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Urological Cancers

Bladder Cancers Bladder cancer is the fourth common cancer type among male individuals after prostate, lung and colon cancer. It’s the 8th common among female individuals. 50.000 new bladder cancer cases are received every year in the U.S.A. Between 5-10% of all the cancer types seen among male patients in Europe and the U.S.A. consists […]

Bladder Cancers

Bladder cancer is the fourth common cancer type among male individuals after prostate, lung and colon cancer. It’s the 8th common among female individuals. 50.000 new bladder cancer cases are received every year in the U.S.A. Between 5-10% of all the cancer types seen among male patients in Europe and the U.S.A. consists of bladder cancer and most of these are relapse cases. Although it can be seen at any age, it’s more common during middle age and above, average diagnosis age for male patients is 69 and 71 for female patients. Incidence increases with age. Well-differentiated tumors are more common and the prognosis is better among adolescents and the adults under the age of 30.

There are many factors causing the bladder cancer. It’s led by smoking and followed by age and gender. Advanced age, male gender, and smoking lead to a serious tendency for bladder cancer. Smoking is the most effective factor determined for bladder cancer. It’s a more effective factor than being one for the lung cancer.

 

Other risk factors are;

  • Chemical carcinogens
  • Genetic predisposition
  • Chronic urinary tract infections
  • Excessive use of artificial sweeteners
  • Hair dye.

 

Diagnosis of Bladder Cancer

Diagnosis of bladder cancer is made through medical history and radiologic tests. The classic symptom of this disease is the blood in the urine (hematuria). Hematuria in bladder cancer is indolent, Thromb and microscopic. Smoking and indolent Thromb hematuria in a male patient over 40 years old should be regarded as bladder cancer unless otherwise proven. On the other hand, it can be asymptomatic with frequent urination and difficulty during urination and can be diagnosed during a routine urine test or ultrasonography or computed tomography. For a patient applying with the symptom of blood in the urine, the disease should be diagnosed and evaluated through standard ways. The first thing to do with a patient with hematuria is to apply display methods as ultrasonography or intravenous pyelography (IVP). In the cases where pathologic findings are diagnosed through display methods or there is a tumor risk even though there are no pathologic findings, cystoscopy is required. Certain diagnosis of bladder tumor is made through cystoscopy and pathologic examination.

 

 

 

Cystoscopy for the Diagnosis of Bladder Cancer

The most important method for diagnosis is cystoscopy. Cystoscopy which is the display of intravesical area is both a diagnosis and treatment method conducted in the surgery room under the effect of anesthesia. Cystoscopy which is conducted by entering the urinary tract through a device called cystoscope helps to display the bladder cancer directly. Urinary tract, intravesical area, ureter orifice which is the area where prostate and kidneys are connected in male individuals can be seen through cystoscopy. This procedure can be conducted both a rigid device and flexible ones. The biopsy can be conducted on the displayed cancer tumor or it can be treated by cleaning it completely from the intravesical area

Pathologic Examination of Bladder Cancer

Parenchymas are examined through the procedure called transurethral resection (TUR) in the cystoscopy and the pathologic typology is determined. 90% of bladder cancer is transitional epithelial cell cancer (TCC). The remaining 5-10% consists of squamous cell cancers, adenocancers, and other rare tumor types.

The tumor is graded pathologically. Treatment methods and prognosis differ in accordance with the pathological grade. Pathologic grading is as follows according to 2004 WHO report:

  • Urothelial neoplasm with low malign potential
  • Low grade papillary urothelial cancer
  • High graded papillary urothelial cancer

 

Staying Bladder Cancer

If staging is needed for the diagnosed bladder cancer, advanced treatment methods can be determined. Because the treatment is conducted in accordance with the stage. Staging system called TNM system is used. Staging is done as follows:

 

T-Primary Tumor

  • Ta: non-invasive papillary cancer
  • Tis: carcinoma in situ

 

 

(transurethral resection in bladder cancer)

 

  • T1: tumor has spread to subepithelial connective tissue. (lamina propria invasion)
  • T2: tumor has spread around muscle tissue.
  • T2a: tumor has spread around superficial muscle tissue
  • T2b: tumor has spread around deep muscle tissue.
  • T3: tumor has spread around perivesical tissue.
  • T3a: perivesical microscopic invasion
  • T3b: perivesical macroscopic invasion
  • T4: tumor has invaded either prostate, uterus, vagina, pelvic wall or abdominal wall.

 

N-Lymph Node

  • N0: no lymph metastasis.
  • N1: single lymph node metastasis smaller than 2 cm or 2 cm longı
  • N2: single lymph node between 2-5 cm
  • N3: multiple lymph nodes no bigger than 5cm

 

M: Distant Involvement

  • M0: None
  • M1: Available

 

Treatment of Bladder Cancer

Superficial Bladder Cancer

Ta, T1, and Tis constitute the superficial bladder cancers. Tumors with other stages are invasive ones. Treatment of superficial bladder cancer is different than the invasive one. Ta tumors are papillary tumors that are holding only the epithelial tissue. T1 tumors hold the connective tissue called epithelium layman propria in addition to the epithelial tissue. This a.k.a. carcinoma in situ is the high graded anaplastic tumor is the one that is not papillary, is either and not so invasive.

Standard treatment of superficial bladder cancer is TUR (Transurethral resection). The tumor can be eradicated macroscopically through TUR. TUR is a surgical procedure conducted under general or regional anesthesia. 2nd stage TUR might be needed for the patients with superficial bladder cancer in some cases. These cancers are high graded tumors, multifocal tumors, no blood tissue sample in the pathology and incomplete first TUR procedure.

