Diagnosis and Treatment of Prostate Diseases

Prostate Cancer

Prostate cancer is the most common cancer in men.

It is the second most common cause of cancer deaths. The lifetime risk of prostate cancer is approximately 17% for a healthy man. In other words, one out of every 6 men is diagnosed with prostate cancer.

Prostate cancer develops when certain cells of prostate tissue convert into cancerous structure through an abnormal course. The disease may develop either at one part of the gland or at multiple foci.

This disease is generally detected in people older than 65 and it may be asymptomatic at early stages. However, if it is left untreated, it can enlarge and compress urethra over time. For these patients, certain urinary problems can develop.

Cancerous tissues are not confined to the prostate gland or they may spread to surrounding tissues, if diagnosis and treatment delay.

Prostate cancer spreads particularly to bones. Diffuse bone ache is likely in patients with metastasis.

Symptoms of Prostate Cancer

Localized (confined to prostate gland) prostate cancer often develops without any sign. Some symptoms of prostate cancer are as follows:

• Dysuria
• Difficulty in urination and blood in urine
• Blood in semen
• At advanced stages, bone metastases, resultant bon ache and sometimes, fractures

Treatment of prostate cancer cannot be started in a timely manner, if a person ignored regular screening or does not present for routine examinations despite documented cancer. In these cases, the disease starts to progress.

Diagnosis of Prostate Cancer

Today, there is no early diagnosis method to reveal out presence of prostate cancer in a healthy man.

Advancing age, ethnic origin and genetic predisposition are acknowledged risk factors of prostate cancer. In the light of these risk factors, tests are conducted for early diagnosis.

Although prostate cancer screening is recommended for men older than 50 with no family history of prostate cancer, others with family history of prostate cancer are advised to have prostate cancer screening after 45 years of age due to increased risk.

Screening methods are digital rectal examination (for prostate) and PSA analysis in blood specimen.

PSA Test and Prostate Examination in Diagnosis of Cancer

Prostate cancer can be diagnosed early with a PSA (prostate specific antigen) test in a blood specimen. Early diagnosis of prostate cancer is essential to have more treatment options.

Reference for normal range of PSA: Hans-Joachim Luboldt, Joachim F. Schindler, Herbert Rubben .Age-Specific Reference Ranges for Prostate-Specific Antigen as a Marker for Prostate Cancer.eau-ebu update series 5 (2007) 38–48.

40 to 49 years of age: 0- 2.5 ng/ml

50 to 59 years of age: 0- 3.5 ng/ml

60 to 69 years of age: 0- 4.5 ng/ml

70 years or above: 0- 6.5 ng/ml

PSA readings may also be high in case of benign prostate hyperplasia - BPH, prostate inflammation (prostatitis), after sexual intercourse, after digital rectal examination, urinary tract infection and urinary tract procedures (placement of catheter) and surgeries along with prostate cancer.

Therefore, high PSA level does not always verify a cancer, while low PSA level is not sufficient to rule out.

Prostate cancer is detected in 1 out of every 5 patients with normal PSA levels.

Therefore, digital rectal examination is combined with PSA reading in diagnosis of prostate cancer. This examination enables to have an opinion about presence of prostate cancer without PSA analysis.

If these tests lead to a suspicion, some additional tests can be performed for diagnosis of prostate cancer. These tests are as follows:

Multiparametric MRI

For patients with suspicion of prostate cancer, this imaging modality evaluates 3 parameters and the focus with suspicion of cancer in prostate gland can be identified.

One of these parameters (diffusion) detects the increase in cellular density of body. Since cancerous cells are denser, they create higher signals.

Vascularization in tissues (perfusion) is the other parameter.

Since more blood is supplied to cancerous tissues, they are rich in blood vessels and therefore, they can be differentiated from healthy tissues.

In another parameter (spectroscopy), chemical analyses of intact tissues and cancer tissues are made and tissues are differentiated by reviewing a certain substance, namely choline, which originates from cell destruction.

Above mentioned parameters are scored in a multiparametric prostate MRI to clarify whether a patient has a tumor or not.

