Prostate is a nut sized gland located under the urinary bladder, in front of the rectum.
The prostate gland is a secondary sex organ. It creates approximately 1/3 of the ejaculate which comes out during the ejaculation. Some enzymes includes both protect men against infections and arranges some conditions for them to have a child. Cells within all body tissues renew themselves within a certain control mechanism. Thus, the damages tissue is repaired and renewed. Cells which proliferate beyond control creates cell groups called tumor.
Prostate cancer is the most common cancer type seen in men.
It is a cancer type which causes death at the 2nd rank after lung cancers. It is very rare under 50 years. It is generally seen after 70 years and frequency increases by age. It may spread to adjacent tissues after development in the prostate. It spreads into the regional lymphatic organs via lymph vessels. Another spreading pathway is via the blood. Cancerous cells spread into the lung, liver and bones by this path.
WHO ARE UNDER RISK?
If a man lives long enough, for example up to 100 years, prostate cancer develops in almost all men. Risk for development of prostate cancer increases by the age. 85% of prostate cancer cases are detected in men over 65 years. However, prostate cancer may develop in some men within earlier years.
CAUSES FOR PROSTATE CANCER:
Cause for prostate cancer has not been known yet. Main factors blamed are as follows:
- Family history
- African race is more predisposed than the white race.
- Testosterone (masculine hormone): Prostate cancer (ca) is not seen in men who have been castrated before puberty.
- Prostate ca is not detected in patients with chronic pulmonary diseases where estrogen hormone (femininity hormone) increases relatively.
- Some environmental factors such as consumption of fatty foods
- Two essential factors for prostate cancer are AGING and TESTOSTERONE.
SYMPTOMS OF THE PROSTATE CANCER:
Unfortunately, IT MAY NOT PRESENT ANY SYMPTOMS UNTIL LATE PERIODS in many patients. It may not cause any complaints. Therefore, it is very important for you and other men over 50 years within the family to refer to a physician for this disease and to have a regular “check-up” on following years. Symptoms appear after urinary tract obstruction. When any of the following complaints appear, a doctor must be consulted.
- Frequent urination (especially at nights)
- Difficult urination
- Thin and intermittent urination
- Pain or ache during urination
- Presence of blood within the urine
- Back, hip and waist pain
- Presence of blood or inflammation within the urine
- Presence of blood or pain in the ejaculate.
DIAGNOSIS FOR PROSTATE CANCER:
AS IT PROVIDES SYMPTOMS LATE, SCREENING OR CHECK-UPS HAVE A GREAT IMPORTANCE. There are many common stages that should be done either on check-up or on suspicious conditions. On Routine Controls:
- Story is listened
- PSA test is performed
- COMPLETE ABDOMINAL ULTRASONOGRAPHY is performed for general purposes
- Prostate examination is done with TR if necessary
* if we expand the control for both BPH and Prostate Ca, in addition to the above
- A special micturation test called uroflowmetry may be done.
DIGITAL RECTAL EXAMINATION (TOUCHÉ RECTAL):
It means examination of the prostate from the anus by fingers and it is probably one of the rare ageless examination methods in urology. Although fallibility is high, it is essential for the examination. In terms of differentiation of diagnosis that may be confused with cancer (BPH- prostatitis-prostate stones-prostate infarcts- tuberculosis (tbc) of the prostate and hardness (indurations) occurred after the biopsy; factors such as size, consistency, mobility, temperature, existence of pain or not should be considered.
A differentiation is tried to be done between BPH and the prostate cancer via a blood test called PSA (Prostate Specific Antigen). This test is diagnostic and provides information about progression of the treatment for the prostate cancer as well. PSA is a protein produced by prostate gland cells and provides liquidation of the ejaculate.
On normal conditions, total PSA should be below 4 ng/ml. Even some scientists reduce this value to 2.5.
PSA is not specific for prostate cancer. PSA may also increase in other pathologies. However, higher blood PSA level, higher possibility to have prostate cancer.
Although PSA elevation is a valuable diagnosis method, it may be insufficient solely for diagnosis of cancer and it should be coordinated with other diagnosis methods.
Benign pathological conditions that increase PSA or are claimed to modify PSA:
1. DRE (Digital rectal Examination): There is no significant increase- it definitely reduces to normal on 24 hours after TR in any case.
