|
Etiology
Etiology of prostate cancer development is not completely known.
Factors that can influence the creation and development of this type of
cancer include:
genetic factors – increase in risk of falling ill among men with a
positive family history regarding the prostate cancer. Mutations of
suppressor genes are also taken into consideration (p53)
dietetic factors – food rich in saturated fatty acids probably
increases the risk of falling ill whereas the consumption of soya and
rice may have a beneficial protective effect racial and geographical
factors – Afro-Americans are 100% more likely to fall ill, whereas the
lowest death rate is reported in Japan and in China
occupational factors – cancerogenous influence of heavy metals and
toxins infectious factors – viral infection may lead to/ be the cause
of anaplasia of adenocyte cells of prostate
Histopathologically, 95% prostate cancer cases occur in the form of
adenocarcinoma. Other types (primary intracellular cancer, squamous
carcinoma, anaplastic carcinoma, and sarcoma) are rarely met.
Adenocarcinoma usually develops in the peripheral area of the prostate
(85%), in the transition area (25% ) and in the central area (5%).
Symptoms
In symptomatology of the prostate cancer, 4 clinical forms are distinguished:
1) visible form with distinct pathological symptoms 2) latent form
(carcinoma latens) with no distinct pathological symptoms found 3)
hidden form (ca occultum) which is detected in the case of distinct
ailments caused by the existence of remote metastases, however changes
in prostate are not found in the course of per rectum examination 4)
accidentally detected form - based on histopathological test of the
gland that was removed because of prostate overgrowth, or based on
biochemical tests (PSA) During the development of prostate cancer, an
induction phase that lasts about 30 years which is clinically invisible
can be distinguished. During the next stage - in situ phase (5-10
years) and invasive phase (1 year), ailments connected with the local
growth of tumour start to appear. During this period, symptoms
connected with sub bladder obstacle appear including mainly: -
pallakiuria - nycturia - weak urine stream - painful vesical tenesmus -
impression of incompletion of bladder emptying The above-mentioned
symptoms are typical of cancer and in some cases they may suggest mild
overgrowth of prostate, or neurogenic or athermatous bladder disorders.
During the dissemination phase (about 5 years), prostate cancer
develops continuously infiltrating surrounding organs, such as: urinary
bladder, rectum, ureters, pelvic walls and leading to urinary retention
in kidneys and to secondary failure of function. Ailments typical for
this period include: - haematuria - dysuria - urinary incontinence -
erection disorders - aches of perineum, lumbar area and anus -
haematospermia Metastases spread through the lymphatic vessels and the
vascular system. Symptoms caused by the existence of remote metastases
are as follows: - osteodynia and pathological fractures - pressure
symptoms and spinal paralysis - lymphadema of limbs - clotting
disorders - cachexy - coma
DIAGNOSTICS
In order to diagnose the prostate cancer, patient should undergo per
rectum tests (DRE), PSA concentration (prostate specific antigen) in
blood serum should be determined, ultrasonography per rectum
examination (TRUS - transrectal ultrasound) should be done and if there
is a suspicion of prostate cancer, histopathological test of the
material obtained through a per rectum thick-needle biopsy done under
the ultrasound control should take place. Histopathological test is the
only test that confirms the presence of cancerous cells in the prostate
gland area. DRE, which is an examination of sensitivity of 80%
sensitivity and of specificity of 60%, enables to seize changes in the
area of the prostate such as consistency change, palpable nodules and
hardenings. It is the base for sending a patient to a diagnostic
biopsy. At present, it is believed that cytological diagnosis achieved
through a fine-needle biopsy is not sufficient to make a right
diagnosis. It results from the fact that the assessment according to
Gleason’s classification is an important prognostic factor for the
prostate cancer (see: prognostic factors). That is why a thick-needle
biopsy is performed. Ultrasound use enables to take precise samples
from suspicious foci. If there are no changes in TRUS picture, "sextant
biopsy" is done (samples got for several places).
Recommendations for the biopsy of prostate gland: 1) palpable suspicion
of the prostate cancer 2) PSA value over 15ng/ml regardless of DRE or
TRUS tests 3) PSA value between 4 and 15 ng/ml with abnormalities
detected during DRE or TRUS tests 4) PSA value exceeds the norm for a
given age in the case of a positive family history regarding the
prostate cancer
Recommendations for TRUS: 1) PSA between 4 and 12 ng/ml with
abnormalities detected 2) questionable result of DRE test 3) necessity
of a thick-needle biopsy Other diagnostic tests, such as CT and
urography are not routinely performed because their value is
questionable as far as the assessment of local stage and invasion of
adjacent lymph nodes is concerned. Nowadays, magnetic resonance
tomography done using transrectal coli (endorectal coil MRI - ERMR) to
observe the prostate arouses great interest. Despite the increased
sensitivity of the degree of the local stage, costs of the test do not
allow for its routine use in the prostate cancer diagnosis.