Treatment of Bladder Cancer With TUR

Superficial bladder cancer should be treated not only with Tur but also with some medications (BCG, mitomycin, epirubicin) applied to the intravesical area. Medication should be applied in the intravesical area in 6 hours following the TUR procedure. This procedure is called adjuvant intravesical immunotherapy. Advanced immunotherapy can be prescribed after the risk group of the patient is determined. While one dose of immunotherapy is sufficient for the patients with the low-risk group after TUR, 6 weeks of immunotherapy or long-term immunotherapy can be applied on the patients with the medium or high-risk group. Low-risk group patients have a tumor with a single focus and are TA tumor smaller than 3 cm. Patients of the high-risk group are the ones with multifocal, invasive tumors that are bigger than 3 cm, high graded and are T1 and Tis type cancers. The group in between the two groups mentioned before is the medium risk group. Patients of the high-risk group have a high risk of having relapsed tumor. The low-risk group is the opposite of this situation.

 

Treatment of Low-Risk Group Patients

  • Definite layer TUR
  • One dose intravesical medication after TUR
  • No advanced treatment needed until relapse

 

Treatment of High-Risk Group Patients

  • Definite layer TUR
  • One dose intravesical medication after TUR
  • Second stage TUR 4-6 weeks later
  • Full dose BCG after second stage TUR
  • Radical cystectomy in case of high relapse rate and being high graded

 

Intravesical Immunotherapy in Bladder Cancer

For this purpose, the drugs used in the bladder are limited, but the most commonly used and effective is the drug-containing tuberculous microbes called BCG. BCG is injected into the bladder to strengthen the immunocompetent cells in the bladder mucosa with local effect and significantly reduce tumor recurrence rate. BCG application can be given once a week for 6 weeks or for 1 year. The most common side effect after BCG therapy is fever and frequent urination. These effects are temporary.

 

Invasive Bladder Cancer

Invasive bladder cancer is T2-T4 and some high graded T1 tumors. These tumors have a high risk of relapse and tend to spread through muscle layer and deep bladder tissues. The first stage of the treatment is the grading of the patient. After grading, the treatment option is determined. In the cases where lung and abdomen scan is needed in order to display distant metastasis in addition to grading, the bone examination should be conducted.

 

Treatment of Local Invasive Bladder Cancer

This group consists of the patient group whose bladder tumor invades the muscle layer. T2 and T3 patients are grouped under this category. Golden standard treatment for these patients is radical cystectomy and urinary diversion.

Radical cystectomy is the gold standard method for the patients with the local invasive tumor. Radical cystectomy is the procedure for patients where bladder, prostate and surrounding fat tissues, regional lymph nodes in males and bladder, uterus, ovaries, regional lymph nodes and surrounding fat tissues in females are removed. It’s a surgical procedure conducted under general anesthesia. Success rate increases when conducted by specialists. There are two options in addition to radical cystectomy to take out the urine. The first and most common one is the procedure called ileal conduit where urine is taken out by using part of the intestine and adding this part to the urinary tract. Another option is the bladder made of the intestine called orthotopic bladder. Part of the intestine is not taken out in this procedure. The patient can urinate through the normal urinary tract but this procedure has some disadvantages compared to the ileal loop.

While radical cystectomy can be conducted open, it can also be conducted through the technique called laparoscopy where 4-5 sections are open on the abdominal wall.

 

Partial Cystectomy

It’s the removal of part of the bladder. If the tumor is on one focal point or located in the bladder dome, then it can be conducted. The urinary diversion wouldn’t be required after partial cystectomy.

 

Adjuvant Radiotherapy and Chemotherapy

In the cases where lymph nodes have involvement after cystectomy in local invasive bladder cancer or the tumor invaded the surrounding tissues, this procedure can be conducted.

 

Metastatic Disease

Bladder cancer is vulnerable to chemotherapy. Radiotherapy and chemotherapy can be applied to the metastatic disease or the patients with worsening general condition. The emergency protocol should be applied in cases such as macroscopic (visible) hematuria hemoglobin (where the bladder is filled with the blood clot or tumor), anemia with massive bleeding. Transurethral cauterization, angioembolization can be conducted palliatively. In the case of excessive bleeding, cystectomy can be conducted in order to prevent bleeding.

Carcinoma

Carcinoma consists of 2-3% of the total cancer rate in all the societies. In 1998, 30.000 new carcinoma cases were diagnosed in the US and approximately 15.000 people were dead because of carcinoma. It’s most common between the ages of 60 and 70. Prevalence among males is 1,5 times more than in females. Prevalence is increasing with the increase in the use of the method as ultrasonography. However, morbidity due to carcinoma hasn’t changed. Even the morbidity tends to decrease. While there are different factors in terms of etiology, there are no certain reasons known. The most common etiologic factors are smoking, adiposity, antihypertensive treatment, some industrial factors (asbestos, cadmium, oil products), herpes virus infections and last stage kidney failure. The most effective measure would be quitting smoking and avoiding adiposity.

 

Diagnosis and Staging of Carcinoma

Most of the cancer types with renal cells are symptomatic and especially in the last years they are diagnosed by chance through display methods developed recently. Today, approximately 50% of carcinomas have been diagnosed coincidentally. Findings in the patients are not clear ones. Ilium ache can be given as an example. A small part of the patients (5-7%) have symptoms of carcinoma. These symptoms are ilium ache, hematuria and mass felt during the examination. Findings called paraneoplastic syndrome are found with the rate of 20-30%. These findings are caused by some substances released by the kidney with tumor into the blood flow. Conditions such as hypertension, weight loss, amyloidosis, increased sedimentation rate, hypercalcemia may occur. And sometimes findings that are rare such as bone pain, the constant cough may occur.