Multiparametric Prostate MRI can demonstrate whether the tumor exceeds the prostatic capsule and whether it has potentially spread to lymph node(s). Moreover, these MRI images are used as a guide for prostate biopsy. In conclusion, final diagnosis of cancer can only be established through biopsy.

Prostate Biopsy

Biopsy implies taking tissue or cell specimens from any part of the body in order to examine the specimen under microscope or perform various tests.

Various parts of the prostate gland are biopsied in a prostate biopsy.

In standard prostate biopsy, pieces are collected randomly from the prostate gland using a special device that is inserted into rectum under local anesthesia. It is checked whether there is cancerous cell in these tissues or not.

MR Fusion Biopsy

In this method, prior multiparametric MRI images are transmitted to an ultrasound scanner that guides the biopsy procedure in order to locate the tumor accurately.

Thus, the suspicious focus is directly “targeted” and biopsied rather than collecting pieces “randomly” in conventional biopsy. As exact location of tumor or suspected focus can be identified, smaller specimens will be sufficient rather than collecting multiple pieces.

Fusion biopsy can be performed with two methods. One of them is transperineal approach, where the biopsy device is inserted through the perianal skin. The procedure can be performed under general or local anesthesia.

The other one is transrectal method that prefers rectum to access the prostate gland. This procedure can also be performed under local anesthesia.

Treatment of Prostate Cancer

After prostate cancer is diagnosed, treatment is planned considering disease factors (stage, spread) and patient factors (general status, age, co-existing diseases).

Is there any non-surgical treatment option for prostate cancer?

Prostate cancer can be treated with surgery, radiotherapy or hormone therapy. Treatment modality is decided by patient factors and overall health.

What is the most commonly preferred treatment option in prostate cancer?

Today, prostate cancer can be diagnosed at early stages, as screening tests are ever increasingly used.

Surgery is mostly preferred for early-stage local prostate cancer without near or distant metastasis. When necessary, treatment can be combined with hormone therapy or radiotherapy.

Active follow-up:

Prostate cancer progresses slowly at Stage 1; it may, sometimes, be asymptomatic and does not cause any health problem. Your doctor follows up the progression of cancer at this stage with PSA analyses, digital rectal examination and ultrasound. At the same time, risk of spreading is evaluated (scored).

Active follow-up aims close monitoring of patients with low-risk and slowly-progressing disease in order to start treatment, whenever required, such that chance of treatment is not lost. Thus, unnecessary treatments can be prevented in a group of patients.

NanoKnife

NanoKnife is used to treat clinically insignificant tumor that implies prostate cancers with low volume and low risk.

Also used for treatment of certain liver and pancreatic tumors, it is a safe method for focal treatment of prostate cancer.

For NanoKnife ablation, ultrasound guidance is used to place 3 to 4 special electrodes around the tumor located in prostate gland and these electrodes deliver electric current at a very high dose (3000 volt - 50 ampere) for a very short time. An electromagnetic area is formed at the target and permeability of cell wall increases temporarily. In this way, tumor cells lose their viability.

Since this method does not cause temperature changes in tissues, it can be considered for tumors located close to nerves and urethra.

Patient selection is the most crucial part of this technique. The treatment modality should not be used for group of patients who are good candidates of active follow-up.

Since only cancerous cells of prostate gland are damaged after the procedure, there is future risk of cancer in other segment of prostate over time. Should this risk is actually faced; curative (surgery, radiotherapy) treatment is planned. In other words, this treatment option aims to postpone curative surgery as much as possible. Therefore, it is targeted to delay potential side effects of curative treatments.

Surgical Treatment – Radical Prostatectomy in Prostate Cancer

It implies surgical removal of prostate gland to treat localized prostate cancer. This method is called radical prostatectomy. Ten-year survival rate of patients with low-grade tumor and history of radical prostatectomy is over 90%.

What is Robotic-Assisted Surgery?

Robotic-assisted surgery is laparoscopic (closed) performed using Surgical Robotics, called “da Vinci” Surgical System, under 3D image guidance. Many laparoscopic surgeries (urologic, general surgery, gynecology, etc.) can be performed using this system.