Scintigraphy of the skeleton is the most sensitive test (97%) in bone
metastases detection. It is assumed that a patient with PSA under 10
ng/ml does not undergo scintigraphy because the probability of
metastases is low.
Screening:
Screening: It is recommended that patients aged over 50 should undergo per rectum tests and PSA level tests every year.
PROGNOSTIC FACTORS:
Three groups of prognostic factors can be distinguished in the case of the prostate cancer:
1) development stage according to TNM 2) differentiation degree of the
cancer based on the classification of Gleason and Mostofi 3) PSA level
(prostate-specific antigen) in serum TNM classification
Preoperative assessment of the stage of the prostate cancer is made based on the above-mentioned tests.
T-stage: primary tumour
Tx - primary tumour cannot be assessed T0 - no evidence of primary
tumour T1 - clinically unapparent tumour; not palpable or visible by
per rectum imaging T1a - incidental tumour found in histopathological
tests after transurethral resection of the prostate or after
operational adenectomy: found in 5% or less resected tissue T1b - as
above; found in more than 5% resected tissue T1c - tumour identified
histopathologically by a needle biopsy (because of high PSA) T2 -
tumour confined within the prostate gland T2a - tumour involves less
than half of one lobe T2b - tumour involves more than half of one lobe
only T2c - tumour involves both lobes T3 - tumour extends through the
prostatic capsule T3a - extracapsular extensions (unilateral) T3b -
extracapsular extensions (bilateral) T3c - tumour invades seminal
vesicles T4 - tumour is fixed, invades adjacent structures other than
seminal vesicles T4a - tumour invades bladder neck and/or external
sphincter and/or rectum T4b - tumour invades levator muscles and/or
pelvic wall N-stage: regional lymph nodes
Nx - regional lymph nodes cannot be assessed N0 - no regional lymph
node metastases N1 - metastasis to a single regional lymph node with
the diameter under 2cm N2 - metastasis to a single regional lymph node
with the diameter > 2cm but < 5cm N3 - metastases to regional
lymph nodes with the diameter over 5cm M-stage: remote metastases
Mx - remote metastasis cannot be assessed M0 - no remote metastases M1
- remote metastases M1a - non-regional lymph nodes M1b - bones M1c -
other sites According to Whitmor-Catalon classification, grades A, B,
C, and D correspond to T1, T2, T3 and T4 of TNM classification
respectively.
Degree of cancer differentiation:
Degree of differentiation is defined according to 2 classifications: by Mostofi and by Gleason.
Mostofi’s classification uses a 3-grade assessment of differentiation
dependent on the degree of cell anaplasia – grading (G1-G3). The higher
grade, the lower differentiation of cancer tissue, the greater atypy
and at the same time, malignancy. In the case of a 10-grade Gleason
system, the two extreme histological images in the preparation are
assessed and then, added to produce a final grade.
PSA is a proteolyctic enzyme responsible for sperm melting. It is
mainly produced by glandular epithelium, it might be also produced in
organs such as salivary glands, pancreas and mammary gland and by clear
cell carcinoma. Commonly used norm is the following: 0-4 ng/ml. Such
concentration of PSA is found among 97% of men over 40. The level over
12 ng/ml is always connected with pathology. Difficulties with
diagnosis are found among patients who have this level between 5-10
ng/ml because it may both stem from the prostate cancer or a mild
overgrowth of the prostate, which causes the necessity of diagnostic
methods use, such as TRUS. This test makes it possible to determine PSA
density (PSAD - PSA density) - PSA concentration converted to prostate
volume unit. It should be under 0.15 ng/ml/g. In the case of prostate
cancer differentiation and mild overgrowth of prostate, free to total
PSA (PSA F/T) is used. If it is over 20%, one may assume the presence
of cancerous cells in the gland. PSA level does not correlate well
enough with the natural development of the prostate cancer. However, it
is useful as a prognostic factor after the treatment applied and in
prognosis determination. However, high final levels indicate low
survival rate.