The physical examination has a limited role in carcinoma, however, important symptoms may be discovered in some patients. For example, mass in the abdomen, nodules on the neck, varicocele, edema on legs can be important reasons to see your doctor.

The most accurate radiologic diagnostic method for kidney tumor ultrasonography. This technique which can easily detect tumors can also differentiate tumors and cysts. Kidney tomography should be conducted on the patients whose kidney tumor were detected through ultrasonography. If there is a possibility of metastasis in the lungs, then lung tomography can display the presence of this metastasis clearly.

(Ultrasound display of kidney tumor)

The patients applying with hematuria would have IVP (intravenous pyelography) and USG (ultrasonography) first. Through these tests which are easy to conduct, diagnosis of kidney tumors with 75-80% accuracy rate would be possible. CT scan which is the gold standard diagnostic method for the tumors with renal cells is a method that should be conducted in the cases where masses are detected through the methods mentioned before. The accuracy rate of CT scan is approximately 90% and it can provide information about the size of the tumor, lymph node, peripheric metastasis. Magnetic resonance display not only provides information about vascular structures and invasion with the accuracy rate of 96% but also is the display method that has the least side effects and is the easiest to apply the method for the patients with kidney failure or contrast allergy. Renal angiography is a relatively less preferred method since the CT scan is in use. Bone scintigraphy for the patients with the possibility of having metastasis and PET CT for the monitoring and effectiveness of the treatment are the best options.

 

 

(a big RCC, tomography display of carcinoma)

 

Important Steps for the Diagnosis of Carcinoma!

  1. If there are one or more lab findings or physical symptoms are present for a patient, carcinoma can be possible.
  2. Uni-directional lung graphics may be enough for the patients of the low-risk group, however, lung tomography is the most sensitive method.
  3. Tomography and magnetic resonance (MR) examinations on the abdomen area are necessary and sensitive methods for the staging of the disease, especially before surgery.
  4. Patients with increased risk of bone metastasis (increase of blood alkaline phosphatase level, bone pain) should be further tested.
  5. It’s obligatory to check the kidney function of every patient.

 

Staging

In order to treat the diagnosed carcinoma correctly, metastasis level and estimated risk profile should be determined. The first step for correct treatment is a correct staging. In staging the carcinoma, a classification called TNM is used. This classification is as follows:

T: Tumor

  • Tx: Evaluation not possible
  • T0: No proof regarding primary tumor
  • T1: Tumor is limited with kidney and smaller than 7 cm
  • T1a: Tumor is smaller than 4 cm
  • T1b: Tumor size is between 4-7 cm
  • T2: tumor is limited with kidney, however bigger than 7 cm
  • T3: Tumor invaded main kidney venues, holds suprarenal gland, however, hasn’t exceeded gerota fascia covering the kidney
  • T3a: Tumor holds surreal gland or perinephric tissue.
  • T3b: Tumor holds renal vein or vena cava, however, located under the diaphragm.
  • T3c: Tumor holds renal vein and vena cava, however, located over the diaphragm.
  • T4: Tümör gerota fasiasını aşmıştır.

 

 

 

N: Regional Lymph Nodes

  • Nx: Lymph node involvement can’t be evaluated
  • N0: No metastasis
  • N1: Metastasis in 1 regional lymph node
  • N2: Metastasis in multiple regional lymph nodes

 

M: Distant Metastasis

  • M0: No evaluation possible for distant metastasis
  • M1: No metastasis
  • M2: Metastasis

 

 

Grading of carcinoma in accordance with the staging is done as follows:

 

Stage 1……………..T0

 

N0

 

M0

 

Stage 2………………T2

 

N0

 

M0

 

Stage 3………………T3

 

N0

 

M0

 

T1,T2,T3

 

N1

 

M0

 

Stage 4………………T4

 

N0,N1

 

M0

 

Any T

 

N2

 

M0

 

Any T

 

Any N

 

M1

 

 

Prognosis of Carcinoma

In the evaluation of prognosis of carcinoma, TNM classification surely has a great role within anatomic factors. Naturally, a bigger sized tumor, metastasis outside the kidney, the involvement of major venues, metastasis on lymph nodes and distant metastasis would affect the prognosis. There are also some factors to be obtained as a result of the pathologic examination of the tumor in addition to anatomic factors. These are Fuhrman grade, the presence of sarcomatoid type, microvascular invasion, necrosis in tumor and involvement of collecting tubules and they also affect the possible prognosis. Besides these, patient’s general condition (presence of other sides) and the presence of molecular structures are also the factors affecting prognosis.

 

Pathology of Carcinoma

Carcinoma would have a type as a result of pathologic examinations. According to the classification by WHO, there are three most common carcinoma types. Prevalence of clear cell type (clear cell type) is 80-90%, papillary cell cancer is 10-15%, and chromophobe cell cancer is 4-5%. Rest of the carcinoma types are very rare (<1%) and includes collecting ductus carcinoma, renal medullary carcinoma, mucinous cell carcinoma, papillary adenoma, and oncocytoma. Fuhrman system which is used for the pathologic grading of carcinoma is the most common one. This system depends on the tumor’s pathologic behavior. High grade is an undesired prognostic factor.