2. Cystoscopy: There is not any significant increase if there is not any traumatic procedure- however, to test 1 week after or before the procedure is useful.
3. Prostatic infarcts and acute retention
4. Urethral catheter placement
5. Acute bacterial prostatitis
6. Biopsy of the prostate: It should be tested 6 weeks after at the earliest.
7. Transurethral prostate resection: TURP : 6 weeks after at the earliest.
8. Drugs: Proscar (Finasteride = 5-alpha reductase inhibitor) which is used in medical treatment of BPH reduces PSA into half after 6 months.
9. PIN : High grade PIN does not increase PSA by itself, but high PSA is detected as it is together with Prostate ca.
11. Exercise- physical activity- stress- increased sexual intercourse- ejaculation/masturbation: Do not effect PSA.
As we have specified above, PSA is not specific for prostate cancer, therefore;
Different parameters have been searched to differentiate BPH/Prostate Ca efficiently and estimably.
1. PSAD: PSA density: If Serum PSA / prostate volume detected by TRUS is <0.15, it is benign
Here, the PSA value has been divided into the prostate volume detected in transrectal ultrasonography and when the obtained value is above 0.15; it has been accepted as high possibility to be benign.
2. PSA Velocity: Velocity: Annual PSA increase should be <0.75 ng/ml/year in PSA tests taken three times in every 6 months.
Here, annual PSA increases have been controlled in suspicious patients and it has been accepted that annual increase should never be above 0.8 for total PSA.
3. Age induced PSA: Here, most PSA levels according to the age groups of the patients have been detected.
40-49 years : 0 – 2.5 ;
50-59 years : 0 – 3.5 ;
60-69 years : 0 – 4.5 ;
70 years and over : 0 – 6.5 ng / ml
4. Free / Total PSA: <0.25. This test should be applied to individuals within the gray zone where PSA level is between 4 and 10 ng/ml and if this ratio is more than 0.25, biopsy is not necessary as possibility of being benign is high; otherwise; if Free/total PSA <0.25 and PSA is between 4 and 10 ng/ml, BIOPSY (via TRUS) should be performed!!!
* PSA has an assisting role in staging of Prostate Ca and status evaluation after the treatment.
If PSA <4 mg, there is a possibility that cancer is limited by the organ with 80%. However; if PSA > 10, it is limited by the organ with 50%; if PSA > 50, there is lymph metastasis susbtantially. But, it shouldn’t be forgotten that, lymph metastasis may be present with 15% when PSA is normal.
When PSA <10, bone metastasis is almost none. (% 0.5) [ no need for bone scintigraphy ]
After radical prostatectomy, PSA should reduce to an immeasurable level (=0.1) within 3 weeks!!!
If this does not happen, there is a residual tissue or metastasis !!!
PSA after radiotherapy: Should reduce about 1 ng/ml within 1 year !!!
After Androgen Deprivation (hormonal therapy): It should reduced into normal limits within 6 months !!!
The elevation in PSA during or after any treatment reflects 6 to 12 months before a clinical or radiological relapse.
It is an important test to show the prostate cancer and to understand the grade. Ultrasonography may be performed from the abdomen as well as from anus as shown in the illustration; and “trans- rectal ultrasonography (TRUS)” shows the prostate cancer and invasion of the cancer beyond the prostate. TRUS is also used to take biopsy by seeing. It is possible to take different pieces (from 8-12 quadrant) under control from the cancerous area via automated needles inserted from the ultrasound probe. When it is been suspicious from prostate cancer, a piece is taken from the prostate by a needle and examined by pathology department.
Computed Tomography and MRI:
They are used to show the prostate cancer and understand the diffusion grade into lymph glands in particular like the ultrasonography. It is recommended to apply on patients who have a PSA level >20 ng/ml.
Traditional radiographs and medication induces radiographs: They are taken to understand whether the cancer spreads into the bones or lungs.
Bone Scintigraphy: It is a very useful test used to understand whether the cancer has spread into bones. It is recommended to apply on patients who have a PSA level >10 ng/ml.
FREQUENTLY ASKED QUESTIONS ABOUT PROSTATE CANCER
Is early diagnosis possible ?
