Treatment of carcinoma of the prostate
Natural history of prostate cancer
T1
and T2
The progression rate of well-differentiated ha
prostate cancer is very low, being about 10—14 per cent after 8 years
For moderately differentiated tumours the rate
is about 20 per cent, but for T1b tumours the rate is in excess of 35 per cent
Similar rates of progression (20—30 per
cent) are found for T2 disease
T3 and T4 (MO)
About 50 per cent progress to bony metastases
after 3—5 years
M1
The median survival of men with metastatic disease is about 3 years
Prostatic
biopsy
If there is suspicion of prostate cancer,
because of either local findings, a raised PSA or metastatic disease, then a
transrectal biopsy using an automated gun with appropriate antibiotic cover is
indicated. Several cores may be needed to make a diagnosis. The incidence of
sepsis from transrectal biopsy increases if more than three biopsies are taken.
If there are associated symptoms of BOO then either:
•
a TURP can be performed which will provide diagnostic material and
symptomatic relief;
•
transrectal biopsy can be carried out. If the diagnosis is positive and
there is locally advanced disease, then hormone ablation can provide good
symptomatic relief without the need for operation.
Early disease
Curative treatment can only be offered to
patients with early disease (T1a, Tlb, T1c and T2). The treatment of patients
with advanced disease (T3, T4 or any MO) is only palliative.
Radical
prostatectomy
Radical prostatectomy is only suitable for
localised disease (T1 and T2) and should only be carried out in men with a life
Pelvic lymph
node dissection
Pelvic lymph node dissection is carried out
immediately prior to radical prostatectomy when radical treatment is being
considered. In some centres this was combined with the open open implantation of
125j seeds, although with recent surgical modification of radical prostatectomy
this is now only rarely performed.
Radical
radiotherapy for early prostate cancer
Radical radiotherapy to the prostatic bed and
pelvic lymph nodes rather than radical surgery has tended to be the treatment
of choice in the UK for locally confined prostate cancer. The survival rates in
the treatment of T1 to T2 disease are not greatly different from radical
prostatectomy, although histological evidence of persistent tumour is found
within the prostate in about 30 per cent of treated patients. Patients with
locally advanced disease (T3) may be treated by radiotherapy, but most
urologists treat such patients by means of androgen ablation. The treatment
requires the patient to attend hospital on a daily basis for between 4 and 6
weeks. Some local complications are inevitable, namely irritation of the bladder
with urinary frequency, urgency and sometimes urge incontinence and similar
problems affecting the rectum with diarrhoea and, occasionally, late radiation
proctitis.
Advanced
disease
There is still debate about the timing of
androgen ablation treatment in patients with locally advanced or metastatic
disease
without symptoms. The options are androgen deprivation at diagnosis or careful
review, reserving active treatment for the later development of symptoms.
Patients with local or general symptoms should be offered androgen deprivation.
Orchidectomy
Orchidectomy is performed to carry out
androgen ablation in the treatment of locally advanced (T3 or T4) disease or of
metastatic disease. In 1941 prostate cancer was shown to be responsive to such
treatment by Charles Huggins — the only urologist to win the Nobel Prize.
Bilateral orchidectomy, whether total or subcapsular, will eliminate the major
source of testosterone production.
Hypophysectomy
and adrenalectomy
These treatments are no longer carried out. In
the past, patients who had initially responded to hormone treatment but
subsequently relapsed were thought to have a small chance of obtaining further
relief if a hypophysectomy was performed.
General
radiotherapy
General radiotherapy for symptomatic
metastases is an excellent form of palliative treatment often producing
dramatic pain relief in men with- hormone-relapsed prostate cancer. More
recently, hemibody irradiation has been shown to decrease symptoms in men with
widespread bony metastases.
Strontium
Strontium is now being employed as a
bone-seeking isotope which delivers effective radiotherapy to metastatic areas.
It appears to be as effective as hemibody irradiation in the treatment of men
with metastatic hormone-relapsed disease.
Medical forms
of androgen ablation
Medical forms of androgen ablation have been
available since the discovery of stilboestrol. Initially there was great enthusiasm
for this treatment and Honvan® (phosphorylated diethylstilboestrol) could be
given intravenously. Both treatments are effective in producing regression of
prostate cancer, but are associated with significantly increased thrombotic
complications and cardiovascular mortality. Even if stilboestrol is used at a
dose of 1 mg three times a day complications can occur. Other hormones that have
been tried include progestogens and Provera®.
The
other commonly available treatment to reduce testosterone levels to the
castrate range is LHRH agonists. These agents initially stimulate hypothalamic
LHRH receptots, but because of their constant presence (rather than the normal
diurnal rhythm) they then down-regulate them, resulting in cessation of
pituitary LH production and hence a decrease in testosterone production. In the
first 10 days or so serum testosterone levels may increase and it is wise to
give flutamide, bicalutamide (Casodex) or Cyproterone acetate for this period.
LHRH agonists may be given by monthly or 3 monthly depot injection.
Other
treatments have become available recently which block the androgen receptor.
Cyproterone acetate also has some progestogenic effect, whilst flutamide and
bicalutamide are pure antiandrogen. In general, oral monotherapy has not been
shown to be as good as LHRH agonists or orchidectomy.
Complete androgen blockade
Complete androgen blockade has been advocated
as being likely to result in increased life expectancy and an increased time to
progression in a fitter subgroup of men with advanced prostate cancer. The
concept is that of abolishing the testicular secretion of testosterone by means
of
Cytotoxic agents in the treatment of these elderly men have proved disappointing, but
whether this is because the tumour is inherently insensitive or because these
elderly men will not tolerate effective doses is uncertain.
Summary of
treatment
1.
Incidentally diagnosed T1a and
T1b
disease. For men in their 70s conservative treatment would usually be the
correct approach. Radical surgical treatment might be considered in the
younger (<65 years) man with this form of the disease, although even in this
group some men will elect to pursue a conservative course when counselled about
risks versus benefits.
2.
Localised T2 disease. In
younger fitter men (<65 years), this may be treated by radical prostatectomy
or radical radiotherapy. Watchful waiting remains an option — particularly
for more elderly patients. In the elderly patient with outflow obstruction
transurethral resection with or without hormone therapy is indicated. The
benefit of radical treatment over a conservative approach is likely to be at
most 25 per cent, given that progression to metastatic disease is in this order
of magnitude after 10 years.
3.
Locally advanced T3 and T4
disease.
These patients are at significant risk of disease progression. Early
androgen ablation is favoured if close follow-up is not possible. For the
sexually active a careful conservative approach with the adoption of androgen
ablation when symptoms arise is reasonable.
4.
Metastatic disease. Once
metastases have developed the outlook is poor. For patients with symptoms
there is no dilemma; androgen ablation will provide symptomatic relief in over
two-thirds of the patients. For patients with asymptomatic metastases the
timing of treatment is less clear.
There
are few hard and fast rules in the treatment of this cancer, but the surgeon
should avoid making the patients worse through creating more complications as a
result of treatment than the disease would have caused in its own right.