 

Carcinoma Treatment

Treatment of renal cell cancers is based on their stage. Treatment options change according to the stage. Treatment options are:

Local Disease (No distant metastasis)

  1. Surgical treatment
  2. a) Radical nephrectomy
  3. b) Partial nephrectomy
  4. c) Laparoscopic nephrectomy
  5. Embolization
  6. Radiofrequency ablation (RF)
  7. Cryoablation
  8. HIFU

 

Metastatic disease (with distant metastasis)

  1. Surgical treatment
  2. Immunotherapy
  3. Chemotherapy
  4. Radiotherapy

 

Surgical Treatment

It’s the fundamental and most effective treatment option for carcinoma. It can be applied in any stage of the disease. It can be cured through surgical treatment in case of the localized disease. It’s important to decrease the size of the tumor in case of the metastatic disease. While radical nephrectomy which is the method of removing kidney together with its gerota fascia and suprarenal gland completely was the most common one for the surgical treatment of carcinoma, recently the methods where the renal tissue is preserved as much s possible are used.

As mentioned before, radical nephrectomy is the procedure where kidney together with its gerota fascia and the suprarenal gland is removed completely. It can be conducted both open and close or in other words laparoscopically. Selection of the surgical method totally depends on the location and size of the tumor and the availability of technical possibilities. If the tomography before surgery is normal, there is no need for the removal of the suprarenal gland. Removal of regional lymph nodes doesn’t make any contributions to the progress of the disease. Patients that don’t have metastasis but tumor thrombus should have a radical nephrectomy including the removal of thrombus.

Partial nephrectomy is a method of protecting the kidney and applicable for kidney tumors. It’s applied especially in the case of T1a tumors. This technique is also used for some special cases. There must be one anatomic or functional kidney, two-sided kidney tumor, the tumor located outside the kidney and tumor smaller than 4 cm. In this operation, the area with healthy renal tissue is preserved and left in the body of the patient. Only the area with the tumor is removed. It can be open or laparoscopic. Selection of laparoscopic operation type is similar to the one with radical nephrectomy.

 

Minimal Invasive Treatment Options

These methods were suggested as alternatives for the surgical treatment, however, they couldn’t be replaced with the surgical one which is the gold standard method. These techniques are the ones such s radiofrequency ablation (burning with radiofrequency), cryotherapy (freezing treatment), high-density ultrasonic wave ablation (HIFU). These techniques are applied for especially very old patients, various syndromic cases with tumor relapse, tumors with cortical location.

 

Treatment of Metastatic Disease

Radical nephrectomy is only conducted to reduce the effects of tumor in patients with distant metastasis. Surgical treatment doesn’t have any curative effects on these patients. Surgical treatment is selected in the same way with localized disease. Laparoscopic nephrectomy is not a common one. Surgical treatment shouldn’t be applied solely and also immunotherapy should be applied. In the cases with vena kava invasion or single focus metastasis, removal of thrombus through venacavotomy and metastasectomy for the patients with good prognostic factors is significant for recovery. Patients with single lung metastasis are the ones that can benefit from metastasectomy the most.

Immunotherapy can be applied in addition to surgical treatment in case of advanced disease or in the cases where surgical treatment is not possible. Treatments with the medications as IL-2 and IFN supporting immune system can make some contribution for the recovery. Again immunotherapy can be tried after angioembolization (closure of the venue feeding the tumor) in the advanced disease to reduce the effects of the tumor. Some studies have shown that metastasis regress through palliative surgery. Kidney tumors are typically resistant to radiotherapy and chemotherapy. Therefore, chemotherapy and radiotherapy should never be the first option for advanced disease. They should only be applied to release the pain or in the cases resistant to immunotherapy.

 

Treatment of Carcinoma According To Stages

Stage-1 (5 years of life 90-95%)

  • Radical nephrectomy
  • Partial nephrectomy
  • Microinvasive treatment options

 

Stage-2 (5 years of life 55-67%)

  • Radical nephrectomy

 

Stage-3 (5 years of life 20-30%)

  • Radical nephrectomy + lymph node removal
  • Removal of thrombus from main venues

 

Stage-4 (5 years of life 5-10%)

  • Palliative radical nephrectomy
  • Immunotherapy
  • Chemotherapy
  • Radiotherapy

Prostate Cancer

Prostate cancer is among the most important problems of aging male individuals. 2.6 million new cancer cases were discovered in Europe as of the year of 2009. 11% of all cancer cases and 9% of morbidity due to cancer in Europe is caused by prostate cancer. Right now the strongest risk factor is genetic. This means having a prostate cancer in the family history. It’s thought that the change in eating habits may also be effective for the development of prostate cancer.

 

Pathologic type of the prostate cancer is mostly the type called adenocarcinoma. The TNM system is used for classification. ( T: tumor, N: lymph node, M: metastasis). The scoring system called Gleason score is used for pathologic grading.

 

Prostate Cancer Diagnosis

 

 

Prostate cancer is a disease that is typically seen among male individuals in their middle or advanced ages. The disease may proceed slowly and show symptoms late. When the symptoms are seen, it might already be advanced or metastatic. Frequent urination (polyuria), urinating during the night, dysuria (pain during urination) and difficulty in urination can be counted among the symptoms. In the advanced stage; lumbar and joint pain, asthenia and weight loss can be seen. Sometimes the disease may be asymptomatic and may be diagnosed during the biopsy due to high PSA coincidentally or during a routine check. Standard methods used for diagnosis are the digital rectal examination, measurement of PSA level in blood and prostate biopsy along with the ultrasound.

The doctor should suspect prostate cancer in the presence of a bigger prostate and presence of rigid and inactive mass felt during the digital rectal examination. PSA which is another technique used for diagnosis is a hormone and is released by the prostate gland. Since it’s also released by parenchyma, it’s an important aspect for the diagnosis. High PSA level increases the risk of cancer.