What is function of Surgeon in Robotic-Assisted Surgery?

The misconception on concept of robotic surgery is that the surgery is performed solely by the robot. However, it is the surgeon who performs the operation, but not the robot.

What are Complications of Prostate Cancer Surgery with a Robotic-Assisted System?

In anatomic terms, prostate gland is very close to the structures that are responsible for erection and urinary continence. Therefore, the most important complications of prostate surgery are postoperative erectile dysfunction and urinary incontinence.

The main purpose of Robotic-assisted Prostate Surgery is to remove the prostate gland without leaving any residual cancerous tissue, preserve nerves that will ensure maintenance of sexual functions and not to damage the structures that regulate the urinary continence.

Exposing the anatomic plane between the urinary bladder and the prostate gland is defined as “Urinary Bladder Sparing Method” within scope of robotic-assisted prostate surgeries. Rates of incontinence have drastically decreased after surgeries performed with this technique.

How does robotic-assisted surgery differ from open surgery?

An approximately 15-cm incision is made below the belly button in conventional open surgery. Open surgery poses many difficulties for both the patient and the surgical team.

Prolonged postoperative convalescence, longer hospital stay, risk of wound infection and larger incision scar are the adversities that patients face.

There are also some challenges for surgical treatment, including a small room for hand moves due to narrow surgical site, longer duration of surgery due to poor visibility of the surgical site and increased complication rates.

A robotic device, called da Vinci, is conveniently placed above the patient and the surgery is carried out by a surgeon who uses a console to command the surgical instruments of the system. General principles are similar to those of laparoscopic surgery.

Thin robotic instruments, the wide range of moves, ability to eliminate tremor and advanced imaging system of the robotic system allow better protection for significant structures that are nearby the prostate gland in a prostate surgery. Thus, risk of intraoperative complications is minimized, blood loss is reduced and surgery is completed within a shorter time.

Risk of other health problems is also decreased that has substantially adverse effects on social life, such as milder postoperative pain, shorter convalescence, future loss of sexual functions and chronic urinary incontinence.

Irrespective of surgery technique, certain phases of robotic-assisted prostate cancer surgery also require acting very precisely.

Here, the main purpose is to remove the prostate gland without leaving any residual cancerous tissue, preserve nerves that will ensure maintenance of sexual functions and not to damage the structures that regulate the urinary continence.

A new technique is developed that exposes the anatomic plane between the urinary bladder and the prostate gland in robotic-assisted prostate surgeries. This method, called “urinary bladder sparing technique” in the literature, is characterized by very low rate of early- or late-onset urinary incontinence.

Radiotherapy

Radiotherapy uses ionizing radiation to treat cancer. Radiotherapy aims to minimize the damage to healthy tissues, while cancerous cells are killed or their growth is stopped.

Radiotherapy is a local treatment option, similar to surgical methods, and therefore, both therapeutic effects and side effects are local. Although radiotherapy is used as a curative treatment option for localized prostate cancer, it is also a palliative or debulking (to reduce tumor load) modality for patients with prostate cancer that involve nearby organs (locally advanced) or distant organs (metastatic).

What are Side Effects of Radiotherapy?

Side effects of radiotherapy generally emerge in subsequent days rather than first several days, as the cumulative dose increases. They may not always occur and there are also inter-patient variations.

Some of usual side effects include skin irritation and fatigue. Radiation therapy may cause erectile dysfunction and urinary incontinence, if used for treatment of prostate cancer. Additional conditions include but are not limited to frequent urge to urinate and blood in urine (hematuria).

Chemohormonotherapy

Prostate cancer may spread to nearby tissues and distant organs rather than being confined to prostate gland at advanced stages. This is called advanced stage prostate cancer. Medication treatment is preferred at this stage of the disease, since surgical options will lead to undertreatment.

Prostate tissue is sensitive to testosterone (male sex hormone) and therefore, medicines that suppress effect of testosterone (anti-androgenic agents) are used at this stage of the disease. This treatment is called hormone therapy.

Chemotherapy is planned for patients who do not respond to or develop resistance against this treatment. Scientific studies have revealed out that survival is thus increased in patients with advanced-stage prostate cancer.

