abnormality on chromosome 12.
Possession of the testicular germ cell tumour 1 (TGCT1) gene on the man’s X chromosome gene may increase risk of testicular malignancy by up to 50 times. The risk for the disease is higher in first?degree relatives of men with testicular cancer than in the general population. Siblings are at particularly increased risk, as are sons of affected men.
Testicular cancers metastasize in particular fashion, to the retroperineal lymph nodes, with subsequent involvement of the mediastinal lymph nodes, lungs and liver.

Signs and symptoms
Until proven otherwise, any lump or firm area within the testicle should be considered a potential tumour.

Localized disease
The most common presenting symptom is a painless swelling or nodule of one testicle; a lump is palpable in nearly all cases. During physical examination this mass/nodule cannot be separated from the testes. Men with atrophic testes will feel enlargement. There may be a dull ache or heavy sensation in the lower abdomen, and men may complain of a dragging sensation. Men who experience a haematoma with trauma should undergo evaluation in order to rule out testicular cancer as it is probably the trauma that leads the man to examine himself and find the tumour as opposed to being the reason of malignant change.

Metastatic disease
In disseminated disease there are symptoms of lymphatic or haematogenous spread. There may be a neck mass in supraclavicular lymph node, metastatic disease, anorexia, nausea and other gastrointestinal symptoms. Bulky retroperitoneal disease may be felt as back pain. Cough, chest pain, haemoptysis and shortness of breath could be a presenting symptom of mediastinal adenopathy or lung metastasis. Gynaecomastia may occur in some men with testicular germ cell tumours that produce human chorionic gonadotropin (hCG), such as choriocarcinoma, and is a systemic manifestation. Marked overproduction of hCG can develop hyperthyroidism since hCG and thyroid stimulating hormone have a common alpha?subunit and a beta?subunit with considerable homology.
Men who present with a scrotal swelling should be examined carefully and attempts made to discriminate between lumps arising from the testes and other intrascrotal swellings. In order to make the distinction an ultrasound scan should be performed.

Investigations
Investigations will include an assay of tumour markers (see below), bilateral testicular ultrasound and chest X?ray.
Confirmation of diagnosis is usually by ultrasound. Histology can follow an inguinal orchidectomy (pathological diagnosis). Staging of the disease can be undertaken by thoraco?abdominal CT scanning.
Tumour markers are useful in staging and assessing response to treatment:
•â•¢ Alpah?fetoprotein (AFP) is produced by yolk sac elements but not produced by seminomas.
•â•¢ Beta?hCG is produced by trophoblastic elements, there may be elevated levels in teratomas and seminomas.
•â•¢ Lactate dehydrogenase (LDH) should also be measured, particularly in advanced tumours.
The Royal Marsden staging of testicular tumours is used to stage the cancer.

Management
Management will depend on the type of tumour and its stage and is based on national guidelines. Referral to a specialist centre for the management of testicular tumours is required. An inguinal orchidectomy should be performed where possible. All men should be offered testicular prosthesis and when appropriate arrangements should be made for sperm storage for those men who may require chemotherapy or radiotherapy. Where there are metastases and the diagnosis is not in doubt (for example there are high tumour markers and the presence of a testicular mass) referral for immediate chemotherapy should be made.
In most cases inguinal orchidectomy is required, with removal of the testes, the tunica and spermatic cord. Retroperineal lymph node dissection can be performed after orchidectomy in non-seminomas; this is done for staging and therapeutic purposes.
Surgery does have potential complications; there may be infertility and ejaculatory dysfunction. Men with seminoma may have radiotherapy to retroperitoneal lymph glands. Chemotherapy can help prevent non?seminoma (teratoma) returning after orchidectomy. It is used to treat any extra?testicular cancer and to treat testicular cancer returning after initial chemotherapy.
When there is para?aortic lymph gland involvement chemotherapy may be recommended