PSA level

 

Risk of prostate cancer

 

3-4 ng/ml

 

% 34

 

3-4 ng/ml ( between the ages of 50-66 )

 

% 13

 

6-10 ng/ml

 

% 44

 

>10 ng/ml

 

% 71

 

 

 

Since the amount of free PSA (f-PSA) which is a subtype of PSA will increase in the presence of parenchyma, f-PSA / t-PSA ratio under 20% and annual PSA increase speed (PSA velocity) over 0,75 ng/ml shows an increased risk of cancer. Studies show that when PSA level is over 2.5 ng/ml, .2% cancer among males over 50 and 4.4% cancer among males below 50 have been diagnosed. Therefore, biopsy along with ultrasound is conducted on the male patients with PSA level over 2.5, annual PSA velocity over 0.60 ng/ml and genetic risk factors.

Ages Between 40-49

 

PSA 2.0 ng/ml

 

Ages Between 50-59

 

PSA 2.5 ng/ml

 

Ages Between 60-69

 

PSA 4.0 ng/ml

 

70 and above

 

PSA 5.5 ng/ml

 

Biopsy with Ultrasound:: It’s a procedure conducted to establish a final diagnosis of the prostate cancer. It’s conducted by taking 10 pieces from the prostate together with ultrasound probe by applying local anesthetic substance with an 18 G injector to the anus. Parenchyma can be detected after the pieces obtained are analyzed. A positive biopsy helps establishing the final diagnosis, however, the negative biopsy doesn’t always mean an absence of cancer. If the biopsy is negative and the patient has the same risk factors, another biopsy should be conducted. Studies show that the results change in the rate between 30-50% during the reapplied biopsies. Type and grade of the tumor are determined after the pieces are examined pathologically. Majority of prostate cancer is pathologically called adenocarcinoma. Other pathologic types (sarcoma, lymphoma etc.) can also be seen rarely. The pathologic grading system is the Gleason system. It’s possible to learn about the metastasis condition, progress, and treatment type for the disease by grading the tumor according to this system. Gleason score is defined by two numbers as 1+2 and the total score is evaluated. Grading is carried out as follows according to Gleason score:

 

Gleason score (total)

 

Grade

 

2-4

 

Well-differentiated

 

5-6

 

Averagely differentiated

 

7

 

Average-poorly differentiated

 

8-10

 

Poorly differentiated

 

 

STAGING

Staging and grading system required for the treatment of prostate cancer is done after the pathologic diagnosis. After the diagnosis, if the PSA level is over 20 ng/ml, it’s checked if the diseases spread over the bones by conducting a bone scan. Disease with metastasis over bones is an advanced stage one and requires a totally different technique of treatment.

 

The TNM system is used for staging. According to this system;

 

T: Primary tumor

  • Tx: Primary tumor focus couldn’t be found
  • T0: No sign of primary tumor
  • T1: Tumor couldn’t be detected through clinical examination and display methods
  • T1a: Less than 5% of tumor in TUR (transurethral prostate resection) material
  • T1b: Over 5% tumor in TUR material
  • T1c: tumor diagnosed through needle biopsy after high PSA, group with normal DRE (digital rectal examination).

 

  • T2: Tumor has been detected within prostate tissue.
  • T2a: Tumor covers half or less than half of a lobe
  • T2b: Tumor covers more than half of a lobe
  • T2c: Tumor covers both lobes

 

  • T3: Tumor has exceeded prostate capsule
  • T3a: One or two-sided extra capsular metastasis
  • T3b: Metastasis towards seminal vesicles.

 

  • T4: Tumor is fixed and invaded other surrounding organs as bladder neck, external sphincter, rectum and pelvic wall except for seminal vesicle.

 

N: Regional Lymph Nodes

  • Nx: Metastasis over lymph nodes is impossible
  • N0: No metastasis towards lymph nodes
  • N1: Metastasis towards lymph nodes

 

M: Distant Metastasis (Invasion)

  • Mx: Distant Metastasis Impossible
  • M0: No Distant Metastasis
  • M1: Presence of distant metastasis
  • M1a: Metastasis over lymph nodes that are not regional
  • M1b: Bone metastasis
  • M1c: Metastasis over distant organs

 

 

Diagnosis and Staging Principles for Prostate Cancer

 

  1. The doctor should suspect prostate cancer in case of abnormal digital rectal examination finding or increased serum PSA level. The upper level of PSA is 2.5-3 ng/ml.
  2. Diagnosis of prostate cancer requires pathologic confirmation. If the patient needs a further treatment, then prostate biopsy and advanced staging tools should be used.
  3. Biopsy with ultrasound should be conducted in the presence of a prostate cancer suspicion. Minimum 6-10 pieces should be taken from the peripheral zone of the prostate.
  4. The local anesthetic substance should be applied during prostate biopsy.
  5. Obtaining pieces from the central area of the prostate is unnecessary
  6. In case of abnormal examination finding, high PSA level, cancer suspicion after the first biopsy, a second one should be conducted.
  7. For local prostate cancer diagnosis; positive piece number in the biopsy, serum PSA level, and pathologic grade are enough
  8. Lymph node involvement should be considered for the patients that are expected to fully recover.
  9. Lymph node involvement rate is 10% when the clinic stage is T2 or less, Gleason score is 6 or less and PSA level is 20 or less.
  10. Skeletal metastasis is best checked through bone scintigraphy. If the serum PSA level is below 20 and the patient is asymptomatic, then it’s unnecessary to conduct one.