What are Causes of Prostate Cancer?

Age and family history are most prominent risk factors of prostate cancer.

Age: Aging increases incidence of prostate cancer. Microscopic prostate cancer is detected in 50% of men older than 70 and almost in all men older than 90.

Prostate cancer screening is recommended to all men older than 50 for early diagnosis.

The underlying rationale is the aging-related increase in incidence of prostate cancer.

Prostate cancer is most commonly diagnosed in men older than 65 in developed countries. Prostate cancer before 45 years of age is regarded as a rare condition.

Family history: Genetic and environmental factors also affect development and progression of prostate cancer.

Varying incidence of prostate cancer in different races and higher prevalence in men with positive family history indicate the role of genetic factors.

In a study, incidence of prostate cancer increased in men who migrate from Asian countries, where incidence of prostate cancer is low, to the U.S. Therefore, diet and environmental factors are considered to play a role in development of prostate cancer. However, these factors are not known for certain.

For example, although some studies suggest that exposure to cadmium in cigarette, diet rich in saturated fats, obesity and alcohol increase risk of prostate cancer, these results could not be accurately proven.

Nonetheless, these environmental factors should be taken into consideration to prevent prostate cancer, as is the case with other types of cancer.

On the other hand, some studies suggest that licopen, a substance found in dark colored fruits and vegetables (tomato, carrot etc.), decreases the incidence of prostate cancer.

Also, diets rich in soybeans and Omega-3 have been shown to decrease risk of prostate cancer.

Stages of Prostate Cancer

Treatment of prostate cancer is planned depending on grade and stage of tumor.

If prostate biopsy points to a cancer, the cancerous tissue is examined by a pathologist. Gleason Scoring System is the most commonly used grading system. Results give an idea on growth and spread rate of the tumor.

Low grade or low risk implies that tumor will grow slowly and the risk of metastasis is low.

On the other hand, a high-grade or high-risk tumor grows quickly and it may spread to other body parts.

Prostate cancer is staged according to how the tumor extends to prostate gland and surrounding or distant tissues. Following criteria are taken into consideration, when stage is determined.

Size of tumor

Spread of tumor in the prostate gland or surrounding tissue

Whether cancer has spread to lymph nodes

Spread to other parts of body (metastasis)

Tumor is confined to prostate gland in Stage I. Tumor is too small to detect in digital rectal examination.

Tumor spreads deep into prostate tissue in Stage II, but it does not involve the surrounding tissues. Tumor can be felt in digital rectal examination or visualized in imaging modalities (MRI) at this stage.

Tumor has spread beyond the capsule of prostate gland and to surrounding tissues (such as seminal vesicles) at Stage III.

Cancer spreads to other surrounding tissues at stage IV (metastasis). Tumor usually involves lymph nodes, bones, liver or lungs at this stage.

Grade of prostate cancer should be determined, as it is very crucial to select the best treatment option and follow up course of the disease.

Prostate Biopsy

Prostate biopsy is used to diagnose the prostate cancer and to identify the progression rate and aggressiveness of the tumor.

Standard Prostate Biopsy

Trans-rectal ultrasound is more sensitive than transabdominal ultrasound in examination of the prostate gland. However, digital rectal examination is more important in routine tests and therefore, it is not used in routine clinical practice.

Transrectal ultrasound is primarily used by urologists to guide a prostate biopsy.

Biopsy is necessary when the PSA reading is above age-matched ranges or an abnormality is detected in digital rectal examination. An ultrasound probe is inserted into rectum to guide prostate biopsy and specimens are collected using automated biopsy needles. Biopsy is an outpatient procedure which is generally performed under local anesthesia.

Widely acknowledged prostate biopsy guidelines require collecting at least 12 pieces. Additionally, if a suspected area is detected in examination or ultrasound, this zone is also sampled.

Ultrasound guidance ensures the biopsy specimens are collected from the targeted zones in the procedure. It may be necessary to repeat biopsy, if the underlying cause of high PSA readings cannot be revealed out, PSA persists to elevate or result of prostate biopsy is suspicious.