Every man should be examined by an UROLOGIST starting from 50 years and blood PSA level should be tested. By this means, the prostate cancer within an early stage which has not caused any complaint on the patient may be detected. If the physician meets any suspicious finding in the examination or PSA level is higher than expected or over 4 ng/ml kabaca, further tests are ordered.
On patients who have applied with abovementioned complaints, PSA levels are examined first and in examination of patients by fingers, namely “touché rectal = digital rectal examination”, the prostate gland in front of the rectum is sensed and information is obtained about its size and consistency. Furthermore, an opinion about the prostate may be obtained by an ultrasonographic test (transractal ultrasonography- TRUS).
If the physician finds the examination and tests ordered suspicious, she/he may take a part from the prostate “TRUS BIOPSY” by a needle and request it to be examined under the microscope. This procedure is called “tru-cut prostate biopsy”. It does not require anesthesia.
Prostate infection may develop in 1 of every 200 patients after the biopsy as a side effect of TRUS Biopsy procedure. These patients may complain about high fever and twinging during urination, bloody urination. To minimize this possibility, prophylactic antibiotherapy is started for the patients before TRUS Biopsy. Blood within the urine or stool may continue for 2 to 3 days after the procedure. The ejaculate may be bloody “hemospermia” within 2 to 3 weeks after the procedure.
If the biopsy is negative, these patients are followed by medical examinations every 6 to 12 months and by PSA test.
Another diagnosis that should be considered in biopsy is PIN (PROSTATIC INTRAEPITHELIAL NEOPLASIA). There are low and high grade PINs. PIN with low grade is accepted as benign and ignored and it is even recommended not to be mentioned in the pathologist’s report. PIN with high grade is very important and presents an accompaniment with cancer focuses. For this, these patients should be followed with close intervals and more frequent biopsy should be done.
If prostate cancer is diagnosed in the biopsy;
What is the Gleason Score?
After cancer is diagnosed in the biopsy, biopsy samples are subjected to a grading which provides information about reproduction and spreading rate by observing the appearance, size of the nucleus within cancerous cells and shape and is determined as GLEASON SCORE.
Gleason Score ranges between 2 and 10. While “2” defines cancer cells which have a slow progression potential, “10” means the tumor which has a capacity to reproduce and multiply very fast.
Gleason’s Score 2-4: Well differentiated cancer cells
Gleason’s Score 5-6: Intermediately differentiated cancer cells
Gleason’s Score 7-10: Bad differentiated cancer cells
Low “Gleason’s Score” reflects slower and better prognosis.
|Tx||cannot evaluate the primary tumor|
|T0||no evidence of tumor|
|T1||tumor present, but not detectable clinically or with imaging|
|T1a||tumor was incidentally found in less than 5% of prostate tissue resected (for other reasons)|
|T1b||tumor was incidentally found in greater than 5% of prostate tissue resected|
|T1c||tumor was found in a needle biopsy performed due to an elevated serum PSA|
|T2||the tumor can be felt (palpated) on examination, but has not spread outside the prostate|
|T2a||the tumor is in half or less than half of one of the prostate gland’s two lobes|
|T2b||the tumor is in more than half of one lobe, but not both|
|T2c||the tumor is in both lobes|
|T3||the tumor has spread through the prostatic capsule (if it is only part-way through, it is still T2)|
|T3a||the tumor has spread through the capsule on one or both sides|
|T3b||the tumor has invaded one or both seminal vesicles|
|T4||the tumor has invaded other nearby structures|
|Nx||cannot evaluate the regional lymph nodes|
|N0||there has been no spread to the regional lymph nodes|
|N1||there has been spread to the regional lymph nodes|
|Mx||cannot evaluate distant metastasis|
|M0||there is no distant metastasis|
|M1||there is distant metastasis|
|M1a||the cancer has spread to lymph nodes beyond the regional ones|
|M1b||the cancer has spread to bone|
|M1c||the cancer has spread to other sites|
When we simplify T1-T4 staging which has been used most:
- The cancer is limited within the prostate gland in T1-T2.
- The tumor is metastatic to adjacent tissues in T3.
- Distant organ metastasis is present in T4.
In another system which is old, however has still been used:
- Cancer is limited within the prostate gland in Stage A and B.
- The tumor metastatic to adjacent tissues in Stage C.