 

TREATMENT

 

The treatment method is determined according to the stage. Prostate cancer treatment options are:

 

STAGE

 

TREATMENT OPTION

 

REMARK

 

T1a

 

Meticulous Monitoring Treatment

 

It can be treated for the patients that are expected to live less than 10 years. If the life expectancy is more, another evaluation should be carried out.

 

 

 

Radical prostatectomy (complete removal of the prostate)

 

It should be conducted on young patients and the ones that are expected to live for longer periods.

 

 

 

Radiotherapy (brachytherapy-interstitial radiotherapy)

 

It should be conducted on young patients and the ones that are expected to live for longer periods.

 

STAGE

 

TREATMENT OPTION

 

REMARK

 

 

 

Hormonal treatment

 

It’s not an option

 

 

 

Combination treatment

 

It’s not an option.

 

T1b-T2b

 

Meticulous monitoring treatment

 

It can be conducted on the patients with no symptoms and are expected to live less than 10 years.

 

 

 

Radical prostatectomy (complete removal of the prostate)

 

Standard treatment.

 

 

 

Radiotherapy

 

It should be conducted on the patients that are expected to live more than 10 years but can’t have surgical procedures. It can also be applied on weak level tumors with 5-10 years of life expectancy.

 

 

 

Hormonal treatment

 

It should be applied in order to eliminate the symptoms on the patients that aren’t expected to fully recover but are symptomatic.

 

 

 

Combined treatment

 

  1. Hormonal treatment + radical prostatectomy 2. Hormonal treatment + radiotherapy

 

T3-T4

 

Meticulous monitoring treatment

 

It should be applied to asymptomatic T3 tumors and if the life expectancy is less than 10 years on well and average differentiated tumors

 

 

 

Radical prostatectomy (complete removal of the prostate)

 

Selected T3a and the patient is expected to live less than 10 years

 

 

 

Radiotherapy (brachytherapy-interstitial radiotherapy)

 

T3 and patient is expected to live more than 5-10 years

 

STAGE

 

TREATMENT OPTION

 

REMARK

 

 

 

Hormonal treatment

 

Symptomatic patients, T3, T4 and patients with PSA level over 25.

 

 

 

Combination treatment

 

  1. Radiotherapy + hormonal treatment 2.hormonal treatment + radical prostatectomy: no benefits observed

 

N + M0

 

Meticulous monitoring treatment

 

Asymptomatic patients.

 

 

 

Radical prostatectomy (complete removal of the prostate)

 

It’s not the standard treatment.

 

 

 

Radiotherapy (brachytherapy-interstitial radiotherapy)

 

It’s not the standard treatment.

 

 

 

Hormonal treatment

 

It’s not the standard treatment.

 

 

 

Combination treatment

 

It’s not the standard treatment.

 

M + (metastatic)

 

Meticulous monitoring treatment

 

It’s not the standard treatment.

 

 

 

Radical prostatectomy (complete removal of the prostate)

 

Not used

 

 

 

Radiotherapy (brachytherapy-interstitial radiotherapy)

 

Not used

 

 

 

Hormonal treatment

 

It’s the standard treatment option.

 

 

 

Combination treatment

 

Not used

 

 

 

How Is the Meticulous Monitoring Done in Prostate Cancer?

Patients slowly progressing and can’t be treated due to side effects of the treatment can be grouped under this protocol. In the patient group with the monitoring protocol, questions specific to the disease and regular digital rectal examination are carried out along with the serum PSA measurement. PSA measurement on every 3rd month, other biochemical tests and annual prostate needle biopsy is carried out and the progress is monitored. Display techniques such as bone scan can be used if needed.

 

Radical Prostatectomy in Prostate Cancer (SURGERY)

It’s the standard treatment method for the disease which is localized and doesn’t have distant metastasis. Radical prostatectomy is the removing procedure of prostate together with its capsule, seminal vesicles, and surrounding fat tissues.

 

Which patients should have radical prostatectomy?

 

  • The tumor is limited with prostate tissue (T1, T2 and selected T3a)
  • The ones without lymph node involvement
  • The ones without distant metastasis
  • Patients below 75 years old.

 

Prostatectomy types;

  1. Retropubic Prostatectomy: It’s conducted under general anesthesia. This procedure is conducted through the incision (section) under umbilicus. Nerve preserving surgery and removal of lymph nodes procedures can also be conducted through this surgical method.
  2. Perineal Prostatectomy: It’s conducted through a 4 cm incision on anus (perineal area). The advantage of this method is that the lymph nodes can’t be removed. Therefore, it should be applied meticulously on the selected patient group.
  3. Laparoscopic and Robotic Prostatectomy: It’s the procedure of conducting prostate surgery through a couple of holes without any sections on the abdomen. Robotic surgery is a more advanced technique and is based on controlling the devices in the abdomen through the robotic system. With the development of medical equipment and techniques today, various techniques as alternatives to radical prostatectomy have emerged. Laparoscopic Radical Prostatectomy has become an alternative to open surgery because of having the same high curing rates, decreased hospitalization period and cosmetic appearance.

 

 

 

During the 10-year follow-up monitoring of T1 and T2 tumors after prostatectomy, relapse rate ranges between 1-3%. Therefore, the ideal treatment for this patient group is radical prostatectomy.

 

Risks of Radical Prostatectomy

This surgery is an invasive procedure for cancer treatment. It requires 2-5 hours of anesthesia depending on the type of surgery. Therefore, this situation brings along some risks together with the need for anesthesia. The two most important problems of the surgery are urinary incontinence and erection problems. These risks have decreased dramatically in the light of technological advancements in recent years. Studies show that the incontinence rate ranges between 9-27% and the erection problem rate range between 30-49%.