TREATMENT
Proceeding strategy in patients with the prostate cancer depends on the
degree of histological malignancy, the degree of local stage of
development, coexisting diseases and age of a patient. There are many
controversies as far as the choice of treatment is concerned. Radical
treatment is possible in T1, T2 and N0 and Mo stages. In advanced cases
(T3, T4, N-+, M-+), the procedure is restricted to delay the cancer
progression and mitigate its effects (palliative treatment).
Surgery treatment - radical prostatectomy
The surgery consists in the prostate gland removal together with
spermatic vesicles and adjacent tissues. Surgery is done through
retropubic, transcoccgeal, perineal approach or through laparoscopy.
Lymphadenectomy constitutes an integral part of the surgery. If the
approach makes it impossible to remove the gland and lymph nodes
(perineal approach) at the same time, a separate surgery is carried
out. It precedes the operation proper. It is believed that cancerous
cells found in the removed lymph nodes are the reason why prostatectomy
cannot be performed. Invasion of lymph nodes to a certain extent
suggests PSA level over 40ng/ml together with grade >7 in Gleason’s
scale.
Recommendations for surgery:
1) cancer limited to the prostate gland (T1BN0M0Gx - T2N0M0Gx,
T1AN0M0G3) 2) predictable life span over 10 years 3) consent of a
patient If positive chirurgical margins, capsule infiltration or
cancerous changes in the removed lymph nodes are found in postoperative
microscopic assessment, the prognosis is worse – such patients are
qualified for palliative treatment. The death rate in the postoperative
period does not exceed 5%. Intraoperative complications first of all
include: bleeding from Santorini’s plexus, damage of rectum wall,
underpinning of ureter. Early complications after surgery: thrombotic
and embolic complications (phlebothrombosis 3-12%, lung embolism 2-5%)
and lymphocele. Late postoperative complications after prostatectomy
include: urinary incontinence, erection disorders and narrowing of
urethro-vesicular junction).
Radiotherapy
Apart from radical prostatectomy, radiotherapy is an effective method
of treatment for patients with regional advanced prostate cancer. In
radical treatment, the most frequently done using radiation from
external sources, the dose of 50-70 Gy in fractions continuing over 5-7
weeks are given. T1ABC - T2ABCG1 and T1ABCG2 stages require radiation
limited to the prostate. In other cases, area that is radiated includes
adjacent lymph nodes as well. In recent years, multidimensional imaging
with CT (3D conformal radiotherapy) is used in the treatment planning.
Brachytherapy constitutes another method that is used.
Recommendations for radical radiotherapy of the prostate:
1) prostate cancer confined with the organ 2) sufficiently long
predictable survival span 3) no disorders in lower urinary tract 4) no
disorders in rectum and colon 5) consent of patient to carry out
treatment 6) early complications of radiation energy treatment (30% of
patients) include dysuria, haematuria, diarrhoea, rectal tenesmus,
inflammation of large intestine and rectum. Among later complications
(11% of patients) chronic diarrhea, ulceration of rectum, bladder neck
stenosis and intestinal fistula stenosis are observed.
Control of patients after radical prostatectomy and radical radiotherapy:
- per rectum test, PSA level in blood serum each 3 months. PSA level
should be lower than 1 ng/ml (after radical prostatectomy it should be
near to 0). Increase over 0.5 ng/ml within a year means failure of
radiotherapy. Hormonotherapy
Hormonal therapy is mainly used as palliative treatment in advanced
prostate cancer. It makes it possible to stop symptoms of the disease
for some time and then, further progression of the disease takes place.
Nowadays, the use of therapy in pulsation system is considered as it
delays the development of hormone-resistant cell clones.
Ways of hormonal treatment include: 1) surgery castration
(orchidectomy) 2) anti-androgens a) non-steroid b) steroid 3) analogues
LH-RH 4) oestrogens, progestogens, inhibitors of androgens synthetase
Hormonotherapy by analogues LH-RH is also recommended before planned
radical radiotherapy. In the case of hormone-resistant cancer,
treatment with combined cytoctatic and hormone (estramustine), however
without significant effects.
PROGNOSIS
Prognosis depends on the development stage, degree of differentiation and PSA level (see: prognostic factors).
In T1A, B stage prognosis is good. 10-years survival 35-80%, death rate
of the cancer 7-30%. In T2 stage, overall survival equals 34-85%, death
rate equals 8-26%. In T3 stage, among patients who undergo non-invasive
treatment for 9 years, overall death rate equalled 63%, from cancer –
30%. Depending on the degree of cancer differentiation, 10-year
survival of patients is the following: for cells well differentiated -
81%, for cells moderately differentiated - 58% and for cells poorly
differentiated - 26%. |