- Radical prostatectomy: Retropubic – perineal laparoscopic
- Radiotherapy: External – brachytherapy
- HIFU (High intensity focused ultrasound)
- Hormonal therapy: Surgical castration – medical castration
The most important criteria to determined the treatment options are;
General status of the patient, PSA elevation, cell characteristics in the biopsy (Gleason’s score) and Cancer Stage. The urologist, medical oncologist and radiation oncologist should treat the patient with a team approach and determined the treatment plan by considering many factors.
In Localized Prostate Cancer: T1 – T2: EARLY PERIOD TREATMENT
Primary purpose in early stages is to remove the cancer from the body completely or eliminate the cancerous cells.
– Waiting – Radiotherapy (RT) (10 years survey = Radical surgery 80%)
– RADICAL SURGERY (15 years survey is significant)
* If the survey is less than 10 years in low Grade (Gleason’s score 1-4) prostate Cancers which are – limited within the organ-localized;
PSA monitoring and appropriate treatment according to the progression
** If the Grade is intermediate (Gleason’s score 4-7), watchful waiting – RT- Radical surgery are suitable.
*** If the Grade is high (Gleason’s Score 7-10), Radical Surgery is suitable.
Treatment for the Prostate Cancer Which Presents Local Diffusion (T3):
Wait and see; External RT; Brachytherapy; Radical Surgery;
They are treatment alternatives which may be applied solely or with hormonal therapy in addition!
The Purpose is: To control the progression of the diseases and to prevent disruption of the life quality.
Treatment For Prostate Cancer Metastatic To Lymph Nodules (T4):
10 years survival is about 30%.
Radical Surgery + Late Hormonal Therapy; Early hormonal therapy (androgen ablation); Late endocrine therapy; RT; Radical Surgery + Simultaneous Hormonal Therapy; RT + Hormone; Radical Surgery + Adjuvant CT (after the surgery) may be tried.
If the cancer has reached to advanced stages; it means that cancerous cells have proliferated so much as not to be cleaned or eliminated. In this case, treatment options which aim to slow down or stop cancer growing become prominent.
Prostate cancer actually grows up by effect of masculine hormones such as testosterone. 95% of the testosterone within blood circulation is secreted from testicles and 5% is secreted from adrenals (suprarenal glands). However, 3% of the testosterone is free and diffused into the prostate cells. This testosterone diffuses transforms into di-hydrotestosteron (DHT) by 5-alpha reductase enzyme and this DHT is joined into androgen receptors within the nucleus and enters into the nucleus, activates m RNA and protein synthesis and cellular development are provided. When interaction of the testosterone with the prostate cell is prevented, cancer development is suppressed. Treatment of the advanced prostate cancer may be possible to prevent nutrition of cancerous cells by masculine hormones.
When this hormone based purpose is achieved by drugs, it is called MEDICAL CASTRATION (Estrogen treatment; administration of LHRH agonists; Antiandrogens); and when this is tried to be achieved by removal of testicles surgically, it is called SURGICAL CASTRATION (bilateral orchiectomy).
Surgical castration = BILATERAL ORCHIECTOMY: It is the simplest and cheapest method. It causes impotence – hot flush – libido loss.
Estrogen Treatment: It causes reduction in LHRH and thereby Testosterone production by a negative feedback mechanism. It is not used today as it has caused myocardial infarct.
LHRG anologs = medical castration: By administrating the drugs such as leuprorelin- buserelin – triptorelin etc. with monthly or quarterly depot doses from the abdominal skin, a picture equivalent to surgical castration may be obtained. It is quite expensive because it should be applied lifetime.
Testosterone will increase during 15 days in LHRH use. Therefore, use this agents with antiandrogens during this period is appropriate as it will cause spontaneous fractures called flare effect in metastatic patients. It presents the same effect with estrogen, however side effects to cardiovascular system (CVS) is less. Hot flush is more than orchiectomy, Clonidin or cyproteron which are alpha agonists may be given for this reason.
ANTIANDROGENS: They have steroidal and nonsteroidal types.
Steroidal Antiandrogens: CPA : Ciproteron asetat, Megestrol acetate, Medroxyprogesterone acetate They have both antiandrogenic (preventing the mechanism of action of the androgens by binding the androgen receptors on the cell wall of the prostate) and progestational effect (preventing LH secretion).
Pure Antiandrogen: Nonsteroidal Antiandrogen: Flutamide; Bicalutamide; Nilutamide.