 

Radiotherapy in Prostate Cancer (Brachytherapy)

Radiotherapy which is also called brachytherapy is based on high dose radiation on the prostate gland. There are two application methods. First one is external and the second one is internal which is also called interstitial radiotherapy. And this interstitial one is called brachytherapy. Here, the purpose is to prevent the parenchyma DNA from growing by damaging it. Brachytherapy is a different method applied by using specially produced applicators (special tools in which radioactive sources conducting irritation are placed) and plastic tubes placed in prostate gland or body cavities. There are two types of brachytherapies;

 

  1. Long-term low dose brachytherapy: Iodine -125 and Palladium-103 are used
  2. Periodic high dose brachytherapy: Iridium-194 is used.

It can be selected as the starting therapy of prostate cancer. It can be preferred for the patients who have < 6, PSA < 10 Gleason score, doesn’t have anything outside the prostate detected during digital rectal examination and prostate enlargement history. In the cases where this method is applied solely, the success rate is equivalent to surgery. External radiotherapy consists of many sessions and normal tissue can repair itself between the sessions, however, it also allows the tumor tissue to repair itself. Besides, all sides of the mass receive the same dose. Therefore, the dosage provided is limited to normal tissue tolerance. Brachytherapy is applied to a limited area and allows the protection of normal tissues better since the dose becomes less the further from the source. A good combination of brachytherapy and external radiotherapy may provide better tumor control and fewer side effects on normal tissues.

 

What Are the Risks?

Symptoms such as frequent urination, difficulty in urination, urination during the night may occur due to the irritation arising from the implants placed in the prostate. Additionally, mostly sexual problems (erection problems, inability to ejaculate or ejaculating in the bladder) occur after brachytherapy.

Hormonal Treatment in Prostate Cancer

Since prostate cancer is sensitive to the hormone called testosterone, it’s a frequently preferred method. Testosterone is an androgen and its presence is not desired when prostate cancer is the case. Removal of the testosterone within the circulation or prevention of its release is the basic principle of hormonal treatment.

 

Methods used for hormonal treatment;

  1. Orchiectomy (removal of testicles)
  2. Antiandrogen treatment
  3. LHRH analogs
  4. LHRH antagonists
  5. Estrogen treatment
  6. Combined hormonal treatment

 

Hormonal treatment is used in the cases of:

  • Patients with no possibility of having surgical procedures
  • Patients with distant metastasis
  • Patients with relapsing tumor after surgery or brachytherapy
  • Pre-surgical treatment (neoadjuvant hormonotherapy)

 

Side effects of hormonal treatment: Symptoms as sexual problems, breast size increase, nausea, stomach problems, and dizziness may occur due to suppression of testosterone hormone within the circulation.

 

Chemotherapy in Prostate Cancer

It’s used as an option for the cancer types resistant to hormones or advanced cancer types. Medications such as mitoxantrone, doxorubicin, paclitaxel, and estramustine phosphate are used for this purpose. Chemotherapy is a treatment type that is more different than hormonal treatment and has more side effects for the patient.

 

Cryotherapy in Prostate Cancer

Cryotherapy which means the treatment of prostate by freezing is the procedure of cooling and freezing the prostate by entering into the body with needles along with ultrasonography. Cryotherapy which is a new treatment method is a minimally invasive one. However, it’s still debatable whether it should be used as a first-line treatment as brachytherapy. It should be preferred after other first-line treatments or with the patients whose Gleason score is <6, PSA level<10, the tumor doesn’t have metastasis outside the prostate and prostate size is 50 cc and below as a first line treatment. Swelling in the genital area, pain, blood in the urine and sexual problems might occur due to this treatment.

Testicular Cancers

Diagnosis and Treatment of Testicular Cancers

Testicle tumors consist of 1-1.5% part of all malign tumors seen in males and are most common among the young population, unlike other cancer types. Recently the prevalence tends to increase even though it’s a slight one. However, approximately 70% of the diagnosed testicular cancers is stage 1 and almost 100% of these have the chance to be treated and cured. As a result of advancements in diagnostic methods, final tumor-detecting tools used following diagnosis and treatment, advancement in surgical techniques and new generation chemotherapy models, 80-100% of cure rates are possible even in metastatic disease. Testicle tumors are most common in advanced adolescent and early adult periods. The highest incidence is among young adult males. Some factors create risks for the progress of the disease.

 

 

 

 

Risk factors for the development of testicular cancer;

  • Undescended testicle history
  • Presence of Klinefelter syndrome
  • Testicle tumor history in the family
  • Other side testicle tumor history
  • Infertility history

 

Classification

Testicular cancers are typically divided into two. The most common type is germ cell cancer and prevalence is approximately 90%. Within this group, the most common one is seminoma. Seminoma constitutes 30-35% of germ cell tumors.

 

  1. Germ cell tumors
  • Seminoma
  • Embryonal carcinoma
  • Yolk-sac tumors
  • Choriocarcinoma
  • Teratoma
  • Mixed type

 

  1. Sex-cord stromal tumors
  • Leydig cell tumor
  • Sertoli cell tumors
  • Granulosa cell tumors
  • Thecomata
  • Mixed type tumors

 

Diagnosis

Patient history, physical examination, and testicle ultrasonography are the most valuable methods for diagnosis. Clinically painless, rigid and palpable mass lesion in the testicle is a sufficient enough symptom to suspect the tumor. The first thing to do with a patient like this is ultrasonography. Ultrasonography can both display the mass lesion in the testicle and also other pathologies in the abdomen if any.

 

 

(left testicular mass lesion)

 

Another test that is used for diagnosis is tumor markers. Values of these parameters checked in the blood can be high or normal depending on the type. Additionally, these tumor markers have a very important role in follow-up and determining the progress of the disease. Hormones with glycoprotein structures called alpha-fetoprotein (AFP), beta human choir gonado tropine (B-hCG) and lactate dehydrogenase (LDH) are checked as serum tumor markers. These hormones are released by tissues with the tumor, but they aren’t expected to increase in püre seminoma. Limited solid and rigid masses in the testicle should be regarded as testicle tumor unless otherwise proven.

In the case of not being sure in the diagnosis of testicle tumor, a structure of the mass can be analyzed through MR examination. However, the final diagnosis can be established through pathologic examination even though these diagnostic methods exist. Pathologic examination of testicle tumors is carried out by completely removing the testicle. This means that there are no procedures such as needle biopsy for testicle tumors.

 

Staging and Classification

In order to treat and monitor the disease correctly, a correct staging is required. For a correct staging, a full body scan will be needed. Abdomen and lung tomography should be conducted, serum tumor markers should be measured and the Characteristics of the mass in the testicle should be known very well. The TNM classification system is used for staging.

Primary tumor(T)

  • PTx: Primary tumor not found
  • PT0: No proof of primary tumor
  • Pris: Intratubular germ cell neoplasia
  • PT1: Tumor is limited to testicle and epididymis, no vascular or lymphatic invasion
  • PT2: Tumor is limited to testicle and epididymis, vascular or lymphatic invasion exists or tunica vaginalis involvement and metastasis beyond tunica albuginea.
  • PT3: Tumor is invasive in spermatic cord, vascular/lymphatic invasion exists or not
  • PT4: Tumor is invasive in scrotum skin, vascular/lymphatic invasion exists or not

 

Lymph Nodes (N)

  • Nx: Regional lymph node not found
  • N0: No lymph node metastasis
  • N1: Maximum 2 cm or less lymph node involvement or multiple lymph node involvements smaller than 2 cm
  • N2: Single lymph node involvement bigger than 2cm and smaller than 5cm or multiple lymph node involvements either of which is bigger than 2cm and smaller than 5cm
  • N3: Lymph node involvement bigger than 5cm

 

Distant metastasis (M)

  • M0: No sign of distant metastasis
  • M1: Distant metastasis
  • M1a: Lymph node involvement which is not regional or lung metastasis
  • M1b: Organ metastasis except for lungs

 

Serum tumor markers (S)

  • S0: Markers with normal values
  • S1: hCG is below 5000 and AFP is below 1000
  • S2: hCG is between 5000-50000 and AFP is between 1000-10000
  • S3: hCG is over 50000 and AFP is over 10000

 

Staging

It’s done by using the TNM classification system. Treatment and monitoring program is determined according to stages. Staging is as follows:

 

stage 1: T1-4, N0, M0

  • Stage1a: T1, N0, M0,SX
  • Stage1b: T2,3,4, N0, M0, S0

 

Stage2: either one of T, N1-3, M0, S1-3

  • Stage2a: either one of T, N1, M0, S0-1
  • Stage2b: either one of T, N2, M0, S0-1
  • Stage2c: either one of T, N3, M0, S0-1

 

Stage3: either one of T, N, either one of N, M1, SX-3

  • Stage3a: either one of T, either one of N, M1, S0-1
  • Stage3b: either one of T, either one of N, M0-1, S2
  • Stage3c: either one of T, either one of N, M1, either one of S

 

 

Steps for Testicular Cancer Diagnosis

  1. Testicular sonography is a must.
  2. The diagnosis can’t be established without conducting inguinal orchiectomy.
  3. Serum tumor markers should be definitely checked before and after orchiectomy.
  4. Intra-abdominal lymph nodes, lung area, and regional lymph nodes should be examined.

 

Treatment of Testicular Cancer

The first procedure to be conducted on the patients with diagnosed testicle tumor without losing any time is inguinal orchiectomy. This procedure is conducted through a small section on the inguinal (groin) area. After the removal of the testicle, sending it to pathology and acknowledgment of tumor type is required. Afterward, lymph nodes and distant metastasis of the patient are evaluated through lung and abdomen tomographies. After all this evaluation and orchiectomy, treatment should be applied according to tumor stage and type. Treatment options after orchiectomy are as follows:

 

Stage 1 Treatment of Seminomas

  1. Adjuvant radiotherapy: including abdomen and side of the inguinal area where the tumor stands.
  2. Adjuvant chemotherapy: It’s based on carboplatin. It can be used as an alternative to radiotherapy.
  3. Close follow-up.

 

Stage 2 Treatment of Seminomas

  1. Primary chemotherapy (BEP based chemotherapy)
  2. Adjuvant chemotherapy
  3. RPLND: Procedure for removing lymph nodes on the abdomen posterior wall. Success rate increases depending on the experience of the physician.

 

Stage 2 Treatment of Seminomas

  1. Primary chemotherapy (BEP based chemotherapy)
  2. Metastasectomy: Uzak bölgelere yayılan tümröün çıkarılması
  3. Adjuvant chemotherapy

 

Nonseminomataus Germ Cell Tumor Treatment;

Stage-1:

  1. If the patient is in the low-risk group (no vascular metastasis) and the tumor is PT1a, meticulous follow-up can be carried out after orchiectomy.
  2. Adjuvant chemotherapy or RPLND

 

Stage-2, 3

  1. Primary chemotherapy should be conducted at least twice.
  2. Chemotherapy + RPLND

 

Stage-4 Metastatic Disease

  1. At least 3 times of BEP chemotherapy
  2. RPLND if the serum markers are increasing
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