LH level is normal and serum testosterone level is normal or higher. Potency and libido continue.
Complete Hormonal Treatment:
Both surgical castration (orchiectomy) and medical castration (LHRH anologs) remove the effect of testicle originated testosterone. However, they do not impede all testosterone effect within the body. Suprarenal glands also synthesis a hormone which present testosterone effect even minimally. Therefore, additional drugs should be used to remove effects of these hormones. These drugs are called “antiandrogens”. Flutamide –Biculamide – Ciproteron Acetate are within this group. These drugs prevent the testosterone within the blood circulation to reach to prostate cells.
Combining medical or surgical castration with antiandrogen drugs is called complete hormonal therapy. Complete hormonal therapy removes the effect of masculinity hormone within the body completely and slows down the tumor growth.
TREATMENT FOR PROSTATE CANCER REFRACTORY TO HORMONE THERAPY:
All patients become refractory to the hormone after about 1,5 years, namely, PSA levels start to increase. In this case, a SECONDARY hormone therapy or CHEMOTHERAPY should be applied. 50% of patients under total androgen blockage have a mutation on androgen receptors and PSA increases. This case causes discontinuation of the antiandrogen agent and sometimes recovery. This is called antiandrogen withdrawal syndrome. If there is no response, corticosteroids may be tried. Ketaconazole both demolishes the androgen production and has a cytotoxic effect. Tamoxifene may cause regression on bone metastasis. However, all these treatments can not go further than being palliative.
Stronstium-89 – Sanarium 153 or Radiotherapy may be used for pains of the bones.
Addition of Zoedronate has become routine to prevent the bone fractures.
It is a complete removal of the prostate and seminal glands by an operation.
The Purpose is: “To protect from the cancer (to clear cancerous cells from the body by removal of the prostate) + to provide urinary continence and to provide continuation of the sexual life”.
According to the method used, it may have some side effects such as bleeding with various ratios and impotence and urinary incontinence which may develop after the surgery. Thanks to the surgical techniques improved today, the abovementioned complications have been minimized by nerve protection techniques (nerve sparing). It may be applied RETROPUBIC – PERINEAL – LAPAROSCOPIC – ROBOTIC, the purpose is the same.
Anatomical structure of the area after radical prostatectomy:
Cancer focus after radical prostatectomy
Laparoscopic radical prostatectomy
Da vinci radical prostatectomy
a) EXTERNAL BEAM RADIOTHERAPY:
It is a therapy form which is performed by applying radiation beams onto the prostate gland out of the body. External beam therapy lasts for 2 months and causes some urination and defecation problems by effecting the urinary bladder and large intestine.
b) BRACHYTHERAPY (BEAMED NUCLEUS THERAPY):
MODERN THERAPY FOR PROSTATE CANCER: It is a treatment form which is applied by planting small radioactive seeds within the prostate gland.
Thus, the development which has broken a new ground lately is “BRACHIOPTHERAPY” where all these risks and adverse events have been minimized. Actually this method have been started to be tried at the beginning of 20th century and abandoned from time to time and it has been revived merely by development of the technology and started to be used gradually in USA and Europe.
Brachytherapy is a kind of beam therapy which is performed by placing a radiation source which gives eliminator beams to the cancer within the cancerous organ directly. In prostate BRACHYTHERAPY, beam sources like rice grains called seed are placed into the prostate gland via needles inserted from the anus. Beams (radiation) spread from these seeds kill the prostatic cancer cells slowly and treat the disease. Seed placement procedure is done in OR under general anesthesia and the patient is discharged one day after at the latest.
As seed placed into the prostate gland fro prostate BRACHYTHERAPY spread their beams to several millimeters far, they do not give any damage to adjacent organs such as urinary bladder, intestines, surrounding vessels and nerves. Furthermore, adverse events seen in open surgeries such as bleeding, inflammation or wound opening are not met. However, some patients may develop difficult urination temporarily and a catheter may be placed for a while.
Radiation therapy may also cause some side effects such as impotence, diarrhea, abdominal pain, irritability on anus and difficult urination.
APPLICATION METHOD OF BRACHYTHERAPY
The patient is kept on gynecological position under general anesthesia and radioactive seeds are placed with TRUS. BEAM SEEDS PLACED INTO THE PROSTATE IN BRACHYTHERAPY RADIOLOGICAL APPEARANCE OF THE SEEDS AFTER BRACHYTHERAPY
REASONS TO PREFER HIFU:
- Obtaining a complete and efficient result by a single application,
- Possibility to repeat the procedure when necessary,
- Very short hospitalization period,
- Very low complication ratio are main reasons to prefer HIFU.
This treatment option is recommended to:
Bu tedavi seçeneği:
1. Patients with localized prostate cancer on Stage T1-T2,
2. Patients whom radical prostatectomy can not be applied either for their age or any condition,
3. Patients who prefer a minimally invasive method which is alternative to the radical surgery.
4. It may be used as “salvage” treatment for the patients who have received radiotherapy or Radical prostatectomy before and had local relapse.
High intensity and focused ultrasound waves are produced by a probe placed into the rectum. Immediate and strong absorption of ultrasound waves on the focal point causes immediate heat increase at that point (85 to 100 °C) and destroy the cancerous cells on the target area. The area damaged by the heat for each shoot has a length of 19 to 20 mm and a diameter of 2 mm. Thereby, all prostate volume may be destroyed and cleared from cancerous cells with shoots that will be repeated by changing the focal point. In general, 400 to 600 shoots are sufficient.
This quite new minimally invasive method has been started to be used in Europe since 2000 and patients over 11,000 have been treated with this method successfully in different centers in Europe until September, 2006.
The device has been equipped with many security systems. To provide patient safety and optimize the therapy results:
- Continuous control of the therapy probe positions in association with the rectal wall.
- A detector which detects the patient movements.
- A cooling system which keeps the rectal temperature fixed.
When an abnormality is detected related with the operation of the device, all these security systems stop the operation automatically.
A temporary edema occurs on the prostate during the operation and prevents urination under normal conditions by compressing onto the urethra. A catheter is placed into the patient temporarily (3 to 8 days) until edema recovers.
TUR-P is generally applied about three months before Ablatherm® HIFU application to degrade the prostate volume for very large prostates. Also, hormonal therapy which is another option to degrade the gland volume may be started several months before Ablatherm ® application.
In general, regular PSA level monitoring for 3 months is sufficient.
Control biopsy samples may be taken by local anesthesia six months after the treatment. If any cancerous site was left (approximately in 10 to 15% of all cases), a second Ablatherm® application may be done. If cancer is still present after the second application, a low-risk radiotherapy may be recommended for support. This may indicate that cancerous cells have modified and further treatment methods are required.
Results of a multi-centered study conducted on 402 patients with localized prostate cancer in Europe:
According to this study, a negative control biopsy has been obtained in more than 8 of 10 (87.2%) patients who had been treated with Ablatherm® and PSA level has returned to normal with a ratio of 81.4%. Results are averagely 13 months follow-up results. Lyon, France confirms these results in a similar study including follow-up results for a period of over 5 years conducted.
Some advantages of preferring High Intensity Focused Ultrasound (HIFU) as a first option for Localized Prostate Cancer are;
- Destroying and eliminating cancerous tissue by creating a minimal lesion on adjacent organs.
- Not exposing to radiation and its side effects.
- Possibility to be applied by spinal anesthesia when necessary.
- A treatment method providing result for once.
- Short hospitalization period.
- A treatment method that may be repeated when necessary.
- Allowing to proceed with other treatment methods in case of failure to complete the treatment.
- Allowing treatment of local relapses,
It is understood that in USA, 30 % of patients with prostate cancer had disseminated metastasis and 30% of them had extraprostatic disseminated cancer on their first referral and 10% of them have been diagnosed with cancer incidentally on prostatectomy specimen performed because of BPH. Namely, 30% of these patients may have a complete curative treatment. It is also detected that about half of these patients have been on high stages after the radical surgery which is accepted as the most suitable. Consequently, only 15% of patients will have a chance of a real treatment!!! It is predicted that this situation is lower in Turkey! When morbidity of Radiotherapy or Radical surgery and relapse ratios after 10 years are considered, requirement of the treatment is problematic even cancer is detected on early stages.
Question: Is early diagnosis necessary ?
YES, because progression is fast in young, high grade aneuplody cancers. Otherwise, requirement may be interrogated due to the slow